Bio


Dr. Gupta specializes in the treatment of patients with lymphoma in general, and has particular clinical and research interests in patients with primary central nervous system and immunodeficiency-related lymphomas.

Clinical Focus


  • Cancer > Lymphoma
  • Primary Central Nervous System Lymphomas
  • Post-transplant Lymphoproliferative Disorders
  • AIDS-Related Lymphomas
  • Medical Oncology

Academic Appointments


Honors & Awards


  • Saul Rosenberg Faculty Teaching Award, Division of Oncology, Department of Medicine (2020)
  • Saul Rosenberg Faculty Teaching Award, Division of Oncology, Department of Medicine (2018)

Professional Education


  • Fellowship: UCSF Hematology and Medical Oncology Fellowship (2013) CA
  • Board Certification: American Board of Internal Medicine, Medical Oncology (2013)
  • Residency: University of Washington Medical Center Dept of Medicine (2010) WA
  • Medical Education: University of California Davis School of Medicine (2006) CA
  • Fellowship: Memorial Sloan-Kettering Cancer Center (2009) NY
  • Board Certification: American Board of Internal Medicine, Hematology (2014)

Current Research and Scholarly Interests


I have specific interest in the pathobiology and management of individuals with AIDS-related and primary central nervous system lymphomas.

Clinical Trials


  • Study of Tirabrutinib (ONO-4059) in Patients With Primary Central Nervous System Lymphoma (PROSPECT Study) Recruiting

    This study will evaluate the efficacy, safety, and pharmacokinetics of tirabrutinib monotherapy in patients with relapsed or refractory PCNSL (Part A), and tirabrutinib in combination with one of two different high dose methotrexate based regimens (methotrexate/ temozolomide/rituximab or rituximab/methotrexate/procarbazine/ vincristine) as first line therapy in patients with newly diagnosed, treatment naïve PCNSL (Part B)

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  • A Multi-Center Study of Ibrutinib in Combination With MEDI4736 in Subjects With Relapsed or Refractory Lymphomas Not Recruiting

    The purpose of this study is to evaluate the efficacy, safety and tolerability of the combination treatment of ibrutinib and MEDI4736 in subjects with relapsed or refractory lymphomas.

    Stanford is currently not accepting patients for this trial. For more information, please contact Cancer Clinical Trials Office (CCTO), 650-498-7061.

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  • A Study of Duvelisib in Combination With Rituximab or Obinutuzumab in Subjects With Previously Untreated CD20+ Follicular Lymphoma (CONTEMPO) Not Recruiting

    A Two-arm, Phase 1b/2 Study of duvelisib Administered in Combination with Rituximab or Obinutuzumab in Subjects with Previously Untreated CD20+ Follicular Lymphoma.

    Stanford is currently not accepting patients for this trial. For more information, please contact Sipra Choudhury, 650-736-2563.

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  • A Study to Evaluate Safety, Pharmacokinetics, and Clinical Activity of Combination of RO6870810 and Venetoclax, With or Without Rituximab, in Participants With Relapsed/Refractory DLBCL and/or High-Grade B-Cell Lymphoma and/or High Grade B-Cell Lymphoma With MYC and/or BCL2 and/or BCL6 Not Recruiting

    The purpose of this study is to evaluate the safety, tolerability and clinical activity of RO6870810 in combination with venetoclax and when co-administered with rituximab in participants with relapse/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) and/or high-grade B-cell lymphoma with myelocytomatosis oncogene (MYC) and/or B-cell lymphoma 2 (BCL2) and/or B-cell lymphoma 6 (BCL6) gene rearrangements (HGBL-DH/TH).

    Stanford is currently not accepting patients for this trial. For more information, please contact Cancer Clinical Trials Office (CCTO), 650-498-7061.

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  • A Study to Investigate Blinatumomab in Combination With Chemotherapy in Patients With Newly Diagnosed B-Lymphoblastic Leukemia Not Recruiting

    This phase III trial studies how well blinatumomab works in combination with chemotherapy in treating patients with newly diagnosed, standard risk B-lymphoblastic leukemia or B-lymphoblastic lymphoma with or without Down syndrome. Monoclonal antibodies, such as blinatumomab, may induce changes in the body's immune system and may interfere with the ability of cancer cells to grow and spread. Chemotherapy drugs, such as vincristine, dexamethasone, prednisone, prednisolone, pegaspargase, methotrexate, cytarabine, mercaptopurine, doxorubicin, cyclophosphamide, and thioguanine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Leucovorin decreases the toxic effects of methotrexate. Giving monoclonal antibody therapy with chemotherapy may kill more cancer cells. Giving blinatumomab and combination chemotherapy may work better than combination chemotherapy alone in treating patients with B-ALL. This trial also assigns patients into different chemotherapy treatment regimens based on risk (the chance of cancer returning after treatment). Treating patients with chemotherapy based on risk may help doctors decide which patients can best benefit from which chemotherapy treatment regimens.

    Stanford is currently not accepting patients for this trial. For more information, please contact Cancer Clinical Trials Office (CCTO), 650-498-7061.

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  • Brentuximab Vedotin Combined With AVD Chemotherapy in Patients With Newly Diagnosed Early Stage, Unfavorable Risk Hodgkin Lymphoma Not Recruiting

    The purpose of this study is to compare the outcomes across the 4 different treatment groups. The investigators hope that this treatment will improve the ability to cure more patients with HL and also limit the long-term side effects from the treatment. Although eliminating radiation in cohort 4 will eliminate the risk for long-term side effects from radiation, it is also possible that with BV+AVD chemotherapy alone there may be an increased risk of the Hodgkin lymphoma coming back after initial treatment.

    Stanford is currently not accepting patients for this trial. For more information, please contact Ranjana Advani, MD, 650-498-6000.

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  • Combination Chemotherapy & Lenalidomide in Newly Diagnosed Stage II-IV Peripheral T-cell Non-Hodgkin's Lymphoma Not Recruiting

    This phase I/II trial studies the side effects and best dose of lenalidomide when given together with combination chemotherapy and to see how well they work in treating patients with newly diagnosed stage II-IV peripheral T-cell non-Hodgkin's lymphoma. Drugs used in chemotherapy, such as cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and etoposide, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Lenalidomide may stop the growth of peripheral T-cell non-Hodgkin's lymphoma by blocking the growth of new blood vessels necessary for cancer growth. Giving combination chemotherapy with lenalidomide may be a better treatment for peripheral T-cell non-Hodgkin's lymphoma.

