Differential Effect of Graft-versus-Host Disease on Survival in Acute Leukemia according to Donor Type

Abstract

Purpose: The anti-leukemic activity of allogeneic hematopoietic cell transplantation (HCT) depends on both the intensity of conditioning regimen and the strength of the graft-versus-leukemia (GVL) effect. However, it is unclear whether the sensitivity of the GVL effects differs between donor type and graft source. Experimental Design: We retrospectively evaluated the effect of acute and chronic graft-versus-host disease (GVHD) on transplant outcomes for adults with acute leukemia (n = 6,548) between 2007 and 2017 using a Japanese database. In all analyses, we separately evaluated three distinct cohorts based on donor type [(8/8 allele-matched sibling donor, 8/8 allele-matched unrelated donor, and unrelated single-cord blood (UCB)]. Results: The multivariate analysis, in which the development of GVHD was treated as a time-dependent covariate, showed a reductive effect of grade I–II acute GVHD on treatment failure (defined as 1-leukemia-free survival; P < 0.001), overall mortality (OM; P < 0.001), relapse (P < 0.001), and non-relapse mortality (NRM; P < 0.001) in patients receiving from UCB. A reductive effect of limited chronic GVHD on treatment failure (P < 0.001), OM (P < 0.001), and NRM (P < 0.001) was also shown in patients receiving from UCB. However, these effects were not always shown in patients receiving from other donors. The beneficial effects of mild acute and chronic GVHD after UCB transplantation on treatment failure were noted relatively in subgroups of patients with acute myelogenous leukemia and a non-remission status. Conclusions: These data suggested that the development of mild GVHD could improve survival after UCB transplantation for acute leukemia.

Improved trends in survival and engraftment after single cord blood transplantation for adult acute myeloid leukemia

“…Furthermore, although the proportion of patients with adverse cytogenetics increased over time throughout all cohorts, relapse-related mortality was significantly improved in the recent time period in patients with advanced phase at CBT but was not improved in patients with early phase at CBT. Although a reduction in the risk of relapse could depend on both the intensity of conditioning regimen [ 28 , 29 ] and the strength of the graft-versus-leukemia (GVL) effect [ 30 , 31 ], an improvement of relapse-related mortality over time is not entirely clear in patients with advanced phase at CBT. This is likely due to a significantly increased MAC regimen rather than enhanced a GVL effect because there was a progressive increase in MAC regimens over the three time periods among patients with advanced phase at CBT, but the incidences of acute and chronic GVHD did not change.…”

Intensified conditioning regimens improved disease‐free survival and engraftment after unrelated single‐unit cord blood transplantation but not after matched sibling or matched unrelated donor allogeneic hematopoietic cell transplantation

“…However, this effect of excess of acute GVHD might be different between donor type. In fact, our previous studies showed that the development of mild acute GVHD improved survival only after UCB transplants, but these effects were not shown in patients receiving MSD and MUD transplants 45,46 . Furthermore, previous study demonstrated that a significantly higher response rate to systemic corticosteroids for grade II‐IV acute GVHD in UCB transplants compared with adult donor HCT 47 .…”

“…In fact, our previous studies showed that the development of mild acute GVHD improved survival only after UCB transplants, but these effects were not shown in patients receiving MSD and MUD transplants. 45,46 Furthermore, previous study demonstrated that a significantly higher response rate to systemic corticosteroids for grade II-IV acute GVHD in UCB transplants compared with adult donor HCT. 47 These data suggest that intensified conditioning regimen could contribute to the stronger GVL effects after UCB transplants, whereas it could contribute to increasing NRM after MSD and MUD transplants.…”

Cord blood versus haploidentical transplantations for non‐remission acute myeloid leukaemia: Authors' reply

“…One study showed a different magnitude of GVL effect according to donor type; the GVL effect after CBT was more potent than that after BMT or PBSCT. 6 On the other hand, it can be assumed that the GVL effect after haplo-HSCT may not be so strong owing to the use of post-transplant cyclophosphamide or antithymocyte globulin. 7 Taken together, it is tempting to consider that optimal donor selection may depend on conditioning intensity, and CBT may be preferable to haplo-HSCT when MAC is chosen.…”