Abstract 355

Approximately one-third of patients considered for hematopoietic cell transplantation (HCT) have human leukocyte antigen (HLA) matched related donors (MRD). HLA-matched unrelated donor (MUD) HCT is an alternative approach for the others. A prior CIBMTR analysis showed that transplantation from MUD and MRD donors produces similar survival for patients with acute myelogenous leukemia (AML) (Blood 2012; 119(17):3908–16). Patients with myelodysplastic syndromes (MDS) often are older and have more compromised performance status than patients with AML. There are also differences in disease biology and pre-transplant therapies between the disorders that could lead to different outcomes. Therefore, a disease-specific analysis of post-HCT outcomes after MUD vs. MRD was performed. Outcomes of 701 adult MDS patients who underwent allogeneic HCT between 2002 and 2006 were analyzed (MRD, n=176; 8/8 HLA-A, B, C, DRB1 allele matched MUD, n=413; 7/8 MUD, n=112). Median age was 53 years (range, 22–78). Thirty-one percent had Karnofsky performance scores (KPS) <90% at HCT. Sixty-five percent had advanced disease and 19% had therapy-related MDS. Seventy-seven percent received peripheral blood stem cells; 40% received reduced intensity conditioning regimens. The 100-day cumulative incidence of grades B-D (IBMTR Index) acute graft-versus-host disease (GVHD) was significantly lower in MRD HCT recipients than in 8/8 MUD and 7/8 MUD HCT recipients (42%, 54%, and 57%, respectively; p=0.009). The corresponding 3-year cumulative incidences of chronic GVHD were similar among the three groups (51%, 49%, and 41%; p=0.25). In multivariate analyses, 8/8 MUD HCT recipients had similar DFS and survival rates compared to MRD HCT recipients (relative risk [RR] 1.11 (95% confidence intervals [CI] 0.89–1.39) and 1.24 (95% CI 0.98–1.56), respectively); 7/8 MUD HCT recipients had inferior DFS (RR 1.43, 95% CI 1.08–1.91) and survival (1.62, 95% CI 1.21–2.17) when compared to MRD HCT recipients and when compared to 8/8 MUD HCT recipients (RR 1.29, 95% CI 1.00–1.65 for DFS and 1.30, 95% CI 1.01–1.68 for survival) (Tables 1, 2 and Figure). Differences in outcome were largely related to excess TRM; relapse was not significantly different among the three groups (overall p value=0.33) (Tables 1 and 2). In patients with MDS, transplantation from 8/8 MUD and MRD donors produces similar survival, however, 7/8 MUD HCT is associated with inferior outcomes.

Table 1.

Adjusted 3-Year Cumulative Incidences of TRM, Relapse, and 3-Year Probabilities of DFS and Survival in Adult MDS Patients who Underwent HLA-Identical Sibling (MRD) HCT or 8/8 or 7/8 Matched Unrelated Donor (MUD) HCT from 2002–2006*

MRD Probability (95% CI)8/8 MUD Probability (95% CI)7/8 MUD Probability (95% CI)8/8 MUD vs. MRD P value‡7/8 MUD vs. MRD P value‡7/8 MUD vs. 8/8 MUD P value‡
TRM 30 (24-37) 41 (36-46) 42 (33-51) 0.01 0.03 0.77 
Relapse 32 (25-39) 24 (20-28) 27 (19-35) 0.058 0.30 0.59 
DFS 40 (33-47) 35 (30-40) 29 (21-37) 0.22 0.04 0.19 
Survival 47 (40-55) 38 (34-43) 31 (22-39) 0.04 0.003 0.11 
MRD Probability (95% CI)8/8 MUD Probability (95% CI)7/8 MUD Probability (95% CI)8/8 MUD vs. MRD P value‡7/8 MUD vs. MRD P value‡7/8 MUD vs. 8/8 MUD P value‡
TRM 30 (24-37) 41 (36-46) 42 (33-51) 0.01 0.03 0.77 
Relapse 32 (25-39) 24 (20-28) 27 (19-35) 0.058 0.30 0.59 
DFS 40 (33-47) 35 (30-40) 29 (21-37) 0.22 0.04 0.19 
Survival 47 (40-55) 38 (34-43) 31 (22-39) 0.04 0.003 0.11 
*

Adjusting for patient-related (age, gender, KPS), disease-related (International Prognostic Scoring System stage at diagnosis (d-IPSS), white blood cell count at diagnosis, therapy-related MDS, and disease status at HCT), and HCT-related variables (time between diagnosis and HCT, donor-recipient CMV and gender match, graft type, conditioning and GVHD prophylaxis regimens).

‡

Pointwise pairwise comparison.

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Table 2.

Multivariate Analysis for TRM, Relapse, Treatment Failure (Inverse of DFS), and Mortality in Adult MDS Patients who Underwent HLA-Identical Sibling (MRD) HCT or 8/8 or 7/8 Matched Unrelated Donor (MUD) HCT from 2002–2006*

TRM# RR (95 % CI)P valueRelapse± RR (95 % CI)P valueTreatment Failure (Death or Relapse)‡ RR (95 % CI)P valueMortality∥ RR (95% CI)P value
8/8 MUD vs. MRD 1.37 (1.01-1.85) 0.03 0.78 (0.55-1.10) 0.16 1.11 (0.89-1.39) 0.33 1.24 (0.98-1.56) 0.06 
7/8 MUD vs. MRD 1.71 (1.17-2.47) 0.004 0.94 (0.60-1.47) 0.79 1.43 (1.08-1.91) 0.01 1.62 (1.21-2.17) 0.001 
7/8 MUD vs. 8/8 MUD 1.24 (0.90-1.70) 0.17 1.20 (0.80-1.79) 0.37 1.29 (1.00-1.65) 0.04 1.30 (1.01-1.68) 0.03 
TRM# RR (95 % CI)P valueRelapse± RR (95 % CI)P valueTreatment Failure (Death or Relapse)‡ RR (95 % CI)P valueMortality∥ RR (95% CI)P value
8/8 MUD vs. MRD 1.37 (1.01-1.85) 0.03 0.78 (0.55-1.10) 0.16 1.11 (0.89-1.39) 0.33 1.24 (0.98-1.56) 0.06 
7/8 MUD vs. MRD 1.71 (1.17-2.47) 0.004 0.94 (0.60-1.47) 0.79 1.43 (1.08-1.91) 0.01 1.62 (1.21-2.17) 0.001 
7/8 MUD vs. 8/8 MUD 1.24 (0.90-1.70) 0.17 1.20 (0.80-1.79) 0.37 1.29 (1.00-1.65) 0.04 1.30 (1.01-1.68) 0.03 
*

See Table 1 for variables adjusted for in the analysis.

Other Significant factors also include:

#

KPS and female donor into male recipient.

±

Disease status at HCT, d-IPSS, and conditioning regimen.

‡

KPS and d-IPSS.

∥

Age, KPS, and d-IPSS.

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Figure.
Figure.
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Disclosures:

No relevant conflicts of interest to declare.

Topics:
hematopoietic stem cell transplantation, myelodysplastic syndrome, transplantation, human leukocyte antigens, prostatic hypertrophy risk score, graft-versus-host disease, myelodysplastic syndrome, therapy related, allogeneic hematopoietic stem cell transplant, graft-versus-host disease, acute, graft-versus-host disease, chronic

Author notes

*

Asterisk with author names denotes non-ASH members.

This icon denotes a clinically relevant abstract

© 2012 by The American Society of Hematology
2012
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