    Stanford is currently not accepting patients for this trial. For more information, please contact Ranjana H. Advani, 650-725-6456.

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  • Investigation of Tipifarnib in Treatment of Subjects With PTCL That Have Not Responded to Standard Therapy. Not Recruiting

    Phase II study designed to investigate antitumor activity in terms of objective response rate (ORR) of tipifarnib subjects with advanced Peripheral T-Cell Lymphoma (PTCL). Tipifarnib will be administered orally until disease progression.

    Stanford is currently not accepting patients for this trial. For more information, please contact Sipra Choudhury, 650-736-2563.

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  • Lisocabtagene Maraleucel (JCAR017) as Second-Line Therapy (TRANSCEND-PILOT-017006) Not Recruiting

    This is a Phase 2, open-label, multicenter study to determine the efficacy and safety of lisocabtagene maraleucel (JCAR017) in adult subjects who have relapsed from, or are refractory to, a single line of immunochemotherapy for aggressive B-cell non-Hodgkin lymphoma (NHL) and are ineligible for hematopoietic stem cell transplant (based on age, performance status, and/or comorbidities). Subjects will receive treatment with lisocabtagene maraleucel and will be followed for 2 years for safety, pharmacokinetics and biomarkers, disease status, quality of life, and survival.

    Stanford is currently not accepting patients for this trial. For more information, please contact Maria Iglesias, 650-736-0912.

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  • Nivolumab and Brentuximab Vedotin in Treating Older Patients With Untreated Hodgkin Lymphoma Not Recruiting

    This phase II trial studies how well nivolumab and brentuximab vedotin work in treating older patients with untreated Hodgkin lymphoma. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Biological therapies, such as brentuximab vedotin, use substances made from living organisms that may stimulate or suppress the immune system in different ways and stop cancer cells from growing. Nivolumab and brentuximab vedotin may work better in treating older patients with untreated Hodgkin lymphoma.

    Stanford is currently not accepting patients for this trial.

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  • Study of Effectiveness of Axicabtagene Ciloleucel Compared to Standard of Care Therapy in Patients With Relapsed/Refractory Diffuse Large B Cell Lymphoma Not Recruiting

    The goal of this clinical study is to assess whether axicabtagene ciloleucel therapy improves the clinical outcome compared with standard of care second-line therapy in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL).

    Stanford is currently not accepting patients for this trial. For more information, please contact Cancer Clinical Trials Office (CCTO), 650-498-7061.

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  • Study of Pembrolizumab (MK-3475) in Participants With Relapsed or Refractory Classical Hodgkin Lymphoma (MK-3475-087/KEYNOTE-087) Not Recruiting

    This is a study of pembrolizumab (MK-3475) for participants with relapsed/refractory classical Hodgkin Lymphoma (RRcHL) who: 1) have failed to achieve a response or progressed after autologous stem cell transplant (auto-SCT) and have relapsed after treatment with or failed to respond to brentuximab vedotin (BV) post auto-SCT or 2) were unable to achieve a Complete Response (CR) or Partial Response (PR) to salvage chemotherapy and did not receive auto-SCT, but have relapsed after treatment with or failed to respond to BV or 3) have failed to achieve a response to or progressed after auto-SCT and have not received BV post auto-SCT. The primary study hypothesis is that treatment with single agent pembrolizumab will result in a clinically meaningful overall response rate.

    Stanford is currently not accepting patients for this trial. For more information, please contact Tessa Hapanowicz, 650-721-4096.

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  • Study to Investigate the Safety and Tolerability of Odronextamab in Patients With CD20+ B-Cell Malignancies Not Recruiting

    This study has two parts with distinct study objectives and study design. In part A, odronextamab is studied as an intravenous (IV) administration with a dose escalation and a dose expansion phase for B-NHL and CLL. The dose escalation phase for B-NHL and the CLL study are closed at the time of protocol amendment 17. In part B, odronextamab is studied as a subcutaneous (SC) administration with a dose finding and a dose expansion phase for B-NHL.

    Stanford is currently not accepting patients for this trial. For more information, please contact Sipra Choudhury, 650-736-2563.

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  • Trial of Magrolimab (Hu5F9-G4) in Combination With Rituximab or Rituximab + Chemotherapy in Participants With Relapsed/Refractory B-cell Non-Hodgkin's Lymphoma Not Recruiting

    The primary objectives of this study are: - To investigate the safety and tolerability, and to define the recommended Phase 2 dose and schedule (RP2DS) for magrolimab in combination with rituximab and for magrolimab in combination with rituximab, gemcitabine, and oxaliplatin (R-GemOx). - To evaluate the efficacy of magrolimab in combination with rituximab in participants with indolent lymphoma and diffuse large B-cell lymphoma (DLBCL) and to evaluate the efficacy of magrolimab in combination with R-GemOx in autologous stem cell transplant (ASCT) ineligible DLBCL participants.

    Stanford is currently not accepting patients for this trial. For more information, please contact Cancer Clinical Trials Office (CCTO), 650-498-7061.

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All Publications


  • Long-term survival in AIDS-related primary central nervous system lymphoma. Neuro-oncology Gupta, N. K., Nolan, A. n., Omuro, A. n., Reid, E. G., Wang, C. C., Mannis, G. n., Jaglal, M. n., Chavez, J. C., Rubinstein, P. G., Griffin, A. n., Abrams, D. I., Hwang, J. n., Kaplan, L. D., Luce, J. A., Volberding, P. n., Treseler, P. A., Rubenstein, J. L. 2016

    Abstract

    The optimal therapeutic approach for patients with AIDS-related primary central nervous system lymphoma (AR-PCNSL) remains undefined. While its incidence declined substantially with combination antiretroviral therapy (cART), AR-PCNSL remains a highly aggressive neoplasm for which whole brain radiotherapy (WBRT) is considered a standard first-line intervention.To identify therapy-related factors associated with favorable survival, we first retrospectively analyzed outcomes of AR-PCNSL patients treated at San Francisco General Hospital, a public hospital with a long history of dedicated care for patients with HIV and AIDS-related malignancies. Results were validated in a retrospective, multicenter analysis that evaluated all newly diagnosed patients with AR-PCNSL treated with cART plus high-dose methotrexate (HD-MTX).We provide evidence that CD4+ reconstitution with cART administered during HD-MTX correlates with long-term survival among patients with CD4 <100. This was confirmed in a multicenter analysis which demonstrated that integration of cART regimens with HD-MTX was generally well tolerated and resulted in longer progression-free survival than other treatments. No profound differences in immunophenotype were identified in an analysis of AR-PCNSL tumors that arose in the pre- versus post-cART eras. However, we detected evidence for a demographic shift, as the proportion of minority patients with AR-PCNSL increased since advent of cART.Long-term disease-free survival can be achieved in AR-PCNSL, even among those with histories of opportunistic infections, limited access to health care, and medical non-adherence. Given this, as well as the long-term toxicities of WBRT, we recommend that integration of cART plus first-line HD-MTX be considered for all patients with AR-PCNSL.

