ABSTRACT
Background & Aim: Background: Traditionally, ‘fresh’ Hematopoietic progenitors cell (HPC) infusions have been preferred over cryopreserved HPC in Allo-HCT because cryopreservation and thawing leads to cell loss, besides DMSO-related adverse reactions in patients. Emergence of COVID-19 pandemic has severely affected fresh HPC infusions and most professional bodies recommend cryopreservation of HPC products before initiating conditioning chemotherapy. Although some western studies suggest no significant impact of graft manipulation on patient outcome, there is no available data from the developing world.Aim: We compare neutrophil and platelet engraftment in patients undergoing Allo-HCT with fresh and cryopreserved HPC products. Methods, Results & Conclusion: Material and Method: Allo-HCT data from October 2018 to October 2021 were analyzed. Cryopreservation was performed by controlled-rate freezing using 10% DMSO, plasmalyte- A and human albumin ( 1:2:1) as cryoprotectant. Cryopreserved products were stored in vapour-phase of Liquid nitrogen tank. CD34+ enumeration and viablity( by 7-AAD) was done on Flow-cytometry on fresh and post-thaw HPC samples. Neutrophil engraftment was defined as absolute neutrophil count >0.5 ×109/L for 3 days. Platelet engraftment was defined as independence from platelet transfusion for at least 7 days with a platelet count >20 × 109/L. Statistical analysis using Wilcoxon Rank Sum test. Results: Ninety-six patients underwent allo-HCT (46 received fresh and 50 received cryopreserved HPC products) (Table 1). There was no significant difference in neutrophil engraftment with fresh and cryopreserved grafts (p>0.05) in different types of transplants( Matched related/unrelated and haploidentical). 22% (11/50) of cryopreserved graft infusions were associated with Grade-1 DMSO-related adverse reactions, which were managed with symptomatic treatment. Cryopreservation increased the cost of related allogeneic transplants by USD1100. No cryopreserved HPC product was culture positive on microbiological assessment. Conclusion: In our experience, the engraftment kinetics were similar with fresh and cryopreserved HPC products as CD34+cell dose administered was almost the same. Cryopreserved grafts had a median 7% CD34+cell loss, associated with mild DMSO-related adverse reactions and cost increment. Even though, graft cryopreservation is a feasible alternative during the pandemic, it is crucial to ensure graft quality and promptly manage DMSO-related adverse reactions.(Table Presented) Table 1 Comparison of Fresh and cryopreserved HPC products in Allo-HCT
ABSTRACT
Blood is a very important resource for healthcare-based services and there has been a consistently increasing demand for it in most parts of the world. Poor volunteer-based collection system, high-risk of transfusion-transmitted infections, and emergence of new pathogens as evident from the ongoing Coronavirus Disease 2019 (COVID-19) pandemic are potential challenges to the global healthcare systems. It is imperative to explore safe and reliable alternatives to red cell transfusions. Ex vivo culture of red cells (cRBCs) from different sources such as hematopoietic stem cells (HSCs), pluripotent stem cells, and immortalized progenitors (e.g., BELA-2 cells) could revolutionize transfusion medicine. cRBC could be of great diagnostic and therapeutic utility. It may provide a backup in times of acute shortages in patients with rare blood groups, and in cases with multiple antibodies or sickle cell anemia. The CRISP-Cas9 system has been used to develop personalized, multi-compatible RBCs for diagnostic reagents and patients with multiple allo-antibodies. cRBC could be practically feasible for pediatric patients, who require small quantities of red cell transfusions. cRBC produced under good manufacturing practice (GMP) conditions has been reported to survive in human blood circulation for more than 26 days. Recently, a phase I randomized controlled clinical trial called RESTORE was initiated to assess the survival and recovery of cRBCs. However, feasible technological advancement is required to produce enough cRBCs for clinical use. It is crucial to identify sustainable sources for large-scale production of clinically useful cRBCs. Although the potential cost of one unit of cRBC is extrapolated to be around US$ 8000, it is a life-saving product for patients having rare blood groups and is a "ready to use" source of phenotype-matched, homogenous young red cells in emergency situations.
