Impact of reduction of therapy on infectious complications in childhood acute lymphoblastic leukemia

Abstract

Background: Infections are a major cause of morbidity and mortality in childhood acute lymphoblastic leukemia (ALL) and only limited information is available on infectious complications.

Patients and methods: We investigated infectious complications in 293 children during different treatment phases of the multicenter protocol COALL-06-97. We also evaluated whether therapy reduction in prognostically good risk patients receiving either the low risk or high risk treatment arm would lead to fewer infectious complications.

Results: Thirty of 293 patients had no infections; 263 patients had 682 infectious complications (median 2, range 1-9), five of them lethal. Two thirds of the infections occurred during periods of neutropenia. The most frequent infectious episodes were fever of unknown origin (FUO): 483/682 (70.8%), microbiologically documented infections (MDI): 100/682 (14.6%), (61 gram-positive, 36 gram-negative, 3 fungal isolates), and clinically documented infections (CDI): 99/682 (14.5%). With standard reinduction, 44% low risk and 57% high risk patients had infections versus 26% low risk and 38% high risk patients with reduced reinduction therapy (P < 0.01).

Conclusions: Most patients treated with intensive combination therapy for ALL experience one to several serious infections during treatment. The wide range in number of infectious episodes and the lack of infections in a small subset of patients in spite of uniform treatment suggest genetic as well as possibly environmental factors to have a role. Moderate reduction of chemotherapy may significantly reduce the rate of infectious episodes.