    View details for DOI 10.1093/neuonc/now155

    View details for PubMedID 27576871

  • Lisocabtagene Maraleucel as Second-Line Therapy for R/R Large B-Cell Lymphoma in Patients Not Intended for Hematopoietic Stem Cell Transplant: Final Analysis of the Phase 2 PILOT Study Sehgal, A. R., Hoda, D., Riedell, P. A., Ghosh, N., Hamadani, M., Hildebrandt, G., Godwin, J. E., Reagan, P. M., Wagner-Johnston, N., Essell, J., Nath, R., Solomon, S. R., Champion, R., Licitra, E., Fanning, S., Gupta, N. K., Chow, V. A., Yuan, B., Yang, Z., Ogasawara, K., Thorpe, J., Gordon, L. I. AMER SOC HEMATOLOGY. 2023
  • Implications of Contact Days in the Treatment of Relapsed Refractory Diffuse Large B-Cell Lymphoma. The oncologist Bojanini, L., Gupta, N., Khaki, A. R. 2023

    View details for DOI 10.1093/oncolo/oyad204

    View details for PubMedID 37432278

  • Lisocabtagene maraleucel as second-line therapy in adults with relapsed or refractory large B-cell lymphoma who were not intended for haematopoietic stem cell transplantation (PILOT): an open-label, phase 2 study. The Lancet. Oncology Sehgal, A., Hoda, D., Riedell, P. A., Ghosh, N., Hamadani, M., Hildebrandt, G. C., Godwin, J. E., Reagan, P. M., Wagner-Johnston, N., Essell, J., Nath, R., Solomon, S. R., Champion, R., Licitra, E., Fanning, S., Gupta, N., Dubowy, R., D'Andrea, A., Wang, L., Ogasawara, K., Thorpe, J., Gordon, L. I. 2022

    Abstract

    BACKGROUND: Patients with relapsed or refractory large B-cell lymphoma after first-line treatment who are not intended for haematopoietic stem-cell transplantation (HSCT) have poor outcomes and limited treatment options. We assessed the antitumour activity and safety of lisocabtagene maraleucel, an autologous, CD19-directed chimeric antigen receptor (CAR) T-cell product, as second-line treatment in adults with relapsed or refractory large B-cell lymphoma not intended for HSCT.METHODS: PILOT, an open-label, phase 2 trial done at 18 clinical sites in the USA, included adults aged 18 years or older who had relapsed or refractory large B-cell lymphoma and PET-positive disease, had received first-line therapy containing an anthracycline and a CD20-targeted agent, were not intended for HSCT by their physician, and met at least one prespecified transplantation not intended criterion. Patients received lymphodepleting chemotherapy (intravenous fludarabine 30 mg/m2 and intravenous cyclophosphamide 300 mg/m2 daily for 3 days) followed 2-7 days later by two sequential lisocabtagene maraleucel infusions (equal target doses of CD8+ and CD4+ CAR+ T cells for a total target dose of 100*106 CAR+ T cells). The primary endpoint was the overall response rate and was assessed in all patients who received lisocabtagene maraleucel and had confirmed PET-positive disease before lisocabtagene maraleucel administration based on an independent review committee according to the Lugano 2014 criteria. Safety was assessed in all patients who received lisocabtagene maraleucel. Patient follow-up is ongoing. This study is registered with ClinicalTrials.gov, NCT03483103.FINDINGS: Between July 26, 2018, and Sept 24, 2021 (data cutoff for the primary analysis), 74 patients underwent leukapheresis and 61 received lisocabtagene maraleucel (efficacy and safety sets); median age was 74 years (IQR 70-78), 24 (39%) patients were women versus 37 (61%) men, and 54 (89%) patients were White. 16 (26%) of 61 patients had an Eastern Cooperative Oncology Group performance status of 2, 33 (54%) had refractory disease, 13 (21%) relapsed within 1 year of first-line therapy, and 15 (25%) relapsed after 12 months of first-line therapy. Median on-study follow-up was 12·3 months (IQR 6·1-18·0). 49 (80% [95% CI 68-89]; p<0·0001) patients had an overall response. The most common grade 3 or worse treatment-emergent adverse events were neutropenia (29 [48%] patients), leukopenia (13 [21%]), and thrombocytopenia (12 [20%]). Lisocabtagene maraleucel-related serious treatment-emergent adverse events were reported in 13 (21%) patients. There were no treatment-related deaths. Cytokine release syndrome occurred in 23 (38%; grade 3 in one) patients and neurological events in 19 (31%; grade 3 in three) patients, with no grade 4 events or deaths.INTERPRETATION: These results support lisocabtagene maraleucel as a potential second-line treatment in patients with large B-cell lymphoma for whom HSCT is not intended.FUNDING: Juno Therapeutics, a Bristol-Myers Squibb company.

    View details for DOI 10.1016/S1470-2045(22)00339-4

    View details for PubMedID 35839786

  • Lisocabtagene maraleucel (liso-cel) as second-line (2L) therapy for R/R large B-cell lymphoma (LBCL) in patients (pt) not intended for hematopoietic stem cell transplantation (HSCT): Primary analysis from the phase 2 PILOT study. Sehgal, A., Hoda, D., Riedell, P. A., Ghosh, N., Hamadani, M., Hildebrandt, G., Godwin, J. E., Reagan, P., Wagner-Johnston, N. D., Essell, J., Nath, R., Solomon, S. R., Champion, R., Licitra, E., Fanning, S., Gupta, N. K., Dubowy, R. L., D'Andrea, A., Wang, L., Gordon, L. I. LIPPINCOTT WILLIAMS & WILKINS. 2022
  • CD20-Targeted Therapy Ablates De Novo Antibody Response to Vaccination but Spares Pre-Established Immunity. Blood cancer discovery Shree, T., Shankar, V., Lohmeyer, J. J., Czerwinski, D. K., Schroers-Martin, J. G., Rodriguez, G. M., Beygi, S., Kanegai, A. M., Corbelli, K. S., Gabriel, E., Kurtz, D. M., Khodadoust, M. S., Gupta, N. K., Maeda, L. S., Advani, R. H., Alizadeh, A. A., Levy, R. 2022

