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A clinical prediction model identifies a subgroup with inferior survival within intermediate risk acute myeloid leukemia.

ABSTRACT: Intermediate risk acute myeloid leukemia (AML) comprises around 50% of AML patients and is featured with heterogeneous clinical outcomes. The study aimed to generate a prediction model to identify intermediate risk AML patients with an inferior survival. We performed targeted next generation sequencing analysis for 121 patients with 2017 European LeukemiaNet-defined intermediate risk AML, revealing 122 mutated genes, with 24 genes mutated in > 10% of patients. A prognostic nomogram characterized by white blood cell count ≥10×10⁹/L at diagnosis, mutated DNMT3A and genes involved in signaling pathways was developed for 110 patients who were with clinical outcomes. Two subgroups were identified: intermediate low risk (ILR; 43.6%, 48/110) and intermediate high risk (IHR; 56.4%, 62/110). The model was prognostic of overall survival (OS) and relapse-free survival (RFS) (OS: Concordance index [C-index]: 0.703, 95%CI: 0.643-0.763; RFS: C-index: 0.681, 95%CI 0.620-0.741), and was successfully validated with two independent cohorts. Allogeneic hematopoietic stem cell transplantation (alloHSCT) reduced the relapse risk of IHR patients (3-year RFS: alloHSCT: 40.0±12.8% vs. chemotherapy: 8.6±5.8%, P= 0.010). The prediction model can help identify patients with an unfavorable prognosis and refine risk-adapted therapy for intermediate risk AML patients.

SUBMITTER: Hu X

PROVIDER: S-EPMC8247394 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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A clinical prediction model identifies a subgroup with inferior survival within intermediate risk acute myeloid leukemia.

Hu Xiaoxia X Wang Bianhong B Chen Qi Q Huang Aijie A Fu Weijia W Liu Lixia L Zhang Ying Y Tang Gusheng G Cheng Hui H Ni Xiong X Gao Lei L Chen Jie J Chen Li L Zhang Weiping W Yang Jianmin J Cao Shanbo S Yu Li L Wang Jianmin J

Journal of Cancer 20210611 16

Intermediate risk acute myeloid leukemia (AML) comprises around 50% of AML patients and is featured with heterogeneous clinical outcomes. The study aimed to generate a prediction model to identify intermediate risk AML patients with an inferior survival. We performed targeted next generation sequencing analysis for 121 patients with 2017 European LeukemiaNet-defined intermediate risk AML, revealing 122 mutated genes, with 24 genes mutated in > 10% of patients. A prognostic nomogram characterized ...[more]

PMID: 34234861

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Project description:ImportanceLeukemia cutis (LC) is an important yet understudied extramedullary manifestation of leukemia. Previous reports have suggested poor prognosis for patients with LC, but these reports have largely consisted of descriptive studies with a limited number of patients.ObjectivesTo identify patient factors associated with LC and characterize the association of LC with the course of acute myeloid leukemia (AML).Design, setting, and participantsThis retrospective, matched-cohort study included 1683 patients with AML diagnosed from January 1, 2005, to April 1, 2017, with and without biopsy-proven LC seen at a single-center, tertiary care hospital in St Louis, Missouri. To specifically evaluate differences in survival, propensity scoring was used to match patients with AML with LC to patients with AML without LC off the logit of propensity score based on age, race/ethnicity, sex, and leukemia type. Kaplan-Meier methods were used to compare cumulative probability survival. Matched survival analysis was performed with extended Cox regression to determine factors associated with leukemia-specific and overall survival.Main outcomes and measuresLeukemia-specific survival and overall survival.ResultsA total of 1683 patients were reviewed, including 78 patients with biopsy-proven LC of the AML type and 1605 patients with AML without LC. A total of 62 of the patients with AML and LC (mean [SD] age, 58.2 [11.7] years; 33 [53.2%] male) were matched in a 1:3 ratio to 186 patients with AML without LC (mean [SD] age, 58.2 [13.5] years; 103 [55.4%] male). The 5-year survival among the 62 patients with AML with LC was 8.6%, shorter than the 28.3% among the 186 matched patients with AML without LC. Matched survival analysis revealed that patients with AML and LC compared with those without LC had hazard ratios of 2.06 (95% CI, 1.26-3.38; P = .004) for leukemia-specific death and of 1.66 (95% CI, 1.06-2.60; P = .03) for all-cause death. In addition, matched patients with LC had greater odds of extramedullary organ burden (odds ratio, 3.48; 95% CI, 1.72-7.05; P < .001).Conclusions and relevanceThe results suggest that the presentation of LC in patients with AML is associated with decreased overall survival and leukemia-specific survival. Patients with AML presenting with LC may require more intensive treatment and monitoring of their leukemic disease.

Dataset Information

A clinical prediction model identifies a subgroup with inferior survival within intermediate risk acute myeloid leukemia.

Publications

A clinical prediction model identifies a subgroup with inferior survival within intermediate risk acute myeloid leukemia.

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