Sushma Bharadwaj, MD

All Publications

• Multifocal demyelinating leukoencephalopathy and oligodendroglial lineage cell loss with immune effector cell-associated neurotoxicity syndrome (ICANS) following CD19 CAR T-cell therapy for mantle cell lymphoma. Journal of neuropathology and experimental neurology Nie, E. H., Ahmadian, S. S., Bharadwaj, S. N., Acosta-Alvarez, L., Threlkeld, Z. D., Frank, M. J., Miklos, D. B., Monje, M., Scott, B. J., Vogel, H. 2023

  Abstract

  Immune effector cell-associated neurotoxicity syndrome (ICANS) is a prevalent condition seen after treatment with chimeric antigen receptor T-cell (CAR T) therapy and other cancer cell therapies. The underlying pathophysiology and neuropathology of the clinical syndrome are incompletely understood due to the limited availability of brain tissue evaluation from patient cases, and a lack of high-fidelity preclinical animal models for translational research. Here, we present the cellular and tissue neuropathologic analysis of a patient who experienced grade 4 ICANS after treatment with anti-CD19 CAR T therapy for mantle cell lymphoma. Our pathologic evaluation reveals a pattern of multifocal demyelinating leukoencephalopathy associated with a clinical course of severe ICANS. A focused analysis of glial subtypes further suggests region-specific oligodendrocyte lineage cell loss as a potential cellular and pathophysiologic correlate in severe ICANS. We propose a framework for the continuum of neuropathologic changes thus far reported across ICANS cases. Future elucidation of the mechanistic processes underlying ICANS will be critical in minimizing neurotoxicity following CAR T-cell and related immunotherapy treatments across oncologic and autoimmune diseases.

  View details for DOI 10.1093/jnen/nlac121

  View details for PubMedID 36592076

• Outcomes for Acute Myeloid Leukemia Relapse after Allogeneic Hematopoietic Cell Transplantation Remain Poor in the Modern Era Philip, S., Lowsky, R., Johnston, L. J., Arai, S., Meyer, E. H., Negrin, R. S., Rezvani, A. R., Shiraz, P., Shizuru, J. A., Sidana, S., Weng, W., Bharadwaj, S., Frank, M. J., Miklos, D. B., Smith, M., Muffly, L., Agrawal, V. AMER SOC HEMATOLOGY. 2022: 4825-4827

  View details for DOI 10.1182/blood-2022-168546

  View details for Web of Science ID 000893223204372

• Belumosudil Combination Therapy in Refractory Chronic Graft-Versus-Host Disease Chin, M., Shizuru, J. A., Muffly, L., Shiraz, P., Johnston, L. J., Lowsky, R., Rezvani, A. R., Frank, M. J., Bharadwaj, S., Weng, W., Negrin, R. S., Miklos, D. B., Arai, S. AMER SOC HEMATOLOGY. 2022: 4788-4789

  View details for DOI 10.1182/blood-2022-165547

  View details for Web of Science ID 000893223204356

• Geriatrics assessment in older adults referred for hematopoietic cell transplantation. Journal of the American Geriatrics Society Sossenheimer, P. H., Bharadwaj, S., Johnston, L., Periyakoil, V. S. 2022

  View details for DOI 10.1111/jgs.17929

  View details for PubMedID 35708096

• Multifocal demyelinating leukoencephalopathy and oligodendroglial lineage cell loss with CD19 CAR T-cell lymphoma therapy Nie, E., Ahmadian, S., Bharadwaj, S., Acosta-Alvarez, L., Threlkeld, Z., Frank, M., Miklos, D., Born, D., Scott, B., Monje, M., Vogel, H. OXFORD UNIV PRESS INC. 2022: 464

  View details for Web of Science ID 000798368400099

• Allogeneic Hematopoietic Cell Transplantation for Adult Acute Lymphoblastic Leukemia in the Modern Era. Transplantation and cellular therapy Liang, E. C., Craig, J., Torelli, S., Cunanan, K., Iglesias, M., Arai, S., Frank, M. J., Johnston, L., Lowsky, R., Meyer, E. H., Miklos, D. B., Negrin, R., Rezvani, A., Shiraz, P., Shizuru, J., Sidana, S., Weng, W. K., Bharadwaj, S., Muffly, L. 2022

  Abstract

  Allogeneic hematopoietic cell transplantation (HCT) remains an important treatment for adults with acute lymphoblastic leukemia (ALL). We hypothesized that advances in ALL and transplantation have resulted in improved HCT outcomes in recent years.To evaluate the characteristics and outcomes of adult ALL patients undergoing allogeneic HCT over the last decade.Patients with ALL aged ≥18 years old who underwent allogeneic HCT at Stanford University between 2008 and 2019 were included in this study. Patients were divided into two Eras based on year of HCT: 2008-2013 (Earlier Era) and 2014-2019 (Later Era).A total of 285 patients were included: 119 patients underwent HCT in the Earlier Era and 166 in the Later Era. Patients transplanted in the Later Era were more likely to be Hispanic (38% vs. 21%) and to have HCT-Comorbidity Index of ≥ 3 (31% vs. 18%). Donor source for HCT also differed with an increase in the use of HLA-mismatched donor sources (38% vs. 24%), notably umbilical cord blood (UCB) in the Later Era (16% vs. 0%). Patients in the Later Era were less likely to undergo transplant with active disease (4% vs.16%); pre-HCT rates of measurable residual disease (MRD) were similar across the Eras (38% vs. 40%). In unadjusted analyses, overall survival (OS) improved across Eras, with 2-year estimates for the Later and Earlier Eras of 73% (95% CI, 66%-80%) vs. 55% (95% CI, 46%-64%), respectively. Multivariable analysis confirmed the association between Later Era and OS (HR = 0.52, 95% CI, 0.34-0.78). Finally, among patients relapsing after HCT (25% in Later Era and 33% in Earlier Era), the utilization of novel immunotherapies increased in the Later Era (44% vs. 3%), as did the median OS following post-HCT relapse (16 months vs. 8 months, p < 0.001).OS following HCT for adult ALL has improved in recent years. This is due, in part, to a significant improvement in the ability to effectively salvage adults with ALL relapsing after HCT.

