Abstract
Combined direct antineoplastic activity and the long-lasting immunological effects of allogeneic hematopoietic cell transplant (HCT) can cure many hematological malignancies, but broad adoption requires non-relapse mortality (NRM) rates and graft-versus-host disease (GVHD) control. Recently, posttransplant cyclophosphamide (PTCy) given after a bone marrow transplant significantly reduced GVHD-incidence, while PTCy given with tacrolimus/mofetil mycophenolate (T/MMF) showed activity following allogeneic peripheral blood stem cell transplantation (alloPBSCT). Here, we report the experience of a larger cohort (85 consecutive patients) and expanded follow-up period (03/2011–12/2019) with high-risk hematological malignancies who received alloPBSCT from Human-Leukocyte-Antigens HLA-matched unrelated/related donors. GVHD-prophylaxis was PTCy 50 mg/kg (days+3 and +4) combined with T/MMF (day+5 forward). All patients stopped MMF on day+28 with day+110 = median tacrolimus discontinuation. Cumulative incidences were 12% for acute and 7% for chronic GVHD- and no GVHD-attributed deaths. For surviving patients, the 12, 24, and 36-month probabilities of being off immunosuppression were 92, 96, and 96%, respectively. After a 36-month median follow-up, NRM was 4%; median event-free survival (EFS) and overall survival (OS) had yet to occur. One- and two-year chronic GVHD-EFS results were 57% (95% CI, 46–68%) and 53% (95% CI, 45–61%), respectively, with limited late infections and long-term organ toxicities. Disease relapse caused the most treatment failures (38% at 2 years), but low transplant toxicity allowed many patients (14/37, 38%) to receive donor lymphocyte infusions as a post-relapse strategy. We confirmed that PTCy+T/MMF treatment effectively prevented acute and chronic GVHD and limited NRM to unprecedented low rates without loss of disease control efficacy in an expanded patient cohort. This trial is registered at U.S. National Library of Medicine as #NCT02300571.
Highlights
IntroductionTo allow the widespread use of hematopoietic cell transplant (HCT), issues of transplant toxicity and disease relapse require immediate address [2,3,5,6,7]
In recent years, extraordinary advances have been made in therapeutics for many hematological malignancies; allogeneic hematopoietic cell transplant (HCT)represents the only potentially curative and globally affordable treatment for most of them [1,2,3,4,5,6,7].To allow the widespread use of HCT, issues of transplant toxicity and disease relapse require immediate address [2,3,5,6,7]
The analysis considered all posttransplant graft-versus-host disease (GVHD) control systemic treatments: GVHD or engraftment syndrome, GVHD after donor lymphocyte infusion (DLI) or second alloPBSCT, and GVHD prophylaxis for second alloPBSCT
Summary
To allow the widespread use of HCT, issues of transplant toxicity and disease relapse require immediate address [2,3,5,6,7]. The key to both of these issues appears to be graftversus-host disease (GVHD). As the principal cause of death in allogeneic HCT, GVHD prevention or treatment requires immunosuppression, which negatively impacts relapse risk and morbidity [8,9,10]. Given these facts, all avenues to govern GVHD must be pursued. The pair have proven less than fully effective; up to 80% of patients develop GVHD, nearly 30%
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