Publications by authors named "Sachin Punatar"

31 Publications

Real-World Outcomes With Generic Pomalidomide in Relapsed Refractory Multiple Myeloma-Experience From a Tertiary Care Cancer Center.

JCO Glob Oncol 2021 Mar;7:361-367

Department of Medical Oncology, Tata Memorial Hospital, Parel, and Homi Bhabha National Institute, Mumbai, Maharashtra, India.

Purpose: The prognosis of relapsed and refractory multiple myeloma (RRMM) that is refractory to bortezomib and lenalidomide is very poor wherein the median survival is between 3 and 9 months. We did this retrospective analysis to study the pattern of utilization, tolerance, and outcomes with pomalidomide in these patients having RRMM.

Materials And Methods: Retrospective analysis of all the patients who were treated with generic pomalidomide at Tata Memorial Centre, Mumbai, during the period of May 2017 to March 2019 was done. Patients with secretory disease and who had completed at least one cycle of pomalidomide were analyzed for response rates, toxicity, and survival outcomes.

Results: A total of 81 patients received pomalidomide-based therapy during this study period, out of which 75 were included in the survival analysis. Forty-eight patients (59.3%) were refractory to both lenalidomide and bortezomib. Overall response rate was 58.7%. Five patients (6.7%) achieved complete response, very good partial response was seen in 13 patients (17.3%), and partial response was seen in 26 patients (34.7%). After a median follow-up of 11 months (range 2-27 months), median progression-free survival was 9.1 months (95% CI, 5.4 to 12.9 months). Median progression-free survival for patients who were refractory to both lenalidomide and bortezomib versus nonrefractory was 5.5 and 12.6 months, respectively, which was significant statistically ( = .04, hazard ratio, 0.35, 95% CI, 0.28 to 0.97). The median overall survival was not reached. Important toxicities included anemia (28%), neutropenia (16%), pneumonia (16%), and venous thrombosis (5%).

Conclusion: Generic pomalidomide-based therapy is an effective option and is well tolerated in patients with RRMM. Higher response rates and longer survival seen in our study are possibly because of heterogeneity of the study population.
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http://dx.doi.org/10.1200/GO.20.00228DOI Listing
March 2021

Outcomes and prognostic factors in adolescents and young adults with ALL treated with a modified BFM-90 protocol.

Blood Adv 2021 Mar;5(5):1178-1193

Adult Hematolymphoid Unit.

The use of pediatrics-inspired protocols in adolescent and young adult (AYA) acute lymphoblastic leukemia (ALL) results in superior survival compared with the adult protocols. Pediatrics-inspired protocols carry an increased risk of toxicity and treatment-related mortality in low resource settings, which can offset the potential benefits. We studied the outcomes and prognostic factors in the treatment of AYA ALL with a pediatrics-inspired regimen. We retrieved data regarding demographics, investigations, treatment details, and toxicities from the electronic medical records of patients diagnosed with ALL in the 15- to 25-year-old age group who were initiated on a modified Berlin-Frankfurt-Münster 90 (BFM-90) protocol between January 2013 and December 2016 at the Tata Memorial Centre. A total of 349 patients in the 15- to 25-year-old age group were treated with a modified BFM-90 protocol. The use of this pediatrics-inspired protocol resulted in a 3-year event-free survival (EFS) and overall survival (OS) of 59.4% and 61.8%, respectively. Only 15 patients underwent an allogeneic stem cell transplant. Minimal residual disease (MRD) persistence postinduction emerged as the only factor predictive of poor outcomes. A modified BFM-90 protocol is an effective and safe regimen for AYA ALL with an OS and EFS comparable to the published literature.
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http://dx.doi.org/10.1182/bloodadvances.2020003526DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7948264PMC
March 2021

Evaluation of cytogenetic response in CML patients with variant Philadelphia translocation.

Asia Pac J Clin Oncol 2021 Feb 25. Epub 2021 Feb 25.

Homi Bhabha National Institute (HBNI), Anushaktinagar, Mumbai, India.

Background And Aim: Molecular mechanism of translocation and outcome in variant chronic myeloid leukaemia (vCML) has been a topic of debate. While several cytogenetic studies suggest a low response to Imatinib Mesylate, others demonstrate a similar disease course in both classical and vCML. Besides, many studies comprehensively also link tyrosine kinase domain (TKD) mutations with aggressive clinical outcome. Thus, we aim to study the molecular mechanism of translocation, identify the third partner chromosomes and comment on the disease course and clinical outcome.

Method: We cytogenetically characterised 25 vCML cases to determine the third partner chromosome, mechanism of translocation and prognostic outcome. We also compared vCML cases with and without TKD mutation to most appropriately outline the clinical consequence and ascertain the potent cause of unresponsiveness to treatment.

Results: Third partner chromosome in variant translocation was defined by conventional and molecular cytogenetics. Although in our study most cases showed inadequate clinical response attributable to TKD mutation rather than variant translocation, we observed an inferior outcome in cases involving chromosome 5 as the third partner.

Conclusion: Thus, we conclude that characterising and reporting new cases of variant translocations, involving various different chromosomes as third partner (with different breakpoints) by cytogenetics, will lead to a better understanding of the disease. To the best of our knowledge, this kind of delineate study has not been applied to precisely comment on the prospects of cytogenetically characterised vCML.
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http://dx.doi.org/10.1111/ajco.13522DOI Listing
February 2021

Clinical course of severe COVID19 treated with tocilizumab and antivirals post-allogeneic stem cell transplant with extensive chronic GVHD.

