Dr. Bharadwaj is fellowship-trained in blood and marrow transplantation, cellular therapy, hematology, and oncology. She is an instructor in the Stanford School of Medicine Department of Medicine, Division of Blood & Marrow Transplantation and Cellular Therapy.
Dr. Bharadwaj focuses her expertise on diagnosing and treating cancer in blood and bone marrow. For each patient, she develops a personalized, comprehensive, and compassionate care plan. In her diverse experience as a physician and scientist, she has served as an internal medicine doctor, hospitalist, hematologist, oncologist, and blood and marrow transplantation specialist. Dr. Bharadwaj has a degree in clinical research and is currently conducting clinical trials in transplant and cellular therapy.
She has participated in research studies of advances in therapy for chronic lymphocytic leukemia, melanoma, and breast cancer. She has co-authored articles published in Leukemia and Lymphoma and elsewhere. Topics include advances in cell transplantation. She also co-wrote the chapter on genome-driven personalized cancer therapy in the book Precision Medicine in Oncology.
Dr. Bharadwaj has made presentations at meetings of the American Society of Hematology, American Society of Clinical Oncology, and other associations.
Subjects include racial, demographic, and socioeconomic disparities in the treatment of patients with acute myeloid leukemia.
Dr. Bharadwaj is a member of the American Society for Transplantation and Cellular Therapy, American Society of Hematology, and American Society of Clinical Oncology.
- Cancer > Blood and Marrow Transplant
- Cancer > Hematology > Leukemia - Acute and Chronic
- Cancer > Lymphoma
Instructor, Medicine - Blood & Marrow Transplantation
Honors & Awards
ASTCT Clinical Research Training Course Scholar, ASTCT (2022)
Organizational Excellence Award, South Zone Pharmacology Conference, Mangalore, India
Board Certification: American Board of Internal Medicine, Hematology (2021)
Board Certification: American Board of Internal Medicine, Internal Medicine (2021)
Fellowship: Stanford University Bone Marrow Transplant Fellowship (2021) CA
Fellowship: Cook County Health Hematology Oncology Fellowship (2020) IL
Residency: John H Stroger Jr Hospital of Cook County Internal Medicine Residency (2013) IL
Internship: University of Illinois College of Medicine at Peoria (2011) IL
Medical Education: Kasturba Medical College Mangalore (2006) India
Additional Clinical Info
Safety of Myeloablative Conditioning, Orca-T, and Allogeneic, Donor-Derived CD19/CD22-CAR (Chimeric Antigen Receptor) T Cells in Adults With B-cell Acute Lymphoblastic Leukemia (ALL)
To assess the safety of administering allogenic, donor-derived CD19/CD22-CAR T cells that meet established release specifications in adults with B-cell ALL following a myeloablative conditioning regimen and Orca-T to determine if this will augment graft versus leukemia without increasing acute GVHD or graft failure.
Lisocabtagene maraleucel for treatment of relapsed and refractory primary mediastinal large B-cell lymphoma in an adolescent patient.
2024; 5 (1): 153-156
The safety and efficacy of CAR T-cell therapy are unknown in pediatric and adolescent patients with relapsed or refractory primary mediastinal large B-cell lymphoma (R/R PMBCL) which is associated with dismal prognosis. Here, we present a case report of a 16-year-old patient with R/R PMBCL treated with lisocabtagene maraleucel including correlative studies. Patient achieved complete response at 6 months without cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome. She only experienced mild cytopenias, requiring filgrastim once. This report highlights the safety and efficacy of lisocabtagene maraleucel in this population, warranting prospective studies to improve clinical outcomes.
View details for DOI 10.1002/jha2.859
View details for PubMedID 38406546
Clinical Features of Neurotoxicity Following CD19 CAR T-cell Therapy in Mantle Cell Lymphoma.
CD19 chimeric antigen receptor (CAR) T-cell therapy has proven highly effective for treating relapsed/refractory mantle cell lymphoma (MCL). However, immune effector cell-associated neurotoxicity syndrome (ICANS) remains a significant concern. This study aimed to evaluate the clinical, radiological, and laboratory correlatives associated with ICANS development following CD19 CAR T-cell therapy in patients with MCL. All patients (n = 26) who received standard of care brexucabtagene autoleucel until July 2022 at our institution were evaluated. Laboratory and radiographic correlatives including brain magnetic resonance imaging (MRI) and electroencephalogram (EEG) were evaluated to determine the clinical impact of ICANS. Seventeen (65%) patients experienced ICANS after treatment, with a median onset on day 6. Ten (38%) patients experienced severe (≥ grade 3) ICANS. All ICANS patients had antecedent cytokine release syndrome (CRS), but no correlation was observed between ICANS severity and CRS grade. 92% of EEGs revealed interictal changes; no patients experienced frank seizures due to ICANS. 86% of severe ICANS patients with post-infusion brain MRIs demonstrated acute neuroimaging findings not seen on pretreatment MRI. Severe ICANS was also associated with higher rates of cytopenia, coagulopathy, increased cumulative steroid exposure, and prolonged hospitalization. However, severe ICANS did not affect treatment outcomes of patients with MCL. Severe ICANS is frequently associated with a range of post-infusion brain MRI changes and abnormal EEG findings. Longer hospitalization was observed in severe ICANS patients, especially those with abnormal acute MRI or EEG findings, but there was no discernible impact on overall treatment response and survival.
