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Blood, 1 August 2005, Vol. 106, No. 3, pp. 795-802.
Prepublished online as a Blood First Edition Paper on February 17, 2005; DOI 10.1182/blood-2004-08-3198.
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Submitted August 20, 2004
Accepted February 11, 2005
B-cell recovery following rituximab-based therapy is associated with perturbations in stromal derived factor-1 and granulocyte homeostasis
Kieron Dunleavy, Frances Hakim, Hyun Kyung Kim, John E Janik, Nicole Grant, Takayuki Nakayama, Therese White, George Wright, Larry Kwak, Ronald Gress, Giovanna Tosato, and Wyndham H Wilson*
Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health, Bethesda, MD, USA
M.D. Anderson Cancer Center, Houston, TX, USA
* Corresponding author; email: wilsonw{at}mail.nih.gov.
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 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 = 0.04). The median onset was 175 (range: 77-204) days after treatment with a median duration of 14 (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 = 0.04). Rapid B-cell recovery directly correlated with pre-recovery SDF-1 levels (R = 0.65; p = 0.015) and SDF-1 decline (R = -0.67; p = 0.013) post-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.
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