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Treatment of older patients with acute myeloid leukemia (AML): a Canadian consensus.

ABSTRACT: Patients over age 60 comprise the majority of those diagnosed with acute myeloid leukemia (AML), but treatment approaches in this population are variable, with many uncertainties and controversies. Our group conducted a literature review to summarize the latest information and to develop a consensus document with practical treatment recommendations. We addressed five key questions: selection criteria for patients to receive intensive induction chemotherapy; optimal induction and post-remission regimens; allogeneic hematopoietic stem cell transplantation (HSCT); treatment of patients not suitable for induction chemotherapy; and treatment of patients with prior hematological disorders or therapy-related AML. Relevant literature was identified through a PubMed search of publications from 1991 to 2012. Key findings included the recognition that cytogenetics and molecular markers are major biologic determinants of treatment outcomes in the older population, both during induction therapy and following HSCT. Although disease-specific and patient-specific risk factors for poor outcomes are more common in the older population, age is not in itself sufficient grounds for withholding established treatments, including induction and consolidation chemotherapy. The role of HSCT and use of hypomethylating agents are discussed. Finally, suggested treatment algorithms are outlined, based on these recommendations.

SUBMITTER: Brandwein JM

PROVIDER: S-EPMC3649813 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Treatment of older patients with acute myeloid leukemia (AML): a Canadian consensus.

Brandwein Joseph M JM Geddes Michelle M Kassis Jeannine J Kew Andrea K AK Leber Brian B Nevill Thomas T Sabloff Mitchell M Sandhu Irwindeep I Schuh Andre C AC Storring John M JM Ashkenas John J

American journal of blood research 20130505 2

Patients over age 60 comprise the majority of those diagnosed with acute myeloid leukemia (AML), but treatment approaches in this population are variable, with many uncertainties and controversies. Our group conducted a literature review to summarize the latest information and to develop a consensus document with practical treatment recommendations. We addressed five key questions: selection criteria for patients to receive intensive induction chemotherapy; optimal induction and post-remission r ...[more]

PMID: 23675565

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Project description:BackgroundOlder patients (≥ 60 years) with acute myeloid leukemia (AML) often have multiple, sequentially acquired, somatic mutations that drive leukemogenesis and are associated with poor outcome. Beat AML is a Leukemia and Lymphoma Society-sponsored, multicenter umbrella study that algorithmically segregates AML patients based upon cytogenetic and dominant molecular abnormalities (variant allele frequencies (VAF) ≥ 0.2) into different cohorts to select for targeted therapies. During the conception of the Beat AML design, a historical dataset was needed to help in the design of the genomic algorithm for patient assignment and serve as the basis for the statistical design of individual genomic treatment substudies for the Beat AML study.MethodsWe classified 563 newly diagnosed older AML patients treated with standard intensive chemotherapy on trials conducted by Cancer and Leukemia Group B based on the same genomic algorithm and assessed clinical outcomes.ResultsOur classification identified core-binding factor and NPM1-mutated/FLT3-ITD-negative groups as having the best outcomes, with 30-day early death (ED) rates of 0 and 20%, respectively, and median overall survival (OS) of > 1 year and 3-year OS rates of ≥ 20%. All other genomic groups had ED rates of 17-42%, median OS ≤ 1 year and 3-year OS rates of ≤ 15%.ConclusionsBy classifying patients through this genomic algorithm, outcomes were poor and not unexpected from a non-algorithmic, non-dominant VAF approach. The exception is 30-day ED rate typically is not available for intensive induction for individual genomic groups and therefore difficult to compare outcomes with targeted therapeutics. This Alliance data supported the use of this algorithm for patient assignment at the initiation of the Beat AML study. This outcome data was also used for statistical design for Beat AML substudies for individual genomic groups to determine goals for improvement from intensive induction and hopefully lead to more rapid approval of new therapies. Trial registration ClinicalTrials.gov Identifiers: NCT00048958 (CALGB 8461), NCT00900224 (CALGB 20202), NCT00003190 (CALGB 9720), NCT00085124 (CALGB 10201), NCT00742625 (CALGB 10502), NCT01420926 (CALGB 11002), NCT00039377 (CALGB 10801), and NCT01253070 (CALGB 11001).

Project description:BACKGROUND: Children with Down syndrome (DS) are at high risk of infectious toxicity when treated with acute lymphoblastic leukemia chemotherapy protocols optimized in children without DS. Our objective was to determine if children with DS and acute myeloid leukemia (AML) have a different risk of infection when treated with chemotherapy protocols developed for children with DS compared to AML treatment protocols developed for children without DS. METHODS: We conducted a retrospective, population-based cohort study that included DS children???18 years of age with de novo, non-M3 AML diagnosed between January 1995 and December 2004, and treated at 15 Canadian centers. Patients were monitored for infection from initiation of AML treatment until recovery from the last cycle of chemotherapy, conditioning for hematopoietic stem cell transplantation, relapse, persistent disease or death (whichever occurred first). Trained research associates abstracted all information from each site. RESULTS: There were 31 children with DS included; median age was 1.7 (range 0.1-11.1) years. Eleven were treated according to a DS-specific protocol while 20 were treated with non-DS specific protocols. A total of 157 courses of chemotherapy were delivered. Microbiologically documented sterile site infection occurred in 11.9% and 14.3% of DS-specific and non-DS specific AML treatment courses respectively. Sepsis was rare and there were no infection-related deaths. In multiple regression, treatment with a DS-specific protocol was independently associated with a reduction in microbiologically documented sterile site infection (adjusted odds ratio (OR) 0.65, 95% confidence interval (CI) 0.42-0.99; P?=?0.044), and clinically documented infection (adjusted OR 0.36, 95% CI 0.14-0.91; P?=?0.031) but not bacteremia (adjusted OR 0.73, 95% CI 0.44-1.22; P?=?0.231). CONCLUSIONS: Our study suggests that children with DS do not experience excessive infectious toxicity during treatment for AML compared to children without DS. Incorporation of DS-specific AML treatment protocols is associated with a more favorable infection profile for children with DS-AML.

Dataset Information

Treatment of older patients with acute myeloid leukemia (AML): a Canadian consensus.

Publications

Treatment of older patients with acute myeloid leukemia (AML): a Canadian consensus.

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