LY-06. Quality control of peripheral hematopoietic blood stem cells transplants obtained by G-CSF and plerixafor-induced mobilization in patients with multiple myeloma
Zarui K. Simavonyan, Anait D. Davtyan, Irina V. Kobzeva, Tatiana A. Astrelina, Yuliya B. Suchkova, Elena K. Sokolova
A. I. Burnasyan Federal Medical Biophysical Center, Moscow, Russia
Contact: Dr. Zarui K. Simavonyan, phone: +7 (915) 368-91-18, e-mail: zarui@inbox.ru
Summary
Autologous transplantation of peripheral hematopoietic stem cells (PHSC) significantly improves survival rates. Autologous PHSC transplants are included into standard therapy schedule of the patients with multiple myeloma (MM). The harvested transplants should meet the generally accepted quality criteria, in order to implement appropriate transplantation program. High-dose cytostatic therapy followed by PHSC transplantation is known to be performed after induction treatment. The risk of collecting low-quality PHSC transplants increases if the patients underwent several lines of therapy including melphalan, lenalidomide, fludarabine, and irradiation courses. This category of patients is referred to the group of “poor mobilizers”. To improve the quality of transplant preparations, a selective inhibitor of CXCR4 – plerixafor is used which blocks the CXCL12 ligand binding by inhibiting CXCR4, thus promoting release of PHSC with an ideal immunological profile: CD34+CD133+CD90+CD38-CD45+ from the bone marrow. The purpose of this study was to perform quality evaluation of autologous PHSC transplants obtained from MM patients with plerixafor used in the mobilization regimen.
Materials and methods
The study included 13 patients diagnosed with MM referred to the group of “poor mobilizers”, or with history of failure to mobilize PHSC using standard techniques. The treatment schedule was as follows: since the 1st day of mobilization, injections of granulocyte colony-stimulating factor (G-CSF) were started at a dose of 12 μg/kg/day. Daily monitoring of CD45+/CD34+ cells was performed by means of flow cytometry (BD FACS Canto II). In the absence of target PHSC levels, plerixafor was administered on the 4th day (0.24 μg/kg), thus enabling initiation of apheresis on the next day.
Results
The number of collected CD34+/CD45+ cells averaged 5.3×106/kg at the first apheresis, 8.3×106/kg in the second session, thus being sufficient to perform two transplantations at the optimal cell numbers. Immunological tests (CD34+/CD45+ cell counts and cultural assays (assessment of CFU numbers) were used to assess the quality of the harvested transplant after cryostorage. All patients underwent double tandem courses of high-dose cytostatic therapy with autologous PHSC transplantation using conditioning regimen with melphalan (200 mg/m2, or 140 mg/m2 in the patients >65 years). Due to pegfilgrastim injections early post-transplant, we preferred platelet restoration in order to assess the engraftment terms. On day +13, the level of granulocytes in all patients was more than 0,5*103 /µL, the level of platelets exceeded 20*103 /µL (without transfusion support).
Conclusions
Hence, our experience has shown that the addition of plerixafor to the standard mobilization schedules in the patients with a history of collection failure or poor prognosis for mobilization makes it possible to obtain a PHSC leukoconcentrate that meets all quality standards in terms of optimal amount of hematopoietic cells for two transplants.
Keywords
Hematopoietic stem cells, mobilization, multiple myeloma, plerixafor.
