Unfavorable Outcome of Single-Unit Umbilical Cord Blood Transplantation for Elderly Patients with Myelodysplastic Syndromes.
Authors: Aoki Kazunari , Ishiyama Ken , Itonaga Hidehiro , Fukuda Takahiro , Taniguchi Shuichi , Ueda Yasunori , Doki Noriko , Sugio Yasuhiro , Morishima Yasuo , Nagamura Tokiko , Tanaka Junji , Atsuta Yoshiko , Ishikawa Takayuki , Miyazaki Yasushi 
Published: October 2019

Abstract 3118

Introduction:

Elderly patients with myelodysplastic syndromes (MDS) are often lack of suitable human leukocyte antigen (HLA)-matched related donors. Unfortunately, the data on the efficacy of allogeneic transplantation using alternative donor sources are limited. We retrospectively compared the outcomes of HLA 6/6 antigen-matched related bone marrow or peripheral blood progenitor cells (rBM/PBPC) transplantation (6/6rBM/PBPCT), HLA 8/8 allele-matched unrelated bone marrow (uBM) transplantation (8/8uBMT), HLA 7/8 allele-matched uBM transplantation (7/8uBMT), and HLA at least 4/6 antigen-matched single-unit umbilical cord blood (CB) transplantation (sCBT) for elderly patients with MDS.

Method:

The data were obtained from the Transplant Registry Unified Management Program, which includes data from the Japan Society for Hematopoietic Cell Transplantation, the Japan Marrow Donor Program, and the Japan Cord Blood Bank Network.

Patients aged 50–70 years old at transplantation with MDS according to French-American-British (FAB) classification who received first allogeneic transplantation between January 1, 2001 and December 31, 2010 were included. Among 336 rBM/PBPC, 291 uBM, and 215 CB transplantation recipients with complete HLA data, 268 6/6rBM/PBPCT, 147 8/8uBMT, 90 7/8uBMT, and 211 sCBT recipients were included.

Cox proportional-hazards regression model was used for adjusted comparisons of the donor sources on overall survival (OS). Fine and Gray proportional-hazards model was used for adjusted comparisons of the donor sources on non-relapse mortality (NRM), relapse, grade 2–4 acute graft-versus-host disease (aGVHD2–4), and neutrophil engraftment. Recipient age at transplantation (>=60 or 50–59), recipient sex (male or female), performance status (PS) at transplantation (2–4 or 0–1), FAB classification at transplantation (refractory anemia with excess blasts (RAEB) and RAEB in transformation (RAEBt), or refractory anemia (RA) and RA with ringed sideroblasts), latest cytogenetics classification according to International Prognostic Scoring System (good, intermediate, poor, or unevaluable), transplant conditioning regimen (reduced-intensity conditioning or myeloablative conditioning), and the year at transplantation (2001–2005 or 2006–2010) were included in the multivariate models.

Result:

Median follow-up was 2.9 years. The unadjusted 3-year OS rates for recipients of 6/6rBM/PBPCT, 8/8uBMT, 7/8uBMT, and sCBT were 50.7%, 58.2%, 46.2%, and 28.4%, respectively. Multivariate analysis revealed that the OS for sCBT recipients was significantly inferior to those for 6/6rBM/PBPCT (relative risk (RR) [95% confidential interval], 1.9 [1.5–2.5]; P<0.001), 8/8uBMT (RR, 2.3 [1.7–3.2]; P<0.001), and 7/8uBMT (RR, 1.4 [1.0–2.0]; P=0.047) recipients. The OS for 8/8uBMT and 7/8uBMT recipients were comparable with that for 6/6rBM/PBPCT. Other variables associated with significant inferior OS were recipient age >= 60, male sex, PS > 1, FAB classification at transplantation as RAEB/RAEBt, and poor cytogenetics.

The risk of relapse for sCBT recipients was comparable with that for 6/6rBM/PBPCT but significantly higher than those for 8/8uBMT (RR, 2.4 [1.5–3.8]; P<0.001) and 7/8uBMT (RR, 2.3 [1.3–4.2]; P=0.005) recipients. The risk of NRM for sCBT recipients was significantly higher than that for 6/6rBM/PBPCT recipients (RR, 1.7 [1.1–2.4]; P=0.009) but comparable with those for 8/8uBMT and 7/8uBMT recipients. The risk for NRM for 7/8uBMT recipients was significantly higher than that for 6/6rBM/PBPCT (RR, 2.1 [1.4–3.1], P<0.001) and 8/8uBMT (RR, 1.6 [1.1–2.5]; P=0.024) recipients. The risk of aGVHD2–4 for 7/8uBMT recipients was significantly higher than those for 6/6rBM/PBPCT (RR, 1.6 [1.1–2.4]; P=0.008), 8/8uBMT (RR, 1.7 [1.2–2.6], P=0.008), and sCBT (RR, 1.6 [1.0–2.3]; P=0.032) recipients. Neutrophil engraftment for sCBT recipients was significantly slower than those for 6/6rBM/PBPCT (RR, 0.26 [0.21–0.33]; P<0.001), 8/8uBMT (RR, 0.35 [0.29–0.43]; P<0.001), and 7/8uBMT (RR, 0.40 [0.31–0.51]; P<0.001) recipients.

Conclusion:

For elderly patients with MDS, the outcome of sCBT recipient was inferior to those of 6/6rBM/PBPCT, 8/8uBMT, and 7/8uBMT recipients. Decreasing the risk of NRM, which would be brought by improving the neutrophil engraftment, and decreasing the risks of relapse are required to improve the outcome of sCBT.

Disclosures:

No relevant conflicts of interest to declare.