Haploidentical bone marrow transplants with post transplant cyclophosphamide on day + 3 + 5: The Genova protocol

We report 634 patients who underwent unmanipulated haploidentical (HAPLO) bone marrow transplantation (BMT) in two Centers. The diagnosis was acute myeloid leukemia (AML) (n = 251), acute lymphoblastic leukemia (ALL)(n = 107), myelodysplastic syndrome and myelofibrosis (MDS + MF) (n = 125) and chronic lymphoproliferative disorders (n = 151). Median age was 52 years (16-74). Graft versus host disease (GvHD) prophylaxis was intravenous cyclosporin (CSA) starting on day 0, oral mycophenolate on day +1, and post-transplant cyclophosphamide (PTCY) on days +3 + 5. Primary graft failure was seen in 23 patients (3,6%); 17 /23 (74%) were rescued with second HAPLO graft, and were alive at one year. The cumulative incidence of acute GvHD grade II-IV was 29% and 3% for grade III-IV; the cumulative incidence of moderate severe chronic GvHD was 23%: older donor and patients age were significant predictors of both acute and chronic GvHD. The overall non relapse mortality (NRM) at 2 years was 19%: 8%, 21% and 30% in patients aged <40, 41-60 > 60 years. Disease free survival (DFS) at 5 years was 64% for acute leukemia in first remission, 51% for acute leukemia CR2, 25% for acute leukemia advanced disease and 49% for MDS/MPN. We confirm, on a relatively large number of patients, that unmanipulated HAPLO BMT with PTCY on days +3 + 5, mostly after a myeloablative conditioning regimen, is followed by a low incidence of graft failure and grade III-IV GvHD; moderate severe chronic GvHD is 23% and NRM at 2 years 19%; 5 year DFS is influenced by remission status of the underlying disease.