Outcomes after Umbilical Cord Blood Transplantation for Myelodysplastic Syndromes: A Center for International Blood and Marrow Transplant Registry (CIBMTR®) Study
Authors: Gerds Aaron T. , Kalaycio Matt E. , Ahn Kwang Woo , Hu Zhen-Huan , Alyea Edwin P. , Popat Uday R. , Sobecks Ronald M. , Saber Wael 
Published: October 2019

Abstract
Background:
Although, widespread application of innovative sequencing technologies is rapidly unraveling the molecular underpinnings driving the pathogenesis of myelodysplastic syndromes (MDS), allogeneic hematopoietic cell transplantation (HCT) remains the only therapeutic modality that has demonstrated curative potential. However, a significant proportion of patients lack a human leukocyte antigen (HLA)-matched sibling or unrelated donor, and alternative donor sources are needed to extend HCT to patients that are otherwise suitable. There have been few published series solely dedicated to describing the outcomes of adult patients who have undergone umbilical cord blood transplantation (UCBT) for MDS.
Methods:
We identified 176 adult MDS patients who underwent UCBT, at 59 centers, between 2004 and 2013 from the CIBMTR database. The primary endpoints were the estimated incidences of graft-vs-host-disease (GVHD), relapse, transplant-related mortality (TRM), disease free survival (DFS), and overall survival (OS). Multivariate models were built to assess the ability of the revised International Prognostic Scoring System (IPSS-R) to predict post-HCT outcome.
Results:
Median age at the time of transplant was 56 (18-73) with 32%, 27%, 34% having a comorbidity score (HCT-CI) of 0, 1-2, or ≥ 3, respectively. The median time from diagnosis to transplant was 9 (< 1-147) months; 23% of patients did not receive pre-HCT chemotherapy; 72% has a marrow blast count ≤ 5%. IPSS-R scores are shown in Table 1. Myeloablative and reduced-intensity/non-myeloablative conditioning was used in 35% and 65%, respectively; 43% incorporating ATG/alemtuzumab. Double units were used in 80%; median total nucleated cell dose (TNC) of 4 × 107 /kg (< 1-29); considering the unit with the higher number of HLA incompatibilities with the recipient, 60% had ≥ 2 mismatches. The 100-day probability of grade 2-4 acute GVHD was 38%. The 3-year probabilities of chronic GVHD, relapse, TRM, DFS, and OS was 28%, 32%, 40%, 28%, and 31%, respectively. In multivariate analysis using marginal Cox model to adjust for center effect, increasing IPSS-R score at the time of HCT was associated with inferior post-HCT TRM, DFS, and OS (Table 2). IPSS-R was associated with neither GVHD nor relapse. HCT-CI was associated with TRM (P = .001), DFS (P = .02), and OS (P = .001), and conditioning intensity was associated with relapse (P < .001). A higher proportion of myeloablative HCTs were done for those with high-risk disease by IPSS-R, but the interaction between conditioning intensity and IPSS-R for relapse was not significant.
Conclusions:
Treatment decisions and clinical trial design can be informed by providing a descriptive analysis of UCBT for MDS that incorporates a large number of patients from multiple centers. In this analysis, TRM was significantly associated with HCT-CI scores. Interestingly, IPSS-R, a model that specifically quantifies disease risk, at the time of HCT did not predict for post-HCT relapse, but did for TRM.
Table 1. Pre-HCT risk scores IPSS-R prior to transplant Very low 18 (10) Low 41 (23) Intermediate 33 (19) High 34 (19) Very high 22 (13) Missing 28 (16)
Table 2. Multivariate analysis* TRM IPSS-R N RR 95% CI Lower Limit 95% CI Upper Limit P -value OverallP -value Very low/Low 64 1 .006 Intermediate 34 .68 .34 1.35 .30 High/Very high 54 1.76 1.12 2.75 .01 Missing 28 2.05 .93 4.52 .08 DFS IPSS-R N RR 95% CI Lower Limit 95% CI Upper Limit P -value OverallP -value Very low/Low 64 1 .02 Intermediate 34 .83 .50 1.37 .50 High/Very high 54 1.39 1.02 1.91 .04 Missing 28 1.63 .95 2.81 .08 OS IPSS-R N RR 95% CI Lower Limit 95% CI Upper Limit P -value OverallP -value Very low/Low 65 1 .008 Intermediate 35 .88 .51 1.50 .60 High/Very high 55 1.55 1.12 2.14 .01 Missing 28 1.72 .91 3.26 .09 * When adjusting for center effect and HCT-CI

Disclosures
No relevant conflicts of interest to declare.