Cord Blood Unit Dominance Analysis and Effect of the Winning Unit on Outcomes after Double-Unit Umbilical Cord Blood Transplantation in Adults with Acute Leukemia: A Retrospective Study on Behalf of Eurocord, the Cord Blood Committee of Cellular Therapy, Immunobiology Working Party, and the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation

Abstract

Usually, after double umbilical cord blood transplantation (DUCBT), only 1 of the transplanted units persists in the long term. The characteristics of the winning cord blood unit (W-CBU) that determine unit dominance and how they influence the outcomes of DUCBT remain unclear. We retrospectively analyzed 347 patients with acute leukemia transplanted with a DUCBT (694 CBU) from 2005 to 2013 who had documented neutrophil engraftment and a W-CBU identified by chimerism analysis, to identify unit characteristics impacting on dominance. Median age at DUCBT was 40 years and median follow-up was 35 months. Among W-CBUs, 41% were ≥5/6 HLA matched to the recipient and 59% were ≤4/6. Multivariate analysis indicated that ≤4/6 HLA-matched W-CBUs led to lower leukemia-free survival (44% versus 56%; hazard ratio [HR], 1.5; P = .032) and overall survival (49% versus 62%; HR, 1.5; P = .028), increased nonrelapse mortality (26% versus 18%; HR, 1.9; P = .027), and acute graft-versus-host disease (46% versus 35%; HR, 1.7; P = .013). We were unable to predict unit dominance, but we demonstrated that outcomes were strongly influenced by the degree of HLA mismatch between W-CBU and recipient. Therefore, selection of both units with the lower number of HLA mismatches with the recipient is indicated.

Cord Haploidentical Non-In Vitro T Cell Depletion Allogeneic Hematopoietic Stem Cell Transplantation Reduces Relapse of Refractory Acute Leukemia

“…Notably, previous analyses seldom focused on HLA matching between the "loser" unit and the recipient [30]. Overall, the MHMA algorithm should be helpful in predicting whether higher-degree HLA mismatching improves outcomes in terms of relapse and NRM rates [18,20].…”

“…The 100-day cumulative incidences of grade II-IV and grade III-IV acute GVHD were 50.5% (95% CI, 40.2% to 59.9%) and 28.9% (95% CI, 20.2% to 38.1%), respectively, in the cord-haplo group and 51.2% (95% CI, 35.2% to 65.2%) and 31.7% (95% CI, 18.3% to 46.0%), respectively, in the haplo group (P = .683 and .662, respectively) ( Figure 2A and B). The 1-year cumulative incidences of overall and extensive chronic GVHD were 33.0% (95% CI, 23.9% to 42.4%) and 18.6% (95% CI, 11.6% to 26.9%), respectively, in the cord-haplo group and 35.7% (95% CI, 21.7% to 49.9%) and 16.7% (95% CI, 7.3% to 29.3%), respectively, in the haplo group (P = .794 and .976, respectively) ( Figure 2C and D).…”

“…Conventional allogeneic hematopoietic stem cell transplantation (HSCT) yields long-term survival in only 7% to 24% of patients with refractory acute lymphoblastic leukemia and in only 10% to 40% of those with late-stage acute myelogenous leukemia (AML) [1][2][3][4][5][6]. Although several recent studies of allogeneic HSCT using 2 grafts (ie, double-umbilical cord blood [UCB] transplantation [dUCBT]) and haploidentical cord blood (haplo-cord) HSCT have shown an enhanced graft-versus-leukemia (GVL) effect along with a graft-versus-graft (GVG) response [4,[7][8][9][10][11][12][13][14][15][16][17], this finding remains controversial [9,14,18,19]. The outcomes of previous studies were strongly influenced by the extent of HLA mismatching and patient selection [20,21].…”

“…Subsequently, other investigators found that the "loser" graft-specific CD4 + and CD8 + T cells were both responsible for the predominance of the chimerism and reduced rate of relapse [7,8,23]. However, the most recently published population-based clinical study, which was based on more substantial evidence, suggested no correlation between dUCBT and an enhanced GVL effect [18]. Furthermore, the assumption of fewer relapses in UCBT recipients has been disputed, given the previously revealed association between high-degree HLA disparity and reduced relapse [24].…”

Concise Review: Cheating Death for a Better Transplant

“…In first trials, however, this approach did not result in a faster hematopoietic reconstitution compared with single‐unit cord blood transplants, but rather led to poorer platelet reconstitution and greater incidences of both acute and chronic GvHD . Interestingly, only one of two competing cord blood units has been shown to contribute to long‐term hematopoiesis in the recipient but the factors that determine superiority of the dominant cord blood unit remained so far obscure . One factor affecting the transplantation outcome in this setting was the extent of HLA mismatch between the two units .…”