Clinical Focus


  • Acute leukemia
  • Hematology
  • Cancer > Hematology

Academic Appointments


Administrative Appointments


  • Director, Stanford Hospital Hematology Inpatient service (2011 - 2013)
  • Director, Stanford Acute Leukemia Clinical Research Program (2009 - 2013)
  • Panel member adult oncology committee, National comprehensive cancer network (2010 - 2013)
  • Acute Leukemia Panel Member, Southwest Oncology Group (SWOG) (2007 - 2013)
  • Panel Member Multiple Myeloma Committee, National Comprehensive Cancer Network (2007 - 2011)

Professional Education


  • Fellowship:University of Colorado Health Science Center (2005) CO
  • Fellowship, Acute leukemia, Princess Margaret Hospital - University of Toronto (2006)
  • Board Certification: Hematology, American Board of Internal Medicine (2006)
  • Board Certification: Medical Oncology, American Board of Internal Medicine (2005)
  • Residency:University of Colorado Health Science Center (2002) CO
  • Internship:University of Connecticut Health Center (2000) CT
  • Medical Education:University Federal Do Parana (1998) Brazil

Current Research and Scholarly Interests


My clinical activities combine the development of novel therapeutic modalities, translational research activities and epidemiological study of acute leukemia. My special focus is on the development of better, patient tailored therapies for young and elderly patients with acute leukemia.

Clinical Trials


  • Single Agent Lenalidomide in Adult Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia Not Recruiting

    Primary Objective: • Determine the complete response (CR) rate, duration of remission of single agent lenalidomide in patients with relapsed/refractory Acute Lymphoblastic Leukemia (ALL), after at least one previous treatment regimen. Secondary Objective: • Establish the toxicity profile for lenalidomide in this patient population

    Stanford is currently not accepting patients for this trial. For more information, please contact Leonel Gallegos, (650) 723 - 2781.

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  • Decitabine and Midostaurin in Treating Older Patients With Newly Diagnosed Acute Myeloid Leukemia Recruiting

    This phase II trial studies how well giving decitabine together with midostaurin works in treating older patients with newly diagnosed acute myeloid leukemia. Decitabine and midostaurin may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

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  • A Long-Term Study of the Effects of Orally Administered SAR302503 in Patients With Myelofibrosis Not Recruiting

    The purpose of this study is to evaluate the long-term effects of orally administered SAR302503 (TG101348) in patients with myelofibrosis who have completed the MF-TG101348-001 study.

    Stanford is currently not accepting patients for this trial. For more information, please contact Andrea Linder, (650) 725 - 4047.

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  • Combination Chemotherapy in Treating Young Patients With Newly Diagnosed Acute Lymphoblastic Leukemia Not Recruiting

    RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells. PURPOSE: This phase II trial is studying how well combination chemotherapy works in treating young patients with newly diagnosed acute lymphoblastic leukemia.

    Stanford is currently not accepting patients for this trial. For more information, please contact Joselene Sipin-Sayno, (650) 736 - 8113.

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  • Study to Determine the Maximum Tolerated Dose and Evaluate the Efficacy and Safety of CEP-18770 in Patients With Relapsed Multiple Myeloma Refractory to the Most Recent Therapy Not Recruiting

    The primary objective for part 1 of the study is to determine the maximum tolerated dose (MTD) of CEP-18770 in patients with relapsed and refractory multiple myeloma. The primary objective for part 2 is to evaluate the antitumor activity of CEP-18770 in patients treated at the MTD.

    Stanford is currently not accepting patients for this trial. For more information, please contact Leonel Gallegos, (650) 723 - 2781.

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  • To Demonstrate Superiority of Decitabine Over Azacitidine in Subjects With Intermediate- or High-risk MDS. Not Recruiting

    The purpose of this study is to compare the response of patients with Intermediate or High Risk myelodysplastic syndromes (MDS) following treatment with decitabine or azacitidine.

    Stanford is currently not accepting patients for this trial. For more information, please contact Mai Tran, (650) 723 - 8594.

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  • Dose Escalation Study of CAL-101 in Select Relapsed or Refractory Hematologic Malignancies Not Recruiting

    The purpose of this study is to determine the dose that can be safely given to see what effect it may have on your cancer and to determine how the drug is distributed in the body.

    Stanford is currently not accepting patients for this trial. For more information, please contact Michelle Takahashi, (650) 736 - 4032.

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  • Azacitidine + Lenalidomide Combo in the Elderly Previously Treated Acute Myeloid Leukemia (AML) & High-Risk Myelodysplastic Syndromes (MDS) Not Recruiting

    Primary Objective: - Determine the lack of disease progression (CR/CRi/PR/HI rate) after 6 cycles of treatment with the combination of azacitidine plus lenalidomide in previously treated patients with Acute Myeloid Leukemia (AML) and high-risk Myelodysplastic Syndromes (HR-MDS). Secondary Objective: - Determine the 42-day survival after treatment with this combination in elderly patients with previously treated AML/HR-MDS patients

    Stanford is currently not accepting patients for this trial. For more information, please contact Jack Taw, 650-723-2781.

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  • Evaluating the Safety of Long Term Dosing of Romiplostim (Formerly AMG 531) in Thrombocytopenic Subjects With Myelodysplastic Syndromes (MDS) Not Recruiting

    This is an open label extension study of romiplostim for treatment of thrombocytopenia (platelet count ≤ 50 x 10^9/L) in MDS subjects. The study is designed to assess the long-term safety of treatment with romiplostim, as measured by incidence of overall adverse events, the incidence of bleeding events, the utilization of platelet transfusions, and the duration of platelet response. The study will further describe the time to disease progression to acute myeloid leukemia (AML) and survival.

    Stanford is currently not accepting patients for this trial. For more information, please contact Mai Tran, (650) 723 - 8594.

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  • Vorinostat and Gemtuzumab Ozogamicin in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia Not Recruiting

    RATIONALE: Vorinostat may stop the growth of cancer cells by interfering with various proteins needed for cell growth. Monoclonal antibodies, such as gemtuzumab ozogamicin (GO), can block cancer growth in different ways. GO finds cancer cells and helps kill them by carrying a cancer-killing substance to them. Giving vorinostat together with gemtuzumab ozogamicin may kill more cancer cells. PURPOSE: This phase II trial is studying how well giving vorinostat together with gemtuzumab ozogamicin works in treating older patients with previously untreated acute myeloid leukemia.

    Stanford is currently not accepting patients for this trial. For more information, please contact Richa Rajwanshi, (650) 736 - 4031.

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  • A Study Being Conducted at Multiple Locations to Compare the Safety and Effectiveness of Three Different Treatment Regimens; 1) Lenalidomide, 2) Lenalidomide + Azacitidine, or 3) Azacitidine Alone in Newly Diagnosed Acute Myeloid Leukemia in Elderly Subjects ≥ 65 Years of Age Recruiting

    The aim of the study is to investigate the effect of a lenalidomide regimen, a sequential azacitidine plus lenalidomide regimen or an azacitidine regimen in elderly subjects 65 years or older with newly diagnosed AML.

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  • Phase III Study of CPX-351 Versus 7+3 in Patients 60-75 Years Old With Untreated High Risk (Secondary) Acute Myeloid Leukemia Recruiting

    To confirm the efficacy of CPX-351 compared to 7+3 as first line therapy in elderly patients (60-75 yrs) with high risk (secondary) Acute Myeloid Leukemia. The primary efficacy endpoint will be overall survival.

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  • S0535, Gemtuzumab and Combination Chemotherapy in Treating Patients With Previously Untreated Acute Promyelocytic Leukemia Not Recruiting

    RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as gemtuzumab, can block cancer growth in different ways. Some find cancer cells and help kill them or carry cancer-killing substances to them. Others interfere with the ability of cancer cells to grow and spread. Gemtuzumab may also stop the growth of promyelocytic leukemia by blocking blood flow to the cancer. Giving gemtuzumab together with combination chemotherapy may be more effective in treating promyelocytic leukemia. PURPOSE: This phase II trial is studying how well giving gemtuzumab together with combination chemotherapy works in treating patients with previously untreated promyelocytic leukemia.

    Stanford is currently not accepting patients for this trial. For more information, please contact Nini Estevez, (650) 725 - 4041.

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  • Efficacy and Safety of Midostaurin in Patients With Aggressive Systemic Mastocytosis or Mast Cell Leukemia Not Recruiting

    This study will investigate if the drug midostaurin taken orally twice daily is effective and safe in treating patients with aggressive systemic mastocytosis or mast cell leukemia with or without an additional hematological neoplasm.

    Stanford is currently not accepting patients for this trial. For more information, please contact Andrea Linder, (650) 725 - 4047.

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  • Compare Bosutinib To Imatinib In Subjects With Newly Diagnosed Chronic Phase Philadelphia Chromosome Positive CML Not Recruiting

    Two-arm, randomized, open-label trial designed to evaluate the efficacy and safety of bosutinib alone compared to imatinib alone in subjects newly diagnosed with chronic phase Chronic Myelogenous Leukemia (CML). The primary endpoint is cytogenetic response rate at one year.

    Stanford is currently not accepting patients for this trial. For more information, please contact Michelle Takahashi, (650) 736 - 4032.

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  • A Trial of the Combination 5-azacitidine and Gemtuzumab Ozogamicin Therapy for Treatment of Relapsed Acute Myeloid Leukemia (AML) Not Recruiting

    This study will test an experimental combination of the drugs Mylotarg and 5-azacitidine in the hopes of finding a treatment that may be effective against Acute Myeloid Leukemia that has come back after treatment.

    Stanford is currently not accepting patients for this trial. For more information, please contact Jack Taw, (650) 723 - 2781.

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  • A Dose Escalation Study of Lenalidomide in Relapsed or Refractory B-cell Chronic Lymphocytic Leukemia Not Recruiting

    The purpose of this study is to evaluate the safety of lenalidomide and to define the maximum tolerated escalation dose level (MTEDL) when administered by a stepwise dose-escalation schedule in subjects with relapsed or refractory B-cell CLL.

    Stanford is currently not accepting patients for this trial. For more information, please contact Michelle Takahashi, (650) 736 - 4032.

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  • S0703 Azacitidine and Gemtuzumab Ozogamicin in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia Not Recruiting

    This phase II trial is studying the side effects of giving azacitidine together with gemtuzumab ozogamicin to see how well it works in treating older patients with previously untreated acute myeloid leukemia. Drugs used in chemotherapy, such as azacitidine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Azacitidine may also stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as gemtuzumab ozogamicin, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving azacitidine together with gemtuzumab ozogamicin may kill more cancer cells.

    Stanford is currently not accepting patients for this trial. For more information, please contact Joselene Sipin-Sayno, (650) 736 - 8113.

