Results of intensive chemotherapy in 998 patients age 65 years or older with acute myeloid leukemia or high‐risk myelodysplastic syndrome:

Abstract

BACKGROUNDElderly patients (age ≥ 65 years) with acute myeloid leukemia (AML) generally have a poor prognosis. AML‐type therapy results are often derived from studies in younger patients and may not apply to elderly AML. Many investigators and oncologists advocate, at times, only supportive care or frontline single agents, Phase I–II studies, low‐intensity regimens, or ‘targeted’ therapies. However, baseline expectations for outcomes of elderly AML with ‘standard’ AML‐type therapy are not well defined. The aim was to develop prognostic models for complete response (CR), induction (8‐week) mortality, and survival rates in elderly AML, which would be used to advise oncologists and patients of expectations with standard AML type therapy, and to establish baseline therapy results against which novel strategies would be evaluated.METHODSA total of 998 patients age ≥ 65 years with AML or high‐risk myelodysplastic syndrome (> 10% blasts) treated with intensive chemotherapy between 1980 and 2004 were analyzed. Univariate and multivariate analyses of prognostic factors associated with CR, induction (8‐week) mortality, and survival used standard methods.RESULTSThe overall CR rate was 45% and induction mortality 29%. Multivariate analysis of prognostic factors identified consistent independent poor prognostic factors for CR, 8‐week mortality, and survival. These included age ≥ 75 years, unfavorable karyotypes (often complex), poor performance (3–4 ECOG [Eastern Cooperative Oncology Group]), longer duration of antecedent hematologic disorder, treatment outside the laminar airflow room, and abnormal organ functions. Patients could be divided into: 1) a favorable group (about 20% of patients) with expected CR rates above 60%, induction mortality rates of 10%, and 1‐year survival rates above 50%; 2) an intermediate group (about 50–55% of patients) with expected CR rates of 50%, induction mortality rates of 30%, and 1‐year survival rates of 30%; and 3) an unfavorable risk group (about 25–30% of patients) with expected CR rates of less than 20%, induction mortality rates above 50%, and 1‐year survival rates of less than 10%.CONCLUSIONSPrognostic models, based on standard readily available baseline characteristics, were developed for elderly patients with AML, which may assist in therapeutic and investigational decisions. These predictive models, based on a retrospective analysis, will require validation in independent study groups. Cancer 2006. © 2006 American Cancer Society.

Nonbiological factors affecting survival in younger patients with acute myeloid leukemia

“…In addition, comorbidities and performance status, parameters not captured in SEER, are more likely to influence survival in older patients. 29 For each individual case, we extracted age, sex, race/ ethnicity category (REC) (Hispanic vs non-Hispanic), year of diagnosis, ICD-O-3 code, county of residence, marital status, insurance status, median household income in the county of residence, percentage of adult individuals with at least a bachelor's degree in the county of residence, duration of follow-up, and vital status. Information regarding chemotherapy is not routinely released by SEER.…”

Consensus-based definition of unfitness to intensive and non-intensive chemotherapy in acute myeloid leukemia: a project of SIE, SIES and GITMO group on a new tool for therapy decision making

“…13 The performance status at AML presentation is associated with mortality within 30 days from induction. 1,14 In the panelists' opinion, making a realistic judgment about patient's unfitness requires a careful performance status reassessment after adequate intensive supportive treatment. The threshold of performance status chosen for defining unfitness to intensive chemotherapy was a value 42 and the decision was in accordance with the results of the literature.…”

Acute myeloid leukemia—Major progress over four decades and glimpses into the future

“…In our historical experience of AML therapy in older patients, the CR rates were 40-50%, the median survivals 4-6 months, and 1-year survival rates <30% [109,110]. The 4-8 week mortality rates were 26-36%.…”

“…A multivariate analysis identified independent adverse factors predictive of early mortality with intensive chemotherapy: older age (75 years and older); adverse chromosomal abnormalities; presence of antecedent hematologic disorders; poor performance status; high creatinine levels; and whether the patient is treated in a nonprotected environment. The expected 8-week mortality was 10-19% with the presence of 0-1 adverse factors and 36-65% with the presence of 2-5 adverse factors [109]. In the 1990s, faced with the poor results of intensive chemotherapy, investigators proposed that patients unfit for intensive chemotherapy (expected high early mortality) would be considered for investigational approaches including low-intensity therapy, epigenetic therapy, or targeted therapies (monoclonal antibodies; more recently targeted therapies with FLT3 inhibitors and IDH 1/2 inhibitors).…”

“…Hence, there is a need for objective assessments of early mortality (to guide the treatment choice). At our institution, patients are categorized according to their predicted early mortality (based on the multivariate-derived chemotherapy prognostic models) [109,110]. If the expected 4-8 week mortality is <10%, they are offered intensive chemotherapy.…”