Transpl Infect Dis 2021 Feb 1:e13576. Epub 2021 Feb 1.

Department of Medical Oncology, ACTREC - Tata Memorial Centre, Navi Mumbai, Maharashtra, India.

Recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT) are an immunocompromised group who are likely to develop severe complications and mortality because of coronavirus disease 2019 (COVID-19). We report here a 61-year-old male patient of primary myelofibrosis who underwent an allo-HSCT 6 years earlier, had chronic graft-versus-host disease (cGVHD) involving the liver, lung, eyes, and skin, (with recurrent episodes of pulmonary infections) who developed severe COVID-19. The patient was treated with tocilizumab, and a combination of lopinavir/ritonavir, ribavirin, interferon-β1b. He was discharged after 31 days with full recovery. Tocilizumab, a humanized monoclonal antibody against IL6, has been shown to benefit respiratory manifestations in severe COVID19. However, this is first report, to our knowledge, of its use and benefit in a post HSCT recipient.
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http://dx.doi.org/10.1111/tid.13576DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994986PMC
February 2021

Pre-transplant use of tyrosine kinase inhibitors and transplant associated thrombotic microangiopathy - a single centre analysis of incidence, risk factors and outcomes.

Bone Marrow Transplant 2021 Jan 29. Epub 2021 Jan 29.

HSCT unit, Department of Medical Oncology Tata Memorial Centre, HSCT unit, ACTREC, Kharghar, Navi Mumbai, 410210, India.

Transplant associated thrombotic microangiopathy (TA-TMA) is life-threatening complication post allogeneic stem cell transplant (ASCT). Risk factors and prognosis of TA-TMA are not well defined. We retrospectively studied consecutive ASCT patients with AML, ALL, and CML from January 2008 to March 2019 to study the incidence, risk factors, and outcomes of TMA. Definitive and probable TA-TMA was defined using Blood and Marrow Transplant Clinical Trials Network (BMT-CTN) and Cho criteria, respectively. Risk factors explored were age, gender, diagnosis, type of transplant, use of tyrosine kinase inhibitors (TKI) pre transplant, conditioning regimen, and acute GVHD. Standard statistical methods were used. Total 241 patients, 179 (74.2 %) males, median age of 29 years were studied. Diagnoses were AML in 104, ALL in 85 (Ph+ve 23) and CML 52. Total 26 (10.7%) patients (22 males) developed TA-TMA at median of day+102. On multivariate analysis, pre-HSCT TKI (OR 2.7, p = 0.028), haplo-HSCT (OR 3.16, p = 0.018) and presence of acute GVHD (OR 4.17, p = 0.003) were significant risk factors. With a median follow up of 60 months, median OS with and without TA-TMA was 18 and 97 months respectively (p = 0.021). The association of pre-HSCT with TKI with TA-TMA merits further exploration in prospective studies.
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http://dx.doi.org/10.1038/s41409-021-01213-0DOI Listing
January 2021

Expression of CD304/neuropilin-1 in adult b-cell lymphoblastic leukemia/lymphoma and its utility for the measurable residual disease assessment.

Int J Lab Hematol 2021 Jan 12. Epub 2021 Jan 12.

Department of Hematopathology Laboratory, ACTREC, Tata Memorial Center, HBNI University, Navi Mumbai, India.

Introduction: Many new markers are being evaluated to increase the sensitivity and applicability of multicolor flow cytometry (MFC)-based measurable residual disease (MRD) monitoring. However, most of the studies are limited to childhood B-cell lymphoblastic leukemia/lymphoma (B-ALL), and reports in adult B-ALL are extremely scarce and limited to small cohorts. We studied the expression of CD304/neuropilin-1 in a large cohort of adult B-ALL patients and evaluated its practical utility in MFC-based MRD analysis.

Methods: CD304 was studied in blasts from adult B-ALL patients and normal precursor B cells (NPBC) from non-B-ALL bone marrow samples using MFC. CD304 expression intensity and pattern were studied with normalized-mean fluorescent intensity (nMFI) and coefficient of variation of immunofluorescence (CVIF), respectively. MFC-based MRD was performed at end of induction (EOI; day-35), end of consolidation (EOC; day 78-80), and subsequent follow-up (SFU) time points.

Results: CD304 was positive in 120/214(56.07%) and was significantly associated with BCR-ABL1 fusion (P = .001). EOI-MRD and EOC-MRD were positive in 129/214(60.3%) and 50/81(61.72%), respectively. CD304 was positive in a significant percentage of EOI (48%, 62/129) and EOC (52%, 26/50) MRD-positive B-ALL samples. Its expression was retained, lost, and gained in 73.7%, 26.3%, and 11.3% of EOI-MRD and 85.7%, 14.3%, and none of EOC-MRD samples, respectively. Low-level MRD (<0.01%) was detectable in 34 of all (EOI + EOC + SFU = 189) MRD-positive samples, and CD304 was found useful in 50% of these samples.

Conclusion: CD304 is commonly expressed in adult B-ALL and clearly distinguish B-ALL blasts from normal precursor B cells. It is a stable MRD marker and distinctly useful in the detection of MFC-based MRD monitoring, especially in high-sensitivity MRD assay.
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http://dx.doi.org/10.1111/ijlh.13456DOI Listing
January 2021

COVID-19 in cancer patients on active systemic therapy - Outcomes from LMIC scenario with an emphasis on need for active treatment.

Cancer Med 2020 12 31;9(23):8747-8753. Epub 2020 Oct 31.

