The treatment of choice for the hematological complications in FA patients is a histocompatible sibling donor HCT. However, as FA is inherited disorder, most patients do not have an HLA-matched non-affected sibling donor and therefore require AD (HLA-mismatched sibling or unrelated) HCT with inherent increased morbidity and mortality. To identify prognostic factors for survival after AD HCT, we evaluated outcomes in 83 FA patients transplanted at the University of Minnesota from 1990 to 2004. Median age at HCT was 11.8 years (range, 0.8–48.5). 82% received bone marrow (BM) grafts and 18% received unrelated cord blood (UCB). In univariate analysis, factors associated with significantly higher 3-year survival included: age [42% (<18 years, n=67) vs 16% (>18 years, n=16) p=0.01]; recipient CMV serostatus [45% (negative, n=55) vs 19% (positive) p=0.01]; blood product transfusion 82% [(none, n=11) vs 28%(any, n= 67) p= 0.03], prior infection (gram negative bacteria or fungal) [46% (absent, n=62) vs 8%(present, n=19) p= 0.01], and use of fludarabine (FLU) in preparative regimen [45% (present, n=54) vs 24% (absent, n=29) p=0.03]. In multivariate analysis, factors associated with improved survival were young age, negative recipient CMV serostatus, no prior infections and no severe acute GVHD (Table 1). If age <18 yrs, CMV negativity, and absence of prior infections defines ‘standard risk’, 3 year survival is 68% (95% CI, 50–85%) compared to 20% (95% CI, 7–32%) for those with ‘high risk’ disease (p =0.01). Disease status at HCT, androgen use, number of malformations, gender, donor source and HLA disparity did not have a demonstrable effect on survival.

Table 1:

Cox regression on survival

FactorsRelative Risk(95% CI)P-value
Note:*-reference category 
Model(X2=33.5, p<0.01)   
Age at transplant(X10) 1.62 (1.15-2.28) <0.01 
Recipient CMV   
Negative 1.0 *  
Positive 3.41(1.82-6.37) <0.01 
Prior Infection   
No 1.0 *  
Yes 2.33 (1.24-4.36) <0.01 
Grade 3-4 acute GvHD   
No 1.0 *  
Yes 5.04 (2.34-10.88) <0.01 
FactorsRelative Risk(95% CI)P-value
Note:*-reference category 
Model(X2=33.5, p<0.01)   
Age at transplant(X10) 1.62 (1.15-2.28) <0.01 
Recipient CMV   
Negative 1.0 *  
Positive 3.41(1.82-6.37) <0.01 
Prior Infection   
No 1.0 *  
Yes 2.33 (1.24-4.36) <0.01 
Grade 3-4 acute GvHD   
No 1.0 *  
Yes 5.04 (2.34-10.88) <0.01 
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These data suggest that patients with FA should receive AD HCT before the development of preventable high risk features, namely older age and serious infections. FLU based preparative regimens and measures to prevent acute GVHD should also be used to improve survival. Mismatched BM and UCB donor may provide greater donor options for timely transplants in FA patients.

Topics:
donors, fanconi anemia, hematopoietic stem cell transplantation, prognostic factors, infections, graft-versus-host disease, acute, human leukocyte antigens, androgens, blood products, congenital abnormality

Author notes

Corresponding author

2005, The American Society of Hematology
2005
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