Abstract 3100


Hematopoietic cell transplantation (HCT) can cure bone marrow failure in patients with Fanconi Anemia (FA), and it is generally accepted that these patients should receive low intensity conditioning due to the underlying DNA repair defect in their cells. Outcomes of recipients of matched related HCT have generally been favorable, but only few studies have scrutinized the factors that may impact on the eventual outcome of these patients. Thus, the current study was designed to use data from King Faisal Specialist Hospital & Research Center (KFSHRC) to evaluate the impact of different key variables on outcome of related HCT in these patients.

Patients and Methods:

This is a retrospective analysis of 94 pediatric patients (age ≤ 14 years) with FA who underwent related HCT at KFSHRC from 1993 to 2011. Overall survival (OS) probability was estimated using the Kaplan-Meier method. Univariate analyses were conducted to evaluate the impact of key variables on survival as well as on the incidence of graft failure, graft versus host disease (GVHD), and hemorrhagic cystitis. The small sample size precluded multivariate analysis. Forty-six (48.9%) were male. Eleven had evidence of myelodysplasia and/or abnormal cytogenetic clone (MDS) in bone marrow pre-HCT. Two doses of cyclophosphamide (CY) were used in the conditioning: CY 60 mg/kg, when used alone with ATG (N= 40) and CY 20 mg/kg when used in combination with ATG, and radiation (total body irradiation -TBI-; N=12, or thoraco-abdominal irradiation -TAI-; N=22), or when used in combination with ATG and fludarabine (N=21). Donor source was HLA-matched sibling in 86 patients, HLA-matched parent in 3, and HLA-class I single-antigen-mismatched sibling or parent in 5.


Absolute neutrophil count (ANC) recovery occurred in all patients, median of 14 days (range, 9–33 days). Platelet-transfusion independence occurred in 92 patients, median of 29 days (range, 14–97 days). The cumulative incidences of acute GvHD grade II-IV and III-IV were 8.51 % (95% CI: 8.35%-8.67%), and 5.32% (95% CI: 5.12%-5.42%), respectively. Chronic GvHD cumulative incidence was 9.8% (95% CI: 9.6% to 9.10%). Cumulative incidence of secondary graft-failure was 4.3% (95% CI 4.2%-4.4%). Survival probabilities (OS) were 92.5%, 89%, and 86% at 1, 5, and 10 years, respectively. In univariate analysis, survival was not affected by any of the following variables: age at HCT (< 10 years vs. 10–14 years), recipient or donor gender, presence of MDS pre-HCT, use of fludarabine in the conditioning regimen. Only two variables significantly affected survival: use of higher dose CY (60mg/kg) conditioning was associated with a better 10-year OS than lower dose CY (20mg/kg) conditioning (91 % vs. 82 %, respectively; P =0.035), and use of radiation-containing regimens was associated with a lower 10-year OS than non-radiation regimens (76 % vs. 91 %, respectively; P =0.005). Incidence of graft failure, and GVHD was not affected by any of the variables analyzed, but use of higher dose of CY (60mg/kg) was associated with a significantly increased incidence of hemorrhagic cystitis (20% vs. 5.6% respectively; P=0.049). Three patients (3%) developed squamous cell carcinoma (2 oropharyngeal and one genitourinary), at 9.5, 5.5, 14 years post HCT; 2 of them had radiation containing conditioning.


Our analysis indicates that related HCT for pediatric FA patients is associated with excellent long-term survival, and suggests that, for patients transplanted ≤ 14 years, early HCT (below 10 years vs. 10–14 years) does not improve survival. Our data also suggest that a higher dose CY (60 mg/kg) conditioning regimen is associated with better survival but is also associated with a significantly increased risk of hemorrhagic cystitis. On the other hand, radiation-containing regimens are associated with significantly lower survival. Our data also show, that in our patient cohort, the presence of pre-HCT MDS does not adversely affect survival.


No relevant conflicts of interest to declare.

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Author notes


Asterisk with author names denotes non-ASH members.