Saravanan Ganesan
Christian Medical College & Hospital
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Featured researches published by Saravanan Ganesan.
Blood | 2012
Ezhilarasi Chendamarai; Poonkuzhali Balasubramanian; Biju George; Auro Viswabandya; Aby Abraham; Rayaz Ahmed; Ansu Abu Alex; Saravanan Ganesan; Kavitha M. Lakshmi; Usha Sitaram; S. C. Nair; Mammen Chandy; Nancy Beryl Janet; Vivi M. Srivastava; Alok Srivastava; Vikram Mathews
Data on minimal residual disease (MRD) monitoring in acute promyelocytic leukemia (APL) are available only in the context of conventional all-trans retinoic acid plus chemotherapy regimens. It is recognized that the kinetics of leukemia clearance is different with the use of arsenic trioxide (ATO) in the treatment of APL. We undertook a prospective peripheral blood RT-PCR-based MRD monitoring study on patients with APL treated with a single agent ATO regimen. A total of 151 patients were enrolled in this study. A positive RT-PCR reading at the end of induction therapy was significantly associated on a multivariate analysis with an increased risk of relapse (relative risk = 4.9; P = .034). None of the good risk patients who were RT-PCR negative at the end of induction relapsed. The majority of the relapses (91%) happened within 3 years of completion of treatment. After achievement of molecular remission, the current MRD monitoring strategy was able to predict relapse in 60% of cases with an overall sensitivity and specificity of 60% and 93.2%, respectively. High-risk group patients and those that remain RT-PCR positive at the end of induction are likely to benefit from serial MRD monitoring by RT-PCR for a period of 3 years from completion of therapy.
PLOS ONE | 2015
Ezhilarasi Chendamarai; Saravanan Ganesan; Ansu Abu Alex; Vandana Kamath; Sukesh C. Nair; Arun Jose Nellickal; Nancy Beryl Janet; Vivi M. Srivastava; Kavitha M. Lakshmi; Auro Viswabandya; Aby Abraham; Mohammed Aiyaz; Nandita Mullapudi; Raja C. Mugasimangalam; Rose Ann Padua; Christine Chomienne; Mammen Chandy; Alok Srivastava; Biju George; Poonkuzhali Balasubramanian; Vikram Mathews
There is limited data on the clinical, cellular and molecular changes in relapsed acute promyeloytic leukemia (RAPL) in comparison with newly diagnosed cases (NAPL). We undertook a prospective study to compare NAPL and RAPL patients treated with arsenic trioxide (ATO) based regimens. 98 NAPL and 28 RAPL were enrolled in this study. RAPL patients had a significantly lower WBC count and higher platelet count at diagnosis. IC bleeds was significantly lower in RAPL cases (P=0.022). The ability of malignant promyelocytes to concentrate ATO intracellularly and their in-vitro IC50 to ATO was not significantly different between the two groups. Targeted NGS revealed PML B2 domain mutations in 4 (15.38%) of the RAPL subset and none were associated with secondary resistance to ATO. A microarray GEP revealed 1744 genes were 2 fold and above differentially expressed between the two groups. The most prominent differentially regulated pathways were cell adhesion (n=92), cell survival (n=50), immune regulation (n=74) and stem cell regulation (n=51). Consistent with the GEP data, immunophenotyping revealed significantly increased CD34 expression (P=0.001) in RAPL cases and there was in-vitro evidence of significant microenvironment mediated innate resistance (EM-DR) to ATO. Resistance and relapse following treatment with ATO is probably multi-factorial, mutations in PML B2 domain while seen only in RAPL may not be the major clinically relevant cause of subsequent relapses. In RAPL additional factors such as expansion of the leukemia initiating compartment along with EM-DR may contribute significantly to relapse following treatment with ATO based regimens.
