Matched unrelated donor hematopoietic stem cell transplantation (MUD HSCT) is a potentially curative treatment for patients with acute myeloid leukemia (AML). The graft-versus-leukemia (GVL) effect may be potent enough to overcome the otherwise poor prognosis associated with AML though its efficacy for high risk cytogenetic subgroups is uncertain. To test this hypothesis, we analyzed outcomes by cytogenetic risk group in 324 patients in first complete remission (CR1), and 440 in CR2 undergoing NMDP-facilitated MUD HSCT between 1988–2002. Using the SWOG/ECOG classification of cytogenetic risk groups (Slovak et al. Blood, 2000) cytogenetics were classified as favorable in 14% of patients, intermediate in 71% and unfavorable in 16%. 56% of the patients were male and 42% were > 35 years at HSCT. 76% of patients and donors were matched at HLA-A, -B and -DRB1, 17% were mismatched at one or more loci and 7% were potentially matched (serologically matched at HLA-A and -B and potentially allele matched at -DR).

Disease StatusNKaplan-Meier Estimate for Survival at 5 yearsKaplan-Meier Estimate for Disease-Free Survival at 5 yearsCumulative Incidence for 100 Day Transplant-Related MortalityCumulative Incidence for Relapse at 5 years
* p-value indeterminate; ** p=0.01 
CR1 324 32 ± 6% 32 ± 5% 32 ± 5% 18 ± 4% 
    Intermediate 227 33 ± 7% 32 ± 7% 31 ± 6% 16 ± 5%* 
    Unfavorable 85 31 ± 11% 31 ± 10% 29 ± 10% 23 ± 9%* 
CR2 440 36 ± 5% 35 ± 5% 25 ± 4% 16 ± 3% 
    Favorable 93 46 ± 10% 44 ± 10% 25 ± 9% 10 ± 6%** 
    Intermediate 313 33 ± 6% 32 ± 5% 27 ± 5% 16 ± 4%** 
    Unfavorable 34 37 ± 17% 38 ± 16% 15 ± 12% 32 ± 15%** 
Disease StatusNKaplan-Meier Estimate for Survival at 5 yearsKaplan-Meier Estimate for Disease-Free Survival at 5 yearsCumulative Incidence for 100 Day Transplant-Related MortalityCumulative Incidence for Relapse at 5 years
* p-value indeterminate; ** p=0.01 
CR1 324 32 ± 6% 32 ± 5% 32 ± 5% 18 ± 4% 
    Intermediate 227 33 ± 7% 32 ± 7% 31 ± 6% 16 ± 5%* 
    Unfavorable 85 31 ± 11% 31 ± 10% 29 ± 10% 23 ± 9%* 
CR2 440 36 ± 5% 35 ± 5% 25 ± 4% 16 ± 3% 
    Favorable 93 46 ± 10% 44 ± 10% 25 ± 9% 10 ± 6%** 
    Intermediate 313 33 ± 6% 32 ± 5% 27 ± 5% 16 ± 4%** 
    Unfavorable 34 37 ± 17% 38 ± 16% 15 ± 12% 32 ± 15%** 
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These data suggest that with the exception of the 5-year relapse rate, results of cytogenetics have little apparent influence on the outcome for patients undergoing MUD HSCT for AML in CR1. In CR2, results in patients with favorable cytogenetics appear to be better than those with intermediate or unfavorable cytogenetics, but are not statistically significantly different. Effective GVL and protection against relapse is observed, even in high risk cytogenetic subgroups. In this retrospective study, other prognostic factors may influence the outcome, but overall survival for patients with unfavorable cytogenetics appears at least as good as previously reported for matched sibling HSCT.

Topics:
cytogenetics, donors, hematopoietic stem cell transplantation, mismatch, hla-a antigens, hla-a2 antigen, complete remission, electrocorticogram, leukemia, leukemia, myelocytic, acute

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2005, The American Society of Hematology
2004
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