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Rituximab administration in pediatric patients with newly diagnosed acute lymphoblastic leukemia


Polyethylene glycol (PEG)-asparaginase (pegaspargase) is a key agent in chemotherapy for acute lymphoblastic leukemia (ALL), but recipients frequently experience allergic reactions. We hypothesized that by decreasing antibody-producing CD20-positive B cells, rituximab may reduce these reactions. Children and adolescents (aged 1–18 years) with newly diagnosed B-ALL treated on the St. Jude Total XVII study were randomized to induction therapy with or without rituximab on day 3 (cohort 1) or on days 6 and 24 (cohort 2). Patient clinical demographics, CD20 expression, minimal residual disease (MRD), rituximab reactions, pegaspargase allergy, anti-pegaspargase antibodies, and pancreatitis were evaluated. Thirty-five patients received rituximab and 37 did not. Among the 35 recipients, 16 (45.7%) experienced a grade 2 or higher reaction to rituximab. There were no differences between recipients and non-recipients in the incidence of pegaspargase reactions (P  >  0.999), anti-pegaspargase antibodies (P  =  0.327), or pancreatitis (P  =  0.480). CD20 expression on day 8 was significantly lower in rituximab recipients (P  <  0.001), but there were no differences in MRD levels on day 8, 15, or at the end of induction. Rituximab administration during induction in pediatric patients with B-ALL was associated with a high incidence of infusion reactions with no significant decrease in pegaspargase allergies, anti-pegaspargase antibodies, or MRD.

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Fig. 1: Randomization schema for this study.
Fig. 2: Frequencies of pegaspargase reactions and anti-pegaspargase antibodies.
Fig. 3: Changes in blast percentage in peripheral blood mononuclear cells and in CD20 positivity in leukemia blasts.

Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.


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The authors thank Keith A. Laycock, PhD, ELS, for scientific editing of the manuscript. This work was supported by National Institutes of Health (NIH) grants P30CA021765, R01CA142665, and R35GM141947; by the American Lebanese Syrian Associated Charities (ALSAC); and by Sevier Pharmaceuticals, LLC. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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Authors and Affiliations



KH, AMM, and HI contributed to writing and critically revising the manuscript, extracting and analyzing data, and interpreting results. JKC was responsible for reviewing the leukemia pathology. YZ and CC were responsible for statistical design and analysis. NHB, SJ, SEK, RCR, CHP, and HI contributed patients and to the design of the study. CGM, JJY, MVR, CHP, and HI were responsible for study conceptualization, study design, and critical review of the manuscript. HI was the principal investigator for the trial, and CHP was the co-principal investigator.

Corresponding author

Correspondence to Hiroto Inaba.

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This work was funded partially by Servier Pharmaceuticals, LLC. The company had no role in the study design, the collection or analysis of data, or the decision to publish.

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Hoshitsuki, K., Zhou, Y., Miller, A.M. et al. Rituximab administration in pediatric patients with newly diagnosed acute lymphoblastic leukemia. Leukemia 37, 1782–1791 (2023).

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