Publications by authors named "Anant Gokarn"

28 Publications

  • Page 1 of 1

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
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.
View Article and Find Full Text PDF

Download full-text PDF

Source
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.
View Article and Find Full Text PDF

Download full-text PDF

Source
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.
View Article and Find Full Text PDF

Download full-text PDF

Source
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.
View Article and Find Full Text PDF

Download full-text PDF

Source
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.
View Article and Find Full Text PDF

Download full-text PDF

Source
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.
View Article and Find Full Text PDF

Download full-text PDF

Source
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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/jayao.2020.0061DOI Listing
October 2020

Over expression of brain and acute leukemia, cytoplasmic and ETS-related gene is associated with poor outcome in acute myeloid leukemia.

Hematol Oncol 2020 Dec 16;38(5):808-816. Epub 2020 Sep 16.

Department of Medical Oncology, Adult Hematolymphoid Disease Management Group, Tata Memorial Centre, Mumbai, India.

The high expression of brain and acute leukemia, cytoplasmic (BAALC) and ETS-related gene (ERG) has been reported to influence the outcome in acute myeloid leukemia (AML), but due to limited prospective studies, their role as prognostic factors is unclear. At diagnosis, the prognostic value of BAALC and ERG expression with respect to other cytogenetic and molecular markers was analyzed in 149 AML patients. Patients were divided into quartiles which resulted in the formation of four groups (G1-G4) based on expression values of BAALC and ERG and clinical response defined across groups. Groups with similar survival probabilities were merged together and categorized subsequently as high versus low expressers. Patients with high BAALC and ERG expression had significantly lower overall survival (OS; BAALC: p = 0.001 at 5 years 29.4% vs. 69.8%; ERG: p < 0.0001 at 5 years 4% vs. 50.4%) and disease-free survival (BAALC: p = 0.001 at 5 years 19.5% vs. 69.8%; ERG: p < 0.0001 at 5 years 4.2% vs. 47%). Patients were further stratified combining BAALC and ERG expression in an integrative prognostic risk score (IPRS). After a median follow-up of 54 months (95% CI 45-63 months) among survivors, IPRS for high versus low expressers was a significant predictor for OS (BAALC + ERG: 4% vs. 71.6%, p < 0.0001) and DFS (BAALC + ERG: 4.5% vs. 74.1%, p < 0.0001). In a multivariate model, IPRS of BAALC + ERG expression retained prognostic significance for OS (hazard ratio [HR] 2.96, 95%CI 1.91-4.59, p < 0.001) and DFS (HR 3.61, 95%CI 2.26-5.76, p < 0.001).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hon.2800DOI Listing
December 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12185-020-02973-zDOI Listing
December 2020

Machine learning derived genomics driven prognostication for acute myeloid leukemia with .

Leuk Lymphoma 2020 12 5;61(13):3154-3160. Epub 2020 Aug 5.

Haematopathology Laboratory, ACTREC, Tata Memorial Centre, Navi Mumbai, India.

Panel based next generation sequencing was performed on a discovery cohort of AML with . Supervised machine learning identified mutation and absence of mutations in and genes as well as a low mutation to be associated with favorable outcome. Based on this data patients were classified into favorable and poor genetic risk classes. Patients classified as poor genetic risk had a significantly lower overall survival (OS) and relapse free survival (RFS). We could validate these findings independently on a validation cohort ( = 61). Patients in the poor genetic risk group were more likely to harbor measurable residual disease. Poor genetic risk emerged as an independent risk factor predictive of inferior outcome. Using an unbiased computational approach based we provide evidence for gene panel-based testing in AML with and a framework for integration of genomic markers toward clinical decision making in this heterogeneous disease entity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/10428194.2020.1798951DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7116445PMC
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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0963689720912925DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7444217PMC
June 2020

Utility of Immunophenotypic Measurable Residual Disease in Adult Acute Myeloid Leukemia-Real-World Context.

Front Oncol 2019 13;9:450. Epub 2019 Jun 13.

Haematopathology Laboratory, ACTREC, Tata Memorial Centre, Mumbai, India.

One of the mainstays of chemotherapy in acute myeloid leukemia (AML) is induction with a goal to achieve morphological complete remission (CR). However, not all patients by this remission criterion achieve long-term remission and a subset relapse. This relapse is explained by the presence of measurable residual disease (MRD). We accrued 451 consecutive patients of adult AML (from March 2012 to December 2017) after informed consent. All patients received standard chemotherapy. MRD testing was done at post-induction and, if feasible, post-consolidation using 8- and later 10-color FCM. Analysis of MRD was done using a combination of difference from normal and leukemia-associated immunophenotype approaches. Conventional karyotyping and FISH were done as per standard recommendations, and patients were classified into favorable, intermediate, and poor cytogenetic risk groups. The presence of -ITD, , and mutations was detected by a fragment length analysis-based assay. As compared to Western data, our cohort of patients was younger with a median age of 35 years. There were 62 induction deaths in this cohort (13.7%), and 77 patients (17.1%) were not in morphological remission. The median follow-up was 26.0 months. Poor-risk cytogenetics and the presence of -ITD were significantly associated with inferior outcome. The presence of post-induction MRD assessment was significantly associated with adverse outcome with respect to OS ( = 0.01) as well as RFS ( = 0.004). Among established genetic subgroups, detection of MRD in intermediate cytogenetic and mutated groups was also highly predictive of inferior outcome. On multivariate analysis, immunophenotypic MRD at the end of induction and -ITD emerged as independent prognostic factors predictive for outcome. This is the first data from a resource-constrained real-world setting demonstrating the utility of AML MRD as well as long-term outcome of AML. Our data is in agreement with other studies that determination of MRD is extremely important in predicting outcome. AML MRD is a very useful guide for guiding post-remission strategies in AML and should be incorporated into routine treatment algorithms.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2019.00450DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6584962PMC
June 2019

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.