View details for DOI 10.1182/bloodadvances.2023011896
View details for PubMedID 38295285
TIGIT is Frequently Expressed in the Tumor Microenvironment of Select Lymphomas: Implications for Targeted Therapy.
The American journal of surgical pathology
Immune checkpoint inhibitors against Programmed Cell Death Protein 1/Programmed Cell (PD-1/PD-L1) and CTLA-4/B7 axes have had limited success in hematologic malignancies, requiring the need to explore alternative targets such as T-cell immunoreceptor with Ig and ITIM domains (TIGIT)/CD155 to improve durable clinical responses. We undertook this study to investigate the expression profile of TIGIT such that the potential efficacy of TIGIT blockade could be mapped among lymphoma subtypes. We validated an immunohistochemical assay for TIGIT and evaluated its expression in lymphoma and tumor microenvironment (TME) cells in 661 lymphoma/leukemia biopsies. Multiplex immunofluorescence was used for correlation with normal TME cell subsets. Tumor or TME TIGIT-positivity was defined as moderate to strong membrane staining in at least 10% of tumor or TME cells, respectively. TME TIGIT expression was correlated with overall survival and progression-free survival and comparison with PD-L1 expression. In most cases, lymphoma cells were TIGIT-negative except for angioimmunoblastic and peripheral T-cell lymphomas, which showed 91% and 47% positivity, respectively. A high proportion of small B-cell lymphoma and anaplastic large cell lymphoma cases had TIGIT-positive TME cells. Chronic lymphocytic leukemia/small lymphocytic lymphoma patients with TIGIT-negative TME cells showed significantly shorter overall survival (P=0.04). No other statistically significant differences were found. When TIGIT was expressed in TME cells, there were a comparable number of TIGIT-positive only and dual TIGIT/PD-L1 positive cases except for more TIGIT-positive only cases in CLL/SLL. TIGIT expression shows distinctive profiles among lymphoma subtypes. Chronic lymphocytic leukemia/small lymphocytic lymphoma and anaplastic large cell lymphoma demonstrated high TME TIGIT expression compared with PD-L1, with a high proportion of dual TIGIT and PD-L1-positivity. Our results are likely to contribute to the design and correlative study of therapeutic response in clinical trials targeting TIGIT alone or in combination with PD1/PDL1.
View details for DOI 10.1097/PAS.0000000000002168
View details for PubMedID 38148663
Single Center Randomized Trial of T-reg graft alone versus T-reg graft Plus Tacrolimus for the Prevention of Acute GVHD.
Allogeneic hematopoietic cell transplantation (HCT) is a curative therapy for hematological malignancies for which graft-versus-host disease (GVHD) remains a major complication. The use of donor T regulatory cells (Tregs) to prevent GVHD appears promising, including in our previous evaluation of an engineered graft product (T-reg graft) consisting of the timed, sequential infusion of CD34+ hematopoietic stem cells and high-purity Tregs followed by conventional T cells. However, whether immunosuppressive prophylaxis can be removed from this protocol remains unclear. We report the results of the first stage of an open-label single-center phase 2 study (NCT01660607) investigating T-reg graft in myeloablative HCT of HLA-matched and 9/10 matched recipients. Twenty-four patients were randomized to receive T-reg graft alone (n=12) or T-reg graft plus single-agent GVHD prophylaxis (n=12) to determine if T-reg graft alone was non-inferior in preventing acute GVHD. All patients developed full donor myeloid chimerism. Patients with T-reg graft alone versus with prophylaxis had an incidence of grade II-IV acute GVHD of 58% versus 8% (p=0.005) and grade III-IV of 17% versus 0% (p=0.149), respectively. The incidence of moderate to severe chronic GVHD was 28% in the T-reg graft alone arm versus 0% with prophylaxis (p=0.056). Among patients with T-reg graft and prophylaxis, CD4+ T cell:Treg ratios were reduced after transplantation, gene-expression profiles showed reduced CD4+ proliferation, and the achievement of full donor T cell chimerism was delayed. This study indicates that T-reg graft with single-agent tacrolimus is preferred to T-reg graft alone for the prevention of acute GVHD. Clinical Trial #: NCT01660607.
