Showing papers by "Salvatore Siena published in 1994"

High-dose sequential chemoradiotherapy, a widely applicable regimen, confers survival benefit to patients with high-risk multiple myeloma.

Abstract: PURPOSETo assess the toxicity, efficacy, and applicability of high-dose therapy with bone marrow and/or peripheral-blood autotransplantation in high-risk, previously untreated patients with multiple myeloma.PATIENTS AND METHODSThirteen consecutive patients with high-labeling index (LI) multiple myeloma received a novel high-dose sequential (HDS) regimen consisting in the high-dose administration of cyclophosphamide (7 g/m2) followed by vincristine (1.4 mg/m2) plus methotrexate (8 g/m2 with leucovorin rescue), etoposide (2 g/m2) and, finally, total-body irradiation (TBI; 10 Gy) plus melphalan (120 mg/m2) with autografting of peripheral-blood hematopoietic progenitor cells. Recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF; 5 micrograms/kg/d) was continuously infused after cyclophosphamide and etoposide both to accelerate hematopoietic recovery and to expand/mobilize the hematopoietic progenitor-cell pool.RESULTSAmong 13 patients, 12 completed the program; 10 (or 77%) achieved a c...

Primitive hematopoietic progenitor cells are present in peripheral blood autografts.

Abstract: In this report we have used an in vitro assay for long-term culture-initiating cells (LTC-IC) to detect primitive hematopoietic progenitor cells (HPC) in the peripheral blood (PB) of cancer patients who received high-dose cyclophosphamide (HD-CTX) followed by a combination of recombinant hematopoietic growth factors (C-HGF) including either interleukin-3 (IL-3) + granulocyte colony-stimulating factor (G-CSF), IL-3 + granulocyte-macrophage colony-stimulating factor (GM-CSF) or IL-3/GM-CSF fusion protein (PIXY-321). In addition, we have developed a quantitative assay for cells capable of generating additional colony-forming cells (pre-CFC) as a means of determining primitive HPC present in mobilized PB cells. CD34+ human leukocyte A (HLA)-DR- cells isolated from the mobilized PB were capable of initiating long-term hematopoiesis in vitro that persisted for 10 weeks, while CD34+ HLA-DR- cells obtained from the nonmobilized PB or BM were capable of sustaining long-term hematopoiesis in vitro for only 4 weeks and 8 weeks, respectively. As determined by a limiting dilution analysis of mobilized PB CD34+ HLA-DR- cells, the frequency of pre-CFC was 4.3% (range, 1.0-8.3%). Pre-CFC comprised 0.01% (range, 0.001-0.02%) of mobilized PB mononuclear cells, and 151 pre-CFC were calculated to be present in one milliliter of mobilized PB (range, 20-310/ml). These results suggest that PB mononuclear cells collected by leukapheresis following mobilization with HD-CTX + C-HGFs contain not only differentiated HPCs but also more primitive HPC.

Large-scale enrichment of mobilized CD34+ peripheral blood hematopoietic progenitors by removal of nylon wool-adherent mature cells

Abstract: With the aim of facilitating the ex vivo manipulation of peripheral blood hematopoietic progenitors (CPCs=circulating progenitor cells) collected by leukapheresis, we removed polymorphonuclear cells and monocytes that naturally adhere to nylon wool fibers. Leukapheresed cells harvested at the time of hematopoietic recovery after cancer therapy with high-dose cyclophosphamide plus hematopoietic growth factors were incubated with nylon wool fibers for 1 h at 37 o C. Evaluation of the cells non-adherent to the nylon wool in all experiments (n=14) showed that the median recovery of nucleated cells and CPCs detected as CD34 + cells, CFU-GM and BFU-E was 16.4% (range 4.8%-34.0%), 60.0% (range 30.8-80.8%), 60.9% (range 33.4-74.5%) and 65.5% (range 30.8-69.2%), respectively. Therefore exposure to the nylon wool determined a selective removal of mature cells and a complementary enrichment of CPCs. The wide range of results depended on the significantly different cell compositions of the unmanipulated leukaphereses. The latter from patients receiving rhG-CSF (n=10) comprised a median of 88.5% (range 77.8-93.8%) and 11.5% (range 6.2-22.2%) polymorphonuclear and mononuclear cells, respectively. In contrast, leukaphereses from patients receiving rhGM-CSF or PIXY321 (n=4) comprised a median of 71.1% (range 55.4-85.0%) and 28.9% (range 15.0-44.6%) polymorphonuclear and mononuclear cells, respectively. Accordingly, the fold-enrichment and recovery of hematopoietic progenitor cells was significantly higher for leukapheresed cells from patients receiving rhG-CSF (fold-enrichment=median 4.8, range 3.5-14.6; recovery=median 63.0%, range 57.9-80.9%) than from patients receiving rhGM-CSF or PIXY321 (fold-enrichment=median 1.7, range 1.4-2.0; recovery=median 34.4%, range 30.8-47. 1 %). Nylon wool adherence represents a rapid and efFicient method for the enrichment of CPCs for clinical use