title: Late-onset neutropenia following rituximab results from a hematopoietic lineage competition due to an excessive BAFF-induced B-cell recovery.
abstract: Rituximab is used in the treatment of lymphoma and autoimmune diseases, for which late-onset neutropenia (LON) were reported. LON-related mechanisms remain unclear. To obtain insights into the mechanisms, we assessed serum, peripheral blood and bone marrow (BM) samples of a patient with LON. Factors classically associated with neutropenia such as anti-neutrophil antibodies, T-LGL, soluble Fas Ligand were not detectable. We then evaluated the kinetics of various cytokines involved in B-cell and granulocyte homeostasis. We found that LON is related to a lack of granulopoiesis in the BM that coincides with a very high level of BAFF, a strong stimulator of B-cell recovery, and hypothesized a hematopoietic lineage competition due to an excessive B-cell recovery in the BM by promotion of B-cell lymphopoiesis over granulopoiesis within common developmental niches. Assessment of serum BAFF levels following rituximab could detect patients at risk of developing LON.
authors.affiliation: Department of Hematology, Hôpital Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris, Université Paris V-René Descartes, Paris, France.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Terrier
authors.forename: Marc
authors.initials: M
authors.lastname: Ittah
authors.forename: Léa
authors.initials: L
authors.lastname: Tourneur
authors.forename: Fawzia
authors.initials: F
authors.lastname: Louache
authors.forename: Vassili
authors.initials: V
authors.lastname: Soumelis
authors.forename: Frédéric
authors.initials: F
authors.lastname: Lavie
authors.forename: Nicole
authors.initials: N
authors.lastname: Casadevall
authors.forename: Sophie
authors.initials: S
authors.lastname: Candon
authors.forename: Aurélie
authors.initials: A
authors.lastname: Hummel
authors.forename: Xavier
authors.initials: X
authors.lastname: Mariette
authors.forename: Agnès
authors.initials: A
authors.lastname: Buzyn
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D058846:Antibodies, Monoclonal, Murine-Derived; D053264:B-Cell Activating Factor / Q000097:blood / Q000502:physiology*; D001402:B-Lymphocytes / Q000187:drug effects / Q000473:pathology*; D001853:Bone Marrow / Q000473:pathology; D019070:Cell Lineage; D002478:Cells, Cultured / Q000187:drug effects; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000627:therapeutic use; D016207:Cytokines / Q000097:blood; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D038041:Lymphopoiesis / Q000502:physiology*; D008875:Middle Aged; D038042:Myelopoiesis / Q000502:physiology*; D009503:Neutropenia / Q000139:chemically induced* / Q000503:physiopathology; D000069283:Rituximab; D013997:Time Factors; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use; D008258:Waldenstrom Macroglobulinemia / Q000097:blood / Q000188:drug therapy*
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D053264:B-Cell Activating Factor; D016207:Cytokines; D007155:Immunologic Factors; C505719:TNFSF13B protein, human; D000069283:Rituximab; D003520:Cyclophosphamide; D014740:Vidarabine; C024352:fludarabine