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Stem cell mobilization for autologous and allogeneic stem cell transplantation - a summary

Today, haematopoietic stem cell transplantation is a standard of care in a number of haematological diseases. Peripheral blood stem cells (PBSC) are used in the vast majority of autologous transplantations and are increasingly often used in the allogeneic setting as well, where they represent the stem cell source for most of the patients. Principal reasons for the shift from bone marrow stem cells towards PBSCs in allogeneic transplantation include faster stem cell engraftment/donor chimerism following transplantation as well as easier stem cell collection. However, PBSC mobilization, both in the auto- and the allo- setting, remains a demanding task that requires careful planning with high level of coordination and cooperation of medical professionals of different profiles. Despite the advances in this field, some patients with haematologic diseases still fail to mobilize sufficient autologous PBSCs and therefore cannot be treated with potentially curative therapeutic options that require stem cell support. Insights into the physiology of PBSC mobilization have recently revealed the crucial role of the CXCR4/SDF1-alpha axis. This receptor ligand interaction is responsible for stem cell retention in the bone marrow and agents used for stem cell mobilization act by disrupting this axis. Granulocyte colony stimulating factor (G-CSF) is currently the most widely used cytokine for mobilization. It is used in different schedules and dosing schemes, in its pegylated and nonpegylated form, and while in the allogeneic setting it is used alone, in the autologous setting it often follows chemotherapy priming. Its mechanism of action is indirect - by inducing release of metalloproteinases which disrupt the CXCR4/SDF-1 axis it leads to release of haematopoietic stem cells into the blood stream. Direct CXCR4 antagonists have recently been developed as novel, alternative mobilizing agents. AMD3100 (plerixafor) works by directly inhibiting the interaction between SDF-1 and its receptor CXCR4, and it can mobilize haematopoietic stem cells within hours. Plerixafor has been tested alone or in combination with growth factors in clinical trials in both autologous and allogeneic settings. Results of these studies have been recently published and are very promising. Given in combination with G-CSF it was efficient in yielding sufficient number of CD34+ cells in lymphoma and myeloma patients previously failing mobilization with chemotherapy and/or cytokine treatment. Another study has demonstrated that allografts from HLA-matched sibling donors can be succesfully mobilized and collected using plerixafor without G-CSF. Sufficient numbers of PBSC have been collected in two third of donors after just one dose of plerixafor and transplants with these cells showed rapid and complete engraftment. Plerixafor was well tolerated in these studies producing only mild and transient adverse side effects. Although the experience with plerixafor is still relatively limited and further data on its efficacy and safety are eagerly awaited, a new drug on the horizon is always an exciting event for the whole transplant community.

stem cell; mobilization; plerixafor

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