Translational Biomedicine

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CXCR4 inhibitor plerixafor and G-CSF allow for an effective peripheral blood stem cell collection in patients who failed previous mobilization attempt

Grzegorz Wladyslaw Basak , Elzbieta Urbanowska , Magdalena Witkowska , Dorota Zdunczyk , Anna Waszczuk-Gajda , Kamila Skwierawska , Joanna Drozd-Sokolowska , Monika Skibinska , Magdalena Glazer , Krzysztof Madry , Tigran Torosian , Kazimierz Halaburda , Maria Krol , Karolina Serzysko , Patrycja Rusicka , Maciej Gontarewicz , Wieslaw Wiktor-Jedrzejczak

Background: Plerixafor is a CXCR4 receptor inhibitor, which was recently introduced for stem cell mobilization in myeloma and lymphoma patients prior to their transplantation. Since March 2009, we performed 16 mobilizations using plerixafor in combination with G-CSF in 10 patients with multiple myeloma, 3 Non-Hodgkin’s lymphoma and 3 Hodgkin’s lymphoma, who failed previous mobilization attempts with G-CSF in combination with chemotherapy.

Methods and Findings: Our protocol consisted of daily s.c. injections of G-CSF (2 x 5 µg/kg) on days 1 through 7 and plerixafor (240 µg/kg) on day 4, 5 and 6. In three patients, plerixafor was added to chemotherapy-based mobilization regimen, in case when No. of CD34+ cell was too low to start cell collections. The median No. of circulating CD34+ cells after first administration of plerixafor was 23/µL (range 11-62) and in 13/16 patients it exceeded minimum of 15 cells/µL required to begin leukapheresis on that day. However, due to high peripheral blood leukocytosis (median 36.5 G/L; range, 11.4-72.5) the frequency of CD34+ cells was low (median 0.067%, range 0.030-0.215) that affected low collection efficiency of CD34+ cells. Moreover, this required collection and freezing of abundant No. of nucleated cells (median 9.3 x 108 NCs/kg, range 6.15-24.05). In our setting, high nucleated cell count translated into high volume of stem cell product (median 1260 mL; range 500-2050). Nevertheless, the final stem cell products contained median of 2.8 x 106 CD34+ cells/kg b.w. (range, 0.57-4.5 x 106) and in 12/16 patients (75%) it exceeded 2.0 x 106 CD34+ cells/kg b.w., which is required for stem cell transplantation. Eight patients have already been transplanted and median time to neutrophil (>0.5 G/L) recovery was 12 days (11-14) and platelet (>20 G/L) recovery was 14 days (10-25) that is satisfactory.

Conclusions: Stem cell mobilization with plerixafor and G-CSF provides solution for majority of patients requiring autologous hematopoietic stem cell transplantation and failing mobilization with G-CSF in combination with chemotherapy. However, due to high leukocytosis, this protocol requires modification of stem cell collection and freezing procedures in order to avoid large volumes of stem cell product.