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  • COntrolled MyeloFibrosis Study With ORal JAK Inhibitor Treatment: The COMFORT-I Trial Not Recruiting

    This was a randomized, double-blind study comparing the efficacy and safety of ruxolitinib (INCB018424) tablets to matching placebo tablets in patients diagnosed with Myelofibrosis (either Primary Myelofibrosis (PMF) or Post-Polycythemia Vera Myelofibrosis (PPV-MF) or Post-Essential Thrombocythemia Myelofibrosis (PET-MF).

    Stanford is currently not accepting patients for this trial. For more information, please contact Andrea Linder, (650) 725 - 4047.

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  • Vorinostat, Azacitidine, and Gemtuzumab Ozogamicin in Treating Older Patients With Relapsed or Refractory Acute Myeloid Leukemia Not Recruiting

    The purpose of this study is to test the safety of vorinostat (Zolinza) and azacitidine (Vidaza) when combined with gemtuzumab ozogamicin (GO) at different dose levels. These drugs increase the effect of GO against leukemia cells in the test tube, but we don't know yet whether they also increase the anti-leukemia effect of GO in people.

    Stanford is currently not accepting patients for this trial. For more information, please contact Leonel Gallegos, (650) 723 - 2781.

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  • Phase I Bortezomib (VELCADE) in Combo With Pralatrexate in Relapsed/Refractory MM Not Recruiting

    This is an open-label Phase I dose-escalation safety study of VELCADE in combination with pralatrexate in patients with previously treated multiple myeloma. In a standard 3+3 dose escalation trial design, escalating doses of pralatrexate in combination with VELCADE will be studied sequentially, with at least 3 patients in each dose level until the MTD is determined. Dose limiting toxicity (DLT) and MTD are determined during cycle 1 of treatment.

    Stanford is currently not accepting patients for this trial. For more information, please contact Vani Jain, (650) 725 - 5459.

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  • Panobinostat or Placebo With Bortezomib and Dexamethasone in Patients With Relapsed Multiple Myeloma Not Recruiting

    Panobinostat (LBH589) is a highly potent pan-deacetylase inhibitor (pan-DACi), inclusive of HDAC6, which disrupts aggresome function, promotes accumulation of cytotoxic misfolded protein aggregates and triggers myeloma cell death. Combination of pan-DAC and protease inhibition by co-treatment with panobinostat (PAN) and bortezomib (BTZ) has demonstrated synergistic cytotoxicity in vitro and in vivo in pre-clinical experiments. Furthermore, clinical experience in advanced multiple myeloma (MM) patients treated by oral panobinostat and i.v bortezomib ± dexamethasone showed very encouraging results for efficacy and manageable toxicity profile. Given the medical need for improved treatment strategies for patients with previously treated and relapsed MM, the purpose of this prospective, multinational, randomized, double-blind, placebo-controlled, parallel group Phase III study is to compare the results in progression-free survival of 2 combination therapies, panobinostat with bortezomib and dexamethasone or placebo with bortezomib and dexamethasone, in patients with previously treated MM whose disease has recurred or progressed.

    Stanford is currently not accepting patients for this trial. For more information, please contact Nini Estevez, (650) 725 - 4041.

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  • Bortezomib and Dexamethasone With or Without Lenalidomide in Treating Patients With Multiple Myeloma Previously Treated With Dexamethasone Not Recruiting

    This randomized phase III trial is studying bortezomib, dexamethasone, and lenalidomide to see how well they work compared with bortezomib and dexamethasone in treating patients with multiple myeloma previously treated with dexamethasone. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Lenalidomide may stimulate the immune system in different ways and stop cancer cells from growing. It is not yet known whether giving bortezomib together with dexamethasone is more effective with or without lenalidomide in treating multiple myeloma.

    Stanford is currently not accepting patients for this trial. For more information, please contact Nancy Mori, (650) 724 - 0201.

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  • Phase II Study of AS1411 Combined With Cytarabine to Treat Acute Myeloid Leukemia Not Recruiting

    The overall aim of this study is to assess the efficacy and safety of AS1411, over a range of doses, when combined with cytarabine, in the treatment of patients with primary refractory or relapsed acute myeloid leukemia (AML).

    Stanford is currently not accepting patients for this trial. For more information, please contact Richa Rajwanshi, (650) 736 - 4031.

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  • Allogeneic HCT Using Nonmyeloablative Host Conditioning With TLI & ATG vs SOC in AML Not Recruiting

    Acute myeloid leukemia (AML) is a cancer of the bone marrow that mostly affects older adults. Even with the best chemotherapy, two-year disease-free survival is achieved in a minority of patients. Bone marrow transplantation from a sibling donor may improve cure rates; however, patients over 50 years of age have a high risk of complications and therefore generally are excluded from this treatment option. Recently our group developed a transplantation strategy for older cancer patients that protects against transplant-associated complications, yet does not interfere with the ability of the transplanted donor cells to destroy cancer cells. With this new method, we can now safely evaluate transplantation as a curative therapy for AML patients over the age of 50. We have assembled clinical and scientific researchers throughout the state of California to study and compare bone marrow transplantation using our new approach with the best standard of care chemotherapy in AML patients over the age of 50. The results of this study have the potential to establish a new treatment standard that will improve survival of older AML patients.

    Stanford is currently not accepting patients for this trial. For more information, please contact BMT Referrals, 650-725-1647.

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  • S0919 Idarubicin, Cytarabine, and Pravastatin in Treating Patients With Relapsed Acute Myeloid Leukemia Recruiting

    RATIONALE: Drugs used in chemotherapy, such as idarubicin and cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Pravastatin may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Pravastatin may also help idarubicin and cytarabine work better by making cancer cells more sensitive to the drugs. Giving idarubicin and cytarabine together with pravastatin may kill more cancer cells. PURPOSE: This phase II trial is studying how well giving idarubicin and cytarabine together with pravastatin works in treating patients with relapsed acute myeloid leukemia.

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  • Safety & Efficacy Study of Oral Panobinostat (LBH589) With Chemotherapy in Patients < 65 Years Old With Acute Myeloid Leukemia (AML) Recruiting

    This study will be conducted to assess the maximum tolerated dose (MTD) of panobinostat given 3 times a week (administered on weeks 2 and 3 of a 4 week cycle) in combination with induction chemotherapy (idarubicin and cytarabine) in newly diagnosed patients with a cytopathologically confirmed diagnosis of high-risk AML, and to investigate the safety of the combination in this regimen.

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  • Phase I/II of Azacitidine + Lenalidomide for Previously Untreated Elderly Patients With Acute Myeloid Leukemia Not Recruiting

    The purpose of this study is to first determine the highest dose of the drugs that can be safely taken. The study will look at the side effects of the combination and whether the treatment schedule is tolerated. After the right dose is determined, the study will look at whether the combination is effective in patients with AML who are older than 60 and have never been treated before.

    Stanford is currently not accepting patients for this trial. For more information, please contact Leonel Gallegos, (650) 723 - 2781.

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  • S0910 Epratuzumab, Cytarabine, and Clofarabine in Treating Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia Not Recruiting

    RATIONALE: Monoclonal antibodies, such as epratuzumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy, such as cytarabine and clofarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving epratuzumab together with cytarabine and clofarabine may kill more cancer cells. PURPOSE: This phase II trial is studying the side effects and how well giving epratuzumab together with cytarabine and clofarabine works in treating patients with relapsed or refractory acute lymphoblastic leukemia.

    Stanford is currently not accepting patients for this trial. For more information, please contact Nini Estevez, (650) 725 - 4041.

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  • Study to Investigate Idelalisib in Combination With Chemotherapeutic Agents, Immunomodulatory Agents and Anti-CD20 Monoclonal Antibody (mAb) in Subjects With Relapsed or Refractory Indolent B-cell Non-Hodgkin's Lymphoma, Mantle Cell Lymphoma or Chronic Lymphocytic Leukemia Recruiting

    The purpose of this study is to evaluate the safety and clinical activity of idelalisib in combination with CD20 mAb chemotherapeutic agents, Immunomodulatory Agents, mTOR inhibitors and proteasome inhibitor in participants with hematologic malignancies.

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  • Study of Lenalidomide to Evaluate Safety and Efficacy in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia Not Recruiting

    The purpose of this study is to determine the safety and effectiveness of different dose regimen of lenalidomide in patients with relapsed or refractory chronic lymphocytic leukemia.

    Stanford is currently not accepting patients for this trial. For more information, please contact Tessa Hunter, (650) 736 - 4032.

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  • Daunorubicin, Cytarabine, and Midostaurin in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia Not Recruiting

    RATIONALE: Drugs used in chemotherapy, such as daunorubicin and cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Midostaurin may help daunorubicin and cytarabine work better by making cancer cells more sensitive to the drugs. Midostaurin also may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. It is not yet known whether combination chemotherapy is more effective with or without midostaurin in treating acute myeloid leukemia. PURPOSE: This randomized phase III trial is studying giving daunorubicin and cytarabine with or without midostaurin followed by high-dose cytarabine and midostaurin to see how well it works in treating patients with newly diagnosed acute myeloid leukemia.

    Stanford is currently not accepting patients for this trial. For more information, please contact Leonel Gallegos, (650) 723 - 2781.

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  • Safety, Efficacy, & Pharmacokinetic Study of Tamibarotene to Treat Patients With Relapsed or Refractory APL Not Recruiting

    This is a Phase II, open-label, non-randomized study to evaluate the safety, efficacy, and pharmacokinetics of tamibarotene in adult patients with relapsed or refractory acute promyelocytic leukemia (APL) following treatment with all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO). Patients must have received and failed therapy with ATRA and ATO. Treatment may have been administered either as combination therapy or sequentially as single agents. Patients who are intolerant to either drug are eligible for this study.

    Stanford is currently not accepting patients for this trial. For more information, please contact Michelle Takahashi, (650) 736 - 4032.

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  • A Randomized, Double-Blind and Placebo-Controlled Study of Idelalisib in Combination With Rituximab for Previously Treated Chronic Lymphocytic Leukemia (CLL) Not Recruiting

    This Phase 3, randomized, double-blind, placebo-controlled study is to evaluate the effect of idelalisib on the onset, magnitude, and duration of tumor control, combined with rituximab, in participants previously treated for chronic lymphocytic leukemia (CLL). Eligible patients will be randomized with a 1:1 ratio into 1 of the 2 treatment arms to receive either idelalisib or placebo and rituximab. Participants who are tolerating primary study therapy but experience definitive CLL progression are eligible to receive active idelalisib therapy in the extension study, GS-US-312-0117.

    Stanford is currently not accepting patients for this trial. For more information, please contact Tessa Hunter, (650) 736 - 4032.

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  • Extension Study of Idelalisib for Patients With Chronic Lymphocytic Leukemia Who Participated in GS-US-312-0116 Not Recruiting

    This study (GS-US-312-0117) is a multicenter, 2-arm, double-blind, parallel-group extension study that is a companion study to Study GS-US-312-0116, to evaluate the effect of idelalisib on the onset, magnitude, and duration of tumor control.

    Stanford is currently not accepting patients for this trial. For more information, please contact Tessa Hunter, (650) 736 - 4032.

