Bio


Dr. Smith is a board-certified, fellowship-trained medical oncologist and hematologist. She is an assistant professor in the Department of Medicine, Division of Blood & Marrow Transplantation and Cellular Therapy.

She is a physician-scientist who conducts extensive research. She completed a fellowship at the National Institutes of Health (NIH) in the Clinical Research Training (now, the Medical Research Scholars) Program and she was a post-doctoral researcher at Memorial Sloan Kettering Cancer Center. Her research focuses on studies evaluating strategies whereby donor T cells can be administered to improve outcomes following blood and marrow transplant. Specifically, she studies novel treatment strategies using chimeric antigen receptor (CAR) T cell therapy.

Dr. Smith has been invited to present the findings of her research at regional, national, and international conferences. At the Insights in Hematology Conference, she focused on the use of CAR T cells for blood cancers, whereas she presented her investigations on the associations between CAR T cells and the intestinal microbiome at the European Society for Blood and Marrow Transplantation. Further, at the annual meeting of the American Society of Gene & Cell Therapy, she addressed the importance of training scientists from underrepresented populations.

Dr. Smith has co-authored articles on topics within the field of cancer immunology, including cancer immunotherapy, stem cell transplantation, and CAR T cell therapy. Her work has appeared in journals, including Biology of Blood and Marrow Transplantation, Blood Advances, Leukemia, Nature, Nature Immunology, Nature Medicine, and elsewhere.

She serves a peer reviewer for publications in various journals, such as Biology of Blood and Marrow Transplantation, Haematologica, and ImmunoMedicine. She also has co-written chapters in books, including Pocket Oncology, Current Concepts and Controversies in Hematopoietic Cell Transplantation, and Advanced Concepts in Human Immunology: Prospects for Disease Control.

Dr. Smith has also earned numerous honors. The American Society of Hematology, Society for Immunotherapy of Cancer, European Society for Blood and Marrow Transplantation, and many other professional societies and organizations have recognized her achievements as a clinician, researcher, and scholar.

She is a member of the American Society of Hematology (ASH) Subcommittee on Immunotherapy and the co-chair of the Committee on Trainees and Junior Faculty for the American Society of Transplantation and Cellular Therapy (ASTCT). Other positions in service to professional organizations include co-chairing committees and task forces dedicated to promoting diversity among hematology and cell therapy specialists.

Clinical Focus


  • Hematology

Academic Appointments


Administrative Appointments


  • Assistant Professor, Division of Blood & Marrow Transplantation and Cellular Therapy, Stanford University School of Medicine (2021 - Present)

Honors & Awards


  • Women in Cancer Immunotherapy Network (WIN) Leadership Institute, Society for Immunotherapy of Cancer (SITC)
  • Best Basic Science Abstract, European Society for Blood and Marrow Transplantation
  • Mechanistic Insights to Improve Clinical Benefit, Early Career Investigator Travel Award, Keystone Symposium on Cancer Immunotherapy
  • SITC Travel Award, 3rd Forum on Immunotherapy & Translational Immunology of Cancer
  • Abstract Achievement Award, American Society of Hematology (ASH)
  • Loan Repayment Award, National Institutes of Health (NIH)
  • ASH Translational Research Training in Hematology, European Hematology Association
  • Clinical Research Training Course, American Society for Blood and Marrow Transplantation (ASBMT)
  • Minority Faculty Leadership Development, Awarded Competitive Admission to American Association of Medical Colleges (AAMC)
  • 2nd Annual Mentoring Program for SCT Fellows, Future of Stem Cell Transplantation
  • Resident Travel Award for Underrepresented Populations, Conquer Cancer Foundation of American Society of Clinical Oncology
  • ASH Minority Medical Student Award, American Society of Hematology (ASH)

Professional Education


  • Board Certification, American Board of Internal Medicine, Medical Oncology
  • Board Certification, American Board of Internal Medicine, Hematology
  • Board Certification, American Board of Internal Medicine, Internal Medicine
  • Fellowship, Memorial Sloan Kettering Cancer Center, Medical Oncology and Hematology
  • Residency, University of Texas Southwestern Medical School, Internal Medicine
  • Internship, University of Texas Southwestern Medical School, Internal Medicine
  • Medical Education, University of Texas Southwestern Medical School

