Outcomes after Umbilical Cord Blood Transplantation for Myelodysplastic Syndromes: A Center for International Blood and Marrow Transplant Registry (CIBMTRŽ) Study

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	n (%)
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	Overall P-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	Overall P-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	Overall P-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