    Abstract

    To obtain a deeper understanding of poor responses to COVID-19 vaccination in lymphoma patients, we assessed blocking antibodies, total anti-spike IgG, and spike-specific memory B cells in the peripheral blood of 126 patients with lymphoma and 20 age-matched healthy controls 1 and 4 months after COVID-19 vaccination. Fifty-five percent of patients developed blocking antibodies post-vaccination, compared to 100% of controls. Evaluating patients last treated from days to nearly 18 years prior to vaccination, time since last anti-CD20 was a significant independent predictor of vaccine response. None of 31 patients who had received anti-CD20 treatment within 6 months prior to vaccination developed blocking antibodies. In contrast, patients who initiated anti-CD20 treatment shortly after achieving a vaccine-induced antibody response tended to retain that response during treatment, suggesting a policy of immunizing prior to treatment whenever possible.

    View details for DOI 10.1158/2643-3230.BCD-21-0222

    View details for PubMedID 35015688

  • Time Since Last Anti-CD20 Treatment Is a Major Determinant of Sars-Cov-2 Vaccine Response in a Large Cohort of Patients with B-Cell Lymphoma Shree, T., Shankar, V., Czerwinski, D. K., Rodriguez, G., Beygi, S., Schroers-Martin, J. G., Advani, R., Maeda, L. S., Gupta, N. K., Khodadoust, M. S., Kurtz, D. M., Corbelli, K. S., Gabriel, E., Kanegai, A. M., Alizadeh, A. A., Levy, R. AMER SOC HEMATOLOGY. 2021
  • Stage I-II diffuse large B-cell lymphoma treated with rituximab and chemotherapy with or without radiotherapy. Leukemia & lymphoma Binkley, M. S., Hiniker, S. M., Younes, S., Yoo, C., Wignarajah, A., Jin, M., Guo, H. H., Gupta, N. K., Natkunam, Y., Advani, R. H., Hoppe, R. T. 2021: 1–15

    Abstract

    We set to identify prognostic factors in a retrospective cohort of consecutive patients with stage I-II diffuse large B-cell lymphoma treated with rituximab-chemotherapy with or without radiotherapy from 2001 through 2017 at our institution. We identified 143 patients with median follow-up of 7.7years. The majority were male (59.4%), had stage II (53.1%), had stage-modified IPI 0-1 (smIPI, 58.1%), and had non-bulky disease (<7cm, 68.5%). 99 patients (69.2%) received rituximab-chemotherapy followed by radiotherapy, and 44 patients (30.8%) received rituximab-chemotherapy alone. The 5-year progression-free survival (PFS) and overall survival (OS) were 81.2% and 88.9%, respectively. The 5-year PFS for those with smIPI 0-1 versus 2-4 was 89.5% versus 69.7%, respectively (P=0.005). Bulky disease (≥7cm) was associated with worse PFS and OS on univariable and multivariable analyses (P<0.05). Patients with smIPI 0-1 without bulky disease have excellent outcomes. However, patients with smIPI 2-4 or bulky disease have a high risk of progression.

    View details for DOI 10.1080/10428194.2021.1876859

    View details for PubMedID 33622155

  • Autologous tumor cell vaccine induces antitumor T cell immune responses in patients with mantle cell lymphoma: A phase I/II trial. The Journal of experimental medicine Frank, M. J., Khodadoust, M. S., Czerwinski, D. K., Haabeth, O. A., Chu, M. P., Miklos, D. B., Advani, R. H., Alizadeh, A. A., Gupta, N. K., Maeda, L. S., Reddy, S. A., Laport, G. G., Meyer, E. H., Negrin, R. S., Rezvani, A. R., Weng, W. K., Sheehan, K. n., Faham, M. n., Okada, A. n., Moore, A. H., Phillips, D. L., Wapnir, I. L., Brody, J. D., Levy, R. n. 2020; 217 (9)

    Abstract

    Here, we report on the results of a phase I/II trial (NCT00490529) for patients with mantle cell lymphoma who, having achieved remission after immunochemotherapy, were vaccinated with irradiated, CpG-activated tumor cells. Subsequently, vaccine-primed lymphocytes were collected and reinfused after a standard autologous stem cell transplantation (ASCT). The primary endpoint was detection of minimal residual disease (MRD) within 1 yr after ASCT at the previously validated threshold of ≥1 malignant cell per 10,000 leukocyte equivalents. Of 45 evaluable patients, 40 (89%) were found to be MRD negative, and the MRD-positive patients experienced early subsequent relapse. The vaccination induced antitumor CD8 T cell immune responses in 40% of patients, and these were associated with favorable clinical outcomes. Patients with high tumor PD-L1 expression after in vitro exposure to CpG had inferior outcomes. Vaccination with CpG-stimulated autologous tumor cells followed by the adoptive transfer of vaccine-primed lymphocytes after ASCT is feasible and safe.

    View details for DOI 10.1084/jem.20191712

    View details for PubMedID 32558897

  • Role of FNA with core biopsy or cell block in patients with nodular lymphocyte-predominant Hodgkin lymphoma. Cancer cytopathology Gupta, S. n., Long, S. R., Natkunam, Y. n., Kong, C. S., Gupta, N. K., Gratzinger, D. n. 2020