Clinical Trials


  • CD19/CD22 Chimeric Antigen Receptor(CAR) T Cells in Adults With Recurrent/Refractory B Cell Malignancies Recruiting

    This phase I trial studies the side effects of CD19/CD22 chimeric antigen receptor (CAR) T cells when given together with chemotherapy, and to see how well they work in treating patients with CD19 positive diffuse large B-cell lymphoma or B acute lymphoblastic leukemia that has come back or does not respond to treatment. A CAR is a genetically-engineered receptor made so that immune cells (T cells) can attack cancer cells by recognizing and responding to the CD19/CD22 proteins. These proteins are commonly found on diffuse large B-cell lymphoma and B acute lymphoblastic leukemia. Drugs used in chemotherapy, such as cyclophosphamide and fludarabine phosphate, 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. Giving CD19/CD22-CAR T cells and chemotherapy may work better in treating patients with diffuse large B-cell lymphoma or B acute lymphoblastic leukemia.

    View full details

Stanford Advisees


All Publications


  • Burnout in U.S. hematologists and oncologists: impact of compensation models and advanced practice provider support. Blood advances Lee, A. I., Masselink, L. E., De Castro, L. M., Marshall, A. L., Connell, N. T., Dent, G. A., Fritz, J., Homer, M. R., Lucas, T. L., Naik, R. P., Nelson, M., O'Connell, C. L., Rajasekhar, A., Reynolds, R. J., Sharma, D., Smith, M., Weeks, L. D., Erikson, C. E. 2022

    Abstract

    Burnout is prevalent in throughout medicine. Few large-scale studies have examined the impact of physician compensation or clinical support staff on burnout among hematologists and oncologists. In 2019, the American Society of Hematology conducted a practice survey of hematologists and oncologists in the American Medical Association Masterfile; burnout was measured using a validated, single-item burnout instrument from the Physician Work Life Study, while satisfaction was assessed in several domains using a 5-point Likert scale. The overall survey response rate was 25.2% (N = 631). Of 411 respondents with complete responses in the final analysis, 36.7% (N = 151) were from academic practices and 63.3% (N = 260) from community practices; 29.0% (N = 119) were female. Over one-third (36.5%; N = 150) reported burnout, while 12.0% (N = 50) had a high level of burnout. In weighted multivariate logistic regression models incorporating numerous variables, compensation plans based entirely on relative value unit (RVU) generation were significantly associated with high burnout among academic and community physicians, while the combination of RVU + salary compensation showed no significant association. Female gender was associated with high burnout among academic physicians. High advanced practice provider utilization was inversely associated with high burnout among community physicians. Distinct patterns of career dissatisfaction were observed between academic and community physicians. We propose that implementation of compensation models not based entirely on clinical productivity, increased support for women in academic medicine, and expansion of advanced practice provider support in community practices may address burnout among hematologists and oncologists.

    View details for DOI 10.1182/bloodadvances.2021006140

    View details for PubMedID 35476017

  • Gut microbiome correlates of response and toxicity following anti-CD19 CAR T cell therapy. Nature medicine Smith, M., Dai, A., Ghilardi, G., Amelsberg, K. V., Devlin, S. M., Pajarillo, R., Slingerland, J. B., Beghi, S., Herrera, P. S., Giardina, P., Clurman, A., Dwomoh, E., Armijo, G., Gomes, A. L., Littmann, E. R., Schluter, J., Fontana, E., Taur, Y., Park, J. H., Palomba, M. L., Halton, E., Ruiz, J., Jain, T., Pennisi, M., Afuye, A. O., Perales, M., Freyer, C. W., Garfall, A., Gier, S., Nasta, S., Landsburg, D., Gerson, J., Svoboda, J., Cross, J., Chong, E. A., Giralt, S., Gill, S. I., Riviere, I., Porter, D. L., Schuster, S. J., Sadelain, M., Frey, N., Brentjens, R. J., June, C. H., Pamer, E. G., Peled, J. U., Facciabene, A., van den Brink, M. R., Ruella, M. 2022

