Single Antigen–Mismatched Unrelated Hematopoietic Stem Cell Transplantation Using High-Dose Post-Transplantation Cyclophosphamide Is a Suitable Alternative for Patients Lacking HLA-Matched Donors

Abstract

The optimal prophylaxis regimen for graft-versus-host disease (GVHD) in the setting of mismatched unrelated donor (MMUD) allogeneic hematopoietic stem cell transplantation (alloHSCT) is not defined. The use of high-dose post-transplant cyclophosphamide (PTCy) in haploidentical transplantation has proven feasible and effective in overcoming the negative impact of HLA disparity on survival. We hypothesized that PTCy could also be effective in the setting of MMUD transplantation. We retrospectively analyzed 86 consecutive adult recipients of alloHSCT in our institution, comparing 2 contemporaneous groups: PTCy MMUD (n = 26) versus matched unrelated donor (MUD) (n = 60). Graft source was primarily peripheral blood (92%). All PTCy MMUD were HLA 7/8 (differences in HLA class I loci in 92% of patients) and received PTCy plus tacrolimus ± mofetil mycophenolate as GVHD prophylaxis. No differences were observed between PTCy MMUD and MUD in the 100-day cumulative incidence of acute GVHD grades II to IV (31% versus 22%, respectively; P = .59) and III to IV (8% versus 10%, P = .67). There was a trend for a lower incidence of moderate to severe chronic GVHD at 1 year after PTCy MMUD in comparison with MUD (22% versus 41%, P = .098). No differences between PTCy MMUD and MUD were found regarding nonrelapse mortality (25% versus 18%, P = .52) or relapse rate (11% versus 19%, P = .18). Progression-free survival and overall survival at 2 years were similar in both cohorts (67% versus 54% [HR, .84; 95% CI, .38 to 1.88; P = .68] and 72% versus 57% [HR, .71; 95% CI, .31 to 1.67; P = .44], respectively). The 2-year cumulative incidence of survival free of moderate to severe chronic GVHD and relapse tended to be higher in the PTCy MMUD group (47% versus 24%; HR, .60; 95% CI, .31 to 1.14; P = .12). We conclude that HLA 7/8 MMUD transplantation using PTCy plus tacrolimus is a suitable alternative for those patients who lack a MUD.

Post-transplant cyclophosphamide versus antithymocyte globulin in patients with acute myeloid leukemia in first complete remission undergoing allogeneic stem cell transplantation from 10/10 HLA-matched unrelated donors

“…Moreover, there is evidence supporting regulatory T cell importance in mediating long-term post-transplant tolerance and GVHD control with PTCY [18][19][20]. Since then, PTCY has been applied in other settings, including HLAidentical sibling or UD and mismatched unrelated donor (MMUD) [21][22][23][24]. In the 9/10 MMUD setting, PTCY use was described as effective anti-GVHD prophylaxis compared to ATG and likely to provide better outcomes in long-term disease control [25].…”

Impacts of post-transplantation cyclophosphamide treatment after allogeneic hematopoietic stem cell transplantation in acute myeloid leukemia

“…Graft-versus-host disease is a leading cause of non-relapse mortality after allogeneic HSCT 19 . More recently, high dose administration of cyclophosphamide after transplantation has been introduced as an effective method of prophylaxis for GvHD 20 . This protocol is based on the logic that alloreactive donor T lymphocytes can be eliminated, which are induced to proliferate soon after transplant, which induces tolerance.…”

NK cell alloreactivity in acute myeloid leukemia in the post‐transplant cyclophosphamide era

“…Though up until now only retrospectively analyzed, results in single antigen HLA-MMUD SCT with PTCy are comparable to the matched MUD setting. 27 In comparison to the widely used GvHD prophylaxis with ATG in this donor transplantation, PTCy shows comparable results in GvHD and relapse rates 28,29 and sometimes even superiority. 30 Other HaploSCT platforms such as T cell replete haploSCT that incorporate an intense immunosuppressive ATG-based regimen (Beijing protocol), 31 have also been developed and show comparable results to the use of PTCy.…”