Predictive Model for Infection Risk in Myelodysplastic Syndromes, Acute Myeloid Leukemia, and Chronic Myelomonocytic Leukemia Patients Treated With Azacitidine; Azacitidine Infection Risk Model: The Polish Adult Leukemia Group Study

Clin Lymphoma Myeloma Leuk. 2019 May;19(5):264-274.e4. doi: 10.1016/j.clml.2019.01.002. Epub 2019 Jan 23.

Abstract

Background: Myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML), and acute myeloid leukemia (AML) patients, including those treated with azacitidine, are at increased risk for serious infections. The aim of our study was to identify patients with higher infectious risk at the beginning of azacitidine treatment.

Patients and methods: We performed a retrospective evaluation of 298 MDS/CMML/AML patients and included in the analysis 232 patients who completed the first 3 cycles of azacitidine therapy or developed Grade III/IV infection before completing the third cycle.

Results: Overall, 143 patients (62%) experienced serious infection, and in 94 patients (41%) infection occurred within the first 3 cycles. The following variables were found to have the most significant effect on the infectious risk in multivariate analysis: red blood cell transfusion dependency (odds ratio [OR], 2.38; 97.5% confidence interval [CI], 1.21-4.79), neutropenia <0.8 × 109/L (OR, 3.03; 97.5% CI, 1.66-5.55), platelet count <50 × 109/L (OR, 2.63; 97.5% CI, 1.42-4.76), albumin level <35 g/dL (OR, 2.04; 97.5% CI, 1.01-4.16), and Eastern Cooperative Oncology Group performance status ≥2 (OR, 2.19; 97.5% CI, 1.40-3.54). Each of these variables is assigned 1 point, and the combined score represents the proposed Azacitidine Infection Risk Model. The infection rate in the first 3 cycles of therapy in lower-risk (0-2 score) and higher-risk (3-5 score) patients was 25% and 73%, respectively. The overall survival was significantly reduced in higher-risk patients compared with the lower-risk cohort (8 vs. 29 months).

Conclusion: We selected a subset with high early risk for serious infection and worse clinical outcome among patients treated with azacitidine.

Keywords: Acute leukemia; Azacitidine; Chronic myelomonocytic leukemia; Infections; Myelodysplastic syndromes.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anti-Bacterial Agents / therapeutic use
  • Antibiotic Prophylaxis / methods
  • Antifungal Agents / therapeutic use
  • Antimetabolites, Antineoplastic / adverse effects*
  • Azacitidine / adverse effects*
  • Bacterial Infections / chemically induced
  • Bacterial Infections / epidemiology*
  • Bacterial Infections / immunology
  • Bacterial Infections / prevention & control
  • Female
  • Health Status Indicators
  • Humans
  • Kaplan-Meier Estimate
  • Leukemia, Myeloid, Acute / drug therapy*
  • Leukemia, Myeloid, Acute / immunology
  • Leukemia, Myeloid, Acute / mortality
  • Leukemia, Myelomonocytic, Chronic / drug therapy*
  • Leukemia, Myelomonocytic, Chronic / immunology
  • Leukemia, Myelomonocytic, Chronic / mortality
  • Male
  • Middle Aged
  • Mycoses / chemically induced
  • Mycoses / epidemiology*
  • Mycoses / immunology
  • Mycoses / prevention & control
  • Myelodysplastic Syndromes / drug therapy*
  • Myelodysplastic Syndromes / immunology
  • Myelodysplastic Syndromes / mortality
  • Poland / epidemiology
  • Proportional Hazards Models
  • Retrospective Studies
  • Risk Assessment / methods
  • Treatment Outcome

Substances

  • Anti-Bacterial Agents
  • Antifungal Agents
  • Antimetabolites, Antineoplastic
  • Azacitidine