    Abstract

    Anti-CD19 chimeric antigen receptor (CAR) T cell therapy has led to unprecedented responses in patients with high-risk hematologic malignancies. However, up to 60% of patients still experience disease relapse and up to 80% of patients experience CAR-mediated toxicities, such as cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome. We investigated the role of the intestinal microbiome on these outcomes in a multicenter study of patients with B cell lymphoma and leukemia. We found in a retrospective cohort (n=228) that exposure to antibiotics, in particular piperacillin/tazobactam, meropenem and imipenem/cilastatin (P-I-M), in the 4 weeks before therapy was associated with worse survival and increased neurotoxicity. In stool samples from a prospective cohort of CAR T cell recipients (n=48), the fecal microbiome was altered at baseline compared to healthy controls. Stool sample profiling by 16S ribosomal RNA and metagenomic shotgun sequencing revealed that clinical outcomes were associated with differences in specific bacterial taxa and metabolic pathways. Through both untargeted and hypothesis-driven analysis of 16S sequencing data, we identified species within the class Clostridia that were associated with day 100 complete response. We concluded that changes in the intestinal microbiome are associated with clinical outcomes after anti-CD19 CAR T cell therapy in patients with B cell malignancies.

    View details for DOI 10.1038/s41591-022-01702-9

    View details for PubMedID 35288695

  • Custom CARs: Leveraging the Adaptability of Allogeneic CAR Therapies to Address Current Challenges in Relapsed/Refractory DLBCL. Frontiers in immunology Jeyakumar, N., Smith, M. 2022; 13: 887866

    Abstract

    Cellular therapies have transformed the treatment of relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL), which typically does not respond well to salvage chemotherapy. Recently, approximately 40% of r/r DLBCL patients across three different trials achieved a complete remission at 1 year after receiving treatment with autologous chimeric antigen receptor (CAR) T cells (auto-CARs). These successes have prompted studies of auto-CARs in second-line settings, in which axicabtagene ciloleucel and lisocabtagene maraleucel both showed improved event-free survival over autologous hematopoietic cell transplantation (AHCT). While encouraging, this data also highlights that 60% of patients relapse or progress following treatment with auto-CARs. Individual disease characteristics and logistical challenges of cell engineering also limit patients' eligibility for auto-CARs. Allogeneic CAR T cells (allo-CARs) may address some of these limitations as they may mitigate delays associated with auto-CARs, thereby reducing the need for bridging chemotherapies and increasing availability of cellular products for patients with aggressive lymphomas. By being sourced from healthy donors who have never been exposed to cytotoxic chemotherapy, allo-CARs can be created from T cells with better fitness. Allo-CARs made from specific cellular subsets (e.g., stem cell memory or naive/early memory T cells) may also have increased efficacy and long-term persistence. Additionally, allo-CARs have been successfully created from other cell types, including natural killer cells, gamma-delta T-cells and induced pluripotent stem cells. These cell types can be engineered to target viral antigens, enabling precision targeting of virally driven DLBCL. As allogeneic donor cells can be banked and cryopreserved in batches, they can be made more readily available, potentially reducing logistical hurdles and costs compared to engineering auto-CARs. This may ultimately create a more sustainable platform for cell therapies. Challenges with allo-CARs that will need to be addressed include graft versus host disease, alloimmunization, potentially decreased persistence relative to auto-CARs, and antigen escape. In short, the adaptability of allo-CARs makes them ideal for treating patients with r/r DLBCL who have progressed through standard chemotherapy, AHCT, or auto-CARs. Here, we review the published literature on patients with r/r DLBCL treated with allogeneic CAR products manufactured from various cell types as well as forthcoming allogeneic CAR technologies.

