Post-Transplant Cyclophosphamide (PT-Cy) for Graft Versus Host Disease (GVHD) Prophylaxis in Allogeneic Transplantation from HLA Identical Sibling and Matched Unrelated Donor for Patients with Acute Leukemia, on Behalf of ALWP-EBMT

Abstract

Background: Post-transplant Cyclophosphamide (PT-Cy) is being used successfully in the setting of unmanipulated haploidentical transplant as graft versus host disease (GVHD) prophylaxis. Experience with the application of PT-Cy for prevention of GVHD post allogeneic stem cell transplantation (HSCT) from matched sibling donors (MSD) or unrelated donor (UD) is rather limited and it involves mainly single center experience and small numbers of patients.Methods: Study aim was to evaluate the yield of PT-Cy as GVHD prophylaxis post HSCT from MSD and UD transplants for acute leukemia. We analyzed 423 patients (pts) with acute leukemia who received PT-CY alone or in combination to other drugs as GVHD prophylaxis and reported to the ALWP of the EBMT. 78 pts received PT-Cy alone (group 1); 204 received PT-CY in combination with one immunosuppressive (IS) drug -cyclosporine A (CSA) or and methotrexate (MTX) or mycophenolate mofetil (MMF)(group 2), while 141 pts received PT-Cy in combination with 2 IS drugs- CSA+MTX or CSA+MMF (group 3). Transplants were performed from 2007-2015 and median follow up is 16 months.Results: There were some differences among groups: pts in group 1 were younger (median age 37 years, p<0.001) were transplanted in more recent year (2014, p<0.001), with a MSD (80%, p<0.001), and CMV positive donor (73%, p=0.008), received more frequently a reduced intensity conditioning (RIC) (56%, p<0.001) and bone marrow (BM) as source of stem cells (74%, p<0.001), with no ATG (100%, p<0.001). Probability of OS at 2 year was 50%, 52.2% and 62.4%, for the 3 groups, respectively, p=0.06.Overall the cumulative incidence (CI) of grade II-IV acute GVHD was 27.9%, and the CI of chronic GVHD was 33.4%, and 16.5% the CI of extensive cGVHD. The CI of relapse at 2 years was 33.5% and non-relapse mortality (NRM) 18.5%, disease recurrence and GVHD were the most common causes of death in the whole cohort.At 2 years the probability of leukemia free survival (LFS) and overall survival (OS) was 48% and 55%.In multivariate analysis, the addition of IS to the PT-CY did not impact the risk of acute GVHD. Diagnosis of ALL (HR 0.57, p<0.001), unrelated donor (HR 1.65, p=0.02), RIC regimen (HR 1.72, p=0.01) and donor CMV positive (HR 1.77, p=0.01) were associated with the risk of grade II-IV acute GVHD. The use of PBSC (HR 2.41, p=0.01) and the absence of ATG (HR 1.69, p=0.03) were independently associated with an higher risk of chronic GVHD (p=0.005). In comparison to PT-Cy alone the addition of 1 or 2 IS drugs as GVHD prophylaxis were associated with reduced risk of extensive chronic GVHD (PT Cy+ 1 drug, HR 0.25, p=0.02, PT Cy+ 2 drugs, HR 0.77, p=0.01) as well the use of BM (HR 0.21, p<0.001) and the use of ATG (HR 0.22, p<0.001). Notably, the addition of 1 or 2 IS drugs to PT-CY did not impact the risk of relapse. Advance disease status (HR 2.42, p<0.001), was the only factor associated with increased risk of relapse. As for NRM addition of CSA+MTX or CSA+MMF to the PT-Cy (HR 0.35, p=0.04), diagnosis of AML (HR 0.35, p=0.001), and disease status at transplant (HR 2.94, p<0.001), and patients CMV serology (HR 2.04, p=0.04), influenced the NRM.Factors associated with increased OS were the use of PT-Cy in combination with CSA+MTX or CSA+MMF (HR 0.49, p=0.02), diagnosis of AML (HR 0.59, p=0.001), and disease status at HSCT ((CR1 vs CR2 HR 0.58, p=0.02), (CR1 vs advanced disease (HR 0.40, p<0.001)).Conclusions: PT-CY is effective GVHD prophylaxis in MSD and MUD HSCT for acute leukemia. The addition of IS drugs CSA+MTX or CSA+MMF to the PT-Cy shapes its effect and further decrease the risk of severe chronic GVHD, reducing transplant related mortality and improving overall survival. DisclosuresMohty:Sanofi: Honoraria, Speakers Bureau.