IVIG Prophylaxis Significantly Reduces Hospital Admissions for Fever in Pediatrics With ALL

In pediatric patients with medium-risk acute lymphoblastic leukemia (ALL), intravenous immunoglobulin (IVIG) prophylaxis was associated with significantly decreased admissions for fever with negative blood cultures during maintenance treatment, leading to fewer antibiotic treatment courses and fewer adaptations of chemotherapy, according to study results published in Haematologica.¹

Acute lymphoblastic leukemia can cause infections in patients during the course of their treatment. | Image Credit: © toeytoey | stock.adobe.com

Previous studies have investigated IVIG’s role as a tool to prevent infections in patients receiving arduous treatments for their cancer. One study found that supplementation with IVIG reduced the risk of infection in patients with multiple myeloma receiving teclistamab (Tecvayli; Janssen Biotech), especially when IVIG was administered quickly. Whether IVIG can have similar effects in a pediatric ALL population remains unknown, but its discovery is important, as infections can cause mortality in pediatric patients with ALL and can lead to interruptions in leukemia treatment, increasing the risk of relapse.^2,3

The current study investigators sought to investigate the role of IVIG prophylaxis in children with newly-diagnosed ALL, and they noted that the trial is the first multicenter, randomized trial to do so. IVIG’s status as an expensive treatment and the prospect of adverse events (AEs) following administration, along with its previously mentioned possible therapeutic effects, motivated the investigators to conduct the trial.¹

Primarily, the investigators evaluated the number of admissions among pediatric patients with ALL with fever. They also investigated the number of therapeutic antibiotic courses, number of admissions to an intensive care unit (ICU) due to fever, the 5-year cumulative incidence of relapse, disease-free survival (DFS), and overall survival (OS).¹

Ultimately, 165 patients fully adhered to the IVIG protocol for at least a year and were included in the analysis. AEs totaled 122 and were reported in 72 patients (76 in the IVIG prophylaxis group among 40 patients and 46 in the control group among 32 patients). However, only 4 serious AEs were considered possibly related to IVIG, though there were significantly more thromboses in the IVIG prophylaxis group than in the control group.¹

In the IVIG prophylaxis group, 206 patients were admitted for fever, compared with 271 in the control group. During the phase of maintenance treatment, significantly fewer admissions for fever in the IVIG prophylaxis group were reported compared with the group phase; there was also an over 50% reduction in admissions for fever in neutropenia in the maintenance treatment phase compared with the control group. Critically, patients receiving IVIG prophylaxis who were admitted for fever had less antibiotic therapy and adaptations of chemotherapy than the control group, with the difference most significant during maintenance treatment. However, IVIG treatment did not meaningfully affect either DFS, OS, or the incidence of relapse.¹

Unfortunately, the study was not organized to further analyze specific severe AEs that appeared among patients receiving IVIG prophylaxis. Despite this limitation, the study authors noted that the potential for thrombosis in patients receiving IVIG should be kept in mind when prescribing patients IVIG prophylaxis. They also caution interpreters of the results, noting that there was potential bias due to non-blinding, though they write that it did not influence their data considerably.¹

“As IVIG prophylaxis likely prevents viral infections, our data do not support routine use of IVIG prophylaxis for every ALL patient,” the study authors concluded. “However, a subset of patients with a high risk of viral infections might benefit from IVIG prophylaxis, with fewer admissions for fever, in maintenance treatment.”¹

REFERENCES

1. Thus KA, de Groot-Kruseman HA, Winkler-Seinstra P, et al. Immunoglobulin prophylaxis prevents hospital admissions for fever in pediatric acute lymphoblastic leukemia: Results of a multicenter randomized trial. Haematologica. 2025;110(1):47-54. doi:10.3324/haematol.2024.285428

2. Halpern L. IVIG supplementation reduces infection risk in patients with multiple myeloma receiving teclistamab. Pharmacy Times. Published January 9, 2025. Accessed January 15, 2025. https://www.pharmacytimes.com/view/ivig-supplementation-reduces-infection-risk-in-patients-with-multiple-myeloma-receiving-teclistamab

3. Yeoh A, Collins A, Fox K, et al. Treatment delay and the risk of relapse in pediatric acute lymphoblastic leukemia. Pediatric Hematol Oncol. 2017;34(1):38-42. doi:10.1080/08880018.2016.1276253