Early Mortality and Infectious Complications During Induction Therapy in Adults with Acute Lymphoblastic Leukemia

Abstract

Acute lymphoblastic leukaemia is treated as a low-risk setting for invasive fungal infection, and antifungal prophylaxis is accordingly not recommended. Direct comparison shows patients receiving no prophylaxis having the same fungal infection rate as myeloid leukaemia patients who do receive it, despite less than half the duration of neutropenia. Objectives: To review the published evidence on infectious complications during induction therapy for adult acute lymphoblastic leukaemia: how often they occur, which organisms are responsible, when in the course they cluster, which patients are at risk, and whether prophylaxis achieves what is assumed of it.
Material and Methods: Narrative review of prospective and retrospective cohorts, cooperative group trial analyses and comparative studies indexed in PubMed and the major haematology and infectious disease journals. Studies were eligible if they reported the incidence, microbiology, timing or outcome of infection during induction therapy in a defined adult acute lymphoblastic leukaemia population. No new patient data were generated and no patients were recruited; every estimate quoted is one published by the original investigators. Results: Among 240 adults treated on a paediatric-inspired protocol across 18 centres, 145 (60 per cent) experienced at least one infectious episode. Bacterial infections accounted for 74.3 per cent, viral for 13.9, fungal for 10.1 and Pneumocystis for 1.7 per cent, with the bloodstream the commonest site and pneumonia in 14.6 per cent, half of it fungal. Infection clustered in the first course, affecting 40.5 per cent of patients, and invasive fungal infection occurred in 12.5 per cent.
Mortality from infection was 3.3 per cent. Antibacterial, antiviral, antifungal and anti-Pneumocystis prophylaxis were variably given and none was associated with a significant reduction in infection rate. In a separate comparison of 552 chemotherapy episodes, invasive fungal infection occurred in 8.1 per cent of lymphoblastic episodes without antimould prophylaxis against 5.9 per cent of myeloid episodes with it (p = 0.856), despite median neutropenia of 8 against 18 days.
 : The assumption that shorter neutropenia makes lymphoblastic induction a low-risk setting for fungal infection is not supported by direct comparison. Age above 65 is the dominant risk factor, and observational data do not show benefit from the prophylaxis currently given. Abbreviations: ALL – Acute Lymphoblastic Leukaemia, AML – Acute Myeloid Leukaemia, Ph – Philadelphia Chromosome, IFI – Invasive Fungal Infection, BSI – Bloodstream Infection, PJ – Pneumocystis jirovecii, C1 – First Chemotherapy Course, CR – Complete Remission, CCI – Charlson Comorbidity Index, TRM – Treatment-Related Mortality, IRM – Induction-Related Mortality, HSCT – Haematopoietic Stem Cell Transplantation.