Stem cell function and engraftment is not affected by "in vivo purging" with rituximab for autologous stem cell treatment for patients with low-grade non-Hodgkin's lymphoma.
Seminars in Oncology(1999)
摘要
The chimeric anti-CD20 monoclonal antibody rituximab (Rituxan; IDEC Pharmaceuticals, San Diego, CA, and Genentech, Inc, San Francisco, CA) has recently been approved by the US Food and Drug Administration as single-agent treatment of relapsed/refractory low-grade or follicular non-Hodgkin's lymphoma. Initial results from the pivotal clinical trial revealed that response rates to rituximab were higher patients who previously had high-dose therapy and autologous stem cell transplantation. We have initiated a clinical trial that combines the use of rituximab with high-dose chemotherapy followed by autologous stem cell transplantation for patients with chemosensitive relapsed follicular small cleaved or mantle cell lymphoma. A unique feature of this study is that addition to eight maintenance infusions of rituximab after autologous stem cell transplantation, patients also received rituximab 375 mg/m2 2 days before a granulocyte colony-stimulating factor-mobilized stem cell collection as in vivo We report on preliminary results demonstrating the safety and efficacy of the vivo purge on 10 patients undergoing stem cell mobilization, nine of whom have already undergone transplantation. The peripheral blood CD34+ counts were 14.92 and 20 x 10(6)/L on day 4 and day 5, respectively, of the stem cell mobilization with granulocyte colony-stimulating factor. This compares with 11.7 and 11.8 x 10(6)/L, respectively, for the control population. The median CD34 stem cell yield the graft collection was 3.7 x 10(6)/kg patients receiving rituximab vivo purge compared with 3.1 x 10(6)/kg the control population. The target stem cell collection was successfully collected six of 10 patients a 1-day single large-volume leukapheresis collection, while two patients required 2 days and the last two patients required 3 days. Functional assays revealed the stem cell colony-forming unit-granulocyte monocyte and burst-forming unit-erythrocyte to be 55 and 44 colonies per plate, respectively, for the patients receiving the vivo rituximab purge. This compares favorably with 37 and 38.5 colonies per plate, respectively, for the control population. Neutrophil engraftment took a median of 11 days for both cohorts; platelet independence was achieved 8 days compared with 10 days for the control population. The median number of platelet transfusions was two for patients receiving rituximab and 2.5 for the control group. Assessment of serum cytokines immediately before the rituximab infusion during the stem cell mobilization and immediately after revealed a twofold to sevenfold increase interleukin-1beta, tumor necrosis factor-alpha, and interleukin-6. The polymerase chain reaction analysis for minimal residual disease stem cell collections and peripheral blood and bone marrow samples of these patients will help to determine the efficacy of rituximab vivo purge on disease progression.
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关键词
autologous stem cell treatment,lymphoma,rituximab,vivo purging,low-grade,non-hodgkin
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