Page 55 - Haematologica Vol. 110 - January 2025

ARTICLE - Acute Lymphoblastic Leukemia
Immunoglobulin prophylaxis prevents hospital admissions for fever in pediatric acute lymphoblastic leukemia: results of a multicenter randomized trial
Kirsten A. Thus,1 Hester A. de Groot-Kruseman,1 Pauline Winkler-Seinstra,1 Marta Fiocco,1-3 Heidi Segers,4 Cor van den Bos,1,5 Inge M. van der Sluis,1,6 Wim J. E. Tissing,1,7 Margreet A. Veening,1,8 Christian Michel Zwaan,1,6 Cornelis M. van Tilburg,9-13 Rob Pieters1 and Marc Bierings1
1Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands; 2Mathematical Institute Leiden University, Leiden University, Leiden, the Netherlands; 3Department of Biomedical Data Science, Section Medical Statistics, Leiden University Medical Center, Leiden, the Netherlands; 4Department of Pediatric Hemato-Oncology, University Hospitals Leuven, Leuven, Belgium; 5Department of Pediatric Oncology, Emma Children’s Hospital, Amsterdam UMC, Amsterdam, the Netherlands; 6Department of Pediatric Oncology, Erasmus MC-Sophia Children’s Hospital, Rotterdam, the Netherlands; 7Department of Pediatric Oncology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; 8Emma Children’s Hospital, Amsterdam UMC, Vrije Universiteit Amsterdam, Pediatric Oncology, Cancer Center Amsterdam, Amsterdam, the Netherlands; 9Hopp Children’s Cancer Center Heidelberg (KiTZ), Heidelberg, Germany; 10Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany; 11Department of Pediatric Oncology, Hematology, Immunology and Pulmonology, Heidelberg University Hospital, Heidelberg, Germany; 12German Cancer Consortium (DKTK), Heidelberg, Germany and 13National Center for Tumor Diseases (NCT), Heidelberg, Germany
Abstract
Infections lead to substantial morbidity during the treatment of acute lymphoblastic leukemia (ALL) in which the adaptive immune system is severely affected, leading to declining serum immunoglobulin levels. We performed a trial to investigate whether intravenous immunoglobulin (IVIG) prophylaxis in pediatric patients with ALL could prevent admissions for fever. This randomized controlled trial was a subtrial of the national Dutch multicenter ALL study. Patients aged 1-19 years with medium-risk ALL were randomized into two groups receiving either IVIG prophylaxis (0.7 g/kg IVIG given every 3 weeks, starting on day 22 after diagnosis) or well-defined standard of care (control group). Between October 2012 and March 2019, 91 (51%) patients were randomly assigned to IVIG prophylaxis and 86 (49%) to the control arm. In the IVIG prophylaxis group there were 206 admissions for fever versus 271 in the control group (P=0.011). IVIG prophylaxis was not associated with bacteremia. However, there were significantly fewer admissions for fever with negative blood cultures in the IVIG prophy- laxis group than in the control group (113 vs. 200, P<0.001). The difference in number of admissions for fever was observed specifically during maintenance treatment (100 vs. 166, P<0.001) resulting in fewer courses of antibiotic treatment (78 vs. 137, P<0.001) and fewer cases of chemotherapy adaptation (72 vs. 134, P<0.001). In conclusion, in pediatric patients with medium-risk ALL, IVIG prophylaxis was associated with significantly fewer admissions for fever with negative blood cultures during maintenance treatment, resulting in fewer courses of antibiotic treatment and fewer chemotherapy adaptations.
Introduction
Infections are an important cause of mortality and morbid- ity in pediatric patients with acute lymphoblastic leukemia (ALL). In pediatric patients with hematologic malignancies, approximately 20% of deaths are related to treatment, with infection being responsible for more than half of
these deaths.1-3 Alongside the mortality risk, there is sub- stantial morbidity from fever, often leading to admissions to hospital. Moreover, infections may lead to interruption of leukemia treatment, and therefore potentially enhance the risk of relapses.4
During the treatment of ALL, the adaptive immune system is severely affected. This is manifested by persistently low
Haematologica | 110 January 2025
47
Correspondence: M. Bierings m.b.bierings-2@prinsesmaximacentrum.nl
Received: Accepted: Early view:
March 8, 2024. July 29, 2024. August 8, 2024.
https://doi.org/10.3324/haematol.2024.285428
©2025 Ferrata Storti Foundation Published under a CC BY-NC license