Department of Medical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute (HBNI), Mumbai, India.

Background: There is limited data on outcomes in cancer patients with coronavirus disease 2019 (COVID-19) from lower middle-income countries (LMICs).

Patients And Methods: This was an observational study, conducted between 12 April and 10 June 2020 at Tata Memorial centre, Mumbai, in cancer patients undergoing systemic therapy with laboratory confirmed COVID-19. The objectives were to evaluate cumulative 30-day all-cause mortality, COVID-19 attributable mortality, factors predicting mortality, and time to viral negativity after initial diagnosis.

Results: Of the 24 660 footfalls and 7043 patients evaluated, 230 patients on active systemic therapy with a median age of 42 (1-75) years were included. COVID-19 infection severity, as per WHO criteria, was mild, moderate, and severe in 195 (85%), 11 (5%), and 24 (11%) patients, respectively. Twenty-three patients (10%) expired during follow-up, with COVID-19 attributable mortality seen in 15 patients (6.5%). There were no mortalities in the pediatric cohort of 31 (14%) patients. Advanced stage cancer being treated with palliative intent vs others [30-day mortality 24%% vs 5%, odds ratio (OR) 5.6, 95% CI 2.28-13.78, P < .001], uncontrolled cancer status vs controlled cancer (30-day mortality37.5%% vs 4%%, OR 14, 95% CI 4.46-44.16, P < .001) and severe COVID-19 vs mild COVID-19 (30-day mortality 71% vs 3%, OR 92.29, 95% CI 26.43-322.21, P < .001) were significantly associated with mortality. The median time to SARS-CoV-2 RT-PCR negativity was 17 days [interquartile range (IQR)17-28) in the cohort.

Conclusions: The mortality rates in cancer patients with COVID-19 who are receiving systemic anti-cancer therapy in LMICSs are marginally higher than that reported in unselected COVID-19 cohorts with prolonged time to viral negativity in a substantial number of patients. The pediatric cancer patients tended to have favorable outcomes.
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http://dx.doi.org/10.1002/cam4.3423DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724305PMC
December 2020

Hodgkin Lymphoma in Adolescent and Young Adults: Real-World Data from a Single Tertiary Cancer Center in India.

J Adolesc Young Adult Oncol 2020 Oct 22. Epub 2020 Oct 22.

Department of Medical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, India.

There is lack of consensus on management of adolescent and young adult (AYA) Hodgkin lymphoma with respect to chemotherapy approach (adult or pediatric). Hence we sought to evaluate the efficacy and safety of Adriamycin, Bleomycin, Vinblastine and Dacarbazine (ABVD) chemotherapy in AYA Hodgkin lymphoma. It is a retrospective, observational, single-center study. From January 2013 to December 2016, all consecutive patients with AYA (15-25 years, all stages) were analyzed. The primary endpoint of the study was event-free survival (EFS). Secondary endpoints were complete response rates (CR) and overall survival (OS). A total of 220 patients (70% men) with median age 20 years were evaluated. A significant proportion of patients had adverse features such as stage III/IV disease (63%), bulky disease (63%), extranodal involvement (37%), and marrow involvement (22%). After two cycles and end of therapy, 77% patients achieved complete response. Primary progressive disease was seen in 6% patients. With a median follow-up of 2.6 years, 19 (8.6%) patients relapsed, 1 patient developed second malignancy, and 6 patients died. Three-year EFS and OS were 81.3% and 97%, respectively. Bleomycin-induced lung injury was seen in 16% patients. On multivariate analysis stage at presentation, bone marrow involvement, partial response at interim positron emission tomography and International prognosis score (IPS) >3 were predictors of poor EFS. ABVD is an effective and safe regimen in AYA Hodgkin lymphoma. Advanced disease with high IPS (>3) score needs an early escalation approach to escBEACOPP regimen.
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http://dx.doi.org/10.1089/jayao.2020.0061DOI Listing
October 2020

Bortezomib and cyclophosphamide based chemo-mobilization in multiple myeloma.

Int J Hematol 2020 Dec 2;112(6):835-840. Epub 2020 Sep 2.

Department of Medical Oncology, CRC, ACTREC, Tata Memorial Centre, 3rd floor, Paymaster Shodhika, Navi Mumbai, Maharashtra, 410210, India.

Hematopoietic stem and progenitor cell (HSPC) mobilization regimens in multiple myeloma typically use filgrastim (GCSF) alone or combination of GCSF with plerixafor or high-dose cyclophosphamide. Murine model and human studies have shown HSPC mobilization potential of bortezomib. A total of 37 patients underwent mobilization using bortezomib 1.3 mg/m on day 1, 4, 8 and 11, cyclophosphamide 1 g/m on day 8 and 9, and GCSF 10 μg/kg from day 10 (B-Cy-GCSF). This regimen was compared with our earlier cohort of patients where cyclophosphamide was given at dose of 1 g/m on day 1 and day 2 followed by GCSF 10 μg/kg from day 4 (Cy-GCSF). In B-Cy-GCSF group, median CD34 cells collected were 9.21 × 10/kg (range 4.95-17.1) while in the Cy-GCSF cohort, the median CD34 cell yield was 8.2 × 10/kg (0.4-24.2). Target CD34 cells yield of 5 × 10/kg was achieved with single apheresis in 58.6% of patients after B-Cy-GCSF mobilization as compared to 44.3% in Cy-GCSF group (p = 0.07). Three patients failed mobilization after Cy-GCSF, while no patients failed mobilization in bortezomib group. Addition of bortezomib to Cy-GCSF mobilization showed a trend towards increased CD34 collection and reduced need for apheresis sessions.
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http://dx.doi.org/10.1007/s12185-020-02973-zDOI Listing
December 2020

A Limited Sampling Strategy for Therapeutic Drug Monitoring of Mycophenolate Mofetil for Prophylaxis of Acute Graft-Versus-Host Disease in Allogeneic Stem Cell Transplantation.

