Single- or double-unit UCBT following RIC in adults with AL: a report from Eurocord, the ALWP and the CTIWP of the EBMT

Annalisa Ruggeri,Eefke Petersen,Patrice Chevallier,Guillermo Sanz,Jan J Cornelissen,Didier Blaise,Arnon Nagler,Bipin N Savani,Myriam Labopin,Mohamad Mohty,Frédéric Baron,Eric Beohou,Eliane Gluckman

doi:10.1186/s13045-017-0497-9

Abstract

BackgroundThe feasibility of cord blood transplantation (CBT) in adults is limited by the relatively low number of hematopoietic stem/progenitor cells contained in one single CB unit. The infusion of two CB units from different partially HLA-matched donors (double CBT) is frequently performed in patients who lack a sufficiently rich single CB unit.MethodsWe compared CBT outcomes in patients given single or double CBT following reduced-intensity conditioning (RIC) in a retrospective multicenter registry-based study. Inclusion criteria included adult (≥18 years) patients, acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL), complete remission (CR) at the time of transplantation, first single (with a cryopreserved TNC ≥ 2.5 × 107/kg) or double CBT between 2004 and 2014, and RIC conditioning.ResultsData from 534 patients with AML (n = 408) or ALL (n = 126) receiving a first single (n = 172) or double (n = 362) CBT were included in the analyses. In univariate analysis, in comparison to patients transplanted with a single CB, double CB recipients had a similar incidence of neutrophil engraftment but a suggestion for a higher incidence of grade II–IV acute GVHD (36 versus 28%, P = 0.08). In multivariate analyses, in comparison to single CBT recipients, double CBT patients had a comparable incidence of relapse (HR = 0.9, P = 0.5) and of nonrelapse mortality (HR = 0.8, P = 0.3), as well as comparable overall (HR = 0.8, P = 0.17), leukemia-free (HR = 0.8, P = 0.2) and GVHD-free, relapse-free (HR = 1.0, P = 0.3) survival.ConclusionsThese data failed to demonstrate better transplantation outcomes in adult patients receiving double CBT in comparison to those receiving single CBT with adequate TNC after RIC.

Highlights

The feasibility of cord blood transplantation (CBT) in adults is limited by the relatively low number of hematopoietic stem/progenitor cells contained in one single Umbilical cord blood (CB) unit
The Minnesota group pioneered the infusion of two CB units from different partially human leukocyte antigen (HLA)-matched donors for patients who lack a sufficiently rich single CB unit [13]
In the current registry study, we investigated whether these observations remained true in the setting of adults after reduced-intensity conditioning (RIC) CBT, which depends primarily on engraftment of donor immune cells and on graft-versus-leukemia effects for disease eradication

Summary

Introduction

The feasibility of cord blood transplantation (CBT) in adults is limited by the relatively low number of hematopoietic stem/progenitor cells contained in one single CB unit. Many adult patients lack a sufficiently rich CB unit to allow safe CBT Based on these observations, the Minnesota group pioneered the infusion of two CB units from different partially HLA-matched donors (dCBT) for patients who lack a sufficiently rich single CB unit [13]. Based on preliminary encouraging results, this approach has been extended to patients who had a single CB unit containing >2.5 × 107 total nucleated cells (TNC) per kilogram at cryopreservation [14]. This has been the case in the setting of RIC-CBT since it was hypothesized that in comparison with single CBT, double CBT might promote engraftment and increase graft-versus-leukemia effects [15]. The later might be due at least in part via graft-versus-graft alloreactivity as recently demonstrated [16]

Methods

Results

Discussion

Conclusion