Haematologica, Vol 92, Issue 2, e20-e23 doi:10.3324/haematol.11031
Copyright © 2007 by Ferrata Storti Foundation
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Online Only Articles

Late-onset neutropenia following rituximab results from a hematopoietic lineage competition due to an excessive BAFF-induced B-cell recovery

B. Terrier1, M. Ittah2, L. Tourneur3, F. Louache4, V. Soumelis5, F. Lavie2, N. Casadevall6, S. Candon7, A. Hummel8, X. Mariette2, A. Buzyn1,3,

1 Department of Hematology, Hôpital Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris V- René Descartes, Paris
2 Department of Rheumatology, Institut National de la Santé Et de la Recherche Médicale (INSERM) U 802, Hôpital Bicêtre, AP-HP, Université Paris-Sud 11, Le Kremlin Bicêtre
3 Department of Immunology, INSERM U 567, IFR 116, Institut Cochin, Paris
4 INSERM U 362, IFR 54, Institut Gustave Roussy, Villejuif
5 Department of Immunology, INSERM U 653, Institut Curie, Paris;
6 Department of Biological Hematology, Hôtel-Dieu, AP-HP, Université Paris-Descartes, Paris
7 Department of Immunology, Hôpital Necker-Enfants Malades, AP-HP, Université Paris-Descartes, Paris
8 Department of Nephrology, Hôpital Necker-Enfants Malades, AP-HP, Université Paris-Descartes, Paris, France

Correspondance: Pr Agnès Buzyn, Service d’Hématologie Adultes, Hôpital Necker-Enfants Malades, 149-161 rue de Sèvres, 75743 Paris cedex 15, France. Tel: 33 1 44 49 52 86, Fax: 33 1 44 49 52 80, E-mail: agnes.buzyn{at}nck.aphp.fr

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.

Key words: Neutropenia, rituximab, BAFF, niches, granulopoiesis, lymphopoiesis, lineage competition.




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W.-K. Weng, R. S. Negrin, P. Lavori, and S. J. Horning
Immunoglobulin G Fc Receptor Fc{gamma}RIIIa 158 V/F Polymorphism Correlates With Rituximab-Induced Neutropenia After Autologous Transplantation in Patients With Non-Hodgkin's Lymphoma
J. Clin. Oncol., January 10, 2010; 28(2): 279 - 284.
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