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  • Determination of Safe and Effective Dose of Romiplostim (AMG 531) in Subjects With Myelodysplastic Syndrome (MDS)Receiving Hypomethylating Agents Not Recruiting

    The purpose of this study is to evaluate the effect of Romiplostim (AMG 531) on the incidence of clinically significant thrombocytopenic events (grade 3 or 4 and/or receipt of platelet transfusions) in subjects with low or intermediate risk Myelodysplastic Syndrome (MDS) receiving hypomethylating agents. It is hypothesized that Romiplostim administration, at the appropriate dose and schedule, will result in reduction in the incidence of clinically significant thrombocytopenic events in low or intermediate risk MDS subjects receiving hypomethylating agents.

    Stanford is currently not accepting patients for this trial. For more information, please contact Mai Tran, (650) 723 - 8594.

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  • Phase I/II Amrubicin in Combo With Lenalidomide + Weekly Dexamethasone in Relapsed/Refractory Multiple Myeloma Recruiting

    PRIMARY OBJECTIVES - Establish the maximum tolerated dose (MTD) and toxicity profile for the combination of amrubicin with lenalidomide and dexamethasone in previously treated adult patients with multiple myeloma during Phase I - Determine the combined rate of complete response (CR) and very good partial response (VGPR) for this combination in this population as defined by the International Myeloma Working Group Uniform Response Criteria (IMWGURC) SECONDARY OBJECTIVES - Determine the overall response rate (CR, VGPR and PR) - Assess additional evidence of ant-tumor activity as measured by duration of response (DOR), progression-free survival (PFS), time to tumor progression (TTP), and overall survival (OS)

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  • Azacitidine With or Without Entinostat in Treating Patients With Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia, or Acute Myeloid Leukemia Not Recruiting

    This randomized phase II trial is studying azacitidine and entinostat to see how well they work compared to azacitidine alone in treating patients with myelodysplastic syndromes, chronic myelomonocytic leukemia, or acute myeloid leukemia. Drugs used in chemotherapy, such as azacitidine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Entinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving azacitidine together with entinostat may kill more cancer cells.

    Stanford is currently not accepting patients for this trial. For more information, please contact Mai Tran, (650) 723 - 8594.

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  • Combination Chemotherapy With or Without Donor Stem Cell Transplant in Treating Patients With Acute Lymphoblastic Leukemia Not Recruiting

    This phase II trial is studying the side effects of giving combination chemotherapy together with or without donor stem cell transplant and to see how well it works in treating patients with acute lymphoblastic leukemia. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells. Giving chemotherapy and total-body irradiation before a donor stem cell transplant helps stop the growth of cancer cells. It also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect).

    Stanford is currently not accepting patients for this trial. For more information, please contact Vani Jain, (650) 725 - 5459.

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  • Phase II Study of VELCADE for Relapsed or Refractory T-cell Prolymphocytic Leukemia Not Recruiting

    We hope to learn more about the clinical efficacy of bortezomib in T-cell prolymphocytic leukemia. Patients will be selected as a possible participant in this study because they have a bone marrow disorder known as T-cell prolymphocytic leukemia (T-cell PLL) which does not tend to respond well to conventional treatment with chemotherapy.

    Stanford is currently not accepting patients for this trial. For more information, please contact Richa Rajwanshi, (650) 736 - 4031.

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  • Phase 3 Study Comparing Carfilzomib, Lenalidomide, and Dexamethasone (CRd) vs Lenalidomide and Dexamethasone (Rd) in Subjects With Relapsed Multiple Myeloma Not Recruiting

    To compare progression-free survival in subjects with relapsed multiple myeloma who are receiving CRd vs subjects receiving Rd in a randomized multicenter setting.

    Stanford is currently not accepting patients for this trial. For more information, please contact Nini Estevez, (650) 725 - 4041.

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  • Phase II Temozolomide + Vorinostat in Patients (>60) w/ Newly Diagnosed or Relapse/Refractory AML Recruiting

    The primary endpoint of the study is to determine the clinical efficacy as determined by the rate of morphological complete remission, of 2 different treatment regimens of temozolomide and vorinostat in patients with AML and poor prognostic features.

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  • Safety Study of CAT-8015 Immunooxin in Patients With HCL With Advance Disease Not Recruiting

    RATIONALE: The CAT-8015 immunotoxin can bind tumor cells and kill them without harming normal cells. This may be an effective treatment for hairy cell leukemia(HCL) that has not responded to chemotherapy, surgery or radiation therapy. PURPOSE: Phase I dose escalation study to determine the maximum tolerated dose of CAT-8015 immunotoxin in treating patients who have hairy cell leukemia (HCL) that has not responded to treatment.

    Stanford is currently not accepting patients for this trial. For more information, please contact Michelle Takahashi, (650) 736 - 4032.

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  • Efficacy and Safety Study of Idelalisib in Patients With Indolent B-Cell Non-Hodgkin Lymphoma Not Recruiting

    The purpose of this study is to evaluate the efficacy and safety of idelalisib in patients with previously treated indolent Non-Hodgkin Lymphoma (iNHL) that is refractory both to rituximab and to alkylating-agent-containing chemotherapy. The primary objective will be to assess the overall response rate. Eligible patients will initiate oral therapy with idelalisib at a starting dose of 150 mg taken twice per day. Treatment with idelalisib can continue in compliant patients as long as the study is still ongoing and the patients appear to be benefiting from treatment with acceptable safety.

    Stanford is currently not accepting patients for this trial. For more information, please contact Tessa St.Rose, (650) 736 - 4032.

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  • Extension Study Evaluating the Long Term Safety and Efficacy Study of CYT387 in Primary Myelofibrosis (PMF) or Post-polycythemia Vera (PV) or Post-essential Thrombocythemia (ET) Not Recruiting

    This extension protocol to the core study CCL09101 allows patients who have tolerated the drug and derived a clinical benefit, to continue to receive treatment beyond the 9 cycles of the core protocol. Long term safety and efficacy of CYT387 will be evaluated.

    Stanford is currently not accepting patients for this trial. For more information, please contact Andrea Linder, (650) 725 - 4027.

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  • Efficacy Study of Oral Sapacitabine to Treat Acute Myeloid Leukemia in Elderly Patients Not Recruiting

    The main objective of this study is to learn which sapacitabine treatment is more likely to keep the cancer in check for at least one year in AML patients who are at least 70 years of age or older and in MDS patients who are at least 60 years of age.

    Stanford is currently not accepting patients for this trial. For more information, please contact Michelle Takahashi, (650) 736 - 4032.

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  • Clofarabine, Cytarabine, and Filgrastim in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia, Advanced Myelodysplastic Syndrome, and/or Advanced Myeloproliferative Neoplasm Not Recruiting

    This phase II trial is studying how well giving clofarabine and cytarabine together with filgrastim works in treating patients with newly diagnosed acute myeloid leukemia (AML), advanced myelodysplastic syndrome (MDS), and/or advanced myeloproliferative neoplasm. Drugs used in chemotherapy, such as clofarabine and cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving the drugs in different doses may kill more cancer cells. Colony stimulating factors, such as filgrastim, may increase the number of immune cells found in bone marrow or peripheral blood and may help the immune system recover from the side effects of chemotherapy.

    Stanford is currently not accepting patients for this trial. For more information, please contact Leonel Gallegos, (650) 723 - 2781.

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  • Analysis of Cutaneous and Hematologic Disorders by High-Throughput Nucleic Acid Sequencing Recruiting

    The goal of this study is to identify genetic changes associated with the initiation, progression, and treatment response of response of cutaneous and hematologic disorders using recently developed high-throughput sequencing technologies. The improved understanding of the genetic changes associated with cutaneous and hematologic disorders may lead to improved diagnostic, prognostic and therapeutic options for these disorders.

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  • MLN4924 for the Treatment of Acute Myelogenous Leukemia, Myelodysplastic Syndrome, and Acute Lymphoblastic Leukemia Not Recruiting

    An open-label, multicenter, phase 1, dose escalation study of MLN4924 in adult patients with acute myelogenous leukemia (AML), high-grade myelodysplastic syndrome (MDS). The patient population will consist of adults previously diagnosed with AML including high-grade MDS for which standard curative, life-prolonging treatment does not exist or is no longer effective.

    Stanford is currently not accepting patients for this trial. For more information, please contact Leonel Gallegos, (650) 723 - 2781.

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  • Phase 2 Study of Temozolomide to Treat Poor Risk / Refractory Acute Myeloid Leukemia Not Recruiting

    Open-label, non-randomized, parallel assignment, phase 2 trial assessing the safety and efficacy of distinct temozolomide treatment regimens for patients with AML and poor prognosis

    Stanford is currently not accepting patients for this trial. For more information, please contact Richa Rajwanshi, (650) 736 - 4031.

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  • Safety and Efficacy Study of CYT387 in Primary Myelofibrosis (PMF) or Post-polycythemia Vera (PV) or Post-essential Thrombocythemia (ET) Not Recruiting

    This study seeks to (i) determine a safe and tolerated dose of CYT387 given to patients with PMF, post-PV or post-ET and, (ii) assess the effectiveness of orally-administered CYT387 as a treatment for PMF, post-PV or post-ET.

    Stanford is currently not accepting patients for this trial. For more information, please contact Andrea Linder, (650) 725 - 4047.

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  • A Study of Idelalisib and Rituximab in Elderly Patients With Untreated CLL or SLL Recruiting

    This study is to evaluate the safety and clinical activity of idelalisib alone and in combination with rituximab in patients with CLL or SLL. This Phase 2 study will be the first time that idelalisib is administered to previously untreated patients with hematologic malignancies. Idelalisib has demonstrated clinical activity as a single agent in relapsed or refractory CLL and SLL with acceptable toxicity, which supports its evaluation in previously untreated patients. The study population is limited to patients over 65 years of age because younger patients are generally appropriate for standard immunochemotherapy regimens that are highly active. Since the mechanism of action of idelalisib is distinct from rituximab, it is hypothesized that the combination will be more active than either agent alone. This study will establish initial safety and clinical activity of idelalisib in combination with rituximab in patients with CLL or SLL. Cohort 2 of this study will establish safety and clinical activity of idelalisib alone in subjects with untreated CLL or SLL.

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  • A Study of Clofarabine and Cytarabine for Older Patients With Relapsed or Refractory Acute Myelogenous Leukemia (AML)(CLASSIC I) Not Recruiting

    Clofarabine (injection) is approved by the Food and Drug Administration (FDA) for the treatment of pediatric patients 1 to 21 years old with relapsed acute or refractory lymphoblastic leukemia (ALL) who have had at least 2 prior treatment regimens. There is no recommended standard treatment for relapsed or refractory acute myelogenous leukemia in older patients. Cytarabine is the most commonly used drug to treat these patients. This study will determine if there is benefit by combining clofarabine with cytarabine. Patients will be randomized to receive up to 3 cycles of treatment with either placebo in combination with cytarabine or clofarabine in combination with cytarabine. Randomization was stratified by remission status following the first induction regimen (no remission [i.e., CR1 = refractory] or remission <6 months vs CR1 = remission ≥6 months). CR1 is defined as remission after first pre-study induction regimen. The safety and tolerability of clofarabine in combination with cytarabine and cytarabine alone will be monitored throughout the study.

