Prognostic impact of pre-transplant chromosomal aberrations in peripheral blood of patients undergoing unrelated donor hematopoietic cell transplant for acute myeloid leukemia
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 b...
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2021
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oai:doaj.org-article:e700d72e5c1b4de9b3ebf243780465142021-12-02T16:17:18ZPrognostic impact of pre-transplant chromosomal aberrations in peripheral blood of patients undergoing unrelated donor hematopoietic cell transplant for acute myeloid leukemia10.1038/s41598-021-94539-02045-2322https://doaj.org/article/e700d72e5c1b4de9b3ebf243780465142021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-94539-0https://doaj.org/toc/2045-2322Abstract 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.Youjin WangWeiyin ZhouLisa J. McReynoldsHormuzd A. KatkiElizabeth A. GriffithsSwapna ThotaMitchell J. MachielaMeredith YeagerPhilip McCarthyMarcelo PasquiniJunke WangEzgi KaraesmenAbbas RizviLeah PreusHancong TangYiwen WangLoreall PoolerXin ShengChristopher A. HaimanDavid Van Den BergStephen R. SpellmanTao WangMichelle KuxhausenStephen J. ChanockStephanie J. LeeTheresa E. HahnLara E. Sucheston-CampbellShahinaz M. GadallaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021) |
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Medicine R Science Q Youjin Wang Weiyin Zhou Lisa J. McReynolds Hormuzd A. Katki Elizabeth A. Griffiths Swapna Thota Mitchell J. Machiela Meredith Yeager Philip McCarthy Marcelo Pasquini Junke Wang Ezgi Karaesmen Abbas Rizvi Leah Preus Hancong Tang Yiwen Wang Loreall Pooler Xin Sheng Christopher A. Haiman David Van Den Berg Stephen R. Spellman Tao Wang Michelle Kuxhausen Stephen J. Chanock Stephanie J. Lee Theresa E. Hahn Lara E. Sucheston-Campbell Shahinaz M. Gadalla Prognostic impact of pre-transplant chromosomal aberrations in peripheral blood of patients undergoing unrelated donor hematopoietic cell transplant for acute myeloid leukemia |
| description |
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. |
| format |
article |
| author |
Youjin Wang Weiyin Zhou Lisa J. McReynolds Hormuzd A. Katki Elizabeth A. Griffiths Swapna Thota Mitchell J. Machiela Meredith Yeager Philip McCarthy Marcelo Pasquini Junke Wang Ezgi Karaesmen Abbas Rizvi Leah Preus Hancong Tang Yiwen Wang Loreall Pooler Xin Sheng Christopher A. Haiman David Van Den Berg Stephen R. Spellman Tao Wang Michelle Kuxhausen Stephen J. Chanock Stephanie J. Lee Theresa E. Hahn Lara E. Sucheston-Campbell Shahinaz M. Gadalla |
| author_facet |
Youjin Wang Weiyin Zhou Lisa J. McReynolds Hormuzd A. Katki Elizabeth A. Griffiths Swapna Thota Mitchell J. Machiela Meredith Yeager Philip McCarthy Marcelo Pasquini Junke Wang Ezgi Karaesmen Abbas Rizvi Leah Preus Hancong Tang Yiwen Wang Loreall Pooler Xin Sheng Christopher A. Haiman David Van Den Berg Stephen R. Spellman Tao Wang Michelle Kuxhausen Stephen J. Chanock Stephanie J. Lee Theresa E. Hahn Lara E. Sucheston-Campbell Shahinaz M. Gadalla |
| author_sort |
Youjin Wang |
| title |
Prognostic impact of pre-transplant chromosomal aberrations in peripheral blood of patients undergoing unrelated donor hematopoietic cell transplant for acute myeloid leukemia |
| title_short |
Prognostic impact of pre-transplant chromosomal aberrations in peripheral blood of patients undergoing unrelated donor hematopoietic cell transplant for acute myeloid leukemia |
| title_full |
Prognostic impact of pre-transplant chromosomal aberrations in peripheral blood of patients undergoing unrelated donor hematopoietic cell transplant for acute myeloid leukemia |
| title_fullStr |
Prognostic impact of pre-transplant chromosomal aberrations in peripheral blood of patients undergoing unrelated donor hematopoietic cell transplant for acute myeloid leukemia |
| title_full_unstemmed |
Prognostic impact of pre-transplant chromosomal aberrations in peripheral blood of patients undergoing unrelated donor hematopoietic cell transplant for acute myeloid leukemia |
| title_sort |
prognostic impact of pre-transplant chromosomal aberrations in peripheral blood of patients undergoing unrelated donor hematopoietic cell transplant for acute myeloid leukemia |
| publisher |
Nature Portfolio |
| publishDate |
2021 |
| url |
https://doaj.org/article/e700d72e5c1b4de9b3ebf24378046514 |
| work_keys_str_mv |
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