    View details for DOI 10.3389/fimmu.2022.887866

    View details for PubMedID 35663947

  • The Composition of the Intestinal Microbiota Correlates with Response and Toxicity after CAR T cell Immunotherapy in Patients with B-cell Malignancies Smith, M. Nature Medicine . 2021
  • A Question of Beneficence: Comorbidity Assessment to Ascertain Potential Benefit of CD19 Chimeric Antigen Receptor T Cells for Patients with Diffuse Large B Cell Lymphoma TRANSPLANTATION AND CELLULAR THERAPY Smith, M. 2021; 27 (1): 2-3
  • Relapse after allogeneic stem cell transplantation of acute myeloid leukemia and myelodysplastic syndrome and importance of second cellular therapy. Smith, M. Transplantation and Cellular Therapy. 2021
  • Alloreactive T cells deficient of the short-chain fatty acid receptor GPR109a induce less graft-versus-host disease Smith, M. Blood. 2021
  • The gut microbiota is associated with immune cell dynamics in humans NATURE Schluter, J., Peled, J. U., Taylor, B. P., Markey, K. A., Smith, M., Taur, Y., Niehus, R., Staffas, A., Dai, A., Fontana, E., Amoretti, L. A., Wright, R. J., Morjaria, S., Fenelus, M., Pessin, M. S., Chao, N. J., Lew, M., Bohannon, L., Bush, A., Sung, A. D., Hohl, T. M., Perales, M., van den Brink, M. M., Xavier, J. B. 2020; 588 (7837): 303-307

    Abstract

    The gut microbiota influences development1-3 and homeostasis4-7 of the mammalian immune system, and is associated with human inflammatory8 and immune diseases9,10 as well as responses to immunotherapy11-14. Nevertheless, our understanding of how gut bacteria modulate the immune system remains limited, particularly in humans, where the difficulty of direct experimentation makes inference challenging. Here we study hundreds of hospitalized-and closely monitored-patients with cancer receiving haematopoietic cell transplantation as they recover from chemotherapy and stem-cell engraftment. This aggressive treatment causes large shifts in both circulatory immune cell and microbiota populations, enabling the relationships between the two to be studied simultaneously. Analysis of observed daily changes in circulating neutrophil, lymphocyte and monocyte counts and more than 10,000 longitudinal microbiota samples revealed consistent associations between gut bacteria and immune cell dynamics. High-resolution clinical metadata and Bayesian inference allowed us to compare the effects of bacterial genera in relation to those of immunomodulatory medications, revealing a considerable influence of the gut microbiota-together and over time-on systemic immune cell dynamics. Our analysis establishes and quantifies the link between the gut microbiota and the human immune system, with implications for microbiota-driven modulation of immunity.

    View details for DOI 10.1038/s41586-020-2971-8

    View details for Web of Science ID 000592644600005

    View details for PubMedID 33239790

    View details for PubMedCentralID PMC7725892

  • Hematopoietic recovery in patients receiving chimeric antigen receptor T-cell therapy for hematologic malignancies BLOOD ADVANCES Jain, T., Knezevic, A., Pennisi, M., Chen, Y., Ruiz, J. D., Purdon, T. J., Devlin, S. M., Smith, M., Shah, G. L., Halton, E., Diamonte, C., Scordo, M., Sauter, C. S., Mead, E., Santomasso, B. D., Palomba, M., Batlevi, C. W., Maloy, M. A., Giralt, S., Smith, E., Brentjens, R., Park, J. H., Perales, M., Mailankody, S. 2020; 4 (15): 3776-3787

    Abstract

    Factors contributing to hematopoietic recovery following chimeric antigen receptor (CAR) T-cell therapy have not been well studied. In an analysis of 83 patients with hematologic malignancies treated with CAR T-cell therapy, we describe patterns of hematopoietic recovery and evaluate potentially associated factors. We included patients who received axicabtagene ciloleucel (n = 30) or tisagenlecleucel (n = 10) for B-cell lymphoma, CD19-28z CAR T therapy for B-cell acute lymphoblastic leukemia (NCT01044069; n = 37), or B-cell maturation antigen targeting CAR T cells for multiple myeloma (NCT03070327; n = 6). Patients treated with CAR T cells who had not progressed, died, or received additional chemotherapy had "recovered" (per definition in Materials and methods section) hemoglobin, platelet, neutrophil, and white blood cell counts at rates of 61%, 51%, 33%, and 28% at month 1 postinfusion and 93%, 90%, 80%, and 59% at month 3 postinfusion, respectively. Univariate analysis showed that increasing grade of immune effector cell-associated neurological syndrome (ICANS), baseline cytopenias, CAR construct, and higher peak C-reactive protein or ferritin levels were statistically significantly associated with a lower likelihood of complete count recovery at 1 month; a similar trend was seen for cytokine release syndrome (CRS). After adjustment for baseline cytopenia and CAR construct, grade ≥3 CRS or ICANS remained significantly associated with the absence of complete count recovery at 1 month. Higher levels of vascular endothelial growth factor and macrophage-derived chemokines, although not statistically significant, were seen patients without complete count recovery at 1 month. This remains to be studied further in larger prospective studies.