    Stanford is currently not accepting patients for this trial. For more information, please contact Richa Rajwanshi, (650) 736 - 4031.

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  • Cytarabine and Daunorubicin Hydrochloride or Idarubicin and Cytarabine With or Without Vorinostat in Treating Younger Patients With Previously Untreated Acute Myeloid Leukemia Recruiting

    This randomized phase III trial studies cytarabine and daunorubicin hydrochloride or idarubicin and cytarabine with or without vorinostat to see how well they work in treating younger patients with previously untreated acute myeloid leukemia. Drugs used in chemotherapy, such as cytarabine, daunorubicin hydrochloride, idarubicin, and vorinostat, work in different ways to stop the growth of cancer cells, either by killing the cells or stopping them from dividing. Giving more than one drug (combination chemotherapy) and giving the drugs in different doses and in different combinations may kill more cancer cells. It is not yet known which combination chemotherapy is more effective in treating acute myeloid leukemia.

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  • An Extension Study for Subjects Who Are Deriving Benefit With Idelalisib (GS-1101; CAL-101) Following Completion of a Prior Idelalisib Study Recruiting

    This is a long-term safety extension study of idelalisib (GS-1101; CAL-101) in patients with hematologic malignancies who complete other idelalisib studies. It provides the opportunity for patients to continue treatment as long as the patient is deriving clinical benefit. Patients will be followed according to the standard of care as appropriate for their type of cancer. The dose of idelalisib will generally be the same as the dose that was administered at the end of the prior study, but may be titrated up to improve clinical response or down for toxicity. Patients will be withdrawn from the study if they develop progressive disease, unacceptable toxicity related to idelalisib, or if they no longer derive clinical benefit in the opinion of the investigator.

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  • Study of MLN4924 Plus Azacitidine in Treatment-Naïve Patients With Acute Myelogenous Leukemia (AML) Who Are 60 Years or Older Recruiting

    This study is an open-label, multicenter, phase 1b, dose-escalation study of MLN4924 in combination with azacitidine in adult patients with AML. The patient population will consist of patients 60 years of age or older, previously diagnosed with World Health Organization(WHO)-defined AML, who are unlikely to benefit from standard induction therapy and who have not received definitive treatment for AML or prior treatment with azacitidine or decitabine.

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  • Efficacy and Safety of GS-6624 in Adults With Primary, Post Polycythemia Vera or Post Essential Thrombocythemia Myelofibrosis Recruiting

    This study is to evaluate the efficacy and safety of GS-6624 on bone marrow fibrosis either alone or in combination with ruxolitinib in participants with Primary myelofibrosis (PMF) and Post Polycythemia Vera or Post Essential Thrombocythemia Myelofibrosis (ET/PV MF). The study is designed as a two stage trial. In the stage 1, patients will be randomized into two cohorts to receive either 200 or 700 mg of study drug. In the stage 2, patients on ruxolitinib will be randomized to receive either 200 or 700 mg of study drug.

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  • Study to Determine Efficacy and Safety of Lenalidomide Plus Low-dose Dexamethasone Versus Melphalan, Prednisone, Thalidomide in Patients With Previously Untreated Multiple Myeloma Not Recruiting

    The purpose of this study is to compare the safety and efficacy of Lenalidomide plus low dose dexamethasone to that of the combination of melphalan, prednisone and thalidomide.

    Stanford is currently not accepting patients for this trial. For more information, please contact Nini Estevez, (650) 725 - 4041.

    View full details

2013-14 Courses


Journal Articles


  • Preleukemic mutations in human acute myeloid leukemia affect epigenetic regulators and persist in remission. Proceedings of the National Academy of Sciences of the United States of America Corces-Zimmerman, M. R., Hong, W., Weissman, I. L., Medeiros, B. C., Majeti, R. 2014; 111 (7): 2548-2553

    Abstract

    Cancer is widely characterized by the sequential acquisition of genetic lesions in a single lineage of cells. Our previous studies have shown that, in acute myeloid leukemia (AML), mutation acquisition occurs in functionally normal hematopoietic stem cells (HSCs). These preleukemic HSCs harbor some, but not all, of the mutations found in the leukemic cells. We report here the identification of patterns of mutation acquisition in human AML. Our findings support a model in which mutations in "landscaping" genes, involved in global chromatin changes such as DNA methylation, histone modification, and chromatin looping, occur early in the evolution of AML, whereas mutations in "proliferative" genes occur late. Additionally, we analyze the persistence of preleukemic mutations in patients in remission and find CD34+ progenitor cells and various mature cells that harbor preleukemic mutations. These findings indicate that preleukemic HSCs can survive induction chemotherapy, identifying these cells as a reservoir for the reevolution of relapsed disease. Finally, through the study of several cases of relapsed AML, we demonstrate various evolutionary patterns for the generation of relapsed disease and show that some of these patterns are consistent with involvement of preleukemic HSCs. These findings provide key insights into the monitoring of minimal residual disease and the identification of therapeutic targets in human AML.

    View details for DOI 10.1073/pnas.1324297111

    View details for PubMedID 24550281

  • Unsuccessful diagnostic cytogenetic analysis is a poor prognostic feature in acute myeloid leukaemia BRITISH JOURNAL OF HAEMATOLOGY Medeiros, B. C., Othus, M., Estey, E. H., Fang, M., Appelbaum, F. R. 2014; 164 (2): 245-250

    Abstract

    Chromosome banding analysis is the gold standard method for the identification of recurrent cytogenetic abnormalities in acute myeloid leukaemia (AML). It allows stratification of AML patients into subgroups with distinct responses to therapy and survival. Unfortunately, a variety of issues hamper cytogenetic evaluation in c. 10% of cases [unsuccessful cytogenetics (UC)] and the outcome of these patients is poorly understood. To better define the significance of UC in patients with AML, we compared the baseline characteristics and the prognostic impact of 94 (6%) patients, whose standard metaphase analysis yielded unacceptable results, to the remaining 1403 AML patients with successful cytogenetic analysis treated on successive Southwestern Oncology Group protocols. The incidence of UC increased with age, with peak incidence in patients older than 60 years. These patients had a lower response rate to induction chemotherapy (complete remission rate of 43%) and dismal 5-year survival rates (16%), which was especially poor in patients older than 60 years (<5%). The complete remission and survival rates were similar to those seen in patients with unfavourable karyotype. The early death rate was not increased. These results suggest that UC increases with age and predict for poor outcomes, similar to the outcomes of patients with unfavourable karyotype.

    View details for DOI 10.1111/bjh.12625

    View details for Web of Science ID 000329178100011

    View details for PubMedID 24383844

  • Sequential azacitidine plus lenalidomide combination for elderly patients with untreated acute myeloid leukemia. Haematologica Pollyea, D. A., Zehnder, J., Coutre, S., Gotlib, J. R., Gallegos, L., Abdel-Wahab, O., Greenberg, P., Zhang, B., Liedtke, M., Berube, C., Levine, R., Mitchell, B. S., Medeiros, B. C. 2013; 98 (4): 591-596

    Abstract

    There are limited treatment options for older patients with acute myeloid leukemia and prognosis of these patients remains poor, thereby warranting development of novel therapies. We evaluated the efficacy and safety of azacitidine in combination with lenalidomide as front-line therapy for older patients with acute myeloid leukemia. Patients ? 60 years of age with untreated acute myeloid leukemia received azacitidine 75 mg/m2 for 7 days followed by escalating doses of lenalidomide daily for 21 days starting on day 8 of each cycle every 6 weeks. Patients received continued therapy until disease progression, unacceptable toxicity, or completion of 12 cycles. Forty-two patients (median age, 74 years) were enrolled with equal distribution according to European LeukemiaNet risk. The overall response rate was 40% (rate of complete remission with or without complete recovery of blood counts = 28%). The median time to complete remission with or without complete recovery of blood counts was 12 weeks, and duration of this status was 28 weeks (range, 4 - >104 weeks). Therapy-related acute myeloid leukemia and a high score on the Hematopoietic Cell Transplantation Comorbidity Index were negative predictors of response. Early death was noted in 17% of patients. Grades ? 3 toxicities were uncommon and most adverse events were gastrointestinal, fatigue and myelosuppression. In conclusion, a sequential combination of azacitidine plus lenalidomide has clinical activity in older patients with acute myeloid leukemia, and further studies of this combination are underway.

    View details for DOI 10.3324/haematol.2012.076414

    View details for PubMedID 23242596

  • Impact of body-mass index on the outcome of adult patients with acute myeloid leukemia HAEMATOLOGICA-THE HEMATOLOGY JOURNAL Medeiros, B. C., Othus, M., Estey, E. H., Fang, M., Appelbaum, F. R. 2012; 97 (9): 1401-1404

    Abstract

    Obesity increases the risk of treatment-related complications and reduces survival in children with acute myeloid leukemia. Little is known about the impact of obesity on the outcome of adult patients with acute myeloid leukemia.We compared the baseline characteristics and effect on treatment and survival in 1,974 previously untreated adult patients with acute myeloid leukemia undergoing treatment, according to international classification of body-mass index.The median body-mass index was 26.7 (15.5-61) and 63% of patients were overweight/obese. After adjustment for other confounders, such as age, gender, performance status, karyotype, white blood cell, platelet and peripheral blast counts, obese patients had better complete remission rates (P=0.0046), lower rates of resistant disease (P=0.038) but similar rates of survival and severe adverse events.In the treatment of acute myeloid leukemia in adults, obesity was associated with increased response rates and no apparent increase in toxicity. Obesity should not, therefore, be a criterion for excluding patients from aggressive therapy.

    View details for DOI 10.3324/haematol.2011.056390

    View details for Web of Science ID 000308908300020

    View details for PubMedID 22315487

  • Blood consult: monosomal karyotype acute myeloid leukemia BLOOD Garcia, J. S., Medeiros, B. C., Appelbaum, F. R. 2012; 119 (24): 5659-5660

    View details for DOI 10.1182/blood-2012-01-405225

    View details for Web of Science ID 000307396500015

    View details for PubMedID 22498746

  • Safety, efficacy and biological predictors of response to sequential azacitidine and lenalidomide for elderly patients with acute myeloid leukemia LEUKEMIA Pollyea, D. A., Kohrt, H. E., Gallegos, L., Figueroa, M. E., Abdel-Wahab, O., Zhang, B., Bhattacharya, S., Zehnder, J., Liedtke, M., Gotlib, J. R., Coutre, S., Berube, C., Melnick, A., Levine, R., Mitchell, B. S., Medeiros, B. C. 2012; 26 (5): 893-901

    Abstract

    Acute myeloid leukemia (AML) is a disease of the elderly. Poor outcomes with standard therapies necessitate novel approaches. Outpatient regimens sufficiently potent and well tolerated to induce remissions and enable continuation therapy may be beneficial. In this phase-1 study, we determined the maximum tolerated dose (MTD) and the efficacy for sequential azacitidine and lenalidomide as remission induction and continuation therapy in elderly, previously untreated patients. We investigated the impact on global DNA methylation and bone marrow cytokines, and sought biological predictors of response. Eighteen patients were enrolled. The MTD was not reached. Median follow-up was 8.2 months (10.3 months for survivors). Common adverse events included fatigue, injection site reactions, constipation, nausea, pruritus and febrile neutropenia. Ten patients responded (56%), and the rate of complete remissions (CRs) or CRs with incomplete recovery of blood counts for evaluable patients was 44% (7/16). The median response duration was 6.2 months. DNA demethylation and changes in bone marrow cytokines were observed; responders had a unique cytokine profile and a trend towards lower methylation levels. Sequential azacitidine and lenalidomide was well tolerated with encouraging clinical and biological activity in previously untreated elderly AML patients. This trial is registered at ClinicalTrials.gov (NCT00890929).

