Mobilization with cyclophosphamide reduces the number of lymphocyte subpopulations in the leukapheresis product and delays their reconstitution after autologous hematopoietic stem cell transplantation in patients with multiple myeloma

BACKGROUND: Autologous hematopoietic stem cell transplantation is considered the standard of care for younger patients with multiple myeloma. Several mobilization regimens are currently used, most commonly growth factors alone or in combination with chemotherapy. The aim of our study was to investigate the differences in lymphocyte subpopulation counts between three different mobilization regimens on collection day, in the leukapheresis product and on day 15 after autologous hematopoietic stem cell transplantation. PATIENTS AND METHODS: In total 48 patients were prospectively enrolled in three different mobilization regimens; (i) filgrastim (20), (ii) pegfilgrastim (19) and (iii) cyclophosphamide + filgrastim (9). Lymphocytes, CD16+/56+ natural killer and CD4+/CD25(high) T regulatory cells were determined by flow cytometry. RESULTS: We found a statistically significant difference between the mobilization regimens. Cyclophosphamide reduced lymphocyte and natural killer (NK) cell counts on collection day (lymphocytes 1.08 × 10(9)/L; NK cells 0.07 × 10(9)/L) compared to filgrastim (lymphocytes 3.08 × 10(9)/L; NK cells 0.52 × 10(9)/L) and pegfilgrastim (lymphocytes 3 × 10(9)/L; NK cells 0.42 × 10(9)/L). As a consequence lymphocyte and NK cell counts were also lower in the leukapheresis products following cyclophosphamide mobilization regimen (lymphocytes 50.1 × 10(9)/L; NK cells 4.18 × 10(9)/L) compared to filgrastim (lymphocytes 112 × 10(9)/L; NK cells 17.5 × 10(9)/L) and pegfilgrastim (lymphocytes 112 × 10(9)/L; NK cells 14.3 × 10(9)/L). In all mobilization regimens T regulatory cells increased 2-fold on collection day, regarding the base line value before mobilization. There was no difference in T regulatory cell counts between the regimens. CONCLUSIONS: Mobilization with cyclophophamide reduces the number of mobilized and collected lymphocytes and NK cells as compared to mobilization with growth factors only and results in their delayed reconstitution following autologous hematopoietic stem cell transplantation. We found no difference between filgrastim and pegfilgrastim mobilization.