    View details for DOI 10.1182/bloodadvances.2020002509

    View details for Web of Science ID 000560095100034

    View details for PubMedID 32780846

    View details for PubMedCentralID PMC7422135

  • Impaired mitochondrial oxidative phosphorylation limits the self-renewal of T cells exposed to persistent antigen. Nature immunology Vardhana, S. A., Hwee, M. A., Berisa, M., Wells, D. K., Yost, K. E., King, B., Smith, M., Herrera, P. S., Chang, H. Y., Satpathy, A. T., van den Brink, M. R., Cross, J. R., Thompson, C. B. 2020

    Abstract

    The majority of tumor-infiltrating T cells exhibit a terminally exhausted phenotype, marked by a loss of self-renewal capacity. How repetitive antigenic stimulation impairs T cell self-renewal remains poorly defined. Here, we show that persistent antigenic stimulation impaired ADP-coupled oxidative phosphorylation. The resultant bioenergetic compromise blocked proliferation by limiting nucleotide triphosphate synthesis. Inhibition of mitochondrial oxidative phosphorylation in activated T cells was sufficient to suppress proliferation and upregulate genes linked to T cell exhaustion. Conversely, prevention of mitochondrial oxidative stress during chronic T cell stimulation allowed sustained T cell proliferation and induced genes associated with stem-like progenitor T cells. As a result, antioxidant treatment enhanced the anti-tumor efficacy of chronically stimulated T cells. These data reveal that loss of ATP production through oxidative phosphorylation limits T cell proliferation and effector function during chronic antigenic stimulation. Furthermore, treatments that maintain redox balance promote T cell self-renewal and enhance anti-tumor immunity.

    View details for DOI 10.1038/s41590-020-0725-2

    View details for PubMedID 32661364

  • Associations between hematology/oncology fellows' training and mentorship experiences and hematology-only career plans BLOOD ADVANCES Masselink, L. E., Erikson, C. E., Connell, N. T., De Castro, L. M., Dent, G. A., Marshall, A. L., Naik, R. P., Nelson, M., O'Connell, C. L., Rajasekhar, A., Sharma, D., Smith, M., Lee, A. 2019; 3 (21): 3278-3286

    Abstract

    As the adult hematology and oncology fellowship training pathways have merged in the United States and concerns have arisen about the aging of practicing hematologists, the American Society of Hematology and hematology education leaders are looking to improve their understanding of the factors that contribute to fellows' plans to enter hematology-only careers. With the support of the American Society of Hematology, we collected and analyzed data from a survey of hematology/oncology fellows (n = 626) to examine the relationship between training and mentorship experiences and fellows' plans to enter hematology-only careers. Fellows who planned to enter hematology-only careers were significantly more likely to report having clinical training and mentorship experiences in hematology throughout their training relative to fellows with oncology-only or combined hematology/oncology career plans. After controlling for prior interest in hematology and demographic characteristics, exposure to hematology patients in medical school and fellowship, hematology research experiences, and hematology mentorship (research collaboration and career coaching) were positively and significantly associated with hematology-only career plans. These findings suggest that increasing opportunities for exposure to hematology patients, research opportunities and mentors throughout training could be helpful in building a strong pipeline of potential hematologists.

