Optimization of regimes of mobilization of blood hemopoietic stem cells in patients with multiple myeloma

Aim. To determine an optimal cyclophosphamide dose in the mobilization scheme providing adequate collection of CD34+ cells in patients with multiple myeloma (MM), to optimize the time of initiation of granulocytic colony-stimulating factor (G-CSF) administration, to study effects of induction therapy schemes on results of mobilization and collection of CD34+ cells. Material and methods. Department of hemoblastoses chemotherapy and bone marrow transplantation of the Russian Hematological Center performed mobilization of autologous blood hemopoietic stem cells (BHSC) in 93 MM patients treated in 2001-2010. This was done with cyclophosphamide and G-CSF. The former was used in 59 cases in a dose 6 g/m2, in 34 cases - 4 g/m2. Results. Myelotoxic agranulocytosis after cyclophosphamide administration developed in all the patients and was observed for 3-10 days (median 5 days). Agranulocytosis ran without documented infections in 51 (54.8%) patients, with febril fever - in 42 (45.2%) patients. Cepticemia, pneumonia, necrotic enteropathy, stomatitis, herpetic lesion of the skin were registered in 9, 4, 11, 14 and 6 cases, respectively. Severe thrombocytopenia (< 30x109/l) occurred more frequently in administration of 6 g/ m2 cyclophosphamide. It was corrected with 2-5 transfusions of thromboconcentrates, only 1 transfusion was needed after the dose 4 g/m2. Collection of CD34+ cells started in leukocyte level over 3.5x109/l on mobilization day 12-20 (median day 15). The day of the first leukocytapheresis did not depend on the day of the first introduction of G-CSF. Duration of G-CSF administration was significantly shorter in the start of its use after leukocyte count decrease under 1.0x109/l. Conduction of 1 to 5 (median 2) leukocytapheresis was needed for collection of BHSC. Sufficient for 2 autotransplantations number of BHSC were stored in 90 of 93 patients. Cyclophosphamide administration in a dose 6 g/m2 allowed collection of cells sufficient for one autotransplantation for the first leukapheresis in 52 (88.1) patients. A total number of CD34+ cells over 4x106 cells/kg were collected in 56 (94.9%) patients. In administration of cyclophosphamide in a dose 4 g/m2 mobilization was effective in all 34 patients. The first leukapheresis provided sufficient for one autotransplantation number of cells in 29 (85.3%) patients. Conclusion. Administration of high cyclophosphamide doses in combination with G-CSF is an effective and safe method of BHSC mobilization providing collection of adequate number of CD34+ cells for double autotransplantation in 96.8% patients. Cost effective is the start of G-CSF administration in the fall of leukocytes under 1.0x109/l. Cyclophosphamide dose 4 g/m2 provides collection of CD34+ cells number sufficient for two autotransplantations in moderate thrombocytopenia and in less number of substitute transfusions in the absence of serious toxic complications.