Prediction of adverse events during Intensive Induction chemotherapy for acute myeloid leukemia or high-grade myelodysplastic syndromes.

Publication Type:

Journal Article


American journal of hematology, Volume 89, Issue 4, p.423-8 (2014)


2014, Center-Authored Paper, Clinical Research Division, Flow Cytometry Core Facility, January 2014, Public Health Sciences Division, Research Trials Office Core Facility - Biostatistics Service, Shared Resources, Specimen Processing Core Facility


Intensive chemotherapy for newly diagnosed acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) is associated with significant treatment-related morbidity and mortality. Herein, we investigate how pre-treatment characteristics relate to early adverse outcomes in such patients, studying 205 consecutive patients receiving curative-intent induction chemotherapy with cytarabine and an anthracycline ("7+3"; n=175) or a "7+3"-like regimen (n=30). Among the entire cohort, baseline grade 4 neutropenia (i.e. absolute neutrophil count <500 cells/µL) was associated with development of fever (P=0.04), documented infection (P<0.0001), and bacteremia (P=0.002) but not requirement for intensive care unit-level care; after exclusion of the 30 patients who received "7+3"-like induction, baseline grade 4 neutropenia remained associated with documented infection (P<0.0001) and bacteremia (P=0.0005). Among patients achieving a complete remission with the initial course cycle, grade 4 neutropenia was associated with delayed neutrophil count recovery (P<0.0001). Low monocyte and lymphocyte counts at baseline were similarly associated with increased risk of documented infection or bacteremia. After adjustment for age, gender, disease type, cytogenetic risk, and performance status, the risk of documented infection or bacteremia was 2.51 (95% confidence interval: 1.59-3.96)-fold and 1.82 (1.04-3.19)-fold higher in patients with initial grade 4 neutropenia. There was no relationship between adverse events and age, gender, disease type, disease risk, anthracycline type/dose, or initial peripheral blood blast count. Together, our studies identify severe baseline neutropenia as a risk factor for infection-associated adverse events after induction chemotherapy and may provide the rationale for the risk-adapted testing of myeloid growth factor support in this high-risk AML/MDS patient subset.