Allogeneic Hematopoietic Cell Transplantation Outcomes in Patients Carrying Isocitrate Dehydrogenase Mutations
| Autor: | David S. Snyder, Sally Mokhtari, Milhan Telatar, Guido Marcucci, Margaret R. O'Donnell, Vinod Pullarkat, Dongqing Gu, Samer K. Khaled, Stephen J. Forman, Monzr M. Al Malki, Raju Pillai, Ahmed Aribi, Elizabeth Budde, Anthony S. Stein, Ibrahim Aldoss, Dennis D. Weisenburger, Ryotaro Nakamura, Patricia Aoun, Karamjeet S. Sandhu, Matthew Mei, Amandeep Salhotra, Haris Ali, Dongyun Yang, Diana Weigel, Michelle Afkhami, Joyce Murata-Collins |
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| Rok vydání: | 2019 |
| Předmět: |
Adult
Male 0301 basic medicine Oncology Cancer Research medicine.medical_specialty IDH1 medicine.medical_treatment medicine.disease_cause Article 03 medical and health sciences 0302 clinical medicine Internal medicine medicine Humans Transplantation Homologous Genetic Predisposition to Disease Prospective cohort study Aged Mutation Chemotherapy business.industry Hazard ratio Hematopoietic Stem Cell Transplantation Disease Management Myeloid leukemia Hematology Middle Aged Prognosis Isocitrate Dehydrogenase Transplantation Leukemia Myeloid Acute Treatment Outcome 030104 developmental biology Isocitrate dehydrogenase 030220 oncology & carcinogenesis Female business |
| Zdroj: | Clin Lymphoma Myeloma Leuk |
| ISSN: | 2152-2650 |
| Popis: | Background Mutations in isocitrate dehydrogenase (IDH)1/2 genes result in nicotinamide adenine dinucleotide phosphate-dependent reduction of α-ketoglutarate and formation of 2-hydroxyglutarate, which blocks normal cellular differentiation and promotes leukemogenesis. Nearly 20% of acute myeloid leukemia (AML) patients carry IDH1/2 mutations. Although multiple investigators have described the prognostic implications of IDH mutations in AML patients receiving chemotherapy, the effect of these mutations on outcomes after allogeneic (allo) hematopoietic cell transplantation (HCT) is unknown. Patients and Methods We report on the clinical outcome of a cohort of AML patients, who were tested for IDH mutations and underwent alloHCT at City of Hope (2015-2017). Of a total of 317 screened patients, 99 (31%) underwent alloHCT, of whom 23 carried and 76 did not carry IDH mutations (control). Results No statistical significance was detected in patient’s overall survival (P = .84). With a median follow-up of 7.8 months, 1-year relapse rate of 29% and 13% was seen in the IDH-mutated and control group, respectively (P = .033). IDH1/2 mutation status remained significantly associated with relapse (hazard ratio, 2.8; P = .046) after inclusion of pre-HCT disease status in a multivariable model. Conclusion Our results, despite low patient numbers, indicate that IDH mutations are associated with higher relapse rate after alloHCT. Further prospective studies on post transplantation IDH inhibition is required to improve outcomes in AML patients who carry IDH mutations. |
| Databáze: | OpenAIRE |
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