    Abstract

    Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) represents a diagnostic challenge on surgical excisional or incisional biopsy. Classification is further challenging on fine needle aspiration (FNA) material accompanied by needle core and/or cell block biopsy (FNA+core/CB).The authors studied all FNA+core/CB and surgical excisional or incisional biopsies to evaluate for lymphoma in patients who had a prior history of NLPHL or subsequent diagnosis of NLPHL over a 5-year period from 2012 through 2016.Patients who ultimately were diagnosed with NLPHL represented <0.5% of those who underwent FNA+core/CB for an initial suspicion of lymphoma. FNA+core/CB resulted in a definitive diagnosis in 7 of 13 cases, and surgical excisional or incisional biopsy specimens resulted in a definitive diagnosis in 13 of 13 cases (chi-square statistic, 9.6; P = .002). At initial diagnosis, FNA+core/CB was negative in 2 cases and atypical or suspicious in 3 cases; all 5 of those patients required surgical excisional or incisional biopsy for a definitive lymphoma diagnosis. By contrast, patients who underwent FNA+core/CB for recurrent lymphoma required surgical excisional or incisional biopsy in only 1 of 8 cases (chi-square statistic, 9.5; P = .002). Flow cytometry was positive for a light-chain-restricted B-cell population in only 1 of 11 biopsies that were involved by lymphoma.Surgical excisional or incisional biopsy remains the gold standard for NLPHL diagnosis and for distinguishing progression to a T-cell/histiocyte-rich large B-cell lymphoma pattern. At a tertiary cancer center with routine collaborative diagnosis of lymphoma on FNA+core/CB by cytopathologists and hematopathologists, FNA+core/CB performs well to assess for recurrent or transformed NLPHL, rarely requiring subsequent surgical excisional or incisional biopsy. FNA+core/CB has limited sensitivity in the initial diagnosis setting.

    View details for DOI 10.1002/cncy.22286

    View details for PubMedID 32343479

  • Prognostic Value of Circulating Tumor DNA in Diffuse Large B-Cell Lymphoma Reply JOURNAL OF CLINICAL ONCOLOGY Kurtz, D. M., Scherer, F., Jin, M. C., Soo, J., Craig, A. M., Esfahani, M. S., Chabon, J. J., Stehr, H., Liu, C., Tibshirani, R., Maeda, L. S., Gupta, N. K., Khodadoust, M. S., Advani, R. H., Newman, A. M., Duehrsen, U., Huettmann, A., Meignan, M., Casasnovas, O., Westin, J. R., Roschewski, M., Wilson, W. H., Gaidano, G., Rossi, D., Diehn, M., Alizadeh, A. A. 2019; 37 (9): 755-+
  • Reply to J. Wang et al. Journal of clinical oncology : official journal of the American Society of Clinical Oncology Kurtz, D. M., Scherer, F., Jin, M. C., Soo, J., Craig, A. F., Esfahani, M. S., Chabon, J. J., Stehr, H., Liu, C. L., Tibshirani, R., Maeda, L. S., Gupta, N. K., Khodadoust, M. S., Advani, R. H., Newman, A. M., Duhrsen, U., Huttmann, A., Meignan, M., Casasnovas, O., Westin, J. R., Roschewski, M., Wilson, W. H., Gaidano, G., Rossi, D., Diehn, M., Alizadeh, A. A. 2019: JCO1801907

    View details for PubMedID 30753108

  • AIDS-Related Kaposi Sarcoma, Version 2.2019, NCCN Clinical Practice Guidelines in Oncology. Journal of the National Comprehensive Cancer Network : JNCCN Reid, E., Suneja, G., Ambinder, R. F., Ard, K., Baiocchi, R., Barta, S. K., Carchman, E., Cohen, A., Crysler, O. V., Gupta, N., Gustafson, C., Hall, A., Johung, K. L., Klopp, A., LaCasce, A. S., Lin, C., Mehta, A., Menon, M. P., Morgan, D., Nathwani, N., Noy, A., Ratner, L., Rizza, S., Rudek, M. A., Sanchez, J., Taylor, J., Tomlinson, B., Wang, C. J., Yendamuri, S., Dwyer, M. A., Freedman-Cass, D. A. 2019; 17 (2): 171–89

    Abstract

    As treatment of HIV has improved, people living with HIV (PLWH) have experienced a decreased risk of AIDS and AIDS-defining cancers (non-Hodgkin's lymphoma, Kaposi sarcoma, and cervical cancer), but the risk of Kaposi sarcoma in PLWH is still elevated about 500-fold compared with the general population in the United States. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for AIDS-Related Kaposi Sarcoma provide diagnosis, treatment, and surveillance recommendations for PLWH who develop limited cutaneous Kaposi sarcoma and for those with advanced cutaneous, oral, visceral, or nodal disease.

    View details for PubMedID 30787130

  • AIDS-Related Kaposi Sarcoma, Version 2.2019 JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Reid, E., Suneja, G., Ambinder, R. F., Ard, K., Baiocchi, R., Barta, S. K., Carchman, E., Cohen, A., Crysler, O. V., Gupta, N., Gustafson, C., Hall, A., Johung, K. L., Klopp, A., LaCasce, A. S., Lin, C., Mehta, A., Menon, M. P., Morgan, D., Nathwani, N., Noy, A., Ratner, L., Rizza, S., Rudek, M. A., Sanchez, J., Taylor, J., Tomlinson, B., Wang, C. J., Yendamuri, S., Dwyer, M. A., Freedman-Cass, D. A. 2019; 17 (2): 171–89
  • Circulating Tumor DNA Measurements As Early Outcome Predictors in Diffuse Large B-Cell Lymphoma JOURNAL OF CLINICAL ONCOLOGY Kurtz, D. M., Scherer, F., Jin, M. C., Soo, J., Craig, A. M., Esfahani, M., Chabon, J. J., Stehr, H., Liu, C., Tibshirani, R., Maeda, L. S., Gupta, N. K., Khodadoust, M. S., Advani, R. H., Levy, R., Newman, A. M., Duehrsen, U., Huettmann, A., Meignan, M., Casasnovas, R., Westin, J. R., Roschewski, M., Wilson, W. H., Gaidano, G., Rossi, D., Diehn, M., Alizadeh, A. A. 2018; 36 (28): 2845-+
  • Circulating tumor DNA (ctDNA) in B-cell lymphoma Scherer, F., Kurtz, D. M., Newman, A. M., Stehr, H., Craig, A. M., Esfahani, M. S., Lovejoy, A. F., Chabon, J. J., Klass, D. M., Green, M. R., Liu, C. L., Zhou, L., Glover, C., Visser, B. C., Poultsides, G. A., Advani, R. H., Maeda, L. S., Gupta, N. K., Davis, R., Levy, R., Ohgami, R. S., Kunder, C. A., Rossi, D., Westin, J., Diehn, M., Alizadeh, A. A. WILEY. 2018: 16–17
  • Circulating Tumor DNA Measurements As Early Outcome Predictors in Diffuse Large B-Cell Lymphoma. Journal of clinical oncology : official journal of the American Society of Clinical Oncology Kurtz, D. M., Scherer, F., Jin, M. C., Soo, J., Craig, A. F., Esfahani, M. S., Chabon, J. J., Stehr, H., Liu, C. L., Tibshirani, R., Maeda, L. S., Gupta, N. K., Khodadoust, M. S., Advani, R. H., Levy, R., Newman, A. M., Duhrsen, U., Huttmann, A., Meignan, M., Casasnovas, R., Westin, J. R., Roschewski, M., Wilson, W. H., Gaidano, G., Rossi, D., Diehn, M., Alizadeh, A. A. 2018: JCO2018785246

