Colony-stimulating activity of fetal liver cells: synergistic role of stem cell factor in bone marrow recovery from aplastic anemia.

Previously, we and others have shown that fetal liver infusion (FLI) leads to autologous hematopoietic improvement in 40-54% of patients with aplastic anemia. However, whether this recovery was spontaneous or the effect of the infused liver cells was not clear. To dissect the role of FLI in autologous hematopoietic recovery, the colony-supporting potential of fetal liver-conditioned medium (FLCM) was evaluated in bone marrow (BM) cells of normal adult and aplastic anemia patients. In both cases, each sample of FLCM supported the growth of colony-forming cells in semi solid culture medium. The FLCM was assayed for the presence of four principal colony-stimulating cytokines, namely stem cell factor (SCF), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), and erythropoietin (Epo). While GM-CSF, IL-3, and Epo were present in insignificant amounts or were altogether absent, 50-635 pg/ml of SCF was found in 8 of the 13 FLCM samples tested. Preliminary results of bioneutralization assay indicated the possible role of SCF, secreted by the FL cells, in colony-supporting activity of aplastic anemia and normal BM cells. Overall, our in vitro study implicates the paracrine role of infused FL cells in regenerating autologous hematopoiesis in aplastic anemia patients.

High dose chemotherapy followed by autologous haemopoietic stem cell transplant in multiple myeloma.

BACKGROUND: High dose chemotherapy followed by autologous stem cell transplant is currently used for the treatment of patients with advanced multiple myeloma. However, there are no reports of the results of this treatment modality in Indian patients. METHODS: Fifty patients with advanced multiple myeloma underwent treatment with high dose melphalan followed by autologous stem cell transplant (bone marrow: 7; peripheral blood stem cells: 43). The patients' ages ranged from 26 to 65 years (median: 52 years) and 35 were men. All patients had received chemotherapy initially with a mean of 9.4 cycles (range: 1-36). Thirty patients had evidence of chemosensitive disease at the time of transplant. The mean interval from diagnosis to transplant was 17.5 months (range: 3-129 months) and the median number of mononuclear cells infused was 4.86 x 10(8) per kg (range: 2-10.48). RESULTS: Post-transplant, 43 of 50 patients engrafted. The median number of days to engraftment (absolute neutrophil count > 500/cmm) was 12 (range: 9-24) and to achieve platelet transfusion independence (> 20,000/cmm) was 13 (range: 8-36). Seven patients died prior to engraftment. Grade III-IV oral mucositis was the major non-haematological toxicity. Excluding the 4 patients who had complete response prior to the transplant and continued in the same status post-transplant, 31/46 patients (67%) responded; complete response was achieved in 25 (54%) and partial response in 6 (13%). Patients with chemosensitive disease had higher rates of complete response; 20 of 26 patients with partial response at transplant achieved complete response compared to 5 of 20 patients with persistent/refractory disease (p < 0.01). Currently, 34 of 50 (68%) patients are alive, 17 (34%) disease-free, 6 with disease are on salvage therapy, 11 (22%) with positive monoclonal protein but asymptomatic are under observation. Nine (18%) patients have died; 8 due to progressive disease and 1 of an unrelated cause. The median follow up for the entire group is 26 months (range: 1-144 months). The Kaplan-Meier probability of overall and progression-free survival for the whole group at 30 months is 62% +/- 8.11% (SE) and 42% +/- 9.54% (SE), respectively. A haemoglobin level < or = 10 g/dl (p < 0.003) affected the survival adversely. Chemosensitive disease (p < 0.008) at transplant and complete response post-transplant (p < 0.0001) were associated with significantly longer survival. CONCLUSION: High dose melphalan followed by autologous stem cell transplantation is an effective treatment for patients with advanced multiple myeloma and achievement of complete response is associated with improved survival.