    View details for DOI 10.1038/leu.2011.294

    View details for Web of Science ID 000303883500005

    View details for PubMedID 22033493

  • Impact of residual normal metaphases in core binding factor acute myeloid leukemia CANCER Medeiros, B. C., Othus, M., Fang, M., Appelbaum, F. R., Estey, E. H. 2012; 118 (9): 2420-2423

    Abstract

    Karyotype allows for stratification of outcomes in acute myeloid leukemia (AML) patients. Previous data suggested that the presence of residual normal cells improved the prognosis in patients with monosomy 7. The Southwest Oncology Group (SWOG) reported the impact of residual normal metaphases in AML patients with monosomal karyotype (MK) and found a similar relationship. We determined the influence of residual normal metaphases in patients with core binding factor (CBF) AML.The presence and total number of normal and abnormal metaphases were tallied for patients with CBF AML treated in 10 consecutive SWOG trials and used as a variable to determine the effect on complete remission, refractory disease, and overall survival (OS) rates.Among 113 CBF AML patients, median age of diagnosis was 45 years (range, 18-77 years), and median OS was 4 years (CI-2 years-not reached). Patients with inv(16) and no normal metaphases had improved OS compared with those with 1+ normal metaphases (P = .00005), whereas no difference was noted for patients with t(8;21). Multivariate analysis demonstrated that having cells with a normal karyotype had a negative impact on survival (HR, 2.11; 95% CI, 1.09-4.08; P = .026). This shorter survival was a consequence of a higher rate of refractory disease in older patients (OR, 1.03; 95% CI, 0.9998-1.06; P = .05) and in those with normal metaphases (HR, 1.26 95% CI, 1.04-1.51; P = .02).In patients with CBF AML, the presence of cells with normal metaphases and increasing age negatively affect the prognosis, especially in patients with inv(16).

    View details for DOI 10.1002/cncr.26557

    View details for Web of Science ID 000303044600011

    View details for PubMedID 21928314

  • Unveiling the complexity of CK+ AML. Blood Medeiros, B. C. 2012; 119 (9): 1958-1959

    Abstract

    In acute myeloid leukemia (AML), cytogenetic abnormalities are present in more than half of patients and these chromosomal alterations are critical factors that determine response to chemotherapy and survival.

    View details for DOI 10.1182/blood-2012-01-401505

    View details for PubMedID 22383788

  • Tailored temozolomide therapy according to MGMT methylation status for elderly patients with acute myeloid leukemia AMERICAN JOURNAL OF HEMATOLOGY Medeiros, B. C., Kohrt, H. E., Gotlib, J., Coutre, S. E., Zhang, B., Arber, D. A., Zehnder, J. L. 2012; 87 (1): 45-50

    Abstract

    Temozolomide sensitivity is determined by methylation of the O(6)-methylguanine-DNA methyltransferase (MGMT) promoter. This study assessed whether the temozolomide dose can be tailored by MGMT promoter status and whether protracted, low-dose temozolomide can "prime" blasts in patients with unmethylated MGMT (unMGMT). Elderly patients with high-risk AML were stratified by MGMT methylation. Patients with methylated MGMT (mMGMT) received temozolomide 200 mg/m(2) orally for 7 days every 4 weeks, while patients with unMGMT received temozolomide 100 mg/m(2) orally for 14 days followed by 200 mg/m(2) orally for 7 days every 6weeks. Of 36 patients (median age, 75 years), 31 (86%) had an unMGMT promoter. Overall response rate for the entire cohort was 36%. Patients with mMGMT and unMGMT had similar response rates (40% vs. 29%). Median duration of response and overall survival (OS) among responders were 29 and 35 weeks, respectively. Induction deaths (ID) occurred in 25% of patients, mostly caused by disease progression. Hematological toxicities were the most common adverse event. Toxicities were similar between patients on conventional versus protracted schedules. High HCT-CI scores were predictive of lower CR rate, higher ID, and shorter OS, while bone marrow blast count <50% at screening predicted for improved responses. Temozolomide, dosed according to MGMT methylation status, demonstrated modest clinical activity in elderly patients with AML, especially in those presenting with fewer comorbidities and low disease burden. The trial was registered on www.ClinicalTrials.gov as #NCT00611247.

    View details for DOI 10.1002/ajh.22191

    View details for Web of Science ID 000298257700010

    View details for PubMedID 22052619

  • Cytarabine Dose for Acute Myeloid Leukemia NEW ENGLAND JOURNAL OF MEDICINE Medeiros, B. C., Othus, M., Appelbaum, F. R. 2011; 364 (22): 2167-2168

    View details for Web of Science ID 000291200700028

    View details for PubMedID 21631340

  • Prognostic impact of monosomal karyotype in young adult and elderly acute myeloid leukemia: the Southwest Oncology Group (SWOG) experience BLOOD Medeiros, B. C., Othus, M., Fang, M., Roulston, D., Appelbaum, F. R. 2010; 116 (13): 2224-2228

    Abstract

    Monosomal karyotype (MK), defined as 2 or more monosomies, or a single monosomy in the presence of structural abnormalities, has recently been reported as identifying a distinct subset of acute myeloid leukemia (AML) patients with an extremely poor prognosis. In an effort to confirm this observation, we analyzed the prognostic impact of MK in 1344 AML patients between the ages of 16 and 88 years treated on Southwest Oncology Group protocols. MK was found in 176 (13%) patients. The proportion of patients with MK increased with age, being present in 4% of patients age 30 or younger, but in 20% of those over age 60. Ninety-eight percent of MK cases were within the unfavorable cytogenetic risk category and comprised 40% of this group. The complete remission rate in patients with unfavorable cytogenetics without MK was 34% versus 18% with MK (P < .01). The 4-year overall survival of patients with unfavorable cytogenetics but without MK was 13% in contrast to a 4-year survival of only 3% with MK (P < .01). Thus, MK defines a sizeable subset of patients with unfavorable cytogenetics who have a particularly poor prognosis.

    View details for DOI 10.1182/blood-2010-02-270330

    View details for Web of Science ID 000282369700008

    View details for PubMedID 20562328

  • Senior Adult Oncology, Version 2.2014 JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Hurria, A., Wildes, T., Blair, S. L., Browner, I. S., Cohen, H. J., deShazo, M., Dotan, E., Edil, B. H., Extermann, M., Ganti, A. K., Holmes, H. M., Jagsi, R., Karlekar, M. B., Keating, N. L., Korc-Grodzicki, B., McKoy, J. M., Medeiros, B. C., Mrozek, E., O'Connor, T., Rugo, H. S., Rupper, R. W., Silliman, R. A., Stirewalt, D. L., Tew, W. P., Walter, L. C., Weir, A. B., Bergman, M. A., Sundar, H. 2014; 12 (1): 82-126

    Abstract

    Cancer is the leading cause of death in older adults aged 60 to 79 years. The biology of certain cancers and responsiveness to therapy changes with the patient's age. Advanced age alone should not preclude the use of effective treatment that could improve quality of life or extend meaningful survival. The challenge of managing older patients with cancer is to assess whether the expected benefits of treatment are superior to the risk in a population with decreased life expectancy and decreased tolerance to stress. These guidelines provide an approach to decision-making in older cancer patients based on comprehensive geriatric assessment and also include diseasespecific issues related to age in the management of some cancer types in older adults.

    View details for Web of Science ID 000330333200009

    View details for PubMedID 24453295

  • Hematopoietic Stem Cell Transplantation for Hematologic Malignancies in Older Adults: Geriatric Principles in the Transplant Clinic JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Wildes, T. M., Stirewalt, D. L., Medeiros, B., Hurria, A. 2014; 12 (1): 128-136

    Abstract

    Hematopoietic cell transplantation (HCT) provides a life-prolonging or potentially curative treatment option for patients with hematologic malignancies. Given the high transplant-related morbidity, these treatment strategies were initially restricted to younger patients, but are increasingly being used in older adults. The incidence of most hematologic malignancies increases with age; with the aging of the population, the number of potential older candidates for HCT increases. Autologous HCT (auto-HCT) in older patients may confer a slightly increased risk of specific toxicities (such as cardiac toxicities and mucositis) and have modestly lower effectiveness (in the case of lymphoma). However, auto-HCT remains a feasible, safe, and effective therapy for selected older adults with multiple myeloma and lymphoma. Similarly, allogeneic transplant (allo-HCT) is a potential therapeutic option for selected older adults, although fewer data exist on allo-HCT in older patients. Based on currently available data, age alone is not the best predictor of toxicity and outcomes; rather, the comorbidities and functional status of the older patient are likely better predictors of toxicity than chronologic age in both the autologous and allogeneic setting. A comprehensive geriatric assessment (CGA) in older adults being considered for either an auto-HCT or allo-HCT may identify additional problems or geriatric syndromes, which may not be detected during the standard pretransplant evaluation. Further research is needed to establish the utility of CGA in predicting toxicity and to evaluate the quality of survival in older adults undergoing HCT.

    View details for Web of Science ID 000330333200010

    View details for PubMedID 24453296

  • Qualitative analysis of practicing oncologists' attitudes and experiences regarding collection of patient-reported outcomes. Journal of oncology practice / American Society of Clinical Oncology Jagsi, R., Chiang, A., Polite, B. N., Medeiros, B. C., McNiff, K., Abernethy, A. P., Zon, R., Loehrer, P. J. 2013; 9 (6): e290-7

    Abstract

    There is growing interest in incorporating routine collection of patient-reported outcomes (PROs) into cancer care. Practicing oncologists are a stakeholder group whose views are not well characterized.We developed an interview guide after literature review and in-depth interviews with leaders in the field. We conducted 45-minute semistructured interviews with a diverse sample of medical oncologists identified through affiliation with the Quality Oncology Practice Initiative or a minority-based Community Clinical Oncology Program until thematic saturation. Multiple analysts independently reviewed and thematically coded verbatim transcripts.Seventeen interviews were conducted with oncologists from 15 states. Emergent themes included variable understanding and experience with PROs. There was enthusiasm for the potential of PROs to improve the efficiency and thoroughness of the patient encounter. Fundamental concerns included information overload, possibility of identifying problems without access to intervention, depersonalization of the physician-patient encounter, cost, and inefficiency. Barriers identified included the need for buy-in from other stakeholders in the practice, lack of appropriate referral resources, staffing needs, and technology concerns. Few identified patient compliance, data sharing/privacy, or medical liability as a major barrier to implementation.Practicing oncologists had variable understanding of the details of PROs but, when introduced to the concept, recognized utility in improving the efficiency and thoroughness of the patient encounter if implemented properly. The time is right to begin pilot testing such measures with community oncologists so they can lend their expertise to national discussions on which measures to use and how best to use them.

