JOURNAL ARTICLE
MULTICENTER STUDY

Chromosomal Aberrations and Survival after Unrelated Donor Hematopoietic Stem Cell Transplant in Patients with Fanconi Anemia

Youjin Wang, Weiyin Zhou, Blanche P Alter, Tao Wang, Stephen R Spellman, Michael Haagenson, Meredith Yeager, Stephanie J Lee, Stephen J Chanock, Sharon A Savage, Shahinaz M Gadalla
Biology of Blood and Marrow Transplantation 2018, 24 (10): 2003-2008
29879518
Studies of chromosomal aberrations in blood or bone marrow of patients with Fanconi anemia (FA) have focused on their associations with leukemic transformation. The role of such abnormalities on outcomes after hematopoietic cell transplantation (HCT) is unclear. We used genome-wide single nucleotide polymorphism arrays to identify chromosomal aberrations in pre-HCT blood samples from 73 patients with FA who received unrelated donor HCT for severe aplastic anemia between 1991 and 2007. Outcome data and blood samples were available through the Center for International Blood and Marrow Transplant Research. For survival analyses, we used the Kaplan-Meier estimator to calculate the survival probabilities and the exact log-rank test to compare the survival differences across groups. Chromosomal aberrations were detected in 16 (22%) patients; most frequent were clonal copy loss in chromosome 7 (9.6%), clonal copy gains in the long arm (q) of chromosome 1 (chr1q+ ) (8.2%), and clonal or complete copy gains in the q arm of chromosome 3 (chr3q+ ) (8.2%). Seven (9.6%) patients had alterations in 3 or more chromosomes. Poor post-HCT overall survival (OS) was noted in patients with chr3q+  (P = .04), or those with abnormalities in ≥3 chromosomes (P = .03). The 1-year OS was 0% versus 45% in patients with either alteration versus its absence. No statistically significant differences in OS were noted in patients carrying deletions in chr7 (1-year OS = 29% versus 42%; log-rank P = .74). The study is limited by the small sample size. A larger, prospective study is warranted to validate our findings in light of recent improvement in transplant modalities and outcomes.

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