Cell Transplant 2020 Jan-Dec;29:963689720912925

Homi Bhabha National Institute, Mumbai, Maharastra, India.

A universally accepted strategy for therapeutic drug monitoring (TDM) of mycophenolate mofetil (MMF) in the prevention of acute graft-versus-host disease (aGVHD) in allogenic hematopoietic stem cell transplantation (alloHSCT) does not exist. We explored the feasibility of developing a limited sampling strategy (LSS) for TDM of MMF in this setting. Patients undergoing alloHSCT received standard MMF-cyclosporine prophylaxis, with MMF administered twice daily (BD) for matched transplant recipients or thrice daily (TID) in haploidentical transplantation. Intensive blood sampling was carried out on day 7 and area under the concentration-time curve (AUC) of mycophenolic acid (MPA), the active metabolite, was estimated using noncompartmental analysis. The ability of MPA exposure defined by AUC to discriminate between responders (patients who did not develop GVHD) and nonresponders (patients who developed GVHD) was determined by receiver operating characteristic curve analysis. Patients were divided into training and validation sets within BD and TID groups. Mathematical equations were developed from the training set to predict AUC from an abbreviated AUC involving a limited number of sampling points. The equations were validated in the validation set by comparing the MPA AUC predicted from LSS with the observed AUC. It was observed that patients with AUC ≤18.99 mg*h/L had a higher risk of developing aGVHD [odds ratio (OR) = 2.63 (1.17 to 5.87), = 0.06]. The benefit was more in matched transplant recipients [OR = 3.5 (1.30 to 9.49), = 0.05] as compared to haploindentical transplant [OR = 2.8 (0.49 to 15.91), = NS]. Using the mathematical equations, the observed AUC was predicted with 92.31% accuracy in the BD subset and 100% accuracy in the TID subset for a combined accuracy of 94.76%. A set of just three samples that constituted the abbreviated AUC was used to develop the predictive models. The LSS could be employed for the therapeutic monitoring of MMF particularly in patients undergoing matched hematopoietic stem cell transplantation.
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http://dx.doi.org/10.1177/0963689720912925DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7444217PMC
June 2020

Leflunomide for chronic musculoskeletal graft versus host disease following allogeneic hematopoietic stem cell transplant.

Bone Marrow Transplant 2020 02 14;55(2):467-469. Epub 2019 May 14.

HSCT unit, Department of Medical Oncology, Tata Memorial Centre, ACTREC, Kharghar, Navi Mumbai, 410210, India.

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http://dx.doi.org/10.1038/s41409-019-0545-xDOI Listing
February 2020

Use of Leflunomide for Treatment of Cytomegalovirus Infection in Recipients of Allogeneic Stem Cell Transplant.

Biol Blood Marrow Transplant 2019 09 2;25(9):1832-1836. Epub 2019 May 2.

Department of Medical Oncology, Tata Memorial Centre, Mumbai, India. Electronic address:

Cytomegalovirus (CMV) reactivations are common after allogeneic stem cell transplants, and pre-emptive therapy has been found to be effective. However, in India, treatment options are limited because of high cost and toxicity of ganciclovir and unavailability of cidofovir and foscarnet. Leflunomide is a cheap and easily available anti-rheumatoid arthritis drug that has been shown to have anti-CMV properties both in vitro and in vivo. It also has been used effectively for CMV reactivation after renal transplants. In this retrospective analysis, we analyzed 70 allogeneic stem cell transplants that were conducted between April 2015 and February 2017. There were 49 episodes of CMV reactivations in 43 patients in this period. Leflunomide was used in 24 episodes. It was effective in CMV clearance in 9 of the 24 episodes (38%). When the CMV copy number was <2 × 10 copies/mL, leflunomide was effective in 9 of 17 (53%) episodes, but when the copy number was >2 × 10, leflunomide was ineffective in all of the 7 episodes. This difference was statistically significant (P= .022 by Fisher exact test), suggesting that leflunomide may be more effective in clearance of CMV when copy numbers are low.
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http://dx.doi.org/10.1016/j.bbmt.2019.04.028DOI Listing
September 2019

Antibiotic lock therapy for salvage of tunneled central venous catheters with catheter colonization and catheter-related bloodstream infection.

Transpl Infect Dis 2019 Feb 19;21(1):e13017. Epub 2018 Nov 19.

Department of Medical Oncology, ACTREC, Tata Memorial Center, Mumbai, India.