    View details for DOI 10.1200/JOP.2012.000823

    View details for PubMedID 23943890

  • A single-center experience of the nationwide daunorubicin shortage: substitution with doxorubicin in adult acute lymphoblastic leukemia. Leukemia & lymphoma Patel, S., Liedtke, M., Ngo, D., Medeiros, B. C. 2013; 54 (10): 2231-2235

    Abstract

    Due to a national shortage of daunorubicin we evaluated the effects of substituting doxorubicin 1:1 in the induction phase for adult patients with newly diagnosed acute lymphoblastic leukemia (ALL). We identified 10 patients receiving doxorubicin instead of daunorubicin as part of their induction on Cancer and Leukemia Group B (CALGB) 9511 or CALGB10403 and retrospectively compared them to 83 patients who received treatment on the same protocols with daunorubicin. Response rates were similar, independent of anthracycline received, with either CALGB9511 or CALGB10403. In either regimen, doxorubicin resulted in longer absolute neutrophil count (ANC) recovery time and hospitalization. Doxorubicin as part of CALGB9511 resulted in greater than three-fold higher mucositis. Sepsis and death during induction were significantly more frequent in patients who received doxorubicin on CALGB10403. While remission rates were similar, the use of doxorubicin was associated with prolonged neutropenia, higher risk of mucositis, infection and sepsis, and prolonged hospitalization. Higher induction mortality observed with doxorubicin substitution in this analysis needs further study.

    View details for DOI 10.3109/10428194.2013.772606

    View details for PubMedID 23383599

  • CD11b expression and MK+ AML: A sign of impending doom? LEUKEMIA RESEARCH Medeiros, B. C. 2013; 37 (2): 121-121
  • 2-Hydroxyglutarate in IDH mutant acute myeloid leukemia: predicting patient responses, minimal residual disease and correlations with methylcytosine and hydroxymethylcytosine levels LEUKEMIA & LYMPHOMA Pollyea, D. A., Kohrt, H. E., Zhang, B., Zehnder, J., Schenkein, D., Fantin, V., Straley, K., Vasanthakumar, A., Abdel-Wahab, O., Levine, R., Godley, L. A., Medeiros, B. C. 2013; 54 (2): 408-410

    View details for DOI 10.3109/10428194.2012.701009

    View details for Web of Science ID 000313285400034

    View details for PubMedID 22680765

  • CD19(-)CD45(low/-)CD38(high)/CD138(+) plasma cells enrich for human tumorigenic myeloma cells LEUKEMIA Kim, D., Park, C. Y., Medeiros, B. C., Weissman, I. L. 2012; 26 (12): 2530-2537

    Abstract

    Multiple myeloma is a hematological neoplasm characterized by the accumulation of clonal plasma cells in the bone marrow. Its frequent relapse following achievement of clinical remissions implicates the existence of therapy-resistant myeloma-initiating cells. To date, results on the identity of myeloma-initiating cells have differed. Here, we prospectively identified a myeloma-initiating population by fractionating and transplanting patient bone marrow cells into human bone-bearing immunocompromised mice. Xenotransplantation of fractionated CD138(+)/CD38(high) cells from 40% of patients (8/20) led to a repopulation of CD19(+)CD38(low) or CD138(+)CD38(+) B-lineage cells in human bone grafts; and these grafts were clonally derived from patient myeloma cells. Meanwhile, CD19(+)CD38(low) xenografts were detected in human bone-bearing mice transplanted with CD19(+)CD38(low/-) B cells from 8 of 22 samples but were not clonally related to patient myeloma cells. Further fractionation and xenotransplantation of CD138(+)CD38(high) cells demonstrated that (CD45(low/-) or CD19(-)) CD38(high)/CD138(+) plasma cells, but not (CD45(high) or CD19(+)) CD38(high)/CD138(+) plasmablasts enrich for myeloma-initiating cells. Quantitative reverse transcription-PCR of two serially transplantable xenografts, which were CD19(-)CD138(+), revealed that they were Pax5 (a B-cell-specific transactivator)-negative. These results suggest that CD19(-)CD45(low/-) fully differentiated plasma cells enrich for long-lived and tumor-initiating cells whereas B cells or plasmablasts do not.

    View details for DOI 10.1038/leu.2012.140

    View details for Web of Science ID 000312186000012

    View details for PubMedID 22733078

  • Hemophagocytic lymphohistiocytosis in pregnancy: a case report and review of treatment options HEMATOLOGY Dunn, T., Cho, M., Medeiros, B., Logan, A., Ungewickell, A., Liedtke, M. 2012; 17 (6): 325-328

    Abstract

    Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening inflammatory disorder characterized by uncontrolled proliferation and activation of histiocytes with phagocytosis of normal hematopoietic cells. A 41-year-old woman, 19 weeks pregnant with twins, and a history of Still's disease, presented with rash, fever, and headache. Laboratory studies revealed transaminitis, hyperbilirubinemia, and eventually severe neutropenia as well as elevations in ferritin, lactate dehydrogenase, and C-reactive protein. A bone marrow biopsy confirmed HLH. She declined standard HLH-treatment but responded well to high-dose corticosteroids. Her blood counts remained stable following corticosteroid taper, and she delivered healthy twin girls at 30-week gestation. Few cases of HLH during pregnancy have been reported. In some cases, the condition has proved fatal. Therefore recognizing signs and symptoms of HLH is essential to avoid treatment delay. In our case, high-dose corticosteroids alone were a safe and effective therapy for the mother and fetuses resulting in long-term disease control.

    View details for DOI 10.1179/1607845412Y.0000000007

    View details for Web of Science ID 000311490800004

    View details for PubMedID 23168071

  • Waldenstrom's Macroglobulinemia/Lymphoplasmacytic Lymphoma, Version 2.2013 Featured Updates to the NCCN Guidelines JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Anderson, K. C., Alsina, M., Bensinger, W., Biermann, J. S., Cohen, A. D., Devine, S., Djulbegovic, B., Faber, E. A., Gasparetto, C., Hernandez-Ilizaliturri, F., Huff, C. A., Kassim, A., Krishnan, A. Y., Medeiros, B. C., Meredith, R., Raje, N., Schriber, J., Singhal, S., Somlo, G., Stockerl-Goldstein, K., Treon, S. P., Tricot, G., Weber, D. M., Yahalom, J., Yunus, F., Kumar, R., Shead, D. A. 2012; 10 (10): 1211-1219
  • Absolute lymphocyte count at day 28 independently predicts event-free and overall survival in adults with newly diagnosed acute lymphoblastic leukemia AMERICAN JOURNAL OF HEMATOLOGY Sun, D., Elson, P., Liedtke, M., Medeiros, B. C., Earl, M., Alizadeh, A., Bates, J., Sekeres, M. A., Coutre, S., Kalaycio, M., Sobecks, R., Copelan, E., Advani, A. S. 2012; 87 (10): 957-960

    Abstract

    We investigated the prognostic impact of absolute lymphocyte count (ALC) following induction chemotherapy in newly diagnosed adult acute lymphoblastic leukemia (ALL). Patients with ALC ?350 cells/?L at day 28 had a median overall survival (OS) of 47.4 months when compared with 17.6 months for those with an ALC <350 cells/?L (HR = 1.98, P = 0.007). Among patients who achieved a complete remission, median event-free survival (EFS) for those with ALC ?350 cells/?L on day 28 was 42.1 months when compared with 13.9 months in those with ALC <350 cells/?L (HR = 2.08, P = 0.006). In multivariable analysis, the ALC on day 28 (<350 cells/?L vs. ?350 cells/?L, P ? .0004 for OS and EFS) along with WBC at diagnosis (?6.0 or >30.0 K/?L vs. >6.0-30.0 K/?L, P ? 0.002 for OS and EFS) and cytogenetics (abnormal vs. normal, P = 0.002 for OS and P = 0.02 for EFS) were independent prognostic factors of both OS and EFS. Combining these three factors segregates patients in three well-defined risk groups. These data suggest that ALC can be used in combination with other prognostic features to better predict outcome and that targeting the immune system to improve ALC may be a worthwhile strategy in ALL.

    View details for DOI 10.1002/ajh.23279

    View details for Web of Science ID 000309065700081

    View details for PubMedID 22729847

  • Novel agents in acute myeloid leukemia INTERNATIONAL JOURNAL OF HEMATOLOGY Ungewickell, A., Medeiros, B. C. 2012; 96 (2): 178-185

    Abstract

    Although complete remissions can be achieved in most patients younger than 60 years of age with untreated acute myeloid leukemia (AML), only 30-40 % of patients remain long-term survivors. Furthermore, long-term survivors represent only 10-15 % of all AML patients older than 60 years of age and <10 % of all patients with relapsed AML. The development of new treatments for AML is therefore needed. Novel therapies should target specific mechanisms and pathways implicated in the development and maintenance of AML, should strive to have better tolerability than conventional combination chemotherapy, be associated with improved quality of life and minimize utilization of health care resources. In this manuscript, we discuss the role of epigenetic regulators and immunomodulatory agents in the treatment of AML. Also, we review the data on inhibitors of protein homeostasis and its synergistic effect to DNA methyltransferase inhibitors, the potential role for inhibitors of heat shock proteins and the mitotic machinery and a novel formulation of conventional chemotherapeutic agents given at a fixed molar concentration. Finally, we briefly share our views on optimal clinical trial design and patient selection for future studies in AML.