    View details for DOI 10.1182/bloodadvances.2019000569

    View details for Web of Science ID 000496921800011

    View details for PubMedID 31698456

    View details for PubMedCentralID PMC6855099

  • Standard Antithymocyte Globulin Dosing Results in Poorer Outcomes in Overexposed Patients after Ex Vivo CD34(+) Selected Allogeneic Hematopoietic Cell Transplantation BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION Scordo, M., Bhatt, V., Hilden, P., Smith, M., Thoren, K., Cho, C., Shah, G. L., Maloy, M. A., Papadopoulos, E. B., Jakubowski, A. A., Avecilla, S. T., O'Reilly, R. J., Castro-Malaspina, H., Tamari, R., Shaffer, B. C., Boelens, J. J., Perales, M., Giralt, S. A. 2019; 25 (8): 1526-1535

    Abstract

    Antithymocyte globulin (ATG) use mitigates the risk of graft rejection and graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation (allo-HCT), but ATG overexposure in the setting of lymphopenia negatively affects immune recovery. We hypothesized that standard empiric weight-based dosing of ATG, used to prevent graft rejection in ex vivo CD34-selected allo-HCT, may lead to serious adverse consequences on outcomes in certain patients. We evaluated 304 patients undergoing myeloablative-conditioned ex vivo CD34-selected allo-HCT with HLA-matched donors for the treatment of hematologic malignancies. Patients received rabbit ATG at a dose of 2.5 mg/kg/day i.v. on days -3 and/or -2. An ATG dosing cutoff of 450 mg was used for statistical analyses to assess the relationship between ATG and overall survival (OS). Among all patients, median total ATG dose was 360 mg (range, 130 to 510 mg); 279 (92%) received a total dose of ATG ≤450 mg, and 25 (8%) received a total dose >450 mg. On the first day of ATG administration (day -3), the median absolute lymphocyte count was .0 K/µL. For patients who received a total dose of ATG >450 mg or ≤450 mg, the incidences of acute and late-acute GVHD grade II-IV were statistically similar. At 3 years post-HCT, for patients who received a total dose of ATG >450 mg or ≤450 mg, nonrelapse mortality (NRM) rates were 35% and 18%, respectively (P = .029), disease-free survival (DFS) rates were 37% and 61%, respectively (P = .003), and OS rates were 40% and 67%, respectively (P = .001). Among all patient and HCT characteristics in multivariable analyses, receipt of a total dose of ATG >450 mg was associated with an increased risk of NRM (hazard ratio [HR], 2.9; P = .01), shorter DFS (HR, 2.0; P = .03), and inferior OS (HR, 2.1; P = .01). In summary, the use of weight-based ATG at a time of relative lymphopenia before ex vivo CD34-selected allo-HCT results in overdosing in heavier patients, leading to higher NRM and lower DFS and OS. Further pharmacokinetic investigation in this setting is critical to determining the optimal dosing strategy for ATG.

    View details for DOI 10.1016/j.bbmt.2019.02.021

    View details for Web of Science ID 000483008500008

    View details for PubMedID 30831208

    View details for PubMedCentralID PMC7302932

  • Posttransplant chimeric antigen receptor therapy BLOOD Smith, M., Zakrzewski, J., James, S., Sadelain, M. 2018; 131 (10): 1045-1052

    Abstract

    Therapeutic T-cell engineering is emerging as a powerful approach to treat refractory hematological malignancies. Its most successful embodiment to date is based on the use of second-generation chimeric antigen receptors (CARs) targeting CD19, a cell surface molecule found in most B-cell leukemias and lymphomas. Remarkable complete remissions have been obtained with autologous T cells expressing CD19 CARs in patients with relapsed, chemo-refractory B-cell acute lymphoblastic leukemia, chronic lymphocytic leukemia, and non-Hodgkin lymphoma. Allogeneic CAR T cells may also be harnessed to treat relapse after allogeneic hematopoietic stem cell transplantation. However, the use of donor T cells poses unique challenges owing to potential alloreactivity. We review different approaches to mitigate the risk of causing or aggravating graft-versus-host disease (GVHD), including CAR therapies based on donor leukocyte infusion, virus-specific T cells, T-cell receptor-deficient T cells, lymphoid progenitor cells, and regulatory T cells. Advances in CAR design, T-cell selection and gene editing are poised to enable the safe use of allogeneic CAR T cells without incurring GVHD.

