Graft-Versus-Host-Disease Prophylaxis with ATG or Ptcy in Patients with Lymphoproliferative Disorders Undergoing Reduced Intensity Conditioning Regimen 9/10 Mmud HCT

Abstract

Introduction: Post-transplant cyclophosphamide (PTCY) has been introduced as a graft-versus-host disease (GvHD) prophylaxis in haploidentical setting with successful results. As a result, PTCY has been applied to other settings such as in mismatched and matched unrelated hematopoietic cell transplant (HCT). However, T-cell depletion with anti-thymocyte globulin (ATG) remains the main strategy in one antigen HLA-mismatched unrelated donor (9/10 MMUD). Data comparing the two GvHD prophylaxis strategies in patients undergoing MMUD 9/10 for lymphoproliferative disease are limited. Methods: We compared PTCY versus ATG as GvHD prophylaxis in patients with lymphoproliferative disease undergoing a first 9/10 MMUD HCT with a reduced intensity conditioning regimen from 2010 to 2021. Adult patients in all disease status for which high-resolution HLA-allele typing was available in the European Society for Blood and Marrow Transplantation (EBMT) data registry were included. Patients receiving PTCY were matched to patients receiving ATG according to the following variables: age, disease status at transplant, female to male donor status, stem cell source and CMV serology. Results: A total of 411 patients were identified (n=341 for ATG group and n=70 for PTCY group). According to the above mentioned variables, 106 patients receiving ATG were identified and matched with 58 patients receiving PTCY. Among the group of 164 patients paired up, diagnosis was Hodgkin Lymphoma in most of the cases (19% and 38% in the ATG and PTCY group, respectively). The median age was 54 (range 21-69) and 52 (range 22-69) years old in the ATG and PTCY group, respectively (p= NS). The majority of patients underwent a previous autologous HCT (72% in the ATG and 68% in the PTCY group, respectively). Disease state at HCT was complete remission in 71% of the patients in both ATG and PTCY group. The most frequent GvHD prophylaxis in the ATG group was cyclosporine A (CsA) and methotrexate (MTX) (n=51; 48%), followed by CsA and mycophenolate mofetil (MMF) (n=31; 29%). In the PTCY group, the majority of patients (n=30; 52%) received CsA and MMF, while tacrolimus and MMF (n=27; 46%) represented the second most used associated immunosuppressive agents. The median follow-up was 5.1 (CI: 3.8-6.7) years for the ATG group and 1.7 (CI 0.9-2.4) years in the PTCY group. The cumulative incidence of neutrophil engraftment was 97% (CI:90.5-99.1) and 100% in ATG and PTCY groups, respectively (p=0.08). Grade III-IV acute GVHD at 100 day was not significantly different between the two groups 11.3% (CI:6-18.6) versus 17.4% (CI: 8.1-29.7) in the ATG and PTCY group, respectively; p=0.60). No differences were observed in 1-y relapse incidence (22.3% (CI: 11.5-27.6) versus 17.3% (CI: 7.4-30.5), p=0.32) and non-relapse mortality (19% versus 32%, p=0.20). GvHD-free, relapse-free survival was not different across the two groups (43.5% (CI: 33.2-53.3) in ATG and 46.9% (CI: 31.2-61.2) in PTCY, p=0.88). The cumulative incidence of 1-year extensive chronic GvHD was 14.4% (CI: 7.8-22.9) in the ATG group and 5.3% (CI: 0.9-15.9) in the PTCY group, respectively (p=0.21). The 1 year-progression free survival was 58.9% (CI: 47.9-68.3) in patients receiving ATG and 50.7% (CI: 34.3-65) in those receiving PTCY (p=0.74) and 1-year overall survival was 65.9% (CI: 55.4-74.4) in the ATG group versus 55.2% (CI: 38.8-68.9) in the PTCY group (p=0.69). Forty-seven patients died in the ATG group, 20 died in the PTCY group. The main cause of death was transplant related complications (n=27 in ATG and n=14 in PTCY patients, respectively) followed by relapse of disease (n=13 in ATG and n=4 in PTCY group). Conclusions: In patients with lymphoproliferative diseases undergoing 9/10 MMUD HSCT, PTCY as GVHD prophylaxis might be a safe option providing similar results to ATG prophylaxis. Due to the limited number of patients, prospective randomized trials are needed to allow better understand the effectiveness of adding PTCY into different platforms, including MMUD 9/10 HSCT.