View Article and Find Full Text PDF

Download full-text PDF

Source
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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbmt.2019.04.028DOI Listing
September 2019

Clinical impact of measurable residual disease monitoring by ultradeep next generation sequencing in mutated acute myeloid leukemia.

Oncotarget 2018 Nov 27;9(93):36613-36624. Epub 2018 Nov 27.

Haematopathology Laboratory, ACTREC, Tata Memorial Centre, Navi Mumbai, India.

Detection of measurable residual disease (MRD) by mutation specific techniques has prognostic relevance in mutated AML ( AML). However, the clinical utility of next generation sequencing (NGS) to detect MRD in AML remains unproven. We analysed the clinical significance of monitoring MRD using ultradeep NGS (NGS-MRD) and flow cytometry (FCM-MRD) in 137 samples obtained from 83 patients of AML at the end of induction (PI) and consolidation (PC). We could monitor 12 different types of mutations at a sensitivity of 0.001% using NGS-MRD. We demonstrated a significant correlation between NGS-MRD and real time quantitative PCR (RQ-PCR). Based upon a one log reduction between PI and PC time points we could classify patients as NGS-MRD positive (<1log reduction) or negative (>1log reduction). NGS-MRD, FCM-MRD as well as mutations were predictive of inferior overall survival (OS) and relapse free survival (RFS). On a multivariate analysis NGS-MRD emerged as an independent, most important prognostic factor predictive of inferior OS (hazard ratio, 3.64; 95% confidence interval [CI] 1.58 to 8.37) and RFS (hazard ratio, 4.8; 95% CI:2.24 to 10.28). We establish that DNA based NGS MRD is a highly useful test for prediction of relapse and survival in AML.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/oncotarget.26400DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6290958PMC
November 2018

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
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.
View Article and Find Full Text PDF

Download full-text PDF

Source
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.
View Article and Find Full Text PDF

Download full-text PDF

Source
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.

View Article and Find Full Text PDF

Download full-text PDF

Source
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.

View Article and Find Full Text PDF

Download full-text PDF

Source
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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5045/br.2017.52.4.307DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5762742PMC
December 2017

The Importance of Brain Metastasis in EGFR Mutation Positive NSCLC Patients.

Chemother Res Pract 2014 7;2014:856156. Epub 2014 Dec 7.

Department of Medical Oncology, Tata Memorial Hospital, Dr. E. Borges Road, Parel, Mumbai, Maharashtra 400012, India.

Introduction. Brain metastasis is a poor prognostic marker in lung cancer. However it is not known whether amongst patients with EGFR mutation those with brain metastases have a worse outcome. Methods. We compared the survival outcomes between EGFR mutation positive patients with and without brain metastases. In this retrospective analysis of prospective database of all metastatic lung cancer patients at our centre between July 2009 and December 2012, patients were treated with either combination chemotherapy or oral TKI. All patients with brain metastases received whole brain radiation. Kaplan Meier method was used for survival analysis and compared using log rank test. Results. 101 patients with EGFR mutated, metastatic lung cancer were studied. Fourteen had brain metastases and 87 did not. The common EGFR mutations were exon 19 deletion (61.3%) and exon 21 L858R mutation (28.7%). Overall response was 64% in extracranial metastasis group as compared to 50% in brain metastasis group. There was a significant worsening of median OS in the patients with brain metastases (11.6 months) compared with only extracranial metastases (18.7 months), P = 0.029. Conclusion. Amongst patients with EGFR mutant NSCLC, the presence of brain metastases leads to a worse outcome as compared to patients with extracranial metastases alone.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2014/856156DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4274819PMC
December 2014

Adherence to antiretroviral therapy.

J Assoc Physicians India 2012 Dec;60:16-20

Department of Hematology, AIIMS, Delhi.

Introduction: The goal of HAART is to achieve maximal and durable suppression of virus replication. Adherence plays a very important role in success of antiretroviral therapy.

Aims And Objectives: To find out the rate of adherence and factors that influence adherence to antiretroviral therapy (ART).

Material And Methods: The present study was conducted in the Department of Medicine in a tertiary care hospital from November 2007 to September 2009. Patients attending ART centre OPD and started on ART for at least 6 months were included in the study. A pretested proforma and MMAS adherence questionnaire of every patient was used for data collection. Univariate and multivariate logistic regression analysis was done to identify factors associated with adherence.

Observations And Results: A total of 300 patients attending ART OPD and satisfying inclusion criteria were studied. Adherence rate of >95% was reported by 290 (97%) patients. On MMAS scale 78% of the patients were found adherent to the treatment. On multivariate analysis factors such as age, addictions, difficulty in remembering treatment, finding treatment to be difficult, taking traditional medicines and having no one to remind about medicines were found to be associated with nonadherence. The most common reason for nonadherence were missing pills while travelling or being out of home.

Conclusions: Adherence to antiretroviral treatment in the ART centre is high. During counseling sessions giving up addictions, avoiding traditional medicines, addressing the apprehensions about treatment, and identifying reminder systems should be emphasized. The patients should be advised to carry medications while traveling and when away from home.
View Article and Find Full Text PDF

Download full-text PDF

Source
December 2012