    Abstract

    Purpose Outcomes for patients with diffuse large B-cell lymphoma remain heterogeneous, with existing methods failing to consistently predict treatment failure. We examined the additional prognostic value of circulating tumor DNA (ctDNA) before and during therapy for predicting patient outcomes. Patients and Methods We studied the dynamics of ctDNA from 217 patients treated at six centers, using a training and validation framework. We densely characterized early ctDNA dynamics during therapy using cancer personalized profiling by deep sequencing to define response-associated thresholds within a discovery set. These thresholds were assessed in two independent validation sets. Finally, we assessed the prognostic value of ctDNA in the context of established risk factors, including the International Prognostic Index and interim positron emission tomography/computed tomography scans. Results Before therapy, ctDNA was detectable in 98% of patients; pretreatment levels were prognostic in both front-line and salvage settings. In the discovery set, ctDNA levels changed rapidly, with a 2-log decrease after one cycle (early molecular response [EMR]) and a 2.5-log decrease after two cycles (major molecular response [MMR]) stratifying outcomes. In the first validation set, patients receiving front-line therapy achieving EMR or MMR had superior outcomes at 24 months (EMR: EFS, 83% v 50%; P = .0015; MMR: EFS, 82% v 46%; P < .001). EMR also predicted superior 24-month outcomes in patients receiving salvage therapy in the first validation set (EFS, 100% v 13%; P = .011). The prognostic value of EMR and MMR was further confirmed in the second validation set. In multivariable analyses including International Prognostic Index and interim positron emission tomography/computed tomography scans across both cohorts, molecular response was independently prognostic of outcomes, including event-free and overall survival. Conclusion Pretreatment ctDNA levels and molecular responses are independently prognostic of outcomes in aggressive lymphomas. These risk factors could potentially guide future personalized risk-directed approaches.

    View details for PubMedID 30125215

  • Cancer in People Living With HIV, Version 1.2018 Clinical Practice Guidelines in Oncology JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Reid, E., Suneja, G., Ambinder, R. F., Ard, K., Baiocchi, R., Barta, S. K., Carchman, E., Cohen, A., Gupta, N., Johung, K. L., Klopp, A., LaCasce, A. S., Lin, C., Makarova-Rusher, O. V., Mehta, A., Menon, M. P., Morgan, D., Nathwani, N., Noy, A., Palella, F., Ratner, L., Rizza, S., Rudek, M. A., Taylor, J., Tomlinson, B., Wang, C. J., Dwyer, M. A., Freedman-Cass, D. A. 2018; 16 (8): 986–1017

    Abstract

    People living with HIV (PLWH) are diagnosed with cancer at an increased rate over the general population and generally have a higher mortality due to delayed diagnoses, advanced cancer stage, comorbidities, immunosuppression, and cancer treatment disparities. Lack of guidelines and provider education has led to substandard cancer care being offered to PLWH. To fill that gap, the NCCN Guidelines for Cancer in PLWH were developed; they provide treatment recommendations for PLWH who develop non-small cell lung cancer, anal cancer, Hodgkin lymphoma, and cervical cancer. In addition, the NCCN Guidelines outline advice regarding HIV management during cancer therapy; drug-drug interactions between antiretroviral treatments and cancer therapies; and workup, radiation therapy, surgical management, and supportive care in PLWH who have cancer.

    View details for DOI 10.6004/jnccn.2018.0066

    View details for Web of Science ID 000441297200010

    View details for PubMedID 30099375

  • Development and Validation of Biopsy-Free Genotyping for Molecular Subtyping of Diffuse Large B-Cell Lymphoma 58th Annual Meeting and Exposition of the American-Society-of-Hematology Scherer, F., Kurtz, D. M., Newman, A. M., Esfahani, M. S., Craig, A., Stehr, H., Lovejoy, A. F., Chabon, J. J., Liu, C. L., Zhou, L., Glover, C., Visser, B. C., Poultsides, G., Advani, R. H., Maeda, L. S., Gupta, N. K., Levy, R., Ohgami, R. S., Davis, E. R., Gaidano, G., Kunder, C. A., Rossi, D., Westin, J. R., Diehn, M., Alizadeh, A. A. AMER SOC HEMATOLOGY. 2016
  • Noninvasive Detection of BCL2, BCL6, and MYC Translocations in Diffuse Large B-Cell Lymphoma Kurtz, D. M., Scherer, F., Newman, A. M., Craig, A., Jin, M., Stehr, H., Chabon, J. J., Esfahani, M., Liu, C., Zhou, L., Glover, C., Visser, B. C., Poultsides, G., Advani, R. H., Maeda, L. S., Gupta, N. K., Levy, R., Ohgami, R. S., Davis, R., Kunder, C. A., Westin, J. R., Diehn, M., Alizadeh, A. A. AMER SOC HEMATOLOGY. 2016
  • Absence of Evidence Implicating Hematopoietic Stem Cells As Common Progenitors for DLBCL Mutations Jan, M., Scherer, F., Kurtz, D. M., Newman, A. M., Stehr, H., Liu, C., Zhou, L., Glover, C., Advani, R. H., Maeda, L. S., Gupta, N. K., Levy, R., Kunder, C. A., Sanchez-Garcia, I., Diehn, M., Alizadeh, A. A. AMER SOC HEMATOLOGY. 2016
  • Distinct biological subtypes and patterns of genome evolution in lymphoma revealed by circulating tumor DNA SCIENCE TRANSLATIONAL MEDICINE Scherer, F., Kurtz, D. M., Newman, A. M., Stehr, H., Craig, A. F., Esfahani, M. S., Lovejoy, A. F., Chabon, J. J., Klass, D. M., Liu, C. L., Zhou, L., Glover, C., Visser, B. C., Poultsides, G. A., Advani, R. H., Maeda, L. S., Gupta, N. K., Levy, R., Ohgami, R. S., Kunder, C. A., Diehn, M., Alizadeh, A. A. 2016; 8 (364)