View details for DOI 10.1182/bloodadvances.2023011625
View details for PubMedID 38091578
- Bendamustine vs. fludarabine/cyclophosphamide lymphodepletion prior to BCMA CAR-T cell therapy in multiple myeloma. Blood cancer journal 2023; 13 (1): 158
Idecabtagene vicleucel chimeric antigen receptor T-cell therapy for relapsed/refractory multiple myeloma with renal impairment.
We evaluated patients with relapsed multiple myeloma with renal impairment (RI treated with standard of care ide-cel, as outcomes with CAR-T therapy are unknown in this population. RI was defined as creatinine clearance (CrCl < 50 ml/min. CrCl of < 30 ml/min or dialysis dependence were defined as severe RI. The study cohort included 214 patients, 28 (13% patients with RI, including 11 patients severe RI (dialysis, n=1. Patients with RI were older, more likely to be female and had higher likelihood of having R-ISS stage 3 disease. Rates and severity of CRS (89% vs 84%, grade ≥ 3: 7% vs 2% and ICANS (23% vs 20% were similar in patients with and without RI, respectively. Patients with RI had higher incidence of short-term ≥ grade 3 cytopenias, although cytopenias were similar by 3 months following CAR-T. Renal function did not worsen after CAR-T in patients with RI. Response rates (93% vs 82% and survival outcomes (median PFS: 9 vs 8 months, p=0.26 were comparable in patients with and without RI, respectively. Treatment with ide-cel is feasible in patients with RI, with a comparable safety and efficacy profile as patients without RI, with notable exception of higher short-term high-grade cytopenias.
View details for DOI 10.3324/haematol.2023.283940
View details for PubMedID 37731379
Detection of Aberrant CD58 Expression in a Wide Spectrum of Lymphoma Subtypes: Implications for Treatment Resistance.
Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc
CD58 or lymphocyte function-associated antigen-3, is a ligand for CD2 receptors on T- and NK-cells and is required for their activation and target cell killing. We recently showed a trend towards higher frequency of CD58 aberrations in patients with diffuse large B-cell lymphoma (DLBCL) who progressed on CAR-T cell treatment compared to those who responded. Given that CD58 status may be an important measure of T-cell mediated therapy failure, we developed CD58 immunohistochemical assay and evaluated CD58 status in 748 lymphomas. Our results show that CD58 protein expression is downregulated in a significant proportion of all subtypes of B- T- and NK-cell lymphomas. CD58 loss is significantly related to poor prognostic indicators in DLBCL and to ALK and DUSP22 rearrangements in anaplastic large cell lymphoma. However, it is not associated with overall or progression free survival in any of the lymphoma subtypes. As eligibility for CAR-T therapy is being extended to a broader spectrum of lymphomas, mechanisms of resistance, such as target downregulation and CD58 loss, may limit therapeutic success. CD58 status is therefore an important biomarker in lymphoma patients who may benefit from next generation T-cell mediated therapies or other novel approaches that mitigate immune escape.
View details for DOI 10.1016/j.modpat.2023.100256
View details for PubMedID 37391168
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
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
- Idecabtagene Vicleucel Chimeric Antigen Receptor T-Cell Therapy for Relapsed/Refractory Multiple Myeloma with Renal Insufficiency: Real World Experience AMER SOC HEMATOLOGY. 2022: 10377-10379
- Higher Rates of Severe Infection and Persistent Cytopenias in Long-Term CAR19 Responders Than after Autologous HCT: A Single Institution Study of 139 Subjects AMER SOC HEMATOLOGY. 2022: 7545-7547
- The Development of Carhlh after Axicabtagene Ciloleucel Is Associated with Poor Outcomes AMER SOC HEMATOLOGY. 2022: 12775-12777
- Analysis of Bendamustine Lymphodepletion, CD19 CART Expansion, Safety and Efficacy in Patients with Rel/Ref NonHodgkin Lymphoma AMER SOC HEMATOLOGY. 2022: 10371-10373
- Belumosudil Combination Therapy in Refractory Chronic Graft-Versus-Host Disease AMER SOC HEMATOLOGY. 2022: 4788-4789
- Outcomes for Acute Myeloid Leukemia Relapse after Allogeneic Hematopoietic Cell Transplantation Remain Poor in the Modern Era AMER SOC HEMATOLOGY. 2022: 4825-4827
- Geriatrics assessment in older adults referred for hematopoietic cell transplantation. Journal of the American Geriatrics Society 2022
Multifocal demyelinating leukoencephalopathy and oligodendroglial lineage cell loss with CD19 CAR T-cell lymphoma therapy
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
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
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
SPRINGERNATURE. 2022: 1046-1048
View details for Web of Science ID 000770360202309
Structural Racism is a Mediator of Disparities in Acute Myeloid Leukemia Outcomes.
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 2020; 61 (8): 2008-2011
Gender and glaucoma: what we know and what we need to know
CURRENT OPINION IN OPHTHALMOLOGY
2010; 21 (2): 91-99
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