{"doi":"10.1002/ajh.26188","title":"Pretreatment clinical and genetic factors predict early post‐treatment mortality in fit <scp>AML</scp> patients following induction","abstract":"Survival after intensive induction chemotherapy for patients with newly diagnosed, previously untreated acute myeloid leukemia (AML) is limited by both treatment-related toxicity and disease resistance to chemotherapy. Early post-treatment mortality, defined as death within 2 months of treatment initiation, ranges from less than 10% to greater than 50%, depending on the patient population, and has been associated with older age and poor performance status, secondary AML, higher hematopoietic cell transplantation comorbidity index score, unfitness by Ferrara criteria,1, 2 and abnormal pretreatment laboratory values.3 Limitations of prior analyses include a selective focus on either early post-treatment mortality or on overall survival (OS), an absence of genetic annotation, and reliance on selected clinical trial cohorts which may not be broadly representative of treated AML patients. Moreover, early mortality remains a consequential problem even among patients predicted to have lower risk based on Ferrara criteria.2 In order to identify distinct factors associated with early post-treatment mortality and with OS, we analyzed an unselected, consecutive series of generally fit, previously untreated adult AML patients treated with intensive induction chemotherapy. We identified 290 adult patients who received intensive induction chemotherapy as the first treatment for newly diagnosed AML at our institution from 2014 to 2019. Patients received “high-dose” anthracycline (60–90 mg/m2 for 3 days), “standard-dose” cytarabine (100–200 mg/m2 for 7 days), and may have received an additional agent, in some cases on a clinical trial (eg FLT3 inhibitor). We collected pretreatment clinical, pathology, and laboratory data, and annotated clinical outcomes. Gene mutations were determined at the time of diagnosis using targeted next-generation sequencing of genes recurrently mutated in AML. We used univariate and multivariate regression models to identify associations between pretreatment clinical or genetic factors and clinical outcomes, including the proportion of patients alive at 60 days, the proportion of patients in remission at 60 days, OS landmarked at 60 days, and relapse-free survival (RFS) landmarked at 60 days (Supplementary Methods). The median age at diagnosis was 61 years (range 19–76); 15% of patients had clinically defined secondary AML and 14% had therapy-related AML (Table S1). Only 2 of 290 patients (0.7%) were identified as unfit by Ferrara criteria.1 CR was reported in 72% (209/290) of patients, of whom 194 had CR with hematologic recovery and 15 had CR with incomplete hematologic recovery. For patients surviving past the first 60 days, median OS and RFS, both landmarked at day 60, were 33.9 months and 28.0 months, respectively. In total, 24 of 290 (8%) patients died within 60 days of starting induction chemotherapy (Figure 1A). Among these patients, median time to death from the start of induction was 25 days; 17% of patients died within the first 15 days, and 71% died within the first 30 days (Figure 1B). Shock (predominantly septic shock) was the most common primary cause of death (42%), followed by respiratory failure (21%) and stroke (hemorrhagic or ischemic; 17%) (Figure 1A). We first examined factors associated with early post-treatment mortality, defined as death within 60 days of AML induction chemotherapy initiation (Figure S1A). In a multivariable logistic regression model, pretreatment albumin <3 g/dL (OR 5.00, p = .009), pretreatment LDH ≥600 U/L (OR 4.19, p = .006), and mutations in RUNX1 (OR 5.31, p = .007) or TET2 (OR 3.03, p = .025) were independently associated with death within 60 days (Figure 1C). Factors not independently associated with early mortality included older age (<60 vs 60 years or older), clinical ontogeny (secondary or treatment-related AML), complex karyotype, and pretreatment blood counts. We next examined factors associated with survival in those alive at 60 days. We generated a multivaria","journal":"American Journal of Hematology","year":2021,"id":205280,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9572,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":459492,"name":"Yael Flamand","orcid":"0000-0003-2150-6732","position":1,"is_corresponding":false},{"id":788219,"name":"Rahul S. Vedula","orcid":"0000-0003-0486-3981","position":2,"is_corresponding":false},{"id":788220,"name":"Jurjen Versluis","orcid":"0000-0003-2372-1663","position":3,"is_corresponding":false},{"id":788603,"name":"Anne Charles","orcid":null,"position":4,"is_corresponding":false},{"id":788604,"name":"Kevin Copson","orcid":null,"position":5,"is_corresponding":false},{"id":34476,"name":"Richard M. Stone","orcid":"0000-0002-7526-2633","position":6,"is_corresponding":false},{"id":284245,"name":"Daniel J. DeAngelo","orcid":"0000-0001-7865-2306","position":7,"is_corresponding":false},{"id":3266,"name":"Donna Neuberg","orcid":"0000-0003-2566-3145","position":8,"is_corresponding":false},{"id":489016,"name":"R. Coleman Lindsley","orcid":"0000-0001-9822-806X","position":9,"is_corresponding":false},{"id":565017,"name":"Marlise R. Luskin","orcid":"0000-0002-5781-4529","position":10,"is_corresponding":false},{"id":289515,"name":"J. Erika Haydu","orcid":"0000-0003-2463-0560","position":0,"is_corresponding":true}],"reference_count":6,"raw_metadata":null,"created_at":"2026-07-18T23:51:30.197308Z","pmid":"33837971","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}