Dr. Vikram Mathews – Department of Haematology

Dr. Vikram Mathews MBBS, MD, DM

Senior Professor

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Career Interests Research Publications Bio data

Career Interests

As a physician-scientist I have been involved in research and management of patients with leukemia over the last 20 years. Following completion of my specialty training in Clinical Hematology under the guidance of Dr. MammenChandy, I spent 3 years in Washington University, St Loius, MO, USA as a post-doctoral fellow in the laboratory of Dr. Timothy Graubert and Dr. John DiPersio. During this period I trained in stem cell and leukemia biology and was involved in establishing mouse models of some of these conditions and in evaluating stem cell plasticity. I have since worked and published on various aspects of diagnosis, prognostication and treatment of acute leukemia in India. An innovative therapeutic strategy and a novel protocol of using arsenic trioxide as frontline therapy in acute promyelocytic leukemia (APL) was reported by us. I have conducted both single and multi-center clinical trials with this agent in India. This cost effective therapy has been widely cited and was instrumental in moving this drug to frontline therapy worldwide in the treatment of APL. I am currently involved in evaluation of mechanisms of resistance in leukemia with a focus on the role of microenvironment on drug resistance in leukemia. We have recently published our work on mechanism the mechanism of resistance to arsenic mediated by the microenvironment and strategies that can overcome it (Leukemia 30 (11), 2169-2178). We have translated of this work into an ongoing clinical trial and we recently reported on promising data from that study (Blood 128 (22), 446-446).

Areas of clinical and laboratory research are:

Acute myeloid leukemia
Acute Promyelocytic leukemia
Evaluation of mechanisms of resistance to arsenic trioxide and impact of novel agents in the management of acute promyelocytic leukemia
Allogeneic stem cell transplant. Improving clinical outcomes by studying risk stratification, modifying conditioning regimens and graft manipulation.

Awards

Early career investigator award from Bayer Hemophilia Awards program 2006
Best abstract and oral presentation award. Asia Pacific BMT meeting. Phuket, Thailand 2010
DBT-Wellcome India Alliance Senior Fellow 2012

Reviewer for the following journals

Indian Journal of Haematology and Transfusion (also editorial board)
Indian Journal of Medical Research
Indian Journal of Pathology and Microbiology
Pediatric Blood and Cancer
Blood
Biology of Blood and Marrow Transplantation
Bone Marrow Transplantation
Leukemia
Plos One (associate editor)

Research

S.No	Study title	Principal Investigator
1.	Randomized, open label, multicenter phase IIIb study evaluating the efficacy and safety of ruxolitinib versus best available therapy in patients with polycythemia vera who are hydroxyurea resistant or intolerant (Response 2) – Novartis	Dr. Vikram Mathews
2.	Myeloproliferative neoplasms Epidemiological Registry in Growing and Emerging markets The MERGE Study (Novartis India)	Dr. Vikram Mathews
3.	A Prospective, Open-label, Multi-centric Study to Evaluate the Efficacy and Safety of Inj. Romiplostim of Intas Pharmaceuticals Ltd. in Adult Indian Patients with Chronic Refractory Idiopathic Thrombocytopenic Purpura (Protocol: 063-15) – INTAS Pharma	Dr. Vikram Mathews
INVESTIGATOR INITIATED STUDIES
1.	Phase II Study to Evaluate the Role of Bortezomib in the Management of Relapsed Acute Promyelocytic Leukemia	Dr. Vikram Mathews

Research grants / Fellowships from other funding agencies

Pl	Nature of Funding (Grant / Fellowship)	Awarding Agency	Title of the Project	Amount awarded (in Lakhs)	Start Date(mm/yy)	End Date(mm/yy)
1	COE Grant	DBT	“Centre of Excellance on Evaluation of Biology and Mechanism of Resistance in Leukemia”	484.81	01/16	01/21
2	The Wellcome –DBT Senior Fellowship	Wellcome Trust / DBT India Alliance	“Study the role of Cell Adhesion mediated drug resistance in Acute Promyelocytic Leukemia treated with Arsenic Trioxide and evaluate the potential role of drugs that can inhibit it	439.13	04/12	04/17
3	DST Grant	SERB,DST,New Delhi	“Evaluation of the role of Research Oxygen Species in the bleeding diathesis of patients with Acute Promyelocytic Leukemia”	51.81	01/15	01/18
4	ICMR Grant	ICMR	“Evaluation of Cellular & Immune Response in Mice & Patients with APML with Arsenic Trioxide”	39.36	06/11	05/13
5	CEFIPRA Grant	CEFIPRA	“Evaluation of Cellular & Immune Response in Mice & Patients with APML with Arsenic Trioxide”	85.00	07/11	06/14

