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Journal of Clinical Oncology, Vol 23, No 16 (June 1), 2005: pp. 3871-3872 © 2005 American Society of Clinical Oncology. DOI: 10.1200/JCO.2005.55.250
Clinical Use of AMD3100 to Mobilize CD34+ Cells in Patients Affected by Non-Hodgkin's Lymphoma or Multiple MyelomaDivision of Medical Oncology, Institute for Cancer Research and Treatment (IRCC), Candiolo, Torino, Italy To the Editor: The article by Devine et al1 in the March 15, 2004, issue of the Journal of Clinical Oncology shows the effectiveness of the compound AMD3100 in mobilizing CD34+ cells in patients affected by non-Hodgkin's lymphoma and multiple myeloma. The results are interesting since an increased stem cell yield can widen the peripheral blood stem cell applications to poor mobilizer patients. Stromal cell–derived factor-1 (SDF-1) and its chemokine receptor CXCR4 are key regulators of stem cell mobilization and homing. Indeed SDF-1 is highly expressed within the bone marrow environment. This ligand activates different proteases that promote the egress of the stem cells and perturbs adhesive interaction with bone marrow stromal cells and hematopoietic stem cells. At the same time, SDF-1 is highly expressed in the liver and lung, and CD34+ cells can be found in both organs under certain circumstances2 due to SDF-1 chemoattraction. Indeed, it is more and more clear this ligand-receptor axis has a central role in the migration and homing of cancer cells in their target tissue. It has been shown to be involved in the metastatic process of solid tumors3-5 and in the activation and trafficking of leukemic,6,7 myeloma,8 and lymphoma cells.9,10 These recent studies all point out CXCR4/SDF-1 axis as a key regulator of migration and homing regardless of the considered cell/tissue (stem cells, cancer cells expressing CXCR4, and tissue expressing SDF-1 like bone marrow, lung, liver). Furthermore, at least in a murine model, antihuman CXCR4 monoclonal antibodies were shown able to prevent: (1) the homing into the lung of osteosarcoma cells11 avoiding the development of metastasis and (2) the growth of cells belonging to large-cell non-Hodgkin's lymphoma lines.12 The action of AMD3100 on CXCR4/SDF-1 axis gives raise to the passage of CD34+ cells into the peripheral blood. At the same time, several studies6-10 show substantial evidences that the disruption of this axis could increase the same passage of hematopoietic cancer cells into the blood stream. The presence of neoplastic cells indicates a potential risk of increased contamination by hematopoietic cancer cells into the apheresis. Moreover, this likely contamination might have a critical role on the final outcome after reinfusion of CD34+ cells. Indeed, patients rescued with CD34+ cells "freed" by hematopoietic cancer cells have had a better outcome.12-16 Thus, it would be of interest to know if tumor cell contamination was explored by Devine et al. In any case, we suggest that techniques aimed to disrupt SDF-1/CXCR4 axis or other adhesion chemokines (eg, VLA-4) in order to collect stem cells should first evaluate the possible contamination by cancer cells. Authors' Disclosures of Potential Conflicts of Interest The authors indicated no potential conflicts of interest. REFERENCES
1. Devine SM, Flomenberg N, Vesole DH, et al: Rapid mobilization of CD34+ cells following administration of the CXCR4 antagonist AMDS 100 to patients with multiple myeloma and non-Hodgkin's lymphoma. J Clin Oncol 22:1095-1102, 2004
2. Storms R, Trujillo A, Springer J, et al: Isolation of primitive human hematopoietic progenitors on the basis of aldehyde dehydrogenase activity. Proc Natl Acad Sci U S A 96:9118-9123, 1999 3. Muller A, Homey B, Soto H, et al: Involvement of chemokine receptors in breast cancer metastasis. Nature 410:50-56, 2001[CrossRef][Medline] 4. Burger M, Glodek A, Hartmann T, et al: Functional expression of CXCR4 (CD184) on small lung cancer cells mediates migration, integrin activation, and adhesion to stromal cells. Oncogene 22:8093-8101, 2003[CrossRef][Medline]
5. Libura J, Drukala J, Maijka M, et al: CXCR4-SDF-1 signaling is active in rhabdomyosarcoma cells and regulates locomotion, chemotaxis and adhesion. Blood 100:2597-2606, 2002
6. Tavor S, Petit I, Porozov S, et al: CXCR4 regulates migration and development of human acute myelogenous leukemia stem cells in transplanted NOD/SCID mice. Cancer Res 64:2817-2824, 2004
7. Spiegel A, Kollet O, Peled A, et al: Unique SDF-1-induced activation of human precursor B- ALL cells as a result of altered expression and signaling. Blood 103:2900-2907, 2004
8. Gazitt Y, Akay C: Mobilization of myeloma cells involves SDF-1/CXCR4 signaling and downregulation of VLA-4. Stem Cells 22:65-73, 2004
9. Corcione A, Arduino N, Ferretti E, et al: CCL19 and CXCL12 trigger in vitro chemotaxis of human mantle cell lymphoma B cells. Clin Cancer Res 10:964-971, 2004 10. Juarez J, Bendall L: SDF-1 and CXCR4 in normal and malignant hematopoiesis. Histol Histopathol 19:299-309, 2004[Medline] 11. Perissinotto E, Fonsato V, Cavalloni G, et al: Tumor progression in osteosarcoma: Role of the CXCR4/SDF-1 system. Proc Am Soc Clin Oncol 23:819, 2004 (abstr 9021)
12. Bertolini F, Dell'Agnola C, Mancuso P, et al: CXCR4 neutralization, a novel therapeutic approach for non-Hodgkin's lymphoma. Cancer Res 62:3106-3112, 2002
13. Gorin NC, Aegerter P, Auvert B, et al: Autologous bone marrow transplatation for acute myeloid leukemia in first remission: A European survey on the role of marrow purging. Blood 75:1606-1614, 1990
14. Corradini P, Voena C, Tarella C, et al: Molecular and clinical remission in multiple myeloma: Role of autologous and allogeneic transplantation of hematopoietic cells. J Clin Oncol 17:208-215, 1999
15. Corradini P, Astolfi M, Cherasco C, et al: Molecular monitoring of minimal residual disease in follicular and mantle cell non-Hodgkin's lymphoma treated with high-dose chemotherapy and peripheral blood progenitor cell autografting. Blood 89:724-731, 1997
16. Freedman AS, Neuberg D, Mauch P, et al: Long-term follow-up of autologous bone marrow transplantation in patients with relapsed follicular lymphoma. Blood 94:3325-3333, 1999 Related Reply
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Copyright © 2005 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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