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- Title
Prognostic impact of pre-transplant chromosomal aberrations in peripheral blood of patients undergoing unrelated donor hematopoietic cell transplant for acute myeloid leukemia.
- Authors
Wang, Youjin; Zhou, Weiyin; McReynolds, Lisa J.; Katki, Hormuzd A.; Griffiths, Elizabeth A.; Thota, Swapna; Machiela, Mitchell J.; Yeager, Meredith; McCarthy, Philip; Pasquini, Marcelo; Wang, Junke; Karaesmen, Ezgi; Rizvi, Abbas; Preus, Leah; Tang, Hancong; Wang, Yiwen; Pooler, Loreall; Sheng, Xin; Haiman, Christopher A.; Van Den Berg, David
- Abstract
To improve risk stratification and treatment decisions for patients with acute myeloid leukemia (AML) undergoing hematopoietic cell transplantation (HCT). We used SNP-array data from the DISCOVeRY-BMT study to detect chromosomal aberrations in pre-HCT peripheral blood (collected 2–4 weeks before the administration of conditioning regimen) from 1974 AML patients who received HCT between 2000 and 2011. All aberrations detected in ≥ 10 patients were tested for their association with overall survival (OS), separately by remission status, using the Kaplan–Meier estimator. Cox regression models were used for multivariable analyses. Follow-up was through January 2019. We identified 701 unique chromosomal aberrations in 285 patients (7% of 1438 in complete remission (CR) and 36% of 536 not in CR). Copy-neutral loss-of-heterozygosity (CNLOH) in chr17p in CR patients (3-year OS = 20% vs. 50%, with and without chr17p CNLOH, p = 0.0002), and chr13q in patients not in CR (3-year OS = 4% vs. 26%, with and without chr13q CNLOH, p < 0.0001) are risk factors for poor survival. Models adjusted for clinical factors showed approximately three-fold excess risk of post-HCT mortality with chr17p CNLOH in CR patients (hazard ratio, HR = 3.39, 95% confidence interval CI 1.74–6.60, p = 0.0003), or chr13q CNLOH in patients not in CR (HR = 2.68, 95% CI 1.75–4.09, p < 0.0001). The observed mortality was mostly driven by post-HCT relapse (HR = 2.47, 95% CI 1.01–6.02, p = 0.047 for chr17p CNLOH in CR patients, and HR = 2.58, 95% CI 1.63–4.08, p < 0.0001 for chr13q CNLOH in patients not in CR. Pre-transplant CNLOH in chr13q or chr17p predicts risk of poor outcomes after unrelated donor HCT in AML patients. A large prospective study is warranted to validate the results and evaluate novel strategies to improve survival in those patients.
- Subjects
CHROMOSOME abnormalities; HEMATOPOIETIC stem cell transplantation; ACUTE myeloid leukemia; SINGLE nucleotide polymorphisms; FOLLOW-up studies (Medicine)
- Publication
Scientific Reports, 2021, Vol 11, Issue 1, p1
- ISSN
2045-2322
- Publication type
Article
- DOI
10.1038/s41598-021-94539-0