Prediction of adverse events during intensive induction chemotherapy for acute myeloid leukemia or high-grade myelodysplastic syndromes

Am J Hematol. 2014 Apr;89(4):423-8. doi: 10.1002/ajh.23661. Epub 2014 Feb 24.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Bacteremia / epidemiology
  • Bacteremia / etiology
  • Blood Cell Count
  • Critical Care / statistics & numerical data
  • Cyclophosphamide / administration & dosage
  • Cyclophosphamide / adverse effects
  • Cytarabine / administration & dosage
  • Cytarabine / adverse effects
  • Daunorubicin / administration & dosage
  • Daunorubicin / adverse effects
  • Febrile Neutropenia / chemically induced*
  • Febrile Neutropenia / complications
  • Febrile Neutropenia / drug therapy
  • Febrile Neutropenia / epidemiology
  • Febrile Neutropenia / prevention & control
  • Female
  • Granulocyte Colony-Stimulating Factor / therapeutic use
  • Humans
  • Immunocompromised Host
  • Infections / epidemiology
  • Infections / etiology
  • Kaplan-Meier Estimate
  • Leukemia, Myeloid, Acute / drug therapy*
  • Male
  • Mercaptopurine / administration & dosage
  • Mercaptopurine / adverse effects
  • Middle Aged
  • Myelodysplastic Syndromes / drug therapy*
  • Proportional Hazards Models
  • Remission Induction
  • Retrospective Studies
  • Young Adult

Substances

  • Cytarabine
  • Granulocyte Colony-Stimulating Factor
  • Cyclophosphamide
  • Mercaptopurine
  • Daunorubicin

Supplementary concepts

  • 7+3 protocol