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.
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.
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Authors: David R Wise; Patrick S Ward; Jessica E S Shay; Justin R Cross; Joshua J Gruber; Uma M Sachdeva; Jesse M Platt; Raymond G DeMatteo; M Celeste Simon; Craig B Thompson Journal: Proc Natl Acad Sci U S A Date: 2011-11-21 Impact factor: 12.779
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Authors: Jan M Middeke; Friedrich Stölzel; Desiree Kunadt; Sebastian Stasik; Klaus H Metzeler; Christoph Röllig; Christoph Schliemann; Philipp A Greif; Karsten Spiekermann; Maja Rothenberg-Thurley; Utz Krug; Jan Braess; Alwin Krämer; Andreas Hochhaus; Sebastian Scholl; Inken Hilgendorf; Tim H Brümmendorf; Edgar Jost; Björn Steffen; Gesine Bug; Hermann Einsele; Dennis Görlich; Cristina Sauerland; Kerstin Schäfer-Eckart; Stefan W Krause; Mathias Hänel; Maher Hanoun; Martin Kaufmann; Bernhard Wörmann; Michael Kramer; Katja Sockel; Katharina Egger-Heidrich; Tobias Herold; Gerhard Ehninger; Andreas Burchert; Uwe Platzbecker; Wolfgang E Berdel; Carsten Müller-Tidow; Wolfgang Hiddemann; Hubert Serve; Matthias Stelljes; Claudia D Baldus; Andreas Neubauer; Johannes Schetelig; Christian Thiede; Martin Bornhäuser Journal: J Hematol Oncol Date: 2022-09-05 Impact factor: 23.168