Central venous catheters (CVCs) represent a significant source of infection in patients undergoing hematopoietic stem cell transplantation and can add to the cost of care, morbidity, and mortality. Organisms forming biofilms on the inner surface of catheters require a much higher local antibiotic concentration to clear the pathogen growth. Antibiotic lock therapy (ALT) represents one such strategy to achieve such high intraluminal concentrations of antibiotics and can facilitate catheter salvage. Patients with catheter colonization (CC) or hemodynamically stable catheter-related bloodstream infection (CRBSI) received ALT per institutional policy. We analyzed the incidence of CC and CRBSI and salvage rate of tunneled CVCs (Hickman) with ALT in patients undergoing hematopoietic stem cell transplant in this retrospective study. Catheter colonization was noted in 9.8% and CRBSI in 10.7% patients. Gram-negative bacilli (GNB) accounted for 45% and 83% of isolates in CC and CRBSI, respectively. In patients with CRBSI, the rate of catheter salvage with the use of ALT in addition to systemic antibiotics was 86% compared to 55% in patients with systemic antibiotics use only (P = 0.06). There was no CRBSI related mortality, and no increase in resistant strains was noted at subsequent CRBSI. In conclusion, ALT represents an important strategy for catheter salvage, especially for gram-negative infections, in a carefully selected patient population.
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http://dx.doi.org/10.1111/tid.13017DOI Listing
February 2019

Lomustine, cytarabine, cyclophosphamide, etoposide - An effective conditioning regimen in autologous hematopoietic stem cell transplant for primary refractory or relapsed lymphoma: Analysis of toxicity, long-term outcome, and prognostic factors.

J Cancer Res Ther 2018 Jul-Sep;14(5):926-933

Department of Medical Oncology, Bone Marrow Transplant Unit, ACTREC, Tata Memorial Centre, Mumbai, Maharashtra, India.

Background: High-dose chemotherapy followed by autologous hematopoietic stem cell transplant (HSCT) is the treatment of choice for patients with relapsed and refractory (RR) lymphoma. We analyzed toxicity and long-term outcome with lomustine, cytarabine, cyclophosphamide, etoposide (LACE) conditioning in patients with primary refractory or relapsed lymphoma undergoing autologous transplant.

Materials And Methods: One-hundred patients with primary refractory (23), chemotherapy sensitive relapse (74) or RR (3) Hodgkin lymphoma (HL - 70 patients), and non-HL (NHL - 30 patients) underwent HSCT with LACE (lomustine 200 mg/m day-7, etoposide 1000 mg/m day-7, cytarabine 2000 mg/m day-6 to day-5, and cyclophosphamide 1800 mg/m day-4 to day-2) conditioning between November 2007 and December 2013. At transplant, 68 patients were in complete remission (CR), 29 in partial remission, 2 had stable disease, and 1 had progressive disease. Patients were followed up for development of transplant-related toxicities and long-term survival outcome.

Results: The incidence of grades 3-4 oral mucositis and grades 3-4 diarrhea was 8% and 4%, respectively. Median days to myeloid and platelet engraftment were 10 and 13. Transplant-related mortality was 7%. At median follow-up of 3 years, probability of overall survival (OS) and progression-free survival (PFS) at 3 years was 70% and 58% in entire cohort, 78% and 62% in HL and 51% and 46% in NHL subgroup, respectively. International Prognostic Score (IPS) >2 at relapse prognosticated for poor OS (P = 0.002) and PFS (P < 0.001) in HL subgroup. Positron emission tomography positivity pretransplant (HL subgroup) and at day + 100 (NHL subgroup) predicted for poor survival.

Conclusion: We conclude that LACE is effective and well-tolerated conditioning regimen. IPS at relapse is the most important prognostic factor in HL transplant.
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http://dx.doi.org/10.4103/0973-1482.181183DOI Listing
November 2018

Long term clinical outcomes of adult hematolymphoid malignancies treated at Tata Memorial Hospital: An institutional audit.

Indian J Cancer 2018 Jan-Mar;55(1):9-15

Department of Pathology, Tata Memorial Hospital, Mumbai, Maharashtra, India.

Introduction: There is paucity of data from India about the outcomes of patients with various hematological malignancies. Since its formation in 2009, the adult hematolymphoid disease management group of the Tata Memorial Centre is dedicated to the treatment of hematological malignancies alone. In this report, we present the outcomes of patients treated at our centre over a 5 year period for various haematological malignancies in both transplant and non-transplant setting.

Methods: This is a retrospective analysis of all patients registered in adult hematolymphoid disease management group between 1st January 2010 to 31st December 2014. Patients not treated at our centre were excluded from survival analysis. The cut off date for survival analysis was 31st January 2016.

Results: Overall, 1869, 3633 and 544 patients with acute leukemias, various lymphomas and myeloma respectively were registered at our centre from 1st January 2010 to 31st December 2014. Of these, 1178 (63%), 3091 (85%) and 454 (83%) respectively received treatment at our centre. The cumulative probability of 5 year overall survival for patients with acute leukemias, Hodgkin's lymphoma, non-Hodgkin lymphoma and myeloma treated at our centre is 40%, 85%, 78% and 40% respectively. Four hundred and fifteen stem cell transplants were done between 14th November 2007 to 31st December 2014 with 46% being allogeneic and 54% being autologous. The 5 year overall survival of patients with allogenic and autologous transplant was 52% and 63% respectively.

Conclusions: This is the largest single centre data on outcomes of various haematological malignancies from India. This real world data identifies areas which need further attention to improve outcomes.
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http://dx.doi.org/10.4103/ijc.IJC_656_17DOI Listing
November 2018

Leflunomide: Is It the Game Changer in Musculoskeletal Chronic Graft Versus Host Disease?

Indian J Hematol Blood Transfus 2018 Jul 12;34(3):566-567. Epub 2018 Feb 12.

HSCT Unit, Department of Medical Oncology, ACTREC, Tata Memorial Centre, Room No. 247, Paymaster Shodhika, Kharghar, Navi Mumbai, 410210 India.

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http://dx.doi.org/10.1007/s12288-018-0929-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6081307PMC
July 2018

Daratumumab at the frontiers of post-transplant refractory T-acute lymphoblastic leukemia-a worthwhile strategy?