    View details for DOI 10.1182/blood-2017-08-752121

    View details for Web of Science ID 000430687200004

    View details for PubMedID 29358181

    View details for PubMedCentralID PMC5865610

  • Allogeneic Hematopoietic Cell Transplantation for Adult T Cell Acute Lymphoblastic Leukemia. Biology of blood and marrow transplantation Hamilton, B. K., Rybicki, L., Abounader, D., Adekola, K., Advani, A., Aldoss, I., Bachanova, V., Bashey, A., Brown, S., DeLima, M., Devine, S., Flowers, C. R., Ganguly, S., Jagasia, M., Kennedy, V. E., Kim, D. D., McGuirk, J., Pullarkat, V., Romee, R., Sandhu, K., Smith, M., Ueda, M., Viswabandya, A., Vu, K., Wall, S., Zeichner, S. B., Perales, M., Majhail, N. S. 2017

    Abstract

    Allogeneic hematopoietic cell transplantation (HCT) is recommended for patients with T cell acute lymphoblastic leukemia (T-ALL) in second or later complete remission (CR) and high-risk patients in first CR. Given its relative rarity, data on outcomes of HCT for T-ALL are limited. We conducted a multicenter retrospective cohort study using data from 208 adult patients who underwent HCT between 2000 and 2014 to describe outcomes of allogeneic HCT for T-ALL in the contemporary era. The median age at HCT was 37 years, and the majority of patients underwent HCT in CR, using total body irradiation (TBI)-based myeloablative conditioning regimens. One-quarter of the patients underwent alternative donor HCT using a mismatched, umbilical cord blood, or haploidentical donor. With a median follow up of 38 months, overall survival at 5 years was 34%. The corresponding cumulative incidence of non-relapse mortality and relapse was 26% and 41%, respectively. In multivariable analysis, factors significantly associated with overall survival were the use of TBI (HR, 0.57; P = .021), age >35 years (HR, 1.55; P = .025), and disease status at HCT (HR, 1.98; P = .005 for relapsed/refractory disease compared with CR). Relapse was the most common cause of death (58% of patients). Allogeneic HCT remains a potentially curative option in selected patients with adult T-ALL, although relapse is a major cause of treatment failure.

    View details for DOI 10.1016/j.bbmt.2017.04.003

    View details for PubMedID 28396160

  • Donor CD19 CART cells exert potent graft-versus-lymphoma activity with diminished graft-versus-host activity NATURE MEDICINE Ghosh, A., Smith, M., James, S. E., Davila, M. L., Velardi, E., Argyropoulos, K. V., Gunset, G., Perna, F., Kreines, F. M., Levy, E. R., Lieberman, S., Jay, H. V., Tuckett, A. Z., Zakrzewski, J. L., Tan, L., Young, L. F., Takvorian, K., Dudakov, J. A., Jenq, R. R., Hanash, A. M., Motta, A. F., Murphy, G. F., Liu, C., Schietinger, A., Sadelain, M., van den Brink, M. M. 2017; 23 (2): 242-249

    Abstract

    Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative therapy for hematological malignancies. However, graft-versus-host disease (GVHD) and relapse after allo-HSCT remain major impediments to the success of allo-HSCT. Chimeric antigen receptors (CARs) direct tumor cell recognition of adoptively transferred T cells. CD19 is an attractive CAR target, which is expressed in most B cell malignancies, as well as in healthy B cells. Clinical trials using autologous CD19-targeted T cells have shown remarkable promise in various B cell malignancies. However, the use of allogeneic CAR T cells poses a concern in that it may increase risk of the occurrence of GVHD, although this has not been reported in selected patients infused with donor-derived CD19 CAR T cells after allo-HSCT. To understand the mechanism whereby allogeneic CD19 CAR T cells may mediate anti-lymphoma activity without causing a significant increase in the incidence of GVHD, we studied donor-derived CD19 CAR T cells in allo-HSCT and lymphoma models in mice. We demonstrate that alloreactive T cells expressing CD28-costimulated CD19 CARs experience enhanced stimulation, resulting in the progressive loss of both their effector function and proliferative potential, clonal deletion, and significantly decreased occurrence of GVHD. Concurrently, the other CAR T cells that were present in bulk donor T cell populations retained their anti-lymphoma activity in accordance with the requirement that both the T cell receptor (TCR) and CAR be engaged to accelerate T cell exhaustion. In contrast, first-generation and 4-1BB-costimulated CAR T cells increased the occurrence of GVHD. These findings could explain the reduced risk of GVHD occurring with cumulative TCR and CAR signaling.

