PF751 POST-TRANSPLANT CYCLOPHOSPHAMIDE AND SIROLIMUS IN HAPLOIDENTICAL TRANSPLANT WITH PBSC GRAFTS: RESULTS IN 151 PATIENTS
Authors: M. Silani, R. Greco, S. Albanese, F. Lorentino, M.T. Lupo Stanghellini, F. Giglio, D. Clerici, L. Lazzari, F. Serio, S. Piemontese, M. Marcatti, S. Mastaglio, A. Assanelli, C. Corti, M. Bernardi, J. Peccatori, F. Ciceri
Journal: HemaSphere (2019)

Background: The use of haploidentical hematopoietic stem cell transplantation (HSCT) with post- transplant cyclophosphamide (PT-Cy) and calcineurin inhibitors (CNI) as graft-versus-host disease (GVHD) prophylaxis is rapidly increasing. Aims: Herein we describe long-term outcomes of haploidentical HSCT from PBSC grafts, using intensified myeloablative conditioning, and GVHD prophylaxis with PT-Cy and sirolimus. Methods: From 2012 to 2017, 151 adult patients received haploidentical HSCT for high-risk hematological malignancies, mainly acute myeloid leukemia (n = 92). Disease risk index (DRI; Armand et al) was low-intermediate in 52, high in 64 and very high in 35 patients. At HSCT, 58% of patients were not in CR; 25% of patients received a previous allogeneic HSCT. Conditioning was myeloablative in 123 and reduced-intensity in 28 patients. It was based on treosulfan-fludarabine, and 116 patients receive a regimen intensified by a 2nd alkylating agent (melphalan or thiotepa). The majority of patients (n = 148) received unmanipulated PBSCs. All pts received PT-Cy (50 mg/kg/day) on days 3 and 4. Sirolimus was given from day 5, and withdrawn 3 months after HSCT. Mycophenolate mofetil (MMF) was initiated on day 5, and withdrawn on day 30. All patients were treated according to current institutional programs upon written informed consent for transplant procedures and for the use of medical records for research. Results: Median follow up was 26 months (3–68). Median PBSC graft CD34+ and CD3+ cell doses were respectively 6x10^6/Kg (range, 5–8) and 2x10^8/Kg (range, 0.8–4.8). The majority of patients reached the neutrophil (86%) and platelet (77%) engraftment within 30 and 90 days after HSCT, respectively. Post-HSCT recovery of lymphocyte subsets was broad and fast, reaching more than 100/ml CD3+ T cells within a median of 33 days (20–799). Clinically relevant CMV and HHV-6 infections occurred in 63 and 60 patients, respectively. Invasive fungal diseases were reported in 14 cases. The cumulative incidence of grades II-IV and III-IV acute GVHD at 100 days was 35% and 20%, respectively. The cumulative incidence of chronic GVHD was 42% at 3 years; we observed severe chronic GVHD only in 16% of pts. The cumulative incidences of relapse and non-relapse mortality (NRM) were respectively 35% and 27% at 3 years. Three-year overall survival (OS) was 44% and progression free survival (PFS) 38%. The composite end point of GVHD-free/relapse-free survival (GRFS) was 24% at 3 years. Multivariate analysis confirmed the effect of DRI on transplant outcomes, with worse PFS in high and very high compared to low-intermediate DRI population. Summary/Conclusion: Extended follow-up in 151 high-risk patients confirms that Sirolimus and PT-Cy association as GvHD prophylaxis is feasible in haploidentical HSCT based on unmanipulated PBSC graft; DRI is still a major issue for transplant long-term outcome.