    Abstract

    Patients with diffuse large B cell lymphoma (DLBCL) exhibit marked diversity in tumor behavior and outcomes, yet the identification of poor-risk groups remains challenging. In addition, the biology underlying these differences is incompletely understood. We hypothesized that characterization of mutational heterogeneity and genomic evolution using circulating tumor DNA (ctDNA) profiling could reveal molecular determinants of adverse outcomes. To address this hypothesis, we applied cancer personalized profiling by deep sequencing (CAPP-Seq) analysis to tumor biopsies and cell-free DNA samples from 92 lymphoma patients and 24 healthy subjects. At diagnosis, the amount of ctDNA was found to strongly correlate with clinical indices and was independently predictive of patient outcomes. We demonstrate that ctDNA genotyping can classify transcriptionally defined tumor subtypes, including DLBCL cell of origin, directly from plasma. By simultaneously tracking multiple somatic mutations in ctDNA, our approach outperformed immunoglobulin sequencing and radiographic imaging for the detection of minimal residual disease and facilitated noninvasive identification of emergent resistance mutations to targeted therapies. In addition, we identified distinct patterns of clonal evolution distinguishing indolent follicular lymphomas from those that transformed into DLBCL, allowing for potential noninvasive prediction of histological transformation. Collectively, our results demonstrate that ctDNA analysis reveals biological factors that underlie lymphoma clinical outcomes and could facilitate individualized therapy.

    View details for DOI 10.1126/scitranslmed.aai8545

    View details for PubMedID 27831904

  • Noninvasive molecular subtyping and risk stratification of DLBCL. Scherer, F., Kurtz, D., Newman, A. M., Stehr, H., Craig, A. M., Esfahani, M. S., Lovejoy, A. F., Chabon, J. J., Klass, D. M., Liu, C., Zhou, L., Glover, C., Advani, R. H., Maeda, L., Gupta, N. K., Levy, R., Ohgami, R. S., Kunder, C., Diehn, M., Alizadeh, A. A. AMER SOC CLINICAL ONCOLOGY. 2016
  • The Transfusion Tether: Bridging the Gap Between End-Stage Hematologic Malignancies and Optimal End-of-Life Care. American journal of hematology Mannis, G. N., McNey, L. M., Gupta, N. K., Gross, D. M. 2016

    View details for PubMedID 26799788

  • Plasmablastic lymphoma is treatable in the HAART era. A 10 year retrospective by the AIDS Malignancy Consortium LEUKEMIA & LYMPHOMA Noy, A., Lensing, S. Y., Moore, P. C., Gupta, N., Aboulafia, D., Ambinder, R., Baiocchi, R., Dezube, B. J., Henry, D., Kaplan, L., Levine, A. M., Mitsuyasu, R., Ratner, L., Reid, E., Remick, S., Sparano, J., Tzachanis, D., Wachsman, W., Chadburn, A. 2016; 57 (7): 1731–34

    View details for DOI 10.3109/10428194.2015.1113281

    View details for Web of Science ID 000377265000037

    View details for PubMedID 26674561

    View details for PubMedCentralID PMC4899288

  • Phase I/II Clinical Trial of CpG-Activated Whole Cell Vaccine in Mantle Cell Lymphoma (MCL): Results in Safety and Efficacy from Planned Interim Analysis Chu, M. P., Brody, J., Kohrt, H. E., Frank, M. J., Khodadoust, M., Reddy, S., Advani, R. H., Gupta, N. K., Laport, G., Maeda, L. S., Meyer, E., Miklos, D. B., Negrin, R., Rezvani, A. R., Weng, W., Sheehan, K., Faham, M., Czerwinski, D. K., Okada, A., Levy, R. AMER SOC HEMATOLOGY. 2015
  • Delayed hematopoietic recovery after auto-SCT in patients receiving arsenic trioxide-based therapy for acute promyelocytic leukemia: a multi-center analysis BONE MARROW TRANSPLANTATION Mannis, G. N., Logan, A. C., Leavitt, A. D., Yanada, M., Hwang, J., Olin, R. L., Damon, L. E., Andreadis, C., Ai, W. Z., Gaensler, K. M., Greene, C. C., Gupta, N. K., Kaplan, L. D., MAHINDRA, A., Miyazaki, Y., Naoe, T., Ohtake, S., Sayre, P. H., Smith, C. C., Venstrom, J. M., Wolf, J. L., Caballero, L., Emi, N., Martin, T. G. 2015; 50 (1): 40-44

    Abstract

    A potential link between arsenic (ATO)-based therapy and delayed hematopoietic recovery after autologous hematopoietic SCT (HSCT) for acute promyelocytic leukemia (APL) has previously been reported. We retrospectively reviewed the clinical histories of 58 patients undergoing autologous HSCT for APL at 21 institutions in the United States and Japan. Thirty-three (56%) of the patients received ATO-based therapy prior to stem cell collection. Delayed neutrophil engraftment occurred in 10 patients (17%): 9 of the 10 patients (90%) received prior ATO (representing 27% of all ATO-treated patients), compared with 1 of the 10 patients (10%) not previously treated with ATO (representing 4% of all ATO-naïve patients; P<0.001). Compared with ATO-naïve patients, ATO-treated patients experienced significantly longer times to ANC recovery (median 12 days vs 9 days, P<0.001). In multivariate analysis, the only significant independent predictor of delayed neutrophil engraftment was prior treatment with ATO (hazard ratio 4.87; P<0.001). Of the available stem cell aliquots from APL patients, the median viable post-thaw CD34+ cell recovery was significantly lower than that of cryopreserved autologous stem cell products from patients with non-APL AML. Our findings suggest that ATO exposure prior to CD34+ cell harvest has deleterious effects on hematopoietic recovery after autologous HSCT.

    View details for DOI 10.1038/bmt.2014.201

    View details for Web of Science ID 000347806800008

    View details for PubMedID 25243620

  • New Meets Old: A Case Study and Review of Novel Therapeutics for the Treatment of CLL in Older Patients JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Gupta, N. K., Andreadis, C. 2014; 12 (10): 1371-1375

    Abstract

    The treatment of older or medically frail patients with chronic lymphocytic leukemia (CLL) presents unique challenges to clinicians attempting to maximize efficacy while avoiding significant toxicity. This case report presents a 75-year-old man with Rai stage II CLL complicated by massive splenomegaly, high-risk cytogenetics, and intolerance to first-line therapy recommended by the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Hodgkin's Lymphomas. A brief summary of his disease and treatment course accompanies a discussion of the special challenges associated with treating this patient population. In addition, emerging novel and targeted therapies, including next-generation monoclonal antibodies and small molecule inhibitors, are reviewed in the broader context of evolving standards of care and the NCCN Guidelines.

