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Predicting Mortality Outcomes After Intensive Chemotherapy for AML


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In a single-institution study reported in the Journal of Clinical Oncology, Palmieri et al found that the Ferrara criteria for determining fitness for intensive chemotherapy—a set of consensus criteria proposed by a panel of experts from the Italian Society of Hematology, Italian Society of Experimental Hematology, and Italian Group for Bone Marrow Transplantation—accurately predicted the probability of short-term mortality in patients receiving intensive therapy for acute myeloid leukemia (AML). 

Study Details

The study involved application of the Ferrara criteria to data from 655 adults with AML or other high-grade myeloid neoplasms receiving curative-intent induction or reinduction chemotherapy at Fred Hutchinson Cancer Research Center between January 2006 and January 2020. Treatment consisted of 7 days of standard-dose cytarabine and 3 days of an anthracycline (“7 + 3”) CLAG-M (cladribine, high-dose cytarabine, granulocyte colony–stimulating factor, and mitoxantrone) or reduced-dose CLAG-M.

Patients were categorized as Ferrara-fit (F-fit) or unfit (F-unfit).

Key Findings

Among the 655 patients, 197 (30%) met at least one of the criteria defining unfitness for intensive chemotherapy (F-unfit).

KEY POINTS

  • Median overall survival was 36.8 months among F-fit patients vs 4.8 months among F-unfit patients.
  • Ferrara unfitness assessment alone was more accurate in predicting day 28 and day 100 mortality than a treatment-related mortality score previously developed by the investigators.

Median overall survival was 36.8 months among F-fit patients vs 4.8 months among F-unfit patients (P < .001). Among patients with sufficient follow-up data, a total of 7 (2%) of 457 F-fit patients vs 28 (14%) of 196 F-unfit patients died within 28 days; 22 (5%) of 444 F-fit patients vs 78 (42%) of 185 F-unfit patients died within 100 days of chemotherapy initiation.

Ferrara unfitness assessment alone was more accurate in predicting day 28 and day 100 mortality than a treatment-related mortality score previously developed by the investigators. Receiver operating characteristic area under the curve values were 0.76 vs 0.66 and 0.79 vs 0.62, respectively.

Models adding additional covariates—including performance status and albumin level—to the Ferrara unfitness assessment improved the prediction of day 28 and day 100 mortality, producing area under the curve values as high as 0.84 to 0.85. Models including age, albumin level, disease risk, disease stage, and treatment-related mortality score improved the ability of the Ferrara unfitness assessment to predict overall survival, producing a c-statistic as high as 0.75.

The investigators concluded, “Ferrara unfitness criteria provide a good prediction tool for shorter-term mortality after intensive AML chemotherapy. Our data may serve as a benchmark for expected outcomes with intensive chemotherapy in F-fit and F-unfit patients.”

Roland B. Walter, MD, PhD, MS, of the Clinical Research Division, Fred Hutchinson Cancer Research Center, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: For full disclosures of the study authors, visit ascopubs.org.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
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