Graduation Date

Spring 5-9-2020

Document Type

Thesis

Degree Name

Master of Science (MS)

Programs

Medical Sciences Interdepartmental Area

First Advisor

James O. Armitage, MD

Second Advisor

Sarah A. Holstein, MD, PhD

Third Advisor

Ann Berger, PhD

Fourth Advisor

Christopher Wichman, PhD

Abstract

Integrating geriatric assessment for patient profiling and genetic profiling of leukemic cells represents an innovative approach to personalize therapy selection in older adults with acute myeloid leukemia (AML). We report results of a pre-planned interim analysis of a pragmatic phase II trial that utilized this strategy to personalize therapy. Patients ≥60 years with a new diagnosis of AML underwent geriatric assessment prior to initiation of treatment. Geriatric assessment of physical function, cognitive function and comorbidity burden were used to determine fitness for chemotherapy. Patients with good or intermediate-risk AML received intensive chemotherapy such as anthracycline and cytarabine (7+3) if determined to be fit. Patients with high-risk AML received low-intensity chemotherapy, or liposomal preparation of anthracycline and cytarabine (CPX 351) if they met the FDA approved indication and were fit. The pre-planned interim analysis results are based on the first 27 AML patients. Characteristics included a median age of 70 years (range 60-84 years), 56% female, and 96% white. Over half of the patients had ≥3 comorbidities, impairment in objective physical function or cognitive screen. Risk categories included adverse (64%), intermediate (16%), and good-risk AML (20%) (2017 European LeukemiaNet criteria). Three patients received intensive chemotherapy; other received low intensity chemotherapy. The median time from enrollment to treatment initiation was 2 days (range 0-9). Mortality at 30 days was 3.7% and at 90 days was 29.6%. In conclusion, our study results demonstrate feasibility of using geriatric assessment and genetic profiling of leukemia cells to personalize therapy selection in older adults with AML.

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