Frontiers in Immunology | 2018
Ansu Abu Alex; Saravanan Ganesan; Hamenth Kumar Palani; Nithya Balasundaram; Sachin David; Kavitha M. Lakshmi; Uday Kulkarni; Nisham Pn; Anu Korula; Anup J. Devasia; Nancy Beryl Janet; Aby Abraham; Alok Srivastava; Biju George; Rose Ann Padua; Christine Chomienne; Poonkuzhali Balasubramanian; Vikram Mathews
Natural killer cells (NK) contribute significantly to eradication of cancer cells, and there is increased interest in strategies to enhance it’s efficacy. Therapeutic agents used in the treatment of cancer can impact the immune system in a quantitative and qualitative manner. In this study, we evaluated the impact of arsenic trioxide (ATO) used in the management of acute promyelocytic leukemia (APL) on NK cell reconstitution and function. In patients with APL treated with single agent ATO, there was a significant delay in the reconstitution of circulating NK cells to reach median normal levels from the time of diagnosis (655 days for NK cells vs 145 and 265 days for T cells and B cells, respectively). In vitro experiments demonstrated that ATO significantly reduced the CD34 hematopoietic stem cell (HSC) differentiation to NK cells. Additional experimental data demonstrate that CD34+ sorted cells when exposed to ATO lead to a significant decrease in the expression of IKZF2, ETS1, and TOX transcription factors involved in NK cell differentiation and maturation. In contrast, exposure of NK cells and leukemic cells to low doses of ATO modulates NK cell receptors and malignant cell ligand profile in a direction that enhances NK cell mediated cytolytic activity. We have demonstrated that NK cytolytic activity toward NB4 cell line when exposed to ATO was significantly higher when compared with controls. We also validated this beneficial effect in a mouse model of APL were the median survival with ATO alone and ATO + NK was 44 days (range: 33–46) vs 54 days (range: 52–75). In conclusion, ATO has a differential quantitative and qualitative effect on NK cell activity. This information can potentially be exploited in the management of leukemia.
Blood | 2016
Vikram Mathews; Anu Korula; Uday Kulkarni; Saravanan Ganesan; Sachin David; Ansu Abu Alex; Nisham Pn; Aby Abraham; Alok Srivastava; Kavitha M. Lakshmi; Poonkuzhali Balasubramanian; Biju George
Blood | 2014
Ansu Abu Alex; Ezhilarasi Chendamarai; Saravanan Ganesan; Nithya Balasundaram; Hamenth Kumar Palani; Sachin David; Vikram Mathews
Blood | 2014
Saravanan Ganesan; Ansu Abu Alex; Ezhilarasi Chendamarai; Nithya Balasundaram; Hamenth Kumar Palani; Sachin David; Jayandharan G Rao; Aby Abraham; Auro Viswabandya; Biju George; Alok Srivastava; Poonkuzhali Balasubramanian; Rose Ann Padua; Christine Chomienne; Vikram Mathews
Clinical Lymphoma, Myeloma & Leukemia | 2017
Saravanan Ganesan; Nithya Balasundaram; Hamenth Kumar Palani; Anup J. Devasia; Ansu Abu Alex; Sachin David; Biju George; Poonkuzhali Balasubramanian; Vikram Mathews
Blood | 2016
Saravanan Ganesan; Vairavan Lakshmanan; Hamenth Kumar Palani; Nithya Balasundaram; Ansu Abu Alex; Sachin David; Anu Korula; Biju George; Poonkuzhali Balasubramanian; Harsha Gowda; Neha Vyas; Dasaradhi Palakodeti; Vikram Mathews
Blood | 2016
Nithya Balasundaram; Saravanan Ganesan; Hamenth Kumar Palani; Ansu Abu Alex; Sachin David; Anu Korula; Biju George; Christine Chomienne; Poonkuzhali Balasubramanian; Vikram Mathews
Blood | 2016
Saravanan Ganesan; Nithya Balasundaram; Hamenth Kumar Palani; Ansu Abu Alex; Sachin David; Anup J. Devasia; Biju George; Poonkuzhali Balasubramanian; Vikram Mathews