Blood progenitor cell (BPC) mobilization studied in multiple myeloma, solid tumor and non-Hodgkin's lymphoma patients after combination chemotherapy and G-CSF

For blood progenitor cell (BPC) mobilization, standard-dose VIP chemotherapy consisting of etoposide, ifosfamide and cisplatin has previously shown effective tumor reduction in solid tumor patients and sufficient progenitor cell mobilization for autologous blood cell transplantation. Mobilization chemotherapy regimens in multiple myeloma (MM) predominantly consist of melphalan or cyclophosphamide that induce marked cytopenia and considerable variability of progenitor cell collection. We studied whether in MM (n = 13), BPCs were efficiently and reproducibly mobilized with etoposide (500 mg/m(2)) and ifosfamide (1500 mg/m(2)), followed by daily s.c. G-CSF (5 mu g/kg). In parallel, patients with solid tumors or non-Hodgkin's lymphomas (n = 28) treated with etoposide (500 mg/m(2)), ifosfamide (1500 mg/m(2)) and cisplatin (150 mg/m(2)) and identical dosing of G-CSF were analyzed. Before chemotherapy (day 0), on day 7 after chemotherapy and on days of leukapheresis (day 9-14), leukocyte numbers, mononuclear cells (MNCs), CD34(+) cells and coexpression of lineage markers were analyzed. Median blood leukocyte numbers were 28 100/mu l (range, 19 600-40 400) on day 10 in myeloma patients and progressively declined over the next 4 days. In contrast, in solid tumor and lymphoma patients leukocyte numbers constantly increased from a median of 12 400/mu l (range, 6000-22 000) to 30 000/mu l (range, 16 300-63 300) between day 10 and day 13 after chemotherapy. Similar to leukocyte counts, median MNC numbers decreased in myeloma patients with successive leukaphereses, but steadily increased in solid tumor and lymphoma patients over the same period. CD34(+) cell numbers in the blood peaked between day 9 and 11 (median: 40/mu l) in myeloma patients and then declined. In the solid tumor and lymphoma group, median CD34(+) counts in the blood peaked an day 12 after mobilization chemotherapy (median: 100/mu l). The median CD34(+) yield per leukapheresis in the myeloma group was 2.2 x 10(6)/kg (range, 1.5-4.7) on day 10, and fell steadily to 0.95 x 10(6)/kg on day 12, whereas in solid tumor/NHL patients median CD34(+) cell yields remained between 3.5 and 3.7 x 10(6)/kg from day 10 to day 12 after mobilization chemotherapy (P < 0.001). To obtain sufficient cell numbers for engraftment a median of 2 (range, 1-3) mobilization chemotherapy cycles were needed in MM compared to 1 (range, 1-10) in solid tumor or lymphoma patients, with a median of 5 (range, 2-8) leukaphereses in MM compared to 1 (range, 1-10) (P < 0.05). Taken together, we found that for patients with MM, VP16 and ifosfamide efficiently and predictably mobilizes progenitor cells into the PB with greater than or equal to 3 x 10(6)/kg CD34(+) cells collected after one to two mobilization chemotherapy cycles.