Revista Brasileira de Hematologia e Hemoterapia Revista Brasileira de Hematologia e Hemoterapia
Rev Bras Hematol Hemoter 2017;39:202-9 DOI: 10.1016/j.bjhh.2016.11.006
Original article
Do immunoglobulin G and immunoglobulin E anti-l-asparaginase antibodies have distinct implications in children with acute lymphoblastic leukemia? A cross-sectional study
Gabriela Galindo-Rodríguez, José C. Jaime-Pérez, , Mario C. Salinas-Carmona, Sandra N. González-Díaz, Ángeles Castro-Corona, Raúl Cavazos-González, Humberto Treviño-Villarreal, Alberto C. Heredia-Salazar, David Gómez-Almaguer
Universidad Autónoma de Nuevo León, Monterrey, Mexico
Recebido 20 Junho 2016, Aceitaram 28 Novembro 2016
Abstract
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.

Keywords
Acute lymphoblastic leukemia, Allergy, Hypersensitivity, l-Asparaginase, Neutralizing antibodies, Silent antibodies
Rev Bras Hematol Hemoter 2017;39:202-9 DOI: 10.1016/j.bjhh.2016.11.006