Team

	Mr. Arvind Venkatraman Senior Research Fellow PhD Student (SCTIMST, Trivandrum) My work focuses on the selective targeting of JAK2 V617F+ cells in Philadelphia chromosome-negative myeloproliferative neoplasms (MPN).
	Mr. Mohammed Yasar Junior Research Fellow PhD Student (Regional Center for Biotechnology, Faridabad) My work focuses on optimizing Chimeric Antigen Receptor(CAR) T-cell function by non-vector strategies.
	Ms. Reeshma Nair Junior Research Fellow PhD Student (Regional Center for Biotechnology, Faridabad) My work focuses on evaluating the roles of innate immune cells in acute myeloid leukemia (AML) biology and their response to therapy.
	Ms. Swathy Palanikumar Junior Research Fellow PhD Student (Regional Center for Biotechnology, Faridabad) My work primarily focuses on understanding the role of mitochondria in predicting response to targeted therapy in acute myeloid leukemia(AML).
	Ms. Majeela Solomon Junior Research Fellow PhD Student (Regional Center for Biotechnology, Faridabad) My study focuses on understanding the mechanisms of resistance in Early T-cell Precursor Acute Lymphoblastic Leukemia (ETP-ALL).
	Ms. Abirami R Junior Research Fellow PhD Student (Regional Center for Biotechnology, Faridabad) My research focuses on understanding the mechanisms of fibrosis and assessment of anti-fibrotic agents in primary myelofibrosis(PMF).

Publications

The detail list of my publications and citations can be accessed at:

https://scholar.google.com/citations?hl=en&user=e-7QSfoAAAAJ&view_op=list_works

My recent and significant publications are:

