Plerixafor in Patients with Decreased Mobilizing Ability of Autologous Hematopoietic Stem Cells
Authors: Kucher Maksim Anatol'evich , Motalkina M.S. , Klimova O.U. , Kondakova E.V. , Kalashnikova O.B. , Alekseev S.M. , Motorin D.V. , Babenetskaya D.V. , Podol'tseva E.I. , Mikhailova N.B. , Estrina M.A. , Babenko E.V. , Pevtcov D.E. , Zaritskii A.Yu. , Afanas'ev B.V. 
Published: June 2016

Background & Aims. Autologous hematopoietic stem cell transplantation (autoHSCT) is an effective treatment for patients with malignant lymphoproliferative disorders, multiple myelomas and solid tumors sensitive to chemotherapy. Harvesting of hematopoietic stem cells (HSC) prior autoHSCT may be ineffective in up to 40 % of cases, if aggravating factors are present. One of methods to overcome the reduced mobilization ability is to include a CXCR4-inhibitor (plerixafor) to the mobilization strategies. The aim was to evaluate the efficacy and safety of different autologous HSC mobilization regimens containing plerixafor. Methods. 63 patients with solid and hematological malignancies were included into the study. 2 mobilization regimens were used: filgrastim + plerixafor (n = 47) and pegfilgrastim + plerixafor (n = 16). Filgrastim was prescribed at a dose 5 p.g/kg twice a day subcutaneously on days 1-4; on day 4, at 12.00 am, plerixafor was prescribed at a dose of 0.24 mg/kg subcutaneously; on day 5, filgrastim 5 p.g/kg was administered subcutaneously, and then a cytapheresis session was performed at 10.00 am. Pegfilgrastim was administered subcutaneously at a dose of 6 mg on day 1; on day 4, plerixafor was administered subcutaneously at a dose of 0.24 mg/kg at 06.00 am; then, 11 hours later, cytapheresis was performed. The cytapheresis was performed at a level of CD34+ cells ≥ 20 х 10<sup>6</sup>/ф_. Results. In 73.7 % of cases (n = 42), patients had an advanced stage disease and underwent more than one chemotherapy line prior to mobilization of autologous HSC. After mobilization with G-CSF (filgrastim or pegfilgrastim), the CD34+ cell count in peripheral blood was 0-17 х 10<sup>6</sup>/μL (median 9.8 х 10<sup>6</sup>/μL). Further injection of plerixafor increased the CD34+ cell count to 2-89 х 10<sup>6</sup>/μL (median 31.6 х 10<sup>6</sup>/ μL) (p = 0.0001). In 85.7 % of cases (n = 54), the sufficient amount of CD34+ cells (≥ 2 х 10<sup>6</sup>/kg; median 5.1 х 10<sup>6</sup>/kg) was harvested for transplantation. The effectiveness of mobilization in two groups was comparable 90.2 % for the filgrastim + plerixafor regimen and 68.7 % for pegfilgrastim + plerixafor (p = 0.08). The use of the filgrastim + plerixafor combination in patients with low baseline CD34+ cell counts increased the number of hematopoietic stem cells up to 6.663 х 10<sup>6</sup>/μL (median 27.1 х 10<sup>6</sup>/μL), thus allowing to harvest a good quality graft in 83.3 % of cases (p = 0.0001). When the level of CD34+ cell counts was in the «grey zone», successful graft harvesting was performed in 90 % of cases: 1.74-4.6 х 10<sup>6</sup>/kg; median 3.1 х 10<sup>6</sup>/kg (p = 0.0001). Complications associated with plerixafor were observed in 2 cases: diarrhea (n = 1) and hypocalcaemia (n = 1). Conclusion. In patients who are poor mobilizers, the use of plerixafor-containing regimens increased the chance of successful graft harvesting with good tolerability.