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Characterization of tumor response after administration of rituximab in pediatric B-NHL
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  • Maria Bethke,
  • Georg Varga,
  • Toni Weinhage,
  • Harshana Sabharwal,
  • Karin Mellgren,
  • Gerrit Randau,
  • Meike Rolfing,
  • Helmut Wittkowski,
  • Dirk Foell,
  • Ulf Michgehl,
  • Birgit Burkhardt
Maria Bethke
Pediatric Hematology and Oncology, University Children's Hospital Muenster
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Georg Varga
Department of Pediatric Rheumatology and Immunology, University Hospital Muenster
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Toni Weinhage
Department of Pediatric Rheumatology and Immunology, University Hospital Muenster
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Harshana Sabharwal
Pediatric Hematology and Oncology, University Children's Hospital Muenster
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Karin Mellgren
Sahlgrenska universitetssjukhuset
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Gerrit Randau
Pediatric Hematology and Oncology, University Children's Hospital Muenster
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Meike Rolfing
Pediatric Hematology and Oncology, University Children's Hospital Muenster
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Helmut Wittkowski
Department of Pediatric Rheumatology and Immunology, University Hospital Muenster
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Dirk Foell
Department of Pediatric Rheumatology and Immunology, University Hospital Muenster
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Ulf Michgehl
Pediatric Hematology and Oncology, University Children's Hospital Muenster
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Birgit Burkhardt
Pediatric Hematology and Oncology, University Children's Hospital Muenster
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Abstract

Background Mature aggressive B-cell lymphoma are heterogenous malignancies that make up more than half of all diagnosed Non-Hodgkin lymphoma in children and adolescents. The overall survival rate increased over the last decades to 80–90%, due to fine tuning of polychemotherapy. However, new therapeutic implications are needed to further increase the overall survival. Current clinical trials analyze the therapeutic effect of rituximab in pediatric patients, while the mechanism of action in vivo is still not fully understood. Methods Effector molecules important for tumor defense were analyzed before and at day five after rituximab treatment via flow cytometry. Serum rituximab levels were measured with an ELISA. Results We evaluated patient parameters that may affect treatment response in relation to rituximab administration and serum rituximab levels. We indeed found a reduction of FcγRII levels after rituximab treatment in monocyte subtypes, while FcγRI expression was significantly increased, pointing to exhaustion of FcγRII mediated B cell depletion and compensation via FcγRI mediated trogocytosis. Serum levels of proinflammatory marker proteins S100A8/A9 and S100A12 significantly decreased after treatment to normal levels from an overall proinflammatory state before treatment. CD57, perforin and granzyme B expression decreased after treatment, probably due to exhaustion of NK cells. Conclusion The highlighted effects of rituximab treatment on patient’s immune response help understanding the biology behind tumor defense mechanisms and effector function. After subsequent studies, these novel insights might be translated into patient care and could contribute to improve treatment of pediatric patients with mature aggressive B-cell lymphoma.

Peer review status:IN REVISION

14 Jun 2021Assigned to Editor
14 Jun 2021Submission Checks Completed
14 Jun 2021Submitted to Pediatric Blood & Cancer
23 Jun 2021Reviewer(s) Assigned
28 Jul 2021Review(s) Completed, Editorial Evaluation Pending
28 Jul 2021Editorial Decision: Revise Major