title: B-cell recovery following rituximab-based therapy is associated with perturbations in stromal derived factor-1 and granulocyte homeostasis.
abstract: The occurrence of delayed neutropenia following rituximab is poorly defined and of unknown cause. We hypothesized it may be related to perturbations of stromal derived factor-1 (SDF-1) and granulocyte homeostasis. Late-onset neutropenia (LON) was investigated in 130 patients with untreated aggressive B-cell lymphoma receiving DA-EPOCH (dose-adjusted etoposide, prednisone, Oncovin [vincristine], cyclophosphamide, and hydroxydaunorubicin) chemotherapy with or without rituximab. All patients were in remission and had no known causes for neutropenia. LON occurred in 6 (8%) of 76 patients receiving rituximab and 0 of 54 patients not receiving rituximab (P = .04). The median onset was 175 days (range, 77-204 days) after treatment with a median duration of 14 days (range, 11-16 days). In a subset of 24 patients, a significant correlation was found between rapid B-cell recovery and granulocyte decline over the 6-month recovery period (R = -0.53; P = .04). Rapid B-cell recovery directly correlated with prerecovery SDF-1 levels (R = 0.65; P = .015) and SDF-1 decline (R = -0.67; P = .013) after recovery. Our results suggest that early B-cell lymphopoiesis is important for B-cell recovery following rituximab, and that perturbation of SDF-1 during B-cell recovery retards neutrophil egress from the bone marrow. These findings illustrate the dual role of SDF-1 in human B-cell and granulocyte homeostasis.
authors.affiliation: Experimental Transplantation and Immunology Branch, CCR, NCI, Bldg 10, Rm 12-N-226, Bethesda, MD, 20892-1868, USA.
authors.forename: Kieron
authors.initials: K
authors.lastname: Dunleavy
authors.forename: Frances
authors.initials: F
authors.lastname: Hakim
authors.forename: Hyun Kyung
authors.initials: HK
authors.lastname: Kim
authors.forename: John E
authors.initials: JE
authors.lastname: Janik
authors.forename: Nicole
authors.initials: N
authors.lastname: Grant
authors.forename: Takayuki
authors.initials: T
authors.lastname: Nakayama
authors.forename: Therese
authors.initials: T
authors.lastname: White
authors.forename: George
authors.initials: G
authors.lastname: Wright
authors.forename: Larry
authors.initials: L
authors.lastname: Kwak
authors.forename: Ronald
authors.initials: R
authors.lastname: Gress
authors.forename: Giovanna
authors.initials: G
authors.lastname: Tosato
authors.forename: Wyndham H
authors.initials: WH
authors.lastname: Wilson
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000627:therapeutic use; D058846:Antibodies, Monoclonal, Murine-Derived; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001402:B-Lymphocytes / Q000502:physiology*; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000097:blood / Q000502:physiology*; D004341:Drug Evaluation; D005260:Female; D006098:Granulocytes / Q000502:physiology*; D006706:Homeostasis; D006801:Humans; D007700:Kinetics; D016393:Lymphoma, B-Cell / Q000150:complications / Q000188:drug therapy; D038041:Lymphopoiesis; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced / Q000209:etiology; D012038:Regeneration; D012189:Retrospective Studies; D000069283:Rituximab
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D000069283:Rituximab
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