ABSTRACT
Sirolimus has emerged as an alternative to calcineurin inhibitors-based (CNI) graft-versus-host disease (GVHD) prophylaxis. This retrospective study compares the outcome of 133 consecutive adult patients with haematological malignancies undergoing haploidentical stem cell transplantation with posttransplant cyclophosphamide (PTCy) and mycophenolate mofetil (MMF), combined with cyclosporine A (PTCy-CsA-MMF, n = 67) or sirolimus (PTCy-Sir-MMF, n = 66) as GVHD prophylaxis strategy. The median follow-up was 48 (range 22-83) and 13 (range 3-33) months, respectively. PTCy-CsA-MMF was associated in multivariate analyses with a higher risk of acute kidney injury (HR 2.1, 95% CI, 1.21-3.57, p = .008) and thrombotic microangiopathy (HR 12.5, 95% CI, 1.66-93.5, p = .014), whereas PTCy-Sir-MMF was associated with a higher risk of hepatic sinusoidal obstruction syndrome (SOS) (HR 10.8, 95% CI, 1.52-77, p = .018), especially late-onset forms, which totally resolved and none of the patients needed discontinuation of sirolimus. Two SOS-related deaths were detected, both in the PTCy-CsA-MMF subgroup. Both GVHD prophylaxis strategies were otherwise comparable in terms of engraftment, GVHD incidence and survival.
ABSTRACT
OBJECTIVE: To compare the efficacy and safety of CD34+ selected ex vivo T-cell depletion (TCD) vs post-transplant cyclophosphamide, sirolimus, and mycophenolate mofetil (PTCy-Sir-MMF) as graft-vs-host disease (GVHD) prophylaxis. METHODS: We retrospectively included patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) with either TCD (n = 38) or PTCy-Sir-MMF (n = 91). RESULTS: Cumulative incidence of neutrophil and platelet recovery was 92% vs 99% (P = .06) and 89% vs 97% (P = .3) in TCD and PTCy-Sir-MMF, respectively. Cumulative incidences of aGHVD grade II-IV, III-IV, and moderate to severe cGVHD were 11% vs 19% (P = .2), 3% vs 2% (P = .9), and 3% vs 36% (P < .001) in TCD and PTCy-Sir-MMF, respectively. The 2-year non-relapse mortality, relapse, disease-free and overall survival were 25% vs 8% (P = .01), 20% vs 16% (P = .2), 55% vs 76% (P = .004), 57% vs 83% (P = .004) for TCD and PTCy-Sir-MMF, respectively. Cumulative incidence of cytomegalovirus and Epstein-Barr infection requiring therapy was 76% vs 40% (P < .001) and 32% vs 0% (P < .001) in TCD and PTCy-Sir-MMF, respectively. PTCy-Sir-MMF platform showed faster T-cell reconstitution. CONCLUSIONS: PTCy-Sir-MMF provides better survival outcomes but is associated with higher risk of cGVHD compared to TCD.