Bone Marrow Transplant 2018 11 8;53(11):1487-1489. Epub 2018 Jun 8.

Stem cell transplant unit, Department of Medical Oncology, ACTREC, Tata Memorial Centre, Kharghar, Navi Mumbai, India.

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http://dx.doi.org/10.1038/s41409-018-0222-5DOI Listing
November 2018

Is long term storage of cryopreserved stem cells for hematopoietic stem cell transplantation a worthwhile exercise in developing countries?

Blood Res 2017 Dec 26;52(4):307-310. Epub 2017 Dec 26.

Department of Medical Oncology and Bone Marrow Transplantation, Tata Memorial Center, Advanced Center for Treatment, Research and Education in Cancer (ACTREC), Mumbai, India.

Background: Stem cell units (SCUs) that are cryopreserved prior to both autologous and allogeneic hematopoietic stem cell transplants (for donor lymphocyte infusion) remain unused or partially used several times, and become an increased burden to blood banks/SCU repositories. Because of the scarcity of data regarding the duration for which the storage is useful, there is no general consensus regarding disposal of SCUs.

Methods: We conducted a retrospective audit of SCU utilization in 435 patients who planned to undergo either autologous stem cell transplantation (auto-SCT) (N=239) or allogeneic stem cell transplantation (allo-SCT) (N=196) at a tertiary cancer care center between November 2007 to January 2015.

Results: Our cohort consisted of 1,728 SCUs stored for conducting auto-SCT and 729 SCUs stored for conducting donor lymphocyte infusions (DLIs) after allo-SCT. Stem cells were not infused in 12.5% of patients who had planned to undergo auto-SCT, and 80% of patients who underwent allo-SCT never received DLI. Forty-one percent of SCUs intended for use in auto-SCT remained unutilized, with a second auto-SCT being performed only in 4 patients. Ninety-four percent of SCUs intended for carrying out DLIs remained unused, with only minimal usage observed one year after undergoing allo-SCT.

Conclusion: The duration of storage of unused SCUs needs to be debated upon, so that a consensus can be reached regarding the ethical disposal of SCU.
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http://dx.doi.org/10.5045/br.2017.52.4.307DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5762742PMC
December 2017

Analysis of factors affecting initial cyclosporine level and its impact on post transplant outcomes in acute leukemia.

J Cancer Res Ther 2017 Oct-Dec;13(6):981-988

Department of Medical Oncology, Bone Marrow Transplant Unit, Tata Memorial Centre, Mumbai, Maharashtra, India.

Background: Trough cyclosporine (CsA) blood level can influence incidence of graft-versus-host disease (GVHD) and relapse in patients with acute leukemia undergoing allogeneic hematopoietic stem cell transplant (HSCT). We sought to determine factors affecting initial trough CsA level (CsA-1) and its impact on transplant outcome in acute leukemia.

Materials And Methods: Seventy-seven patients underwent HSCT for acute leukemia between January 2008 and March 2013 and were included. GVHD prophylaxis included CsA + methotrexate. (MTX) in 53 patients and CsA + mycophenolate mofetil (MMF) in 24 patients CsA-1 was measured on day 3-5 of starting CsA and subsequent dose was modified to achieve therapeutic level of 150-200. ng/mL. According to CsA-1, patients were divided into three groups - 27 in Group A (dose escalated), 13 in Group B (dose de-escalated), and 37 in Group C (same dose continued).

Results: On univariate analysis, cyclophosphamide with total-body irradiation (TBI) based conditioning regimen and lower body mass index (BMI) were associated with lower CsA-1, while use of fludarabine and higher BMI were associated with higher CsA-1. On multivariate analysis, only fludarabine use and BMI affected CsA-1. Incidence of acute and chronic GVHD (aGVHD and cGVHD), transplant-related mortality, relapse incidence, and relapse-free and overall survival (OS) were similar in the three groups.

Conclusion: While fludarabine use in conditioning regimen and higher BMI leads to higher CsA-1, transplant outcomes are not affected by CsA-1.
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http://dx.doi.org/10.4103/0973-1482.157338DOI Listing
July 2018

Phase III randomized trial comparing intravenous to oral iron in patients with cancer-related iron deficiency anemia not on erythropoiesis stimulating agents.

Asia Pac J Clin Oncol 2018 Apr 28;14(2):e129-e137. Epub 2017 Aug 28.

Department of Medical Oncology, Tata Memorial Hospital, Parel, Mumbai, Maharashtra, India.

Aim: We aimed to find the optimal route of iron supplementation in patients with malignancy and iron deficiency (true or functional) anemia not receiving erythropoiesis stimulating agents (ESA).

Methods: Adult patients with malignancy requiring chemotherapy, hemoglobin (Hb) <12 g/dL and serum ferritin <100 mcg/mL, transferrin saturation <20% or hypochromic red blood cells >10% were randomized to intravenous (IV) iron sucrose or oral ferrous sulfate. The primary endpoint was change in Hb from baseline to 6 weeks. Secondary endpoints included blood transfusion, quality of life (QoL), toxicity, response and overall survival.

Results: A total of 192 patients were enrolled over 5 years: 98 on IV arm and 94 on oral arm. Median age was 51 years; over 95% patients had solid tumors. The mean absolute increase in Hb at 6 weeks was 0.11 g/dL (standard deviation [SD]: 1.48) in IV arm and -0.16 g/dL (SD: 1.36) in oral arm, P = 0.23. Twenty-three percent patients on IV iron and 18% patients on oral iron had a rise in Hb of ≥1 g/dL at 6 weeks, P = 0.45. Thirteen patients (13.3%) on the IV iron arm and 14 patients (14.9%) on the oral arm required blood transfusion, P = 1.0. Gastrointestinal toxicity (any grade) developed in 41% patients on IV iron and 44% patients on oral iron, P = 1.0. 5 patients on IV iron and none on oral iron had hypersensitivity, P = 0.06. QoL was not significantly different between the two arms.

