GvHD after umbilical cord blood transplantation for acute leukemia: an analysis of risk factors and effect on outcomes

Abstract

Using the Center for International Blood and Marrow Transplant Research (CIBMTR) registry, we analyzed 1,404 UCBT patients [single (< 18 years) = 810, double (≥ 18 years) = 594] with acute leukemia to define the incidence of acute and chronic graft-vs.-host disease (GVHD), analyze clinical risk factors and investigate outcomes. After single UCBT, 100-day incidence of grades II–IV aGVHD was 39% (95% CI, 36–43%), grades III–IV aGVHD was 18% (95% CI, 15–20%), and 1-year cGVHD was 27% (95% CI, 24–30%). After double UCBT, 100-day incidence of grades II–IV aGVHD was 45% (95% CI, 41%–49%), grades III–IV aGVHD was 22% (95% CI, 19–26%), and 1-year cGVHD was 26% (95% CI, 22–29%). For single UCBT, multivariate analysis showed that absence of anti-thymocyte globulin (ATG) was associated with aGVHD, whereas prior aGVHD was associated with cGVHD. For double UCBT, absence of ATG and myeloablative conditioning were associated with aGVHD, while prior aGVHD predicted for cGVHD. Grades III–IV aGVHD led to worse survival whereas cGVHD had no significant effect on disease-free or overall survival. GVHD is prevalent after UCBT with severe aGVHD leading to higher mortality. Future research in UCBT should prioritize prevention of GVHD.

Factors Associated with Long-Term Risk of Relapse after Unrelated Cord Blood Transplantation in Children with Acute Lymphoblastic Leukemia in Remission

“…Pulsipher et al observed that aGvHD and pre-transplant MRD, independently and in combination, influenced the risk of relapse after HSCT for pediatric ALL after controlling for graft source and other variables 9 . Our results, focused on single cord pediatric recipients with ALL, are consistent with the recent findings of Chen et al after UCBT (single and double) in patients with ALL or AML 26 . They also observed a strong association between ATG use with relapse and NRM, which our results did not support.…”

“…Recently, outcomes are similar to those seen with other donor sources 13, 20, 21 . Outcomes after UCBT for pediatric ALL have been described as part of larger prospective 9, 16, 22, 23 and retrospective 18, 24–26 studies, but a focused examination of factors influencing relapse in pediatric ALL recipients after UCBT is needed. In this report, we describe the long-term outcomes of a collaborative effort between Eurocord, European Society of Blood and Marrow Transplantation (EBMT) and Duke University Pediatric Blood and Marrow Transplant Program (PBMT) to define risk factors associated with relapse and other outcomes after UCBT for pediatric ALL.…”

Occurrence of graft‐versus‐host disease increases mortality after umbilical cord blood transplantation for acute myeloid leukaemia: a report from Eurocord and the ALWP of the EBMT

“…These studies assessed the impact of GVHD on transplantation outcomes throughout the study period and reported conflicting results [20][21][22]. Here we assessed the impact of GVHD on early (the first 18 months after transplantation) and late (thereafter) transplantation outcomes in a large cohort of AML patients given single or double UCBT by calculating the rate of relapse per patient-year for each condition within sequential 90-day intervals after allo-SCT (this method allows assessment of the evolution of the HR for the risk of relapse over time and is not affected by competing risks [23]) and by performing conventional Cox models where acute and chronic GVHD were handled as time-dependent covariates.…”

“…Further, it has been suggested that acute GVHD following UCBT responds better to corticosteroids than acute GVHD following BM or PBSC transplantation [18,19]. Three recent large studies assessed the impact of GVHD on outcomes after UCBT and yielded conflicting results [20][21][22]. Lazaryan et al observed no association between acute (either grade II-IV or grade III-IV) or chronic (limited or extensive) GVHD and nonrelapse mortality after UCBT (n = 711) [20].…”

“…However, only milder forms of GVHD (grade 1-2 acute and limited chronic GVHD) were associated with better survival due to a strong association between severe forms of GVHD and nonrelapse mortality. Finally, in the study by Chen et al, grade III-IV acute GVHD was associated with worse survival, whilst occurrence of chronic GVHD did not have a significant impact on overall survival [22].…”