    View details for DOI 10.1007/s12185-012-1151-5

    View details for Web of Science ID 000307764900006

    View details for PubMedID 22907734

  • New treatment approaches for older adults with multiple myeloma JOURNAL OF GERIATRIC ONCOLOGY Wildes, T. M., Vij, R., Petersdorf, S. H., Medeiros, B. C., Hurria, A. 2012; 3 (3): 279-290
  • Phase II trial of vorinostat and gemtuzumab ozogamicin as induction and post-remission therapy in older adults with previously untreated acute myeloid leukemia HAEMATOLOGICA-THE HEMATOLOGY JOURNAL Walter, R. B., Medeiros, B. C., Powell, B. L., Schiffer, C. A., Appelbaum, F. R., Estey, E. H. 2012; 97 (5): 739-742

    Abstract

    Histone deacetylase inhibitors such as vorinostat enhance gemtuzumab ozogamicin efficacy in vitro. We, therefore, investigated vorinostat+gemtuzumab ozogamicin for adults aged 60 years and over with untreated acute myeloid leukemia. We stratified patients into 2 groups (group 1: patients aged ? 70 years and performance status 2-3; group 2: aged 60-69 years with performance status 0-3 or aged ? 70 years and performance status 0-1). Responses were monitored separately in group 2 patients with normal or favorable cytogenetics (group 2A) and other cytogenetics (group 2B). Among 31 patients, 6 (19.4%) achieved complete remission, and one (3.2%) achieved complete remission with incomplete platelet recovery; these patients had a higher median overall survival than non-responders (553 vs. 131 days, P = 0.0026). Response rates were: group 1, one of 10 (10.0%); group 2A, 6 of 13 (46.2%); and group 2B, none of 8 (0%). These data indicate that vorinostat+gemtuzumab ozogamicin has activity that is mostly confined to patients with normal karyotype disease. ClinicalTrial.gov: NCT00673153.

    View details for DOI 10.3324/haematol.2011.055822

    View details for Web of Science ID 000304669000020

    View details for PubMedID 22133771

  • Aggressive EBV-associated Lymphoproliferative Disorder: A Prodrome to Diffuse Large B-cell Lymphoma? APPLIED IMMUNOHISTOCHEMISTRY & MOLECULAR MORPHOLOGY Batra, R., Medeiros, B. C., Zehnder, J. L., Warnke, R. A., Natkunam, Y. 2012; 20 (3): 325-330

    Abstract

    A 19-year-old male patient presented with intermittent high fever and left cervical lymphadenopathy. The lymph node biopsy findings were interpreted as "Epstein-Barr virus (EBV)-associated lymphoproliferative disorder consistent with infectious mononucleosis." No molecular studies were performed at that time. The patient was followed without treatment. Five months later, the patient again presented with fever, lymphadenopathy, and splenomegaly. The lymph node biopsy showed features of a diffuse large B-cell lymphoma. Molecular studies on this lymph node biopsy showed a clonal EBV population, although polymerase chain reaction studies failed to reveal a clonal B-cell or T-cell population. A concurrent bone marrow biopsy showed features consistent with hemophagocytic syndrome. He had elevated ferritin, soluble interleukin-2 receptors and persistent EBV viremia. The patient responded to Rituxan for a short period with undetectable EBV levels. Subsequent right cervical lymph node, liver, and jejunal biopsies showed involvement by diffuse large B-cell lymphoma and the patient expired soon thereafter.

    View details for Web of Science ID 000303140100012

    View details for PubMedID 22505014

  • Senior Adult Oncology JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Hurria, A., Browner, I. S., Cohen, H. J., Denlinger, C. S., deShazo, M., Extermann, M., Ganti, A. K., Holland, J. C., Holmes, H. M., Karlekar, M. B., Keating, N. L., Mckoy, J., Medeiros, B. C., Mrozek, E., O'Connor, T., Petersdorf, S. H., Rugo, H. S., Silliman, R. A., Tew, W. P., Walter, L. C., Weir, A. B., Wildes, T. 2012; 10 (2): 162-209

    View details for Web of Science ID 000300067400005

    View details for PubMedID 22308515

  • "It doesn't matter if you're black or white", does it? LEUKEMIA RESEARCH Medeiros, B. C. 2012; 36 (2): 127-127
  • Phase I trial of a novel human monoclonal antibody mAb216 in patients with relapsed or refractory B-cell acute lymphoblastic leukemia HAEMATOLOGICA-THE HEMATOLOGY JOURNAL Liedtke, M., Twist, C. J., Medeiros, B. C., Gotlib, J. R., Berube, C., Bieber, M. M., Bhat, N. M., Teng, N. N., Coutre, S. E. 2012; 97 (1): 30-37

    Abstract

    This phase I trial was conducted to determine the safety and pharmacokinetics of monoclonal antibody 216, a human monoclonal Immunoglobulin M antibody targeting a linear B-cell lactosamine antigen, administered alone and in combination with vincristine in patients with relapsed or refractory B-cell acute lymphoblastic leukemia, and to preliminarily assess tumor targeting and efficacy.Three cohorts of patients received escalating doses of monoclonal antibody 216 administered as an intravenous infusion. In the case of poor response to the first dose of monoclonal antibody 216 alone, defined as less than 75% reduction in peripheral blood blast count, a second dose of the antibody with vincristine was given between days 4 and 7. Responses were assessed weekly until day 35. Serum concentration of monoclonal antibody 216 was measured before and after infusion. Monoclonal antibody 216 targeting was determined with an anti-idiotypic antibody to monoclonal antibody 216 and preliminary efficacy was analyzed by changes in peripheral blood blasts.Thirteen patients were enrolled. One episode of grade 3 epistaxis was the only dose-limiting toxicity observed. All patients showed a poor response to the first monoclonal antibody 216 infusion with a decrease in peripheral blasts from 6-65% in 9 patients. In 8 patients, addition of vincristine to monoclonal antibody 216 resulted in an average reduction of the peripheral blasts of 81%. One patient without peripheral blasts achieved a hypoplastic marrow without evidence of leukemia after one infusion of monoclonal antibody 216 and monoclonal antibody 216/vincristine each. Monoclonal antibody 216 was detected on peripheral blasts in all patients.Treatment with monoclonal antibody 216 in combination with vincristine is feasible and well tolerated in patients with relapsed or refractory B-cell acute lymphoblastic leukemia. Binding of monoclonal antibody 216 to leukemic blasts was efficient, and favorable early responses were observed.

    View details for DOI 10.3324/haematol.2011.045997

    View details for Web of Science ID 000299870500009

    View details for PubMedID 21993685

  • Treatment advances have not improved the early death rate in acute promyelocytic leukemia HAEMATOLOGICA-THE HEMATOLOGY JOURNAL McClellan, J. S., Kohrt, H. E., Coutre, S., Gotlib, J. R., Majeti, R., Alizadeh, A. A., Medeiros, B. C. 2012; 97 (1): 133-136

    Abstract

    Early mortality in acute promyelocytic leukemia has been reported to occur in less than 10% of patients treated in clinical trials. This study reports the incidence and clinical features of acute promyelocytic leukemia patients treated at Stanford Hospital, CA, USA since March 1997, focusing on early mortality. We show that the risk of early death in acute promyelocytic leukemia patients is higher than previously reported. In a cohort of 70 patients who received induction therapy at Stanford Hospital, 19% and 26% died within seven and 30 days of admission, respectively. High early mortality was not limited to our institution as evaluation of the Surveillance, Epidemiology and End Results Database demonstrated that 30-day mortality for acute promyelocytic leukemia averaged 20% from 1977-2007 and did not improve significantly over this interval. Our findings show that early death is now the greatest contributor to treatment failure in this otherwise highly curable form of leukemia.

    View details for DOI 10.3324/haematol.2011.046490

    View details for Web of Science ID 000299870500022

    View details for PubMedID 21993679

  • Multiple Myeloma JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Anderson, K. C., Alsina, M., Bensinger, W., Biermann, J. S., Chanan-Khan, A., Cohen, A. D., Devine, S., Djulbegovic, B., Faber, E. A., Gasparetto, C., Huff, C. A., Kassim, A., Medeiros, B. C., Meredith, R., Raje, N., Schriber, J., Singhal, S., Somlo, G., Stockerl-Goldstein, K., Treon, S. P., Tricot, G., Weber, D. M., Yahalom, J., Yunus, F. 2011; 9 (10): 1146-1183

    View details for Web of Science ID 000295721800005

    View details for PubMedID 21975914

  • Unfavorable-risk cytogenetics in acute myeloid leukemia EXPERT REVIEW OF HEMATOLOGY Hong, W., Medeiros, B. C. 2011; 4 (2): 173-184

    Abstract

    Cytogenetic analysis at diagnosis is one of the most significant prognostic factors in acute myeloid leukemia (AML). AML patients with unfavorable-risk cytogenetic abnormalities account for 16-30% of younger adult patients and have poor response to standard treatment, with only 32-55% achieving a complete response. Overall survival is also extremely poor with only 5-12% patients alive at 5-10 years after diagnosis. Owing to the poor response in this subset of patients, risk-adapted treatment has been investigated. Allogeneic stem cell transplant has been shown to provide a survival benefit in patients with unfavorable-risk cytogenetic abnormalities in complement receptor 1. Other risk-adapted treatment strategies, such as reduced-intensity conditioning regimens prior to allogeneic stem cell transplant for older patients with AML, have also shown some survival benefit, without increasing treatment-related toxicities. Risk-stratification models that include cytogenetic abnormalities, as well as other molecular markers, are being developed to allow for individualized risk-adapted treatment for patients with AML. Prospective multicenter trials will be needed to validate these prognostic models.

    View details for DOI 10.1586/EHM.11.10

    View details for Web of Science ID 000290371000014

    View details for PubMedID 21495927

  • Targeting protein neddylation: a novel therapeutic strategy for the treatment of cancer EXPERT OPINION ON THERAPEUTIC TARGETS Wang, M., Medeiros, B. C., Erba, H. P., DeAngelo, D. J., Giles, F. J., Swords, R. T. 2011; 15 (3): 253-264

    Abstract

    The NEDD8 (neural precursor cell-expressed developmentally downregulated 8) conjugation pathway regulates the post-translational modification of oncogenic proteins. This pathway has important potential for cancer therapeutics. Several proteins vital in cancer biology are regulated by protein neddylation. These observations led to the development of a small molecule inhibitor that disrupts protein neddylation and leads to cancer cell death and important activity in early phase clinical trials.This review provides an extensive coverage of cellular protein homeostasis with particular emphasis on the NEDD8 conjugation pathway. Insights into a new investigational drug that specifically disrupts the NEDD8 pathway are discussed. The clinical data for this agent are also updated.Neddylation controls key cellular pathways found to be dysregulated in many cancers. Protein neddylation is a relatively under-explored pathway for pharmacologic inhibition in cancer. Selective disruption of this pathway has demonstrated clinical activity in patients with myeloid neoplasms and is worth exploring further in combination with other anti-leukemia agents.

    View details for DOI 10.1517/14728222.2011.550877

    View details for Web of Science ID 000287203500003

    View details for PubMedID 21219242

  • Acute myeloid leukaemia in the elderly: a review BRITISH JOURNAL OF HAEMATOLOGY Pollyea, D. A., Kohrt, H. E., Medeiros, B. C. 2011; 152 (5): 524-542

    Abstract

    The majority of patients with acute myeloid leukaemia (AML) are elderly. Advancements in supportive care and regimen intensification have resulted in improvements in clinical outcomes for younger AML patients, but analogous improvements in older patients have not been realized. While outcomes are compromised by increased comorbidities and susceptibility to toxicity from therapy, it is now recognized that elderly AML represents a biologically distinct disease that is more aggressive and less responsive to therapy. Some patients tolerate and benefit from intensive remission-induction approaches, while others are best managed with less aggressive strategies. The challenge is to differentiate these groups based on host-related and biological features, in order to maximize the therapeutic benefit and minimize toxicity. As more is understood about the complicated pathogenesis and molecular basis of AML, there are more opportunities to develop and test targeted therapies. Elderly patients, with their narrow therapeutic window, are well positioned to derive a benefit from these novel agents, and therefore, despite a difficult past, there are reasons to be optimistic about the future of elderly AML.

