Intravenous immunoglobulin supplementation during pediatric B-lymphoblastic leukemia treatment – Associations with receipt and outcomes Open Access

Abstract

Background: Children with B-cell acute lymphoblastic leukemia (B-ALL) experience severe infections during treatment, which intravenous immunoglobulin (IVIG) supplementation may mitigate. IVIG supplementation currently occurs in approximately 30% of children with B-ALL, but evidence for its indications and benefits is sparse.

Objective: To compare disease and demographic characteristics by receipt of IVIG amongst children with B-ALL, and to evaluate outcomes following IVIG supplementation.

Methods: A retrospective cohort analysis examined children age 1-21 years with B-ALL treated at Children’s Healthcare of Atlanta from 2010 to 2017. Demographic, disease, treatment, and outcome data were collected from the electronic medical record. Patient characteristics were compared between patients with an immunoglobulin G (IgG) level checked vs. not checked, and by IVIG receipt among those with an IgG level checked. Multivariable logistic regression models identified factors associated with IVIG receipt. For IVIG recipients, general estimating equation modeling with Poisson distribution was used to compare rates of outcomes between IVIG supplemented and non-supplemented days.

Results: In total, 373 patients met inclusion criteria. IVIG was administered to 114 (30.5%) patients. An IgG level was checked in 251 (67.3%) patients. Median IgG nadir was lower for IVIG recipients vs non-recipients (404 vs 675mg/dL, p<0.01). IVIG recipients were younger at diagnosis (4 vs 6 years, p<0.01) and had more severe infections per 1,000 treatment days (4.2 vs 2.5, p<0.01). The odds of IVIG administration were lower for Non-White patients (Odds ratio (OR) 0.43, 95% Confidence interval (CI) 0.22-0.83), higher for patients with more than 2 severe infections during treatment (OR 2.57, 95% CI 1.28-5.18) and higher for National Cancer Institute standard risk patients with IgG nadir <500mg/dL (OR 7.45, 95% CI 3.54-15.70), adjusting for covariates. Rates of emergency department (ED) visits, hospitalization days, febrile neutropenia episodes and severe infections were lower during IVIG supplemented days vs. non-supplemented days (Rate ratio (RR) 0.52, CI [0.42-0.63]; RR 0.35, CI [0.26-0.46]; RR 0.29, CI [0.19-0.43]; RR 0.37, CI [0.27-0.49], respectively).

Conclusion: Patient characteristics differed by IVIG receipt status. IVIG supplementation can be beneficial in children with B-ALL to reduce infection-related outcomes. Prospective studies can help establish guidelines for IVIG supplementation and IgG monitoring.

Table of Contents

Introduction…………………………………………………………………………………………………………..……………………1

Background…………………………………………………………………………………………………………………………………3

Methods……………………………………………………………………………………………………………………………………..7

Results………………………………………………………………………………………………………………………………………14

Discussion…………………………………………………………………………………………………………………………………21

References………………………………………………………………………………………………………………………………..29             

Tables and Figures…………………………………………………………………………………………………………………….33             

             Figure 1………………………………………………………………………………………………………………………..33

             Figure 2………………………………………………………………………………………………………………………..34

             Table 1………………………………………………………………………………………………………………………….35

             Table 2………………………………………………………………………………………………………………………….36

             Table 3………………………………………………………………………………………………………………………….37

             Table 4………………………………………………………………………………………………………………………….38

             Table 5………………………………………………………………………………………………………………………….39

             Table 6………………………………………………………………………………………………………………………….40

             Table 7………………………………………………………………………………………………………………………….41

             Table 8………………………………………………………………………………………………………………………….42

             Table 9………………………………………………………………………………………………………………………….43

             Table 10……………………………………………………………………………………………………………………….44

             Table 11……………………………………………………………………………………………………………………….45

             Table 12……………………………………………………………………………………………………………………….46

             Table 13……………………………………………………………………………………………………………………….47

             Table 14……………………………………………………………………………………………………………………….48

Appendix…………………………………………………………………………………………………………………………………..49

             Supplemental Table A…………………………………………………………………………………………………..49

             Supplemental Table B…………………………………………………………………………………………………..50

             Supplemental Table C…………………………………………………………………………………………………..51

             Supplemental Table D…………………………………………………………………………………………………..52

             Supplemental Table E…………………………………………………………………………………………………..53

             Supplemental Table F…………………………………………………………………………………………………..54

             Supplemental Table G…………………………………………………………………………………………………..55     

About this Master's Thesis

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School	Laney Graduate School
Department	Clinical Research
Degree	M.S.
Submission	Master's Thesis
Language	English
Research Field	Health Sciences, Medicine and Surgery
Keyword	Immunoglobulin Pediatrics Leukemia
Committee Chair / Thesis Advisor	Mertens, Ann, Emory University
Committee Members	Miller, Tamara, Emory University Castellino, Sharon, Emory University McGee, Matt, Emory University

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