Conclusion: IV iron was not superior to oral iron in patients with malignancy on chemotherapy and iron deficiency anemia.
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http://dx.doi.org/10.1111/ajco.12762DOI Listing
April 2018

Cyclosporine Plus Methotrexate or Cyclosporine Plus Mycophenolate Mofetil as Graft Versus Host Disease Prophylaxis in Acute Leukemia Transplant: Comparison of Toxicity, Engraftment Kinetics and Transplant Outcome.

Indian J Hematol Blood Transfus 2016 Sep 6;32(3):248-56. Epub 2015 Aug 6.

Bone Marrow Transplant Unit, Department of Medical Oncology, ACTREC, Tata Memorial Centre, Sector 22, Room No. 247, Paymaster Shodhika, Kharghar, Navi-Mumbai, 410210 India.

We sought to compare two graft-versus-host disease (GVHD) prophylaxis regimen, cyclosporine and methotrexate (CsA+MTX) with CsA+mycophenolate mofetil (MMF) in 77 acute leukemia patients who underwent hematopoietic stem cell transplant (HSCT) between January 2008 and March 2013. Fifty-three patients received CsA+MTX while 24 received CsA+MMF. The incidence of grade 3-4 mucositis and grade 3-4 diarrhea was 74 and 6 % with CsA+MTX compared to 33 % and 21 % with CsA+MMF (P = 0.001 and 0.09 respectively). Forty-two (79 %) patients in CsA+MTX group required total parenteral nutrition compared to 14 (58 %) in CsA+MMF group (P = 0.09). The incidence of engraftment fever was 17 % with CsA+MTX and 41 % with CsA+MMF (P = 0.02). The median time to neutrophil and platelet engraftment was 14 days and 13 days with CsA+MTX compared to 12 days and 10 days with CsA+MMF (P = 0.003 and 0.08 respectively). The incidence of any grade and grade II-IV acute GVHD was 45 and 13 % with CsA+MTX compared to 42 and 29 % with CsA+MMF (P = NS). Incidence of overall and extensive chronic GVHD was 57 and 38 % with CsA+MTX compared to 42 and 17 % with CsA+MMF (P = NS). Incidence of relapse was 38 % with CsA+MTX compared to 33 % with CsA+MMF (P = NS). TRM was 6 % with CsA+MTX and 21 % with CsA+MMF (P = NS). At 2 years, overall survival (OS) was 64 % in CsA+MTX group compared to 46 % in CsA+MMF group (P = NS). We conclude that CsA+MMF is associated with lesser toxicity, faster myeloid engraftment and similar rates of acute and chronic GVHD, TRM, relapse and OS compared to CsA+MTX in acute leukemia transplant.
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http://dx.doi.org/10.1007/s12288-015-0577-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4930757PMC
September 2016

Sunitinib-induced thrombotic microangiopathy.

J Cancer Res Ther 2016 Jan-Mar;12(1):6-11

Department of Medical Oncology, Tata Memorial Hospital, Mumbai, Maharashtra, India.

Sunitinib-induced thrombotic microangiopathy (TMA) is a secondary TMA caused by sunitinib. Despite the extensive use of sunitinib in patients with renal cell carcinoma and other malignancies, little is known about this complication of sunitinib. No clinical trials of sunitinib have studied this complication in any group of patients. We here review the normal physiology of vascular endothelial growth factor in the kidney, and discuss the pathogenesis, clinical and laboratory manifestations, pathological changes in the kidney, and the management of this uncommon complication of sunitinib.
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http://dx.doi.org/10.4103/0973-1482.172575DOI Listing
December 2016

Chronic Graft Versus Host Disease in Acute Leukemia Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplant: Analysis of Risk Factors, Pattern and Long Term Outcome.

Indian J Hematol Blood Transfus 2016 Mar 20;32(1):32-8. Epub 2015 Jan 20.

Bone Marrow Transplant Unit, Department of Medical Oncology, ACTREC, Tata Memorial Centre, Mumbai, 410210 India.

Chronic graft versus host disease (cGVHD) is a common late complication of allogenic hematopoietic stem cell transplant (HSCT). We analyzed risk factors, pattern and long term transplant outcomes of cGVHD at a tertiary cancer centre. Seventy-seven consecutive patients who underwent HSCT for acute leukemia were included. Forty (52 %) patients developed cGVHD; 24 (60 %) extensive stage while 16 (40 %) limited stage. Oral cavity was the commonest site of involvement (25 patients) followed by liver, skin and lung. We found that female donor to male recipient transplant and diagnosis of acute lymphoblastic leukemia (ALL) were the only factors associated with increased risk of cGVHD. The incidence of leukemia relapse was 18 % in patients who developed cGVHD compared to 51 % in those who did not (P = 0.002). Four year overall survival and relapse free survival (RFS) were 62 and 46 % in patients who developed cGVHD compared to 29 % (P < 0.001) and 29 % (P < 0.001) in patients who did not develop cGVHD, respectively. We conclude that cGVHD is more common in male patients with female donors and in patients transplanted for ALL. Oral cavity is the commonest site of cGVHD in our patients and transplant related survival outcomes are superior in patients who develop cGVHD.
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http://dx.doi.org/10.1007/s12288-015-0506-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4733673PMC
March 2016

A Novel Variant of Bartter's Syndrome.

