Impact of IDH1 and IDH2 mutational subgroups in AML patients after allogeneic stem cell transplantation
© 2022. The Author(s)..
BACKGROUND: The role of allogeneic hematopoietic cell transplantation (alloHCT) in acute myeloid leukemia (AML) with mutated IDH1/2 has not been defined. Therefore, we analyzed a large cohort of 3234 AML patients in first complete remission (CR1) undergoing alloHCT or conventional chemo-consolidation and investigated outcome in respect to IDH1/2 mutational subgroups (IDH1 R132C, R132H and IDH2 R140Q, R172K).
METHODS: Genomic DNA was extracted from bone marrow or peripheral blood samples at diagnosis and analyzed for IDH mutations with denaturing high-performance liquid chromatography, Sanger sequencing and targeted myeloid panel next-generation sequencing, respectively. Statistical as-treated analyses were performed using R and standard statistical methods (Kruskal-Wallis test for continuous variables, Chi-square test for categorical variables, Cox regression for univariate and multivariable models), incorporating alloHCT as a time-dependent covariate.
RESULTS: Among 3234 patients achieving CR1, 7.8% harbored IDH1 mutations (36% R132C and 47% R132H) and 10.9% carried IDH2 mutations (77% R140Q and 19% R172K). 852 patients underwent alloHCT in CR1. Within the alloHCT group, 6.2% had an IDH1 mutation (43.4% R132C and 41.4% R132H) and 10% were characterized by an IDH2 mutation (71.8% R140Q and 24.7% R172K). Variants IDH1 R132C and IDH2 R172K showed a significant benefit from alloHCT for OS (p = .017 and p = .049) and RFS (HR = 0.42, p = .048 and p = .009) compared with chemotherapy only. AlloHCT in IDH2 R140Q mutated AML resulted in longer RFS (HR = 0.4, p = .002).
CONCLUSION: In this large as-treated analysis, we showed that alloHCT is able to overcome the negative prognostic impact of certain IDH mutational subclasses in first-line consolidation treatment and could pending prognostic validation, provide prognostic value for AML risk stratification and therapeutic decision making.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:15 |
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| Enthalten in: |
Journal of hematology & oncology - 15(2022), 1 vom: 05. Sept., Seite 126 |
| Sprache: |
Englisch |
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| Links: |
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| Anmerkungen: |
Date Completed 08.09.2022 Date Revised 19.09.2022 published: Electronic ClinicalTrials.gov: NCT03188874, NCT00180115, NCT00180102, NCT00266136, NCT00180167, NCT01382147, NCT00893373 Citation Status MEDLINE |
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| doi: |
10.1186/s13045-022-01339-8 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM345817567 |
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| 245 | 1 | 0 | |a Impact of IDH1 and IDH2 mutational subgroups in AML patients after allogeneic stem cell transplantation |
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| 500 | |a Date Completed 08.09.2022 | ||
| 500 | |a Date Revised 19.09.2022 | ||
| 500 | |a published: Electronic | ||
| 500 | |a ClinicalTrials.gov: NCT03188874, NCT00180115, NCT00180102, NCT00266136, NCT00180167, NCT01382147, NCT00893373 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2022. The Author(s). | ||
| 520 | |a BACKGROUND: The role of allogeneic hematopoietic cell transplantation (alloHCT) in acute myeloid leukemia (AML) with mutated IDH1/2 has not been defined. Therefore, we analyzed a large cohort of 3234 AML patients in first complete remission (CR1) undergoing alloHCT or conventional chemo-consolidation and investigated outcome in respect to IDH1/2 mutational subgroups (IDH1 R132C, R132H and IDH2 R140Q, R172K) | ||
| 520 | |a METHODS: Genomic DNA was extracted from bone marrow or peripheral blood samples at diagnosis and analyzed for IDH mutations with denaturing high-performance liquid chromatography, Sanger sequencing and targeted myeloid panel next-generation sequencing, respectively. Statistical as-treated analyses were performed using R and standard statistical methods (Kruskal-Wallis test for continuous variables, Chi-square test for categorical variables, Cox regression for univariate and multivariable models), incorporating alloHCT as a time-dependent covariate | ||
| 520 | |a RESULTS: Among 3234 patients achieving CR1, 7.8% harbored IDH1 mutations (36% R132C and 47% R132H) and 10.9% carried IDH2 mutations (77% R140Q and 19% R172K). 852 patients underwent alloHCT in CR1. Within the alloHCT group, 6.2% had an IDH1 mutation (43.4% R132C and 41.4% R132H) and 10% were characterized by an IDH2 mutation (71.8% R140Q and 24.7% R172K). Variants IDH1 R132C and IDH2 R172K showed a significant benefit from alloHCT for OS (p = .017 and p = .049) and RFS (HR = 0.42, p = .048 and p = .009) compared with chemotherapy only. AlloHCT in IDH2 R140Q mutated AML resulted in longer RFS (HR = 0.4, p = .002) | ||
| 520 | |a CONCLUSION: In this large as-treated analysis, we showed that alloHCT is able to overcome the negative prognostic impact of certain IDH mutational subclasses in first-line consolidation treatment and could pending prognostic validation, provide prognostic value for AML risk stratification and therapeutic decision making | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Acute myeloid leukemia | |
| 650 | 4 | |a Allogeneic hematopoietic cell transplantation | |
| 650 | 4 | |a IDH mutations | |
| 650 | 7 | |a Nucleophosmin |2 NLM | |
| 650 | 7 | |a 117896-08-9 |2 NLM | |
| 650 | 7 | |a IDH2 protein, human |2 NLM | |
| 650 | 7 | |a EC 1.1.1.41 |2 NLM | |
| 650 | 7 | |a Isocitrate Dehydrogenase |2 NLM | |
| 650 | 7 | |a EC 1.1.1.41 |2 NLM | |
| 650 | 7 | |a IDH1 protein, human |2 NLM | |
| 650 | 7 | |a EC 1.1.1.42. |2 NLM | |
| 700 | 1 | |a Stasik, Sebastian |e verfasserin |4 aut | |
| 700 | 1 | |a Metzeler, Klaus H |e verfasserin |4 aut | |
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| 700 | 1 | |a Schliemann, Christoph |e verfasserin |4 aut | |
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| 700 | 1 | |a Rothenberg-Thurley, Maja |e verfasserin |4 aut | |
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| 700 | 1 | |a Krämer, Alwin |e verfasserin |4 aut | |
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