Rapid Mobilization of CD34+ Cells Following Administration of the CXCR4 Antagonist AMD3100 to Patients With Multiple Myeloma and Non-Hodgkin's Lymphoma
| Autor: | Neal Flomenberg, Gary Calandra, David H. Vesole, Daniel J. Weisdorf, John F. DiPersio, Jane L. Liesveld, Steven M. Devine, Karin Badel |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Adult
Male Benzylamines Receptors CXCR4 Cancer Research medicine.medical_specialty Antigens CD34 Cyclams CXCR4 Statistics Nonparametric Heterocyclic Compounds Internal medicine medicine Humans Multiple myeloma Aged CXCR4 antagonist Dose-Response Relationship Drug business.industry Lymphoma Non-Hodgkin Plerixafor Antagonist Middle Aged medicine.disease Hematopoietic Stem Cell Mobilization Lymphoma Non-Hodgkin's lymphoma Dose–response relationship Endocrinology Oncology Female Multiple Myeloma business medicine.drug |
| Zdroj: | Journal of Clinical Oncology. 22:1095-1102 |
| ISSN: | 1527-7755 0732-183X |
| DOI: | 10.1200/jco.2004.07.131 |
| Popis: | Purpose Interactions between the chemokine receptor CXCR4 and its ligand stromal derived factor-1 regulate hematopoietic stem-cell trafficking. AMD3100 is a CXCR4 antagonist that induces rapid mobilization of CD34+ cells in healthy volunteers. We performed a phase I study assessing the safety and clinical effects of AMD3100 in patients with multiple myeloma (MM) and non-Hodgkin's lymphoma (NHL). Patients and Methods Thirteen patients (MM, n = 7; NHL, n = 6) received AMD3100 at a dose of either 160 μg/kg (n = 6) or 240 μg/kg (n = 7). WBC and peripheral blood (PB) CD34+ cell counts were analyzed at 4 and 6 hours following injection. Results AMD3100 caused a rapid and statistically significant increase in the total WBC and PB CD34+ counts at both 4 and 6 hours following a single injection. The absolute CD34+ cell count increased from a baseline of 2.6 ± 0.7/μL (mean ± SE) to 15.6 ± 3.9/μL and 16.2 ± 4.3/μL at 4 hours (P = .002) and 6 hours after injection (P = .003), respectively. The absolute CD34+ cell counts observed at 4 and 6 hours following AMD3100 were higher in the 240 μg/kg group (19.3 ± 6.9/μL and 20.4 ± 7.6/μL, respectively) compared with the 160 μg/kg group (11.3 ± 2.7/μL and 11.3 ± 2.5/μL, respectively). The drug was well tolerated and only grade 1 toxicities were encountered. Conclusion AMD3100 appears to be a safe and effective agent for the rapid mobilization of CD34+ cells in patients who have received prior chemotherapy. Further studies in combination with granulocyte colony-stimuating factor in patients with lymphoid malignancies are warranted. |
| Databáze: | OpenAIRE |
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