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, Wyndham H. Wilson

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)795-802
Number of pages8
JournalBlood
Volume106
Issue number3
DOIs
StatePublished - Aug 1 2005

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Granulocytes
Homeostasis
B-Lymphocytes
Cells
Neutropenia
Recovery
Vincristine
Therapeutics
Lymphopoiesis
B-Cell Lymphoma
Etoposide
Prednisone
Chemotherapy
Cyclophosphamide
Rituximab
Neutrophils
Bone Marrow
Bone
Drug Therapy

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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B-cell recovery following rituximab-based therapy is associated with perturbations in stromal derived factor-1 and granulocyte homeostasis. / Dunleavy, Kieron; Hakim, Frances; Kim, Hyun Kyung; Janik, John E.; Grant, Nicole; Nakayama, Takayuki; White, Therese; Wright, George; Kwak, Larry; Gress, Ronald; Tosato, Giovanna; Wilson, Wyndham H.

In: Blood, Vol. 106, No. 3, 01.08.2005, p. 795-802.

Research output: Contribution to journalArticle

Dunleavy, K, Hakim, F, Kim, HK, Janik, JE, Grant, N, Nakayama, T, White, T, Wright, G, Kwak, L, Gress, R, Tosato, G & Wilson, WH 2005, 'B-cell recovery following rituximab-based therapy is associated with perturbations in stromal derived factor-1 and granulocyte homeostasis', Blood, vol. 106, no. 3, pp. 795-802. https://doi.org/10.1182/blood-2004-08-3198
Dunleavy, Kieron ; Hakim, Frances ; Kim, Hyun Kyung ; Janik, John E. ; Grant, Nicole ; Nakayama, Takayuki ; White, Therese ; Wright, George ; Kwak, Larry ; Gress, Ronald ; Tosato, Giovanna ; Wilson, Wyndham H. / B-cell recovery following rituximab-based therapy is associated with perturbations in stromal derived factor-1 and granulocyte homeostasis. In: Blood. 2005 ; Vol. 106, No. 3. pp. 795-802.
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AU - Janik, John E.

AU - Grant, Nicole

AU - Nakayama, Takayuki

AU - White, Therese

AU - Wright, George

AU - Kwak, Larry

AU - Gress, Ronald

AU - Tosato, Giovanna

AU - Wilson, Wyndham H.

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AB - 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.

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