The limited use of autologous hematopoietic stem cell transplant for fit older patients with multiple myeloma in India: a retrospective analysis.

BACKGROUND: Multiple myeloma (MM) predominantly affects older patients; many of whom do not undergo autologous hematopoietic stem cell transplant (AHSCT) despite the associated survival benefits. This study was conceived to investigate the patterns of AHSCT among MM patients with due regard to their age and standardized fitness assessments. METHODS: Fitness scores as per the hematopoietic stem cell transplant-comorbidity index (HSCT-CI) and risk scores as per the revised-myeloma comorbidity index (R-MCI) of MM patients treated between January 2017 and December 2019 were analyzed to assess fitness for AHSCT. Proportions of patients who underwent AHSCT were calculated with regard to age and fitness for AHSCT. RESULTS: Of the 81 eligible patient records with a median age of 62 years, the HSCT-CI classified 79.6% and 77.8% of patients aged ≤65 years and >65 years as AHSCT eligible (p 1). Using the R-MCI, 96.3% and 81.5% of patients aged ≤65 years and >65 years, respectively, were classified as eligible for AHSCT (p 0.0381). Overall, patients aged ≤65 years underwent AHSCT with a greater frequency compared to those aged >65years (38.9 vs. 14.8%, p 0.0402). Irrespective of the age group, there was a statistically significant difference (p 0.0167) in terms of survival which favored those who underwent AHSCT. CONCLUSIONS: Both the HSCT-CI and the R-MCI revealed that nearly 80% of patients aged >65 years were fit enough to receive AHSCT. However, far fewer patients of this age group underwent AHSCT. We propose that the routine inclusion of objective fitness assessment could ensure that fit older patients undergo AHSCT and thus do not miss out on the benefits of the same.

Sequential Treatment of Arsenic Trioxide Followed by All Trans Retinoic Acid with Anthracyclines has Excellent Long-Term Cure in Acute Promyelocytic Leukemia.

Acute promyelocytic leukemia (APL) remains the most curable myeloid leukemia made feasible through effective use of two differentiating agents, all trans retinoic acid (ATRA) and arsenic trioxide (ATO) with or without chemotherapy (CT). However, early morbidity and mortality remains a problem. With the objective of reducing early death a strategy of sequential induction ATO followed by consolidation ATRA in combination with CT was adopted by our group. The long-term outcomes of patient of APL treated on this sequential approach at our center was analyzed. In this retrospective analysis of prospectively maintained database consecutive adult patients with APL irrespective of their Sanz risk group were treated using a protocol of ATO (10 mg IV infusion over 3 h daily for 45 days) in the first phase followed by ATRA (45 mg/m2 for 60 days) in combination with Daunorubicin (60 mg/m2 for 3 days × 3 cycles) in second phase. All patients received maintenance ATRA (45 m/m2 for 15 days every 3 months) for a period of 18 months in phase 3. Patients were monitored for cytogenetic and molecular responses after phase 1 and 2. All patients were followed up for toxicity, event free and overall survival. 131 consecutive patients were treated in this study. At a median follow up of 60 months, 84.81% patients are alive with an overall event free survival (EFS) of 77.82%. Sanz low risk patients fared better (85%) versus intermediate and high-risk patients who had a 76% EFS. Proportion of patients alive at last follow up were 100% in Sanz low risk group and 82% in intermediate and high-risk group. The sequential schedule showed excellent tolerance and toxicity profile when treating newly diagnosed APL. The long-term follow-up data shows comparable if not better survival compared with the published real-world data and this has been consistent across all risk group.

Retrospective Analysis of Outcomes of Patients with Relapsed, Refractory and Metastatic Sarcomas who have received Metronomic Chemotherapy.

INTRODUCTION: Paediatric soft tissue sarcoma treatments and outcomes have improved significantly in the last few decades. However, a significant number of patients still succumb to the disease. In low-middle income countries there are dual problems of advanced disease at presentation and financial burden leading to poor compliance to therapy. Hence, we designed a low-cost oral metronomic chemotherapy protocol for these patients and studied the responses and toxicities to therapy in a tertiary referral hospital. PATIENTS AND METHODS: This is retrospective, single institutional, observational study. We retrospectively reviewed data of patients with relapsed, refractory or metastatic soft tissue sarcoma (STS) [ Ewing Sarcoma (ES); Rhabdomyosarcoma (RMS) or other STS] who were treated with the metronomic protocol of oral Tamoxifen, Etoposide and Cyclophosphamide (TEC) during the period April 1998 to September 2013, at the Tata Memorial Hospital, Parel, Mumbai. Patients with ES and RMS were primarily treated on our Institutional protocols. The patients included in the analysis were those who had relapsed after the primary protocols and then treated with metronomic TEC protocol; or those with primary refractory or metastatic disease (RMS, ES) and received metronomic TEC therapy. RESULTS: 49 patients were enrolled. Among the 49 patients, 32 were diagnosed ES, 13 RMS and 4 other STS. For the whole cohort response rates (RR) were 59% and clinical benefit rate (CBR) was 79%. Patients in the study were grouped into the following subgroups. Systemic recurrent/relapsed disease (N=24), metastatic disease at presentation (N=15) and local disease (refractory/recurrent) (N=10). None of the patients required blood or platelet support or admission for supportive care. The PFS for the above groups were 16.8 months, 12.5 months and 126.68 months respectively. This compares favorably with other historical cohorts in a similar setting. CONCLUSIONS: This study provides a preliminary evidence efficacy and tolerability of metronomic chemotherapy in poor risk ES and RMS. It also demonstrates that with this low-cost low risk treatment few patients could go into long term remissions despite high disease burden.

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

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.

Successful Treatment of Transplant Associated Thrombotic Microangiopathy (TA-TMA) with Low Dose Defibrotide.

Transplant associated microangiopathy (TA-TMA) is a potentially serious complication of stem cell transplantation. Though stopping calcineurin/mTOR inhibitor is the first step in managing TA-TMA, this is not always adequate. The pathophysiology of TA-TMA is different from microangiopathy seen in other settings. Many drugs have been used in TA-TMA with modest responses. Defibrotide has been explored in TA-TMA in the past with good results. However, its availability is erratic and cost of therapy very high. Hence its routine use in low middle income country (LMIC) is financially demanding. We report the use of low dose defibrotide safely and successfully in this case series. This is pertinent more to LMIC's and warrants prospective evaluation.

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

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.