ABSTRACT
Introduction: Pomalidomide is a third-generation immunomodulatory drug approved for relapsed and/or refractory Multiple Myeloma (RRMM). In the phase 3 OPTIMISMM trial, pomalidomide, bortezomib, and dexamethasone demonstrated superior efficacy in patients with RRMM. PRIME study (CTRI/2019/10/021618) is testing this combination in Newly Diagnosed Multiple Myeloma (NDMM) Aim: To determine safety of Pomalidomide in combination with Bortezomib and dexamethasone (VPD) in NDMM Study design: A prospective, single arm, phase II study from a tertiary center. Both transplant eligible and ineligible patients with NDMM aged between 18-70 years are being recruited in the study. Patients with Plasma cell leukemia, POEMS and amyloidosis were excluded. The regimen consists of weekly Bortezomib 1.3mg/sq.m (subcutaneous), Tab. Pomalidomide 2-4mg once daily for 21days, and Tab Dexamethasone 20mg twice weekly, with the cycle repeating every 28 days, 9-12 cycles. Here we report the adverse events (AE) by NCI CTCAE v5.0, upon recruiting 26 patients, as predetermined in the study. Results: Of the proposed 45-50 patients, 26 patients were enrolled in the study between April 2020 to May 2021 and 23 (88.4%) have completed 4 cycles of VPD. The median age is 55years (18-70), and gender ratio 1:1. At disease presentation, bone lesions were the commonest (96.2%, n=25), IMWG high risk cytogenetics were seen in 42.4% (n=11), RISS-2 in 69.3% (n=18), IgG kappa paraproteinemia in 54% (n=14) patients and ECOG performance score 2-3 in 57.6%(n=15). Ten (38.5%) patients have completed 9 cycles, and 3 underwent auto-transplant (between Cycle 4 & 6). Protocol adherence was 96.1% (25/26 patients). Table-1 shows drug-induced toxicity, hematological toxicities were the commonest. Two patients withdrew consent in view of bortezomib-induced peripheral neuropathy. Serious adverse events (SAE) were reported in 9 (34.6%) patients and were considered unrelated to the regimen by the safety committee (PSVT=1, Bony pain=2, dyspnea=1, pneumonia=1, constipation=1, diarrhea=1, hypotension=1) and one death due to SARS-CoV2 pneumonia. Treatment delays of 2 weeks in 4 patients (SARS-CoV2 = 3, Syncope = 1) After 4 cycles (n=23), 6 (26%) patients were in stringent Complete Response (sCR), 17(74%) in Very Good partial response (VGPR) and 13 (56.5%) are Measurable Residual Disease (MRD) negative. Of 10 patients who completed cycle 9, 9 were MRD negative and 1 showed disease progression. Conclusion: Safety data from the PRIME study demonstrates that VPD regimen has a favorable tolerance profile in patients with NDMM. Early efficacy signals are encouraging, and recruitment continues. [Formula presented] Disclosures: Radhakrishnan: Dr Reddy's Laboratories: Honoraria, Membership on an entity's Board of Directors or advisory committees;Emcure Pharmaceuticals: Research Funding;Intas Pharmaceuticals: Research Funding;Janssen India: Honoraria;NATCO Pharmaceuticals: Research Funding;Novartis India: Membership on an entity's Board of Directors or advisory committees;Roche India: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding;AstraZeneca India: Honoraria, Speakers Bureau;Bristol-Myers-Squibb India: Membership on an entity's Board of Directors or advisory committees, Research Funding;Cipla Pharmaceuticals India: Research Funding;Aurigene: Speakers Bureau. Garg: Dr Reddys Laboratories: Honoraria, Speakers Bureau. Nair: Dr Reddy's Laboratories: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Intas pharmaceuticals: Honoraria, Speakers Bureau;Mylan pharmaceuticals: Honoraria;Novartis India: Honoraria;Fresenius Kabi India: Honoraria;Cipla Pharmaceuticals: Honoraria, Speakers Bureau;Janssen India: Honoraria, Speakers Bureau. Chandy: Janssen: Honoraria;Pfizer: Honoraria;Intas Pharmaceuticals: Research Funding.