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•Post-transplantation cyclophosphamide (PTCy) delays neutrophil engraftment compared with standard cyclosporine A-based GVHD prophylaxis in matched related donor hematopoietic stem cell transplantation.•PTCy increases RBC and platelet transfusion requirements and delays the time to transfusion independence.•Our data suggest lower rates of acute and chronic graft-versus-host disease and better survival outcomes with PTCy.

Central nervous system (CNS) involvement in Epstein–Barr virus-related post-transplant lymphoproliferative disorders (EBV-PTLDs) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is poorly defined. We analyzed the incidence, clinical and pathological characteristics, and impact on outcomes of EBV-PTLDs with CNS involvement (CNS-PTLDs) in 1009 consecutive adult patients undergoing allo-HSCT at a single-center institution. Four hundred eighty-two patients received matched sibling donor (MSD) transplants, 388 umbilical cord blood transplants (UCBTs), 56 matched unrelated donor (MUD) transplants, and 83 haploidentical transplants. We detected 25 cases of biopsy-proven EBV-PTLDs. Of these, nine patients (36%) had CNS-PTLDs: six after UCBT (67%), one after MSD transplantation (11%), one after MUD transplantation (11%), and one after haploidentical transplantation (11%). The 5-year cumulative incidence risk of CNS-PTLDs was 0.9%. Median time from transplant to CNS-PTLDs was 187 days, and all patients had neurological symptoms at diagnosis. Six out of the nine cases (67%) occurred with systemic involvement, and three cases (33%) had isolated CNS involvement. The most frequent histological subtype was monomorphic EBV-PTLD, and laboratory characteristics were similar to EBV-PTLDs without CNS involvement. We observed statistical differences in the rate of positive EBV DNA detection in plasma between isolated CNS-PTLDs (detection in one out of three, 33%) and the rest of the EBV-PTLDs (100%) (P = .01). Treatment strategies included chemotherapy, radiotherapy, and T cell therapy. However, seven out of nine patients died due to progression of the CNS-PTLDs at a median time of 17 days (range, 8 to 163) from diagnosis. The 5-years overall survival in patients who developed CNS-PTLDs was 22% (95% confidence interval [CI], 7% to 75%) and 5-year treatment-related mortality was 78% (95% CI, 51% to 100%), with no statistically significant differences between CNS-PTLDs and the rest of the EBV-PTLDs. In conclusion, despite advances in EBV monitoring and treatment strategies, CNS-PTLDs remain an uncommon but serious complication after allo-HSCT, with very poor prognosis.

Following the success of posttransplant cyclophosphamide (PT-CY) as graft-versus-host disease (GVHD) prophylaxis in haploidentical transplantation, this prevention strategy has progressively been used for allogeneic hematopoietic stem cell transplantation (allo-HSCT) from HLA-matched sibling (MSD) and unrelated donor (MUD). We have introduced PT-CY plus sirolimus and micophenolate mofetil (PT-CY-Sir-MMF) as GVHD prophylaxis in allo-HSCT, irrespective of donor type. This study reports on the safety and efficacy of PT-CY-Sir-MMF in 158 consecutive allo-HSCT from MSD (n= 52), MUD (n= 64), and haploidentical (n= 42) donor. Median age was 53 years and 66% had acute leukemia or myelodysplastic syndrome. Cumulative incidences of acute GHVD grade II–IV, III–IV and moderate to severe cGVHD were 27%, 9% and 27%, respectively. The incidence of hepatic sinusoidal obstruction syndrome was 9.5%. The 1-year cumulative incidence of non-relapse mortality, relapse and event-free survival were 14%, 12% and 75%, respectively. Compared with MSD and MUD, haploidentical transplantation had a higher incidence of CMV DNAemia requiring therapy (34% vs 35% and 52%, respectively, p= 0.04) and was a risk factor for grade III–IV acute GVHD (RR 2.8, p= 0.05). Our study shows that PT-CY-Sir-MMF is not only feasible and effective in preventing GVHD after haploidentical HSCT, but also in allo-HSCT from MSD and MUD.

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