    View details for Web of Science ID 000343275600003

  • Diffuse Large B-cell Lymphoma Cancers in People with HIV and AIDS Gupta, N. K., Kaplan, L. D. Springer. 2014: 175–182
  • How I treat CNS lymphomas BLOOD Rubenstein, J. L., Gupta, N. K., Mannis, G. N., LaMarre, A. K., Treseler, P. 2013; 122 (14): 2318-2330

    Abstract

    The pathogenesis of primary and secondary central nervous system (CNS) lymphoma poses a unique set of diagnostic, prognostic, and therapeutic challenges. During the past 10 years, there has been significant progress in the elucidation of the molecular properties of CNS lymphomas and their microenvironment, as well as evolution in the development of novel treatment strategies. Although a CNS lymphoma diagnosis was once assumed to be uniformly associated with a dismal prognosis, it is now reasonable to anticipate long-term survival, and possibly a cure, for a significant fraction of CNS lymphoma patients. The pathogenesis of CNS lymphomas affects multiple compartments within the neuroaxis, and proper treatment of the CNS lymphoma patient requires a multidisciplinary team with expertise not only in hematology/oncology but also in neurology, neuroradiology, neurosurgery, clinical neuropsychology, ophthalmology, pathology, and radiation oncology. Given the evolving principles of management and the evidence for improvements in survival, our goal is to provide an overview of current knowledge regarding the pathogenesis of CNS lymphomas and to highlight promising strategies that we believe to be most effective in establishing diagnosis, staging, and therapeutic management.

    View details for DOI 10.1182/blood-2013-06-453084

    View details for Web of Science ID 000326078200015

    View details for PubMedID 23963042

    View details for PubMedCentralID PMC3790503

  • Outcome of patients with relapsed/refractory acquired immune deficiency syndrome-related lymphoma diagnosed 1999-2008 and treated with curative intent in the AIDS Malignancy Consortium LEUKEMIA & LYMPHOMA Bayraktar, U. D., Ramos, J. C., Petrich, A., Gupta, N., Lensing, S., Moore, P. C., Reid, E. G., Aboulafia, D. M., Ratner, L., Mitsuyasu, R., Cooley, T., Henry, D. H., Barr, P., Noy, A. 2012; 53 (12): 2383-2389

    Abstract

    No comparative studies exist for relapsed/refractory (rel/rfr) acquired immune deficiency syndrome (AIDS)-related lymphoma (ARL). To determine practices over the last decade and to assess the outcomes of salvage chemotherapy with curative intent and autologous stem cell transplant (ASCT), we retrospectively evaluated treatment outcomes in patients with rel/rfr ARL who were treated in 13 national AIDS Malignancy Consortium (AMC) sites between 1999 and 2008 (n = 88). The most commonly used second-line therapies were ICE (ifosfamide/carboplatin/etoposide, n = 34), dose adjusted EPOCH (etoposide/prednisone/vincristine/cyclophosphamide/doxorubicin, n = 17) and ESHAP (etoposide/methylprednisolone/cytarabine/cisplatin, n = 11). The odds of achieving a response were lower for those with non-Hodgkin lymphoma (NHL) than for those with HL and for those with primary refractory disease than for those with relapse. Overall survival (OS) was significantly longer for those with relapsed disease compared to those with refractory disease and for those with non-Burkitt NHL compared to those with Burkitt. OS was longer in patients who underwent ASCT compared to those who did not (1-year OS: 63.2% vs. 37.2%). However, among 32 patients (36%) who achieved a complete or partial response (CR/PR) after second-line therapy, 1-year OS was not different between the two groups (87.5% for ASCT vs. 81.8% for non-ASCT). Long-term survival in some patients with rel/rfr ARL may be possible without transplant, although transplant remains the standard of care for chemotherapy sensitive disease.

    View details for DOI 10.3109/10428194.2012.697559

    View details for Web of Science ID 000310709000011

    View details for PubMedID 22642936

  • Fourth complete remission with immunosuppression withdrawal and irinotecan after both autologous and allogeneic transplants for diffuse large B cell lymphoma LEUKEMIA & LYMPHOMA Gupta, N. K., Barker, J. N., Young, J. W., Noy, A. 2009; 50 (12): 2075-2077

    View details for DOI 10.3109/10428190903144642

    View details for Web of Science ID 000272753000025

    View details for PubMedID 19637088

  • Differential effects of neurotoxic destruction of descending noradrenergic pathways on acute and persistent nociceptive processing PAIN Martin, W. J., Gupta, N. K., Loo, C. M., Rohde, D. S., Basbaum, A. I. 1999; 80 (1-2): 57-65

    Abstract

    Although many pharmacological studies indicate that bulbospinal noradrenergic projections contribute to antinociception, lesions of the major brainstem noradrenergic cell groups have provided conflicting evidence. Here we used a new immunotoxin, anti-dopamine beta-hydroxylase-saporin, to re-examine the contribution of noradrenergic pathways to nociception and to morphine analgesia. We treated rats intrathecally by lumbar puncture with the immunotoxin and examined dopamine beta-hydroxylase (DbetaH) immunoreactivity seven and 14 days after treatment. There was no change in DbetaH staining at 7 days; however, 14 days after treatment we demonstrated significant destruction of noradrenergic neurons in the locus coeruleus and in the A5 and A7 cell groups. There was a concomitant loss of noradrenergic axons in the dorsal and ventral horns of the lumbosacral and cervical cord. Consistent with the lack of anatomical changes, we found no difference in nociceptive responses in the hot-plate, tail-flick or formalin tests one week post-toxin. On day 14 we examined the behavioral response to injection of formalin into the hindpaw and found that responses during the second phase of pain behavior were significantly reduced. There was no change during the first phase. Formalin-evoked fos expression in the spinal cord was also reduced. We also evaluated morphine analgesia in the formalin test and found that toxin-treated animals exhibited enhanced morphine analgesia. These results establish the utility of using this immunotoxin to selectively destroy subpopulations of noradrenergic cell groups and provide evidence that acute and persistent nociception are differentially regulated by descending noradrenergic pathways.

    View details for Web of Science ID 000079378600007

    View details for PubMedID 10204718