title: Prediction of adverse events during intensive induction chemotherapy for acute myeloid leukemia or high-grade myelodysplastic syndromes.
abstract: 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 pretreatment characteristics relate to early adverse outcomes in such patients, studying 205 consecutive individuals 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 treatment 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/molecular risk, and performance status, the risk of fever, documented infection, or bacteremia was 1.87 (95% confidence interval: 1.04-3.34; P=0.04)-fold, 4.95 (2.20-11.16; P<0.001)-fold, and 3.14 (0.99-9.98; P=0.05)-fold higher in patients with initial grade 4 neutropenia. 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.
authors.affiliation: Department of Medicine, Residency Program, University of Washington, Seattle, Washington.
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Buckley
authors.forename: Megan
authors.initials: M
authors.lastname: Othus
authors.forename: Vladimir
authors.initials: V
authors.lastname: Vainstein
authors.forename: Janis L
authors.initials: JL
authors.lastname: Abkowitz
authors.forename: Elihu H
authors.initials: EH
authors.lastname: Estey
authors.forename: Roland B
authors.initials: RB
authors.lastname: Walter
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D016470:Bacteremia / Q000453:epidemiology / Q000209:etiology; D001772:Blood Cell Count; D003422:Critical Care / Q000706:statistics & numerical data; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects; D003630:Daunorubicin / Q000008:administration & dosage / Q000009:adverse effects; D064147:Febrile Neutropenia / Q000139:chemically induced* / Q000150:complications / Q000188:drug therapy / Q000453:epidemiology / Q000517:prevention & control; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D006801:Humans; D016867:Immunocompromised Host; D007239:Infections / Q000453:epidemiology / Q000209:etiology; D053208:Kaplan-Meier Estimate; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy*; D008297:Male; D015122:Mercaptopurine / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy*; D016016:Proportional Hazards Models; D012074:Remission Induction; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D003561:Cytarabine; D016179:Granulocyte Colony-Stimulating Factor; D003520:Cyclophosphamide; D015122:Mercaptopurine; D003630:Daunorubicin