    View details for DOI 10.1038/nm.4258

    View details for Web of Science ID 000393729000016

    View details for PubMedID 28067900

    View details for PubMedCentralID PMC5528161

  • Long-term event-free and overall survival after risk-adapted melphalan and SCT for systemic light chain amyloidosis LEUKEMIA Landau, H., Smith, M., Landry, C., Chou, J. F., Devlin, S. M., Hassoun, H., Bello, C., Giralt, S., Comenzo, R. L. 2017; 31 (1): 136-142

    Abstract

    Stem cell transplantation (SCT), an effective therapy for amyloid light chain (AL) amyloidosis patients, is associated with low treatment-related mortality (TRM) with appropriate patient selection and risk-adapted dosing of melphalan (RA-SCT). Consolidation after SCT increases hematologic complete response (CR) rates and may improve overall survival (OS) for patients with

    View details for DOI 10.1038/leu.2016.229

    View details for Web of Science ID 000394058700018

    View details for PubMedID 27560108

    View details for PubMedCentralID PMC5220129

  • Tumor immunology and cancer immunotherapy: summary of the 2014 SITC primer JOURNAL FOR IMMUNOTHERAPY OF CANCER Page, D. B., Bourla, A., Daniyan, A., Naidoo, J., Smith, E., Smith, M., Friedman, C., Khalil, D. N., Funt, S., Shoushtari, A. N., Overwijk, W. W., Sharma, P., Callahan, M. K. 2015; 3
  • Racial Differences in the Presentation and Outcomes of Chronic Lymphocytic Leukemia and Variants in the United States CLINICAL LYMPHOMA MYELOMA & LEUKEMIA Shenoy, P. J., Malik, N., Sinha, R., Nooka, A., Nastoupil, L. J., Smith, M., Flowers, C. R. 2011; 11 (6): 498-506

    Abstract

    Chronic lymphocytic leukemia (CLL) is the most common form of adult leukemia in the United States, and prolymphocytic leukemia (PLL) is a related, rare chronic lymphoproliferative disorder.Using the United States Surveillance, Epidemiology and End Results (SEER) data from 13 registries, we examined differences in incidence and survival for CLL, small lymphocytic lymphoma (SLL) and PLL by race. International Classification of Diseases for Oncology 3(rd) edition histology codes 9670, 9823, and 9632-34 were used to identify cases.From 1992 to 2007, 30,622 cases of CLL/SLL and 268 cases of PLL were recorded. Males had higher incidence than females (male-to-female incidence rate ratio CLL/SLL 1.89, 95% confidence interval (CI) 1.85-1.94 and PLL 2.47, 95%CI 1.90-3.20). Black patients were diagnosed at younger age compared to white patients (mean age at diagnosis for white versus black patients for CLL/SLL, 70 versus 67 years, P < .001; for PLL, 71 versus 61 years, P < .001). Greater proportion of black patients with SLL presented with B symptoms, extranodal primary site, and advanced disease compared to white patients (P = .003, P = .012, and P = .009 respectively). White patients with CLL/SLL had better survival rates than black patients (5-year relative survival rate 77.1% versus 63.9%, P < .01). In univariate Cox regression models, black race, male gender, age at diagnosis > 65 years, advanced stage, and B-symptoms were predictors of worse survival (P < .01) among CLL/SLL patients.Black patients with CLL/SLL and PLL present at younger age and black patients with CLL/SLL have worse survival than white patients. Epidemiological studies examining the biological variants of these diseases in concert with race are needed to elucidate the etiology of these disparities.

    View details for DOI 10.1016/j.clml.2011.07.002

    View details for Web of Science ID 000298280200007

    View details for PubMedID 21889433

  • Both naive and memory T cells exert alloreactivity across HLA barriers Smith, M. Biology of Blood and Marrow Transplantation. 2011
  • Clinical, Molecular, and Environmental Risk Factors for Hodgkin Lymphoma Smith, M. Advances in Hematology. 2011