Do immunoglobulin G and immunoglobulin E anti- l -asparaginase antibodies have distinct implications in children with acute lymphoblastic leukemia? A cross-sectional study

Galindo Rodríguez, Gabriela y Jaime Pérez, José Carlos y Salinas Carmona, Mario César y González Díaz, Sandra N. y Castro Corona, Ángeles y Cavazos González, Raúl y Treviño Villarreal, Humberto y Heredia Salazar, Alberto Carlos y Gómez Almaguer, David (2017) Do immunoglobulin G and immunoglobulin E anti- l -asparaginase antibodies have distinct implications in children with acute lymphoblastic leukemia? A cross-sectional study. Revista Brasileira de Hematologia e Hemoterapia, 39 (3). pp. 202-209. ISSN 15168484

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Resumen

Background: l-Asparaginase is essential in the treatment of childhood acute lymphoblastic leukemia. If immunoglobulin G anti-l-asparaginase antibodies develop, they can lead to faster plasma clearance and reduced efficiency as well as to hypersensitivity reactions, in which immunoglobulin E can also participate. This study investigated the presence of immunoglobulin G and immunoglobulin E anti-l-asparaginase antibodies and their clinical associations. Methods: Under 16-year-old patients at diagnosis of B-cell acute lymphoblastic leukemia confirmed by flow cytometry and treated with a uniform l-asparaginase and chemotherapy protocol were studied. Immunoglobulin G anti-l-asparaginase antibodies were measured using an enzyme-linked immunosorbent assay. Intradermal and prick skin testing was performed to establish the presence of specific immunoglobulin E anti-l-asparaginase antibodies in vivo. Statistical analysis was used to investigate associations of these antibodies with relevant clinical events and outcomes. Results: Fifty-one children were studied with 42 (82.35%) having anti-l-asparaginase antibodies. In this group immunoglobulin G antibodies alone were documented in 10 (23.8%) compared to immunoglobulin E alone in 18 (42.8%) patients. Immunoglobulin G together with immunoglobulin E were simultaneously present in 14 patients. Children who produced exclusively immunoglobulin G or no antibodies had a lower event-free survival (p-value = 0.024). Eighteen children (35.3%) relapsed with five of nine of this group who had negative skin tests suffering additional relapses (range: 2–4), compared to none of the nine children who relapsed who had positive skin tests (p-value < 0.001). Conclusion: Children with acute lymphoblastic leukemia and isolated immunoglobulin G anti-l-asparaginase antibodies had a higher relapse rate, whereas no additional relapses developed in children with immunoglobulin E anti-l-asparaginase antibodies after the first relapse.

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