Single- vs double-unit cord blood transplantation for children and young adults with acute leukemia or myelodysplastic syndrome

Abstract

Key Points• A double-unit strategy does not decrease transplantation failure risk when a single unit of cord blood with adequate cell dose is available.• Alloreactivity may be enhanced by double-unit cord blood transplantation.Transplantation of 2 unrelated cord blood (UCB) units instead of 1 has been proposed to increase the cell dose. We report a prospective randomized study, designed to compare single-vs double-UCB transplantation in children and young adults with acute leukemia in remission or myelodysplasia. Eligible patients had at least two 4-6 HLA-identical UCBs with >3 3 10 7 nucleated cells/kg for the first and >1.5 3 10 7 for the second. The primary end point was the 2-year cumulative incidence of transplantation strategy failure, a composite end point including transplant-related mortality (TRM), engraftment failure, and autologous recovery. Randomized patients who did not proceed to transplantation due to refractory disease were considered transplantation failures. A total of 151 patients were randomized and included in the intent-to-treat analysis; 137 were transplanted. Double-UCB transplantation did not decrease transplantation strategy failure (23.4% 6 4.9% vs 14.9% 6 4.2%). Two-year posttransplant survival, disease-free survival, and TRM were 68.8% 6 6.0%, 67.6% 6 6.0%, and 5.9% 6 2.9% after single-unit transplantation compared with 74.8% 6 5.5%, 68.1% 6 6.0%, and 11.6% 6 3.9% after double-unit transplantation. The final relapse risk did not significantly differ, but relapses were delayed after double-unit transplantation. Overall incidences of graft-versus-host disease (GVHD) were similar, but chronic GVHD was more frequently extensive after double-UCB transplantation (31.9% 6 5.7% vs 14.7% 6 4.3%, P 5 .02). In an exploratory subgroup analysis, we found a significantly lower relapse risk after double-unit transplantation in patients receiving total body irradiation without antithymocyte globulin (ATG), whereas the relapse risk was similar in the group treated with busulfan, cyclophosphamide, and ATG. Single-UCB transplantation with adequate cell dose remains the standard of care and leads to low TRM. Double-unit transplantation should be reserved for patients who lack such units. This trial was registered at www.clinicaltrials.gov as #NCT01067300. (Blood. 2016;127(26):3450-3457)

Optimal Practices in Unrelated Donor Cord Blood Transplantation for Hematologic Malignancies

“…In the BMT CTN pediatric myeloablative CBT study that randomized single unit grafts with a TNC dose > 2.5 × 10 7 /kg against the addition of a second unit showed similar neutrophil engraftment and 1-year overall survival (Figure 2) 23 . A recent European study had similar findings although in this study a higher TNC dose threshold was required to be eligible 46 . However, many adults and some larger sized children do not have access to adequately dosed single units.…”

An Integrative Scoring System for Survival Prediction Following Umbilical Cord Blood Transplantation in Acute Leukemia

“…However, given ATG's potential role in reducing GVHD, there is a need for prospective evaluation of its role (8,30,31). In line with previous publications, the conditioning regimen and graft type (single/double unit) were not identified as risk factors (32)(33)(34), most likely reflecting the proper selection of condition type and cell dose. Overall, the score includes the main clinical risk factors impacting on UCBT outcomes.…”

A Novel High-Throughput Screening Platform Reveals an Optimized Cytokine Formulation for Human Hematopoietic Progenitor Cell Expansion

“…Nevertheless, single CB grafts contain limited cell numbers and CB HSCT is associated with delayed early and long-term hematological engraftment [5][6][7]. Indeed, it has been reported that CB units contain 25-to 50-fold fewer early engrafting neutrophil and platelet progenitor cells than mPB [43].…”

“…Its main limitations are its delayed hematological engraftment (early neutrophil and platelet and longer term immune reconstitution), which is associated with defective adhesion receptor fucosylation or reduced homing/engraftment receptor expression on CB hematopoietic stem and progenitor cells (HSPCs) [1][2][3][4], the immaturity of cells, and the limited cell numbers in each CB unit [5,6]. A single CB unit is generally sufficient for pediatric, but not adult, transplant recipients [7]. CB HSPCs can also be used for generating mature blood cells ex vivo for transfusion into difficult-to-transfuse patients or modulating resistance to specific acquired infections and correcting monogenic gene disorders, in dividing HSCs, using new genome editing technologies [8][9][10].…”