Post-transplant cyclophosphamide after matched sibling, unrelated and haploidentical donor transplants in patients with acute myeloid leukemia: a comparative study of the ALWP EBMT

Abstract

Background: The use of post-transplant cyclophosphamide (PTCy) is highly effective in preventing graft-versus-host disease (GVHD) in the haploidentical (Haplo) transplant setting and is being increasingly used in matched sibling (MSD) and matched unrelated (MUD) transplants. There is no information on the impact of donor types using homogeneous prophylaxis with PTCy. Methods: We retrospectively compared outcomes of adult patients with acute myeloid leukemia (AML) in first complete remission (CR1) who received a first allogeneic stem cell transplantation (SCT) with PTCy as GVHD prophylaxis from MSD (n = 215), MUD (n = 235), and Haplo (n = 789) donors registered in the EBMT database between 2010 and 2017. Results: The median follow-up was 2 years. Haplo-SCT carried a significantly increased risk of acute grade II-IV GVHD (HR 1.6; 95% CI 1.1-2.4) and NRM (HR 2.6; 95% CI 1.5-4.5) but a lower risk of relapse (HR 0.7; 95% CI 0.5-0.9) that translated to no differences in LFS (HR 1.1; 95% CI 0.8-1.4) or GVHD/relapse-free survival (HR 1; 95% CI 0.8-1.3). Interestingly, the use of peripheral blood was associated with an increased risk of acute (HR 1.9; 95% CI 1.4-2.6) and chronic GVHD (HR 1.7; 95% CI 1.2-2.4) but a lower risk of relapse (HR 0.7; 95% CI 0.5-0.9).

G-CSF-Primed Peripheral Blood Stem Cell Haploidentical Transplantation Could Achieve Satisfactory Clinical Outcomes for Acute Leukemia Patients in the First Complete Remission: A Registered Study

“…In patients with human leukocyte antigen identical sibling donors (ISDs), engraftment was faster ( 1 – 3 ), the relapse rate was lower ( 4 ), and the leukemia-free survival (LFS) rate was better in the PB group compared with the BM group, particularly for the patients with advanced stage disease ( 1 , 4 ). Similar results were also observed in patients with HLA-unrelated donors (URDs) ( 5 – 7 ). Considering the fact that PB stem cells (PBSCs) collection is a non-surgical procedure, PBSC transplantation (PBSCT) is more convenient and more acceptable for donors.…”

“…Bashey et al (31) analyzed outcomes from a multicenter study comparing HID HSCT with G-CSF-primed PB versus BM and showed the lower relapse risk after PBSCT was limited to patients with leukemia. Several studies also noted that PB grafts had protection against relapse in HID HSCT with PT-CY (7,11,31). However, in other studies, PB grafts were not associated with lower rates of relapse (8,9,12,32,37,38).…”

Immunomodulatory Effects of Bendamustine in Hematopoietic Cell Transplantation

“…This is especially challenging for minority patients [59][60][61]. As such, more and more institutions have begun implementing haploidentical (haplo) HCT [62][63][64][65][66][67][68][69][70]. This both increases donor availability and decreases delays involved in finding and collecting stem cells from an unrelated donor.…”

HLA still matters in allogeneic transplants

“…This is in keeping with a previous study by the Blood and Marrow Transplant Clinical Trial Network, which compared triple PTCY-based prophylaxis to a control group of patients receiving a CNI and methotrexate regimen 10 : GVHD was reduced with the triple PTCY prophylaxis and relapse again was not affected. 10 A recent retrospective study by the EBMT has compared MUD and Haplo grafts in acute myeloid leukemia patients in first complete remission receiving PTCYbased prophylaxis 11 : again, GVHD and TRM were increased in Haplo grafts (hazard ratio [HR], 1.6 and 2.6, respectively), but relapse was reduced (HR, 0.7) as compared with MUD transplants, which translated into comparable leukemia-free survival.…”