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

Abstract

Background The efficacy of umbilical cord blood transplantation (UCBT) as treatment for acute myeloid leukaemia (AML) relies on immune‐mediated graft‐versus‐leukaemia effects. Previous studies have suggested a strong association between graft‐versus‐host disease (GVHD) occurrence and graft‐versus‐leukaemia effects after allogeneic hematopoietic cell transplantation. Methods Here, we evaluated the kinetics of relapse rate in correlation with GVHD occurrence after UCBT. The kinetics of relapse rate over time in correlation to GVHD occurrence were assessed by calculating the relapse rate per patient‐year within sequential 90‐day intervals. The impact of GVHD on relapse and mortality was further studied in multivariate Cox models handling GVHD as a time‐dependent covariate. Results The study included data from 1068 patients given single (n = 567) or double (n = 501) UCBT. The proportion of patients with grade II, III and IV acute GVHD was 20%, 7% and 4%, respectively. At 2 years, the cumulative incidence of chronic GVHD was 42%, the cumulative incidence of relapse was 32%, and overall survival was 32% as well. Relapse rates declined gradually over time during the first 30 months after transplantation. There was a possible suggestion that grade II–IV acute (HR = 0.8, P = 0.1) and chronic (HR = 0.65, P = 0.1) GVHD decreased relapse risk. However, grade II–IV acute GVHD significantly increased early (the first 18 months after UCBT) mortality (HR = 1.3, P = 0.02), whilst chronic GVHD increased each early (HR = 2.7, P < 0.001) and late (HR = 4.9, P < 0.001) mortality after UCBT. Conclusions The occurrence of grade II–IV acute or chronic GVHD each increases overall mortality after UCBT for AML mitigating the possible graft‐versus‐leukemia effect of GVHD.

Impact of Donor Type in Patients with AML Given Allogeneic Hematopoietic Cell Transplantation After Low-Dose TBI-Based Regimen

“…Our study revealed a high incidence of grade III-IV acute GVHD in CBT recipients (15%). A recent study from our group observed that the low incidence of acute GVHD associated with CBT is limited to CBT patients receiving ATG in the conditioning regimen (47). In concordance with this observation, the incidence of grade III-IV acute GVHD in our study was similar to what has been reported by the Seattle (18%; ref.…”

Impact of detectable measurable residual disease on umbilical cord blood transplantation

“…[9][10][11] Despite the rapid growth of T cell replete HLA-haploidentical transplantation, 12 umbilical cord blood transplantation (CBT) has remained an alternative option for patients with high-risk acute leukemia without an HLA-identical sibling donor. [13][14][15][16][17][18] During the last decade, several reports have highlighted the negative impact of detectable measurable residual disease (MRD) at transplantation, on transplantation outcomes in patients transplanted from either HLA-matched related or unrelated donors, as well as in those given cells from HLA-haploidentical donors. [19][20][21][22][23][24][25] This remained true in patients in second complete remission (CR) at transplantation.…”

Cord blood transplantation is associated with good outcomes in secondary Acute Myeloid Leukaemia in first remission

“…While this could be due in part to the relatively high incidence of graft failure observed, we cannot rule out that the frequent use of ATG in our cohort (41%) significantly contributed to this finding. Indeed, previous studies have evidenced than in vivo T-cell depletion had a profound negative impact on immune recovery in CBT recipients and increased NRM in patients with de novo AML [28][29][30]. However, there was no significant association between ATG and NRM in this cohort of patients.…”

“…Two-year incidences of relapse and of NRM were 29% (95% CI, [21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36] and 39% (95% CI, 31-48), respectively. The figures were 25% (95% CI, [17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35] and 35% (95% CI, 25-45), respectively, in patients in CR1, versus 36% (95% CI, 22-49, P = 0.06) and 49% (95% CI, 33-62, P = 0.03), respectively, in patients with active disease at transplantation ( Fig. 1).…”

“…Two-year cumulative incidences of chronic and extensive chronic GVHD were 25% (95% CI, [18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33] and 12% (95% CI, 7-19), respectively. In multivariate analysis, female recipient (HR = 0.36, 95% CI 0.17-0.78, P = 0.01) and higher TNC infused (HR = 0.69, 95% CI 0.49-0.96, P = 0.03) were each associated with a lower incidence chronic GVHD.…”