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Utilization of peripheral blood stem cells (PBSC) in allogeneic transplantation requires a method for their mobilization and collection that is not inconvenient for the donor.We administered rhG-CSF (filgrastim) 16 micrograms/kg subcutaneously for 4 days in five normal subjects (age 18-31, M = 3, F = 2), previously selected as HLA-identical donors of siblings with leukemia. All the donors gave written informed consent. On days 4 and 5 (in one donor on day 6 too), 10:l leukapheretic collection was performed with a CS-3000 (Baxter) or an AS-104 (Fresenius) cell separator through the antecubital vein.The WBC count reached a median peak of 57.0 x 10(9)/L on day 5. The peripheral blood CFU-GM peaked to a median level of 8908/mL on day 5 with a median increase over baseline values of 39.1 times. The CD34+ cells peaked to (median) 147.0 x 10(6)/L on day 4 with a median increase of 65.3 times. A lesser enrichment was recorded for BFU-E (median increase 12.7 times) and CFU-GEMM (median increase 15.2 times). Even CD3+ and CD56+CD3- cells increased (median 1.7 and 1.5 times, respectively). A median of 771 x 10(8) MNC (range 672-1378), 116.4 x 10(6) CFU-GM (range 47.7-145.1) and 754 x 10(6) CD34+ cells (range 477-2599) were apheretically collected. Concerning side effects, mild to moderate back pain and general minor discomfort were reported by all donors. The platelet level regularly but transiently decreased after completion of the apheretic procedures with a median nadir of 69 x 10(9)/L (range 43-126) on (median) day 7, but in no case did thrombocytopenia cause bleeding. The thrombocytopenia was more pronounced with the CS-3000 than the AS-104 apparatus.rhG-CSF 16 micrograms/kg x 4 days is an efficient schedule for PBSC mobilization in healthy donors, but lower doses and even a single apheresis procedure might prove similarly adequate.

Circulating progenitor cells (CPC), when infused in large numbers, rapidly repopulate the marrow after myeloablation with high-dose therapy. In multiple myeloma (MM), as in other disorders, different chemotherapy regimens, including single-as well as multiple-agent chemotherapy, with or without hemopoietic growth factors, have been proposed to mobilize these progenitor cells into the blood. Here we report our experience with a drug combination called VCAD and compare the results to those obtained by adding rhG-CSF to the same combination.Fourteen MM patients were given one course of VCAD, a chemotherapy association of vincristine 2 mg, cyclophosphamide 4 x 0.5 g/m2, adriamycin 2 x 50 mg/m2 and dexamethasone 4 x 40 mg, before undergoing apheresis to collect CPC for autografting. Seven also received rhG-CSF (filgrastim) 5 mcg/kg/day over the period of apheresis. These latter were allocated to rhG-CSF treatment sequentially from the time the drug became available for clinical use.Following VCAD-induced pancytopenia, CFU-GM peaked at a median of 853/mL (range 96-4352; 7.6 times basal level). RhG-CSF administration increased CFU-GM levels but not significantly. With rhG-CSF the CFU-GM peak was reached sooner, toxicity was reduced and granulocytopenia less protracted. Fewer aphereses were run in the rhG-CSF group, there were higher yields per single run, and patients began and completed their collection program more quickly.The VCAD association is able to mobilize CPC in patients with MM, and rhG-CSF is recommended as a fundamental part of the priming schedule.

We analyzed short-term and sustained hematopoietic reconstitution after high-dose therapy with peripheral blood stem cell (PBSC) support in patients with various malignant disorders.Fifty-six patients, all with malignant hematologic disorders, were autografted between 1989 and 1994 using PBSC (47 pts) or PBSC + bone marrow (BM) cells (9 pts). PBSC were collected after mobilization with chemotherapy +/- hematopoietic growth factors (GF).All patients engrafted0.5 x 10(9)/L polymorphonuclear cells (PMN) and50.0 x 10(9)/L Plt at a median of 12 (8-32) and 13 (9-365) days, respectively. Thirty-nine patients were evaluable for long-term graft performance, and their hematologic values at 30 and 100 days, at 6 months and at 1, 2, 3, 4 and 5 years were retrospectively analyzed. Steady counts were recorded over the years. None of the patients had late graft failure.PBSC given after high-dose chemotherapy ensure a fast hematologic recovery with stable graft performance up to five years after autograft. Though this is not definitive proof of the presence of uncommitted stem cells in the PBSC population, it gives further support to the idea that PBSC are as safe as bone marrow for long-term engraftment. A delayed or incomplete recovery of platelets may occur with low PBSC counts or when disease relapse occurs rapidly after autograft.

We report the preliminary results of a study exploring the possibility of collecting circulating progenitor cells (PBSC) with a protocol based on the administration of single doses (4 g/m2) of cyclophosphamide and G-CSF (5 or 10-micrograms/kg) in 9 patients with non Hodgkin's lymphoma. The peak level of CD34+ cells occurred after a median of 10 days (range 8-11), generally coinciding with the median peak level of CFU-GM, with a mean 31.27 fold increase above basal levels. 3 (range 2-5) leukaphereses were required to harvest a median number of 25.1 x 10(4)/kg (8-105) CFU-GM and of 9.4 x 10(6)/kg (1.2-25) CD34+ cells. No difference was recorded between 5 and 10 micrograms/kg of G-CSF in terms of PBSC yield. In transplanted patients, a strong correlation was found between CD34+ cells infused/kg and platelet recovery (r = -0.8, p = 0.002). No toxicity was observed and apheretic procedures were regularly performed outpatiently. Our conclusion is that this protocol is particularly suitable for an outpatient treatment/collection program.