High Impact of Matching Score On Different HSCT Outcomes After Single and Double Umbilical Cord Blood Transplantation for Hematological Malignancies
Authors: Michallet Mauricette , Sobh Mohamad , Morisset Stephane , Labussière-Wallet Hélène , Detrait Marie Y. , Dubois Valerie , Bourgeot Jean-Paul , Ducastelle Sophie , Barraco Fiorenza , Chelghoum Youcef , Mialou Valerie , Chapelle Valérie , Sar Sothiny , Hequet Olivier , Thomas Xavier , Nicolini Franck E. , Bertrand Yves 
Published: October 2019

Abstract
Abstract 1992
Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative treatment for many hematological malignancies for which umbilical cord blood (UCB) represents an alternative source of HSC. In order to overcome the low cellularity of one UCB unit, double (d) UCBT has been developed. The impact of different matching variables between UCB units and recipient including HLA, sex and ABO on the different transplantation outcomes are still unclear and not very well defined yet. On the other hand, a major focus in previous studies has been on cellularity with different thresholds, despite the heterogeneous pre-freezing and post-thawing counting techniques especially without any link to matching variables. In this study, we evaluated the impact of the different matching variables in addition to cellularity and other disease and patient characteristics on single(s) and double UCBT outcomes in pediatric and adult patients between 1998 and 2011. There were 53 adults (37 dUCBT and 16 sUCBT) with a median age of 36 years (18–64) and 48 children (3 dUCBT and 45 sUCBT) with a median age of 2 years (0–14) and a median follow-up of surviving patients of 24 months (1–85). The different patient, UCB, disease and HSCT characteristics have been analyzed and taken into account. The median number of pre-freezing and post-thawing cells was for 1) TNC: 3.3×107/kg (1.9–5.1) and 2.6×107 (1.5–4.6) in adults; 1.6×107 (0.5–4) and 1.18×107 (0.5–3) in children; 2) CD34: 1.89×105 (0.57–4.2) and 1.55×105 (0.5–4.1) in adults; 4×105 (0.6–19.3) and 2.8×105 (0.26–19) in children with a respective cells viability of 54% and 58%. We built a scoring scale that took into account the matching variables (sex, ABO and HLA) between UCB units and recipient and between UCB units each other in case of dUCBT. The median score was 3.8 (1–7) in adults and 3 (1–6) in children; the detailed score calculation method will be communicated later. We evaluated in multivariate analysis separately in adults and children, the impact of the matching score, cellularity, single or double UCBT, type of disease, disease status and conditioning on different HSCT outcomes. We found a positive impact of infused CD34 ≥1.55×105 on neutrophiles recovery in adults [HR=2.1 (1.16–3.8), p=0.015] and infused CD34 ≥2.8×105 on neutrophiles and platelets recovery [HR=2.5 (1.2–5), p=0.007 and HR= 4.4 (1.6–11.6), p=0.002 respectively] in children; no significant factor was observed on the cumulative incidence of acute GVHD≥grade II. In addition, we showed a significant negative impact of matching score > 3.8 on adults overall survival (OS) with a 3 years probability of 19% (6–60) vs. 57% (38–84) for those with score ≤3.8 [HR=3.9 (1.5–9.8), p=0.003]. Similarly, score >3.8 had a significant negative impact also on progression-free survival (PFS) only in adults with a 3 years probability of 13% (3–65) vs. 21% (5–94) for patients with a score ≤3.8 [HR=2.8 (1.01–8), p=0.04]. No significant factor was found to influence transplant related mortality.
In conclusion, cell dose remains a significant impacting factor on short term transplantation outcome while the matching score appears to have a strong impact on adult long term outcomes mainly OS and PFS. These very promising results lead us to evaluate this score in larger number of patients for its validation and in order to include it in the UCB unit choice either in simple or double UCBT.

Disclosures:
Nicolini: Novartis, Bristol Myers-Squibb, Pfizer, ARIAD, and Teva: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.