  View details for DOI 10.1016/j.jtct.2022.05.010

  View details for PubMedID 35584783

• Detection of Aberrant CD58 Expression in a Wide Spectrum of Hodgkin and Non-Hodgkin Lymphomas: Implications for CAR T Cell Resistance Younes, S., Libert, D., Zhao, S., Johnsrud, A., Bharadwaj, S., Majzner, R., Frank, M., Miklos, D., Natkunam, Y. SPRINGERNATURE. 2022: 1046-1048

  View details for Web of Science ID 000770361802309

• Detection of Aberrant CD58 Expression in a Wide Spectrum of Hodgkin and Non-Hodgkin Lymphomas: Implications for CAR T Cell Resistance Younes, S., Libert, D., Zhao, S., Johnsrud, A., Bharadwaj, S., Majzner, R., Frank, M., Miklos, D., Natkunam, Y. SPRINGERNATURE. 2022: 1046-1048

  View details for Web of Science ID 000770360202309

• Structural Racism is a Mediator of Disparities in Acute Myeloid Leukemia Outcomes. Blood Abraham, I. E., Rauscher, G. H., Patel, A. A., Pearse, W., Rajakumar, P., Burkart, M., Aleem, A., Dave, A., Bharadwaj, S., Paydary, K., Acevedo-Mendez, M., Goparaju, K., Gomez, R., Carlson, K. N., Tsai, S. B., Quigley, J. G., Galvin, J. P., Zia, M., Larson, M. L., Berg, S., Stock, W., Altman, J. K., Khan, I. 1800

  Abstract

  Non-Hispanic Black (NHB) and Hispanic patients with acute myeloid leukemia (AML) have higher mortality rates than non-Hispanic white (NHW) patients despite more favorable genetics and younger age. A discrete survival analysis was performed on 822 adult AML patients from six urban cancer centers and revealed inferior survival among NHB (HR=1.59, 95% CI: 1.15, 2.22) and Hispanic (HR=1.25, 95% CI: 0.88, 1.79) compared to NHW patients. A multilevel analysis of disparities was then conducted to investigate the contribution of neighborhood measures of structural racism on racial/ethnic differences in survival. Census tract disadvantage and affluence scores were individually calculated. Mediation analysis of hazard of leukemia death between groups was examined across six composite variables: structural racism (census tract disadvantage, affluence and segregation), tumor biology (ELN risk and secondary leukemia), health care access (insurance and clinical trial enrollment), comorbidities, treatment patterns (induction intensity and transplant utilization) and ICU admission during intensive chemotherapy. Strikingly, census tract measures accounted for nearly all of the NHB-NHW and Hispanic-NHW disparity in leukemia death. Treatment patterns, including induction intensity and allogeneic transplant, as well as treatment complications, as assessed by ICU admission during induction chemotherapy, were additional mediators of survival disparities in AML. This is the first study to formally test mediators for observed disparities in AML survival and highlights the need to investigate the mechanisms by which structural racism interacts with known prognostic and treatment factors to influence leukemia outcomes.

  View details for DOI 10.1182/blood.2021012830

  View details for PubMedID 35061876

• Significance of isolated deletion (20q) in donor cells after allogeneic hematopoietic cell transplantation LEUKEMIA & LYMPHOMA Nathan, S., Bharadwaj, S., Luke, K., Kalas, L., Katz, D. A., Hussain, M., Miller, I., Hsu, W., Shammo, J., Venugopal, P., Ustun, C. 2020; 61 (8): 2008-2011

  View details for DOI 10.1080/10428194.2020.1750609

  View details for Web of Science ID 000527213200001

  View details for PubMedID 32306813

• Gender and glaucoma: what we know and what we need to know CURRENT OPINION IN OPHTHALMOLOGY Vajaranant, T. S., Nayak, S., Wilensky, J. T., Joslin, C. E. 2010; 21 (2): 91-99

  Abstract

  With growing aging populations and an increase in cases of glaucoma and glaucoma blindness worldwide, aging populations are particularly at higher risk of glaucoma and glaucoma blindness. Awareness of the gender differences might increase attention toward populations at risk.Women not only outlive men, but also outnumber men in glaucoma cases worldwide. Women are at higher risks for angle closure glaucoma, but there is no clear gender predilection for open angle glaucoma. Of interest, there is some evidence suggesting that female sex hormones might be protective of the optic nerve. In addition, it is hypothesized that decreased estrogen exposure is associated with increased risk for open angle glaucoma, yet population-based studies present inconsistent results. Presently, there is insufficient evidence to support hormonal replacement therapy use in glaucoma prevention. In addition, it appears that women carry a larger burden of glaucoma blindness due to longevity and disadvantages in socioeconomic/health beliefs.Current evidence suggests that older women are at risk for glaucoma and glaucoma blindness. Further interdisciplinary research involving investigators, specialized in glaucoma, women's health and health disparities, will lead to better understanding of gender health disparities in glaucoma and better targeting populations at risk.

  View details for DOI 10.1097/ICU.0b013e3283360b7e

  View details for Web of Science ID 000275063500001

  View details for PubMedID 20051857

  View details for PubMedCentralID PMC4326058