J Assoc Physicians India 2015 Jul;63(7):58-61

Bartter's syndrome, a rare disorder affecting the renal tubular potassium handling, is characterized by metabolic alkalosis, hypokalemia and renal salt wasting. Here we describe a patient with Bartter's syndrome with hitherto undescribed clinical features and also discuss the various possibilities leading to such variant of Bartter's syndrome.
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July 2015

Risk Factors, Pattern and Clinical Outcome of Acute Graft Versus Host Disease in Acute Leukemia Patients Undergoing Allogeneic Stem Cell Transplant.

Indian J Hematol Blood Transfus 2015 Dec 7;31(4):404-12. Epub 2015 Jan 7.

Bone Marrow Transplant Unit, Department of Medical Oncology, ACTREC, Tata Memorial Centre, Sector 22, Kharghar, Navi Mumbai, 410210 India.

We sought to determine risk factors, pattern and outcome of acute graft versus host disease (aGVHD) in seventy-seven acute leukemia patients who underwent allogeneic stem cell transplant at our centre from January 2008 to March 2013. GVHD prophylaxis with cyclosporine-methotrexate or cyclosporine-mycophenolate mofetil was used. Patients were divided in 2 groups, grade II-IV aGVHD (group A) and grade 0-I aGVHD (group B). Incidence of any grade and grade II-IV aGVHD was 44 and 18 %, respectively. The most common site of aGVHD was gastro-intestinal tract (65 %) followed by skin (35 %). Higher total nucleated cell (TNC) dose infused was associated with increased incidence of grade II-IV aGVHD. Incidence of relapse and incidence of slippage of chimerism was 21 and 36 % in group A while 37 and 27 % in group B respectively. Transplant related mortality (TRM) was 21 % in group A and 13 % in group B. Probability of OS and RFS at 4 years was 63 and 34 % in group A compared with 40 and 38 % in group B, respectively. We conclude that higher TNC dose infused is a risk factor for grade II-IV aGVHD with gut being the commonest site. Grade II-IV aGVHD did not have a significant impact on incidence of relapse, TRM and OS.
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http://dx.doi.org/10.1007/s12288-014-0499-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4542763PMC
December 2015

Hepatitis B-related serological events in hematopoietic stem cell transplant patients and efficacy of lamivudine prophylaxis against reactivation.

Hematol Oncol 2016 Sep 18;34(3):140-6. Epub 2015 Feb 18.

Bone Marrow Transplant Unit, Department of Medical Oncology, ACTREC, Tata Memorial Centre, Mumbai, India.

Reactivation of remote hepatitis B infection (RHBI) is an important cause of morbidity in hematopoietic cell transplant (HCT) patients. We analyzed the prevalence of RHBI in 205 patients who underwent HCT in our centre, serological events related to hepatitis B virus (HBV) reactivation and role of lamivudine prophylaxis in HCT patients with RHBI. The prevalence of RHBI was 14% (28/205 patients). Of these 28 patients, 15 received lamivudine prophylaxis (14 anti-HBcIgG positive and 1 only anti-HBs positive) while 13 did not receive lamivudine prophylaxis (12 anti-HBs positive and 1 anti-HBcIgG positive). None in prophylaxis group developed HBV reactivation while 12 of 13 in no-prophylaxis group reactivated (P < 0.001). The rate of HBV reactivation was 10% (21/205 patients), which included 9 patients with no evidence of RHBI pre-transplant. We conclude that lamivudine prophylaxis protects against HBV reactivation in HCT patients with evidence of RHBI. Lamivudine prophylaxis should be used not only in patients with anti-HBcIgG positivity but also in those with isolated anti-HBs positivity pre-transplant given the high rate of HBV reactivation in these patients. HBV serology cannot identify all cases with RHBI and therefore does not preclude HBV reactivation post-transplant. Copyright © 2015 John Wiley & Sons, Ltd.
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http://dx.doi.org/10.1002/hon.2195DOI Listing
September 2016

Bilateral adenomyoepithelioma of breast.

J Cancer Res Ther 2013 Jul-Sep;9(3):523-5

Department of Medical Oncology, Tata Memorial Cancer Centre, Mumbai, India.

Adenomyoepithelioma is a rare tumor characterized by proliferation of two different cell populations. These tumors have a variable biological behavior. Majority of them are benign but have a tendency to recur locally. Malignant transformation is rare in this disease and distant metastasis is rarer still. We report here an unusual case of bilateral adenomyoepithelioma at an unusual age and showing a remarkable response to an unconventional drug, tyrosine kinase inhibitor "imatinib".
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http://dx.doi.org/10.4103/0973-1482.119370DOI Listing
August 2014

Thyroid cancer in Gardner's syndrome: Case report and review of literature.

South Asian J Cancer 2012 Jul;1(1):43-7

Department of Medical Oncology, Tata Memorial Hospital, Mumbai, India.

Gardner's syndrome is a variant of familial adenomatous polyposis. A multitude of extra-colonic manifestations including various endocrine tumors have been associated with this syndrome, the commonest of which is thyroid cancer. Majority of the patients with thyroid cancer and Gardner's syndrome are females. Here we describe a male patient with Gardner's syndrome who subsequently developed thyroid cancer.
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http://dx.doi.org/10.4103/2278-330X.96510DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3876602PMC
July 2012