Unmanipulated haploidentical bone marrow transplantation and post-transplant cyclophosphamide for hematologic malignanices following a myeloablative conditioning: an update

Abstract

This is a report of 148 patients with hematologic malignancies who received an unmanipulated haploidentical bone marrow transplant (BMT), followed by post-transplant high-dose cyclophosphamide (PT-CY). All patients received a myeloablative conditioning consisting of thiotepa, busulfan, fludarabine (n = 92) or TBI, fludarabine (n = 56). The median age was 47 years (17-74); 47 patients were in first remission (CR1), 37 in second remission (CR2) and 64 had an active disease; all patients were first grafts. The diagnosis was acute leukemia (n = 75), myelodisplastic syndrome (n = 24), myelofibrosis (n = 16), high-grade lytmphoma (n = 15) and others (n = 18). GVHD prophylaxis consisted in PT-CY on days +3 and +5, cyclosporine (from day 0), and mycophenolate (from day +1). The median day for neutrophil engraftment was day +18 (13-32). The cumulative incidence of grades II-IV acute GVHD was 24%, and of grades III-IV GVHD 10%. The incidence of moderate-severe chronic GVHD was 12%. With a median follow-up for the surviving patients of 313 days (100-1162), the cumulative incidence of transplant-related mortality (TRM) is 13%, and the relapse-related death is 23%. The actuarial 22 months overall survival is 77% for CR1 patients, 49% for CR2 patients and 38% for patients grafted in relapse (P o0.001). Major causes of death were relapse (22%), GVHD (2%) and infections (6%). We confirm our initial results, suggesting that a myeloablative conditioning regimen followed by unmanipulated haploidentical BMT with PT-CY, results in a low risk of acute and chronic GVHD and encouraging rates of TRM and overall survival, also for patients with active disease at the time of transplant.Bone Marrow Transplantation (2015) 50, S37-S39; doi:10.1038/bmt.2015.93 PATIENTS AND METHODSClinical characteristics are outlined in Table 1. All patients received a myeloablative regimen with post-transplant cyclophosphamide, between august 2010 and January 2014. A total of 64 patients had an active disease at transplant; 46 were in first remission (CR1) and 39 in second remission (CR2) hematologic remission. The most common diagnosis was acute leukemia (n = 76 ), 48 AML (27% with active disease) and 24 ALL (32% with active disease). Most of the patients with non-Hodgkin lymphoma (60%) also had advanced disease, as well as patients with myelofibrosis. DonorsAll donor/patient pairs were genotypically haplomismatched. A single patient, because of HLA homozigosity, had 0 mismatches in the graft vs host direction and three mismatched in the host vs graft direction. Conditioning regimenThe myeloablative conditioning regimen was based either on chemotherapy-thiotepa, busulfan, fludarabine-or TBI and fludarabine: 92 patients received the thiotepa, busulfan, fludarabine regimen which included thiotepa 5 mg/kg on days − 6 and − 5 (total dose 10 mg/kg), fludarabine 50 mg/m 2 on days − 4, − 3 and − 2 (total dose 150 mg/m 2 ), and busulfan 3,2 mg/kg IV on days − 4, − 3, − 2 (total dose 9,6 mg/kg). Fifty-six patients received the TBI and fludarabine regimen, which incl...

T-replete haploidentical allogeneic transplantation using post-transplantation cyclophosphamide in advanced AML and myelodysplastic syndromes

“…More recently, Bacigalupo et al reported promising results in AML and MDS, especially when Haplo-SCT was performed in CR1. 28 Finally, a CIBMTR registry analysis reported 192 AML patients who underwent PT-Cy Haplo-SCT, with similar outcome but lower chronic GVHD compared with matched unrelated donor Allo-HSCT. 29 Taken together, these results suggest that PT-Cy Haplo-SCT is feasible and effective in high-risk patients with AML or MDS who lack HLA-matched donor.…”

High feasibility and antileukemic efficacy of fludarabine, cytarabine, and idarubicin (FLAI) induction followed by risk‐oriented consolidation: A critical review of a 10‐year, single‐center experience in younger, non M3 AML patients

“…Umbilical cord blood recipients received CyA 1 mofetil-mycophenolate (MMF) and ATG. Recipients of haploidentical (HAPLO) grafts were given CyA from day 0, MMF from day 11, and CY 50 mg/kg on days 13 and 15 [34].…”

Post-transplant cyclophosphamide versus anti-thymocyte globulin as graft- versus -host disease prophylaxis in haploidentical transplant

“…Most publications are mostly from single center studies on various, usually heterogenous, hematologic diseases. 6,8,9,19 However, there is no consensus on the GvHD prophylaxis regimen in the setting of non-T-cell depleted Haplo-SCT using bone marrow (BM) or peripheral blood stem cells (PBSC). The current study aimed to compare these two approaches for GvHD prophylaxis in patients with acute myeloid leukemia (AML) in complete remission (CR) reported to the European Group for Blood and Marrow Transplantation (EBMT) registry.…”