    View details for DOI 10.1111/j.1365-2141.2010.08470.x

    View details for Web of Science ID 000287315600003

    View details for PubMedID 21314823

  • Microfluidic purification and analysis of hematopoietic stem cells from bone marrow LAB ON A CHIP Schirhagl, R., Fuereder, I., Hall, E. W., Medeiros, B. C., Zare, R. N. 2011; 11 (18): 3130-3135

    Abstract

    Hematopoietic stem cells are larger in size than other cells present in bone marrow, with the exception of monocytes. This distinguishing characteristic can be used to separate them from a whole-marrow sample. A microfluidic device was fabricated using an integrated membrane that is porous at defined areas. This allows for simultaneous valving and filtering functionality, which is crucial for preventing irreversible clogging. This device, as well as a separation procedure, was optimized in this work to enrich hematopoietic progenitor cells from diluted bone marrow of leukemia patients without any additional sample preparation. An enrichment of up to 98% was achieved with this method and the process was scaled up to 17.2 ?L min(-1) of processed sample. Additionally, stem cells were stained with specific antibodies for further analysis. Using a custom-made computer program, the filter was scanned to characterize and quantify cells based on fluorescence. The results were evaluated by comparing them against the results obtained from flow cytometry, confocal microscopy, and Coulter counting.

    View details for DOI 10.1039/c1lc20353c

    View details for Web of Science ID 000294263400013

    View details for PubMedID 21799976

  • Second-line mitoxantrone, etoposide, and cytarabine for acute myeloid leukemia: A single-center experience AMERICAN JOURNAL OF HEMATOLOGY Kohrt, H. E., Patel, S., Ho, M., Owen, T., Pollyea, D. A., Majeti, R., Gotlib, J., Coutre, S., Liedtke, M., Berube, C., Alizadeh, A. A., Medeiros, B. C. 2010; 85 (11): 877-881

    Abstract

    The majority of patients with acute myeloid leukemia (AML) will require second-line chemotherapy for either relapsed or refractory disease. Currently, only allogeneic hematopoietic cell transplantation (HCT) offers a curative option in this setting and no preferred regimen has been established. The reported efficacy of second-line regimens is widely disparate, thus limiting informed clinical decision making. A retrospective review of 77 patients receiving therapy between 2001 and 2008 with relapsed, 42, and refractory, 35, AML was performed to determine overall response rate and survival following mitoxantrone (8 mg/m(2)/day), etoposide (100 mg/m(2)/day), and cytarabine (1,000 mg/m(2)/day) chemotherapy administered over 5 days. Among 77 patients (median age of 54 years and 64% intermediate risk karyotype) with median follow-up of 153 days, 18% achieved a complete response and 8% a morphologic leukemia-free state. Fifty-seven (74%) experienced treatment failure, 10 of whom achieved a remission after additional therapy. Median overall survival (OS) was 6.8 months. Among patients achieving a response, 50% received consolidation with allogeneic HCT, autologous HCT (5%), or consolidation chemotherapy alone (45%). A nonsignificant trend in overall response (50%, 27%, and 23.8%) and median OS (8.3, 6.8, and 4.7 months) was observed by cytogenetic stratification into favorable, intermediate, and unfavorable risk. Patients with refractory versus relapsed disease had similar overall responses (20% and 31%, P = 0.41) and median OS (5.3 and 7.6 months, P = 0.36). Despite risk stratification by the European Prognostic Index, our series demonstrates inferior rates of response and survival, illustrating the limited activity of this regimen in our cohort.

    View details for DOI 10.1002/ajh.21857

    View details for Web of Science ID 000283568200010

    View details for PubMedID 20872554

  • Plasma cell leukemia: concepts and management. Expert review of hematology Liedtke, M., Medeiros, B. C. 2010; 3 (5): 543-549

    Abstract

    Plasma cell leukemia (PCL) is a rare and aggressive plasma cell dyscrasia. Patients with PCL have a very poor prognosis with median survival measured in months. PCL can present de novo or following a prodrome of plasma cell myeloma. Patients with PCL tend to present with aggressive clinical features, such as extramedullary disease, bone marrow failure, advanced stage disease and expression of distinct immunophenotypic markers, such as lack of CD56 and presence of CD20. Historically, the treatment of PCL has primarily been palliative, with only a small minority of patients achieving a durable remission. The impact of newer agents, such as bortezomib and lenalidomide, in conjunction with autologous and allogeneic stem cell transplantation is uncertain, but emerging data suggest that use of these modalities may help improve the poor prognosis of patients with PCL.

    View details for DOI 10.1586/ehm.10.52

    View details for PubMedID 21083471

  • Plasma cell leukemia: concepts and management EXPERT REVIEW OF HEMATOLOGY Liedtke, M., Medeiros, B. C. 2010; 3 (5): 539-549

    View details for DOI 10.1586/EHM.10.52

    View details for Web of Science ID 000284746200008

  • Myelomastocytic leukemia versus mast cell leukemia versus systemic mastocytosis associated with acute myeloid leukemia: A diagnostic challenge AMERICAN JOURNAL OF HEMATOLOGY Arredondo, A. R., Gotlib, J., Shier, L., Medeiros, B., Wong, K., Cherry, A., Corless, C., Arber, D. A., Valent, P., George, T. I. 2010; 85 (8): 600-606

    View details for DOI 10.1002/ajh.21713

    View details for Web of Science ID 000280562800011

    View details for PubMedID 20658589

  • Immunophenotypic features of acute myeloid leukemia with inv(3)(q21q26.2)/t(3;3)(q21;q26.2) LEUKEMIA RESEARCH Medeiros, B. C., Kohrt, H. E., Arber, D. A., Bangs, C. D., Cherry, A. M., Majeti, R., Kogel, K. E., Azar, C. A., Patel, S., Alizadeh, A. A. 2010; 34 (5): 594-597

    Abstract

    Immunophenotypic identification of myeloid specific antigens is an important diagnostic tool in the management of patients with acute myeloid leukemia (AML). These antigens allow determination of cell of origin and degree of differentiation of leukemia blasts. AML with inv(3)(q21q26.2)/t(3;3)(q21;q26.2) is a relatively rare subtype of AML. The immunophenotypic characteristics of inv(3) AML patients are somewhat limited. We identified 14 new cases of hematological disorders with increased myeloid blasts carrying inv(3)(q21q26.2)/t(3;3)(q21;q26.2). Also, we identified another 13 cases previously published in the literature, where the immunophenotype of inv(3)(q21q26.2) was documented. As a group, patients with AML with inv(3)(q21q26.2) had high levels of early myeloid (CD13, CD33, CD117 and MPO) and uncommitted markers (CD34, HLA-DR and CD56) and a high rate of monosomy 7 in addition to the inv(3)(q21q26.2). Differential karyotype and expression of certain antigens were noted in patients with de novo AML with inv(3)(q21q26.2) vs. those with inv(3)(q21q26.2)-containing blasts.

    View details for DOI 10.1016/j.leukres.2009.08.029

    View details for Web of Science ID 000276945300009

    View details for PubMedID 19781775

  • Multiple Myeloma JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Anderson, K. C., Alsina, M., Bensinger, W., Biermann, S., Chanan-Khan, A., Cohen, A. D., Devine, S., Djulbegovic, B., Gasparetto, C., Huff, C. A., Jagasia, M., Medeiros, B. C., Meredith, R., Raje, N., Schriber, J., Singhal, S., Somlo, G., Stockerl-Goldstein, K., Tricot, G., Vose, J. M., Weber, D., Yahalom, J., Yunus, F. 2009; 7 (9): 908-942
  • Thalidomide-induced pneumonitis in a patient with plasma cell leukemia: No recurrence with subsequent lenalidomide therapy AMERICAN JOURNAL OF HEMATOLOGY Pretz, J., Medeiros, B. C. 2009; 84 (10): 698-699

    View details for DOI 10.1002/ajh.21495

    View details for Web of Science ID 000270744300022

    View details for PubMedID 19691102

  • Deletion of IKZF1 and Prognosis in Acute Lymphoblastic Leukemia NEW ENGLAND JOURNAL OF MEDICINE Medeiros, B. C. 2009; 360 (17): 1787-1787

    View details for Web of Science ID 000265377800016

    View details for PubMedID 19387020

  • Role of CEBPA in Normal Karyotype Acute Myeloid Leukemia JOURNAL OF CLINICAL ONCOLOGY Medeiros, B. C. 2009; 27 (12): 2105-2105

    View details for DOI 10.1200/JCO.2008.21.5418

    View details for Web of Science ID 000266194700034

    View details for PubMedID 19273693

  • Comparing Apples and Oranges in Normal Karyotype Acute Myeloid Leukemia JOURNAL OF CLINICAL ONCOLOGY Medeiros, B. C. 2009; 27 (3): 474-474

    View details for DOI 10.1200/JCO.2008.19.3011

    View details for Web of Science ID 000262499100031

    View details for PubMedID 19075259

  • Complete remission of primary plasma cell leukemia with bortezomib, doxorubicin, and dexamethasone: a case report. Cases journal Chan, S. M., George, T., Cherry, A. M., Medeiros, B. C. 2009; 2 (1): 121-?

    Abstract

    Plasma cell leukemia (PCL) is a rare lymphoproliferative disorder considered to be a variant of multiple myeloma. It is an aggressive disease with a poor clinical response to standard chemotherapeutic agents.A novel regimen consisting of bortezomib, doxorubicin, and dexamethasone is currently under active evaluation for the treatment of multiple myeloma. We employed this combination as front-line chemoinduction therapy for a case of primary PCL.Complete remission was achieved with rapid normalization of hematologic parameters. The combination of bortezomib, doxorubicin and dexamethasone demonstrates promise in the treatment of PCL.

    View details for DOI 10.1186/1757-1626-2-121

    View details for PubMedID 19192311

Conference Proceedings


  • A Phase I Study of Sequential Azacitidine and Lenalidomide for Elderly Patients with Acute Myeloid Leukemia (AML) Pollyea, D. A., Kohrt, H. E., Gallegos, L., Berube, C., Coutre, S., Gotlib, J., Liedtke, M., Mitchell, B. S., Medeiros, B. C. AMER SOC HEMATOLOGY. 2010: 1347-1347
  • Early Mortality in Acute Promyelocytic Leukemia May Be Higher Than Previously Reported. Alizadeh, A. A., McClellan, J. S., Gotlib, J. R., Coutre, S., Majeti, R., Kohrt, H. E., Medeiros, B. C. AMER SOC HEMATOLOGY. 2009: 420-421