Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation
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Biol. Blood Marrow Transplant. · Jan 2019
Multicenter Study Comparative Study Clinical TrialComparative Analysis of Calcineurin Inhibitor-Based Methotrexate and Mycophenolate Mofetil-Containing Regimens for Prevention of Graft-versus-Host Disease after Reduced-Intensity Conditioning Allogeneic Transplantation.
The combination of a calcineurin inhibitor (CNI) such as tacrolimus (TAC) or cyclosporine (CYSP) with methotrexate (MTX) or with mycophenolate mofetil (MMF) has been commonly used for graft-versus-host disease (GVHD) prophylaxis after reduced-intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (alloHCT), but there are limited data comparing efficacy of the 2 regimens. We evaluated 1564 adult patients who underwent RIC alloHCT for acute myelogenous leukemia (AML) and acute lymphoblastic leukemia (ALL), chronic myelogenous leukemia (CML), and myelodysplastic syndrome (MDS) from 2000 to 2013 using HLA-identical sibling (matched related donor [MRD]) or unrelated donor (URD) peripheral blood graft and received CYSP or TAC with MTX or MMF for GVHD prophylaxis. Primary outcomes of the study were acute and chronic GVHD and overall survival (OS). ⋯ For RIC alloHCT using MRD, there are no differences in outcomes based on GVHD prophylaxis. However, with URD RIC alloHCT, MMF-CYSP was inferior to MTX-based regimens for acute GVHD prevention, but all the regimens were equivalent in terms of chronic GVHD and OS. Prospective studies, targeting URD recipients are needed to confirm these results.
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Biol. Blood Marrow Transplant. · Dec 2018
Low-Dose Anti-T Lymphoglobulin as Prophylaxis for Graft-versus-Host Disease in Unrelated Donor Transplantations for Acute Leukemias and Myelodysplastic Syndromes.
Chronic graft-versus-host disease (cGVHD) is a major complication after stem cell transplantation (HSCT). Several randomized studies already demonstrated that anti-T lymphoglobulin (ATLG) is effective in preventing GVHD after myeloablative unrelated and HLA-identical sibling transplants. However, the issue of doses and the potential increase of relapses still remain unsolved. ⋯ The rates of 3-year overall survival (OS), disease-free survival (DFS), and GVHD-free and relapse-free survival (GRFS) were 60%, 56% and 44%, respectively. Factors such as younger donor, good performance status, and early disease were associated with better outcome in terms of OS, DFS, and GRFS. Our data indicate that doses of ATLG lower that those used in randomized clinical trials can be used for GVHD prevention, even in the adult setting, without clear increases in relapse and infections; these findings need to be further validated by a prospective randomized study.
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Biol. Blood Marrow Transplant. · Nov 2018
Randomized Controlled TrialEffect of Antihuman T Lymphocyte Globulin on Immune Recovery after Myeloablative Allogeneic Stem Cell Transplantation with Matched Unrelated Donors: Analysis of Immune Reconstitution in a Double-Blind Randomized Controlled Trial.
We recently conducted a randomized double-blind study in which we demonstrated that moderate/severe chronic graft-versus-host disease (cGVHD) but not cGVHD-free survival was reduced in patients receiving anti-T lymphocyte globulin (ATLG) versus placebo. In a companion study we performed immunophenotypic analysis to determine the impact of ATLG on immune reconstitution (IR) and to correlate IR with clinical outcomes. The randomized study (n = 254) included patients (aged 18 to 65 years) who underwent myeloablative transplants for acute myeloid leukemia, myelodysplastic syndrome, or acute lymphoblastic leukemia from HLA-matched unrelated donors. ⋯ Higher absolute counts of CD3+, CD4+, CD8+ T, Tregs, and Tconv were associated with improved overall survival, progression-free survival, and nonrelapse mortality but not moderate/severe cGVHD. Although ATLG delays CD3+ and CD4+ T cell recovery post-transplant, it has a relative Treg sparing effect after the early post-HCT period, with possible implications for protection from cGVHD. ATLG severely compromises the generation of naive CD4+ cells (Treg and Tconv), potentially affecting the diversity of the TCR repertoire and T cell responses against malignancy and infection.
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Biol. Blood Marrow Transplant. · Nov 2018
Reduced-Intensity Conditioning and Dual T Lymphocyte Suppression with Antithymocyte Globulin and Post-Transplant Cyclophosphamide as Graft-versus-Host Disease Prophylaxis in Haploidentical Hematopoietic Stem Cell Transplants for Hematological Malignancies.
Haploidentical hematopoietic stem cell transplantation (haploHSCT) with conditioning regimens using post-transplant cyclophosphamide (PTCy) for peripheral blood stem cell (PBSC) grafts is limited by comparably higher rates of acute and chronic graft-versus-host disease (GVHD). Antithymocyte globulin (ATG) may mitigate this risk. We evaluated haploHSCT after reduced-intensity conditioning (RIC) with ATG, PTCy, and cyclosporine to prevent rejection and GVHD. ⋯ Six-month and 1-year overall survival (OS), cumulative incidence of relapse (CIR), and nonrelapse mortality (NRM) were 73.9%, 10.2%, and 19.4%, respectively, and 48.1%, 16% and 38.2%, respectively. Infection was the most common cause of death (18%). Unmanipulated haploidentical PBSC transplantation following RIC with ATG, PTCy, and cyclosporine as a GVHD prevention strategy results in low rates of acute and chronic GVHD.
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Biol. Blood Marrow Transplant. · Nov 2018
Meta AnalysisHuman Herpesvirus-6B Reactivation Is a Risk Factor for Grades II to IV Acute Graft-versus-Host Disease after Hematopoietic Stem Cell Transplantation: A Systematic Review and Meta-Analysis.
Graft-versus-host disease (GVHD) is an important cause of morbidity and mortality after allogeneic hematopoietic cell transplantation (HCT). Many studies have suggested that human herpesvirus-6B (HHV-6B) plays a role in acute GVHD (aGVHD) after HCT. Our objective was to systematically summarize and analyze evidence regarding HHV-6B reactivation and development of aGVHD. ⋯ Meta-analysis of these 11 studies demonstrated a statistically significant association between HHV-6B and subsequent grades II to IV aGVHD (hazard ratio, 2.65; 95% confidence interval, 1.89 to 3.72; P < .001). HHV-6B reactivation is associated with aGVHD, and when studies have a temporal component to their design, HHV-6B reactivation is associated with subsequent aGVHD. Further research is needed to investigate whether antiviral prophylaxis reduces incidence or severity of aGVHD.