Infectious complications after intensive chemotherapy with CLAG-M versus 7+3 for AML and other high-grade myeloid neoplasms

Leukemia. 2023 Feb;37(2):298-307. doi: 10.1038/s41375-022-01786-9. Epub 2022 Dec 12.

Abstract

Contemporary data on infections after intensive chemotherapy for acute myeloid leukemia (AML) are scarce. Cladribine, high-dose cytarabine, G-CSF, and dose-escalated mitoxantrone ("CLAG-M") may result in higher remission rates than standard-dose cytarabine plus anthracycline ("7 + 3") but may result in more infections. We compared moderate to severe infections occurring up to 90 days after the first induction cycle for AML or other high-grade myeloid neoplasms in patients receiving CLAG-M for newly diagnosed (n = 196) or relapsed/refractory disease (n = 131) or 7 + 3 for newly diagnosed disease (n = 115). For newly diagnosed disease, microbiologically documented infections were more frequent after CLAG-M compared to 7 + 3 (adjusted rate ratio, 1.65 [95% CI, 1.06-2.58]; P = 0.03), with a cumulative incidence of 27.8% and 16.5% by day 90, respectively. Patients receiving CLAG-M for relapsed/refractory disease had the highest cumulative incidence of 50.7%. Bacterial bloodstream infections were the most frequent followed by respiratory tract infections. Among 29 patients (7%) who died, infection was a primary or contributing cause of death in 59%. These data indicate that infections continue to cause substantial morbidity in patients treated for AML, especially those treated for relapsed/refractory disease, and are more common with newer, more myelosuppressive regimens such as CLAG-M. Improved strategies for infection prevention are needed.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anthracyclines / administration & dosage
  • Anthracyclines / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols* / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • Bacterial Infections / chemically induced
  • Bacterial Infections / etiology
  • Cladribine / administration & dosage
  • Cladribine / adverse effects
  • Cytarabine / administration & dosage
  • Cytarabine / adverse effects
  • Granulocyte Colony-Stimulating Factor / administration & dosage
  • Granulocyte Colony-Stimulating Factor / adverse effects
  • Humans
  • Infections* / chemically induced
  • Infections* / etiology
  • Leukemia, Myeloid / drug therapy
  • Leukemia, Myeloid / pathology
  • Leukemia, Myeloid, Acute* / drug therapy
  • Leukemia, Myeloid, Acute* / pathology
  • Mitoxantrone* / administration & dosage
  • Mitoxantrone* / adverse effects
  • Respiratory Tract Infections / chemically induced
  • Respiratory Tract Infections / etiology
  • Sepsis / chemically induced
  • Sepsis / etiology
  • Sepsis / microbiology

Substances

  • Cladribine
  • Cytarabine
  • Granulocyte Colony-Stimulating Factor
  • Mitoxantrone
  • Anthracyclines

Supplementary concepts

  • CLAG protocol