Madan V, Shyamsunder P, Han L, Mayakonda A, Nagata Y, Sundaresan J, et al. Comprehensive mutational analysis of primary and relapse acute promyelocytic leukemia. Leukemia. 2016;30(8):1672-81.
Ganzel C, Mathews V, Alimoghaddam K, Ghavamzadeh A, Kuk D, Devlin S, et al. Autologous transplant remains the preferred therapy for relapsed APL in CR2. Bone Marrow Transplant. 2016;51(9):1180-3.
Ganesan S, Alex AA, Chendamarai E, Balasundaram N, Palani HK, David S, et al. Rationale and efficacy of proteasome inhibitor combined with arsenic trioxide in the treatment of acute promyelocytic leukemia. Leukemia. 2016;30(11):2169-78.
Philip C, George B, Ganapule A, Korula A, Jain P, Alex AA, et al. Acute myeloid leukaemia: challenges and real world data from India. Br J Haematol. 2015;170(1):110-7.
Patel S, Guerenne L, Gorombei P, Omidvar N, Schlageter MH, Alex AA, et al. pVAX14DNA-mediated add-on immunotherapy combined with arsenic trioxide and all-trans retinoic acid targeted therapy effectively increases the survival of acute promyelocytic leukemia mice. Blood Cancer J. 2015;5:e374.
Mathews V. De-escalation of treatment for acute promyelocyticleukaemia? The Lancet Haematology. 2015;2(9):e348-9.
Le Pogam C, Patel S, Gorombei P, Guerenne L, Krief P, Omidvar N, et al. DNA-mediated adjuvant immunotherapy extends survival in two different mouse models of myeloid malignancies. Oncotarget. 2015;6(32):32494-508.
Chendamarai E, Ganesan S, Alex AA, Kamath V, Nair SC, Nellickal AJ, et al. Comparison of newly diagnosed and relapsed patients with acute promyelocytic leukemia treated with arsenic trioxide: insight into mechanisms of resistance. PLoS One. 2015;10(3):e0121912.
Abraham A, Devasia AJ, Varatharajan S, Karathedath S, Balasubramanian P, Mathews V. Effect of cytosine arabinoside metabolizing enzyme expression on drug toxicity in acute myeloid leukemia. Ann Hematol. 2015;94(5):883-5.
Warlick ED, Paulson K, Brazauskas R, Zhong X, Miller AM, Camitta BM, et al. Effect of postremission therapy before reduced-intensity conditioning allogeneic transplantation for acute myeloid leukemia in first complete remission. Biol Blood Marrow Transplant. 2014;20(2):202-8.
Mathews V, Srivastava A, Chandy M. Allogeneic stem cell transplantation for thalassemia major. HematolOncolClin North Am. 2014;28(6):1187-200.
Mathews V, Savani BN. Conditioning regimens in allo-SCT for thalassemia major. Bone Marrow Transplant. 2014;49(5):607-10.
Mathews V. Generic imatinib: the real-deal or just a deal? Leuk Lymphoma. 2014;55(12):2678-80.
Mathews V, George B, Viswabandya A, Abraham A, Ahmed R, Ganapule A, et al. Improved clinical outcomes of high risk beta thalassemia major patients undergoing a HLA matched related allogeneic stem cell transplant with a treosulfan based conditioning regimen and peripheral blood stem cell grafts. PLoS One. 2013;8(4):e61637.
Chendamarai E, Balasubramanian P, George B, Viswabandya A, Abraham A, Ahmed R, et al. Role of minimal residual disease monitoring in acute promyelocytic leukemia treated with arsenic trioxide in frontline therapy. Blood. 2012;119(15):3413-9.
Mathews V, Chendamarai E, George B, Viswabandya A, Srivastava A. Treatment of acute promyelocytic leukemia with single-agent arsenic trioxide. Mediterr J Hematol Infect Dis. 2011;3(1):e2011056.
Rajasekar R, Lakshmi KM, George B, Viswabandya A, Thirugnanam R, Abraham A, et al. Dendritic cell count in the graft predicts relapse in patients with hematologic malignancies undergoing an HLA-matched related allogeneic peripheral blood stem cell transplant. Biol Blood Marrow Transplant. 2010;16(6):854-60.
Mathews V, George B, Chendamarai E, Lakshmi KM, Desire S, Balasubramanian P, et al. Single-agent arsenic trioxide in the treatment of newly diagnosed acute promyelocytic leukemia: long-term follow-up data. J ClinOncol. 2010;28(24):3866-71.
Thirugnanam R, George B, Chendamarai E, Lakshmi KM, Balasubramanian P, Viswabandya A, et al. Comparison of clinical outcomes of patients with relapsed acute promyelocytic leukemia induced with arsenic trioxide and consolidated with either an autologous stem cell transplant or an arsenic trioxide-based regimen. Biol Blood Marrow Transplant. 2009;15(11):1479-84.
Rajasekar R, Mathews V, Lakshmi KM, George B, Viswabandya A, Chandy M, et al. Cellular immune reconstitution and its impact on clinical outcome in children with Î² thalassemia major undergoing a matched related myeloablative allogeneic bone marrow transplant. Biology of Blood and Marrow Transplantation. 2009;15(5):597-609.
Mathews V, George B, Lakshmi KM, Viswabandya A, John JM, Sitaram U, et al. Impact of pretransplant splenectomy on patients with beta-thalassemia major undergoing a matched-related allogeneic stem cell transplantation. Pediatr Transplant. 2009;13(2):171-6.
Rajasekar R, Mathews V, Lakshmi KM, Sellathamby S, George B, Viswabandya A, et al. Plasmacytoid dendritic cell count on day 28 in HLA-matched related allogeneic peripheral blood stem cell transplant predicts the incidence of acute and chronic GVHD. Biol Blood Marrow Transplant. 2008;14(3):344-50.
Mathews V, Thomas M, Srivastava VM, George B, Srivastava A, Chandy M. Impact of FLT3 mutations and secondary cytogenetic changes on the outcome of patients with newly diagnosed acute promyelocytic leukemia treated with a single agent arsenic trioxide regimen. Haematologica. 2007;92(7):994-5.
Mathews V, George B, Lakshmi KM, Viswabandya A, Bajel A, Balasubramanian P, et al. Single-agent arsenic trioxide in the treatment of newly diagnosed acute promyelocytic leukemia: durable remissions with minimal toxicity. Blood. 2006;107(7):2627-32.
Mathews V, Desire S, George B, Lakshmi KM, Rao JG, Viswabandya A, et al. Hepatotoxicity profile of single agent arsenic trioxide in the treatment of newly diagnosed acute promyelocytic leukemia, its impact on clinical outcome and the effect of genetic polymorphisms on the incidence of hepatotoxicity. Leukemia. 2006;20(5):881.
Mathews V, Hanson PT, Ford E, Fujita J, Polonsky KS, Graubert TA. Recruitment of bone marrow-derived endothelial cells to sites of pancreatic Î²-cell injury. Diabetes. 2004;53(1):91-8.
Fenske TS, Pengue G, Mathews V, Hanson PT, Hamm SE, Riaz N, et al. Stem cell expression of the AML1/ETO fusion protein induces a myeloproliferative disorder in mice. Proceedings of the National Academy of Sciences of the United States of America. 2004;101(42):15184-9.
Hanson P, Mathews V, Marrus SH, Graubert TA. Enhanced green fluorescent protein targeted to the Sca-1 (Ly-6A) locus in transgenic mice results in efficient marking of hematopoietic stem cells in vivo. Experimental hematology. 2003;31(2):159-67.
Mathews V, Balasubramanian P, Shaji RV, George B, Chandy M, Srivastava A. Arsenic trioxide in the treatment of newly diagnosed acute promyelocytic leukemia: a single center experience. Am J Hematol. 2002;70(4):292-9.

Bio data

Date from (mm/yy)	Date to (mm/yy)	Degree	Subject	University/Institution
06/85	03/91	MBBS	Medicine	Dr.MGR University
03/93	03/96	MD	General Medicine	Dr.MGR University
03/99	03/01	DM	Clinical Haematology	Dr.MGR University
03/01	03/03	Post doctoral fellow	Stem cell biology	Washington University, St. Louis. USA
04/03	04/04	BoneMarrow Transplant fellowship	BMT and Leukemia	Washington University, St. Louis. USA