Recombinant methionyl human stem cell factor and filgrastim for peripheral blood progenitor cell mobilization and transplantation in non-Hodgkin's lymphoma patients--results of a phase I/II trial.

To examine the safety and efficacy of recombinant-methionyl human stem cell factor (r-metHuSCF), 38 patients with intermediate-grade or immunoblastic high-grade non-Hodgkin's lymphoma who were eligible for autologous transplantation were randomized to receive r-metHuSCF (5, 10, 15, or 20 microg/kg/d) plus Filgrastim (10 microg/kg/d) or Filgrastim (10 microg/kg/d) alone to mobilize peripheral blood progenitor cells. Subcutaneous administration of r-metHuSCF was well tolerated in conjunction with a multi-agent pre-medication regimen; local injection site reactions were the most commonly seen adverse event. The total mononuclear cell count, CD34+ cell content, granulocyte-macrophage colony-forming cells (GM-CFC), and burst-forming units-erythroid (BFU-E) per kilogram in the apheresis product was similar when all patients were analyzed by treatment cohort and mobilization regimen (Filgrastim or r-metHuSCF in combination with Filgrastim); however, when prior chemotherapy was taken into account in a supplementary analysis, clinically important differences were observed. Extensive prior therapy was defined as the amount of exposure to specific stem cell toxic chemotherapeutic agents that patients received. These agents include procarbazine, nitrogen mustard, melphalan, nitrosoureas (> or = 2 cycles of any of these drugs) or greater than 7.5 g of cytosine arabinoside. In these patients, there was an increased number of CD34+ cells (1.76 v 0.28 x 10(6)/kg), GM-CFC (20.5 v 5.0 x 10(4)/kg), and BFU-E (36.9 v 8.9 x 10(4)/kg) in patients receiving r-metHuSCF and Filgrastim (N = 18) compared with Filgrastim alone (N = 5). These patients also had a decreased time to an untransfused platelet count of 20 x 10(9)/L that was 10.5 days shorter in the patients who received r-metHuSCF and Filgrastim (12.5 v 23 days). These differences were not found to be statistically significant, possibly because of small size, but are clinically important.

A phase I trial of interleukin 3 (IL-3) pre-bone marrow harvest with granulocyte-macrophage colony-stimulating factor (GM-CSF) post-stem cell infusion in patients with solid tumors receiving high-dose combination chemotherapy.

In humans, interleukin 3 (IL-3) administration increases the cellularity and cycling of bone marrow progenitor cell populations. Initially, in primates and then in humans, IL-3 in sequence with GM-CSF has been shown to stimulate multilineage hematopoiesis. Based upon these effects, we designed a phase I trial of daily IL-3 administered subcutaneously for 10 days at dose levels of 2.5, 5.0, 10.0, 12.5, and 15.0 micrograms/kg followed within 72 h by bone marrow harvest, high-dose chemotherapy, and following chemotherapy, a fixed dose (5.0 micrograms/kg/day) of GM-CSF and bone marrow rescue. The study was designed to assess the toxicity and biological effects of IL-3 administered alone prior to bone marrow harvest and to determine the safety and clinical effects of IL-3 stimulated bone marrow with GM-CSF following high-dose combination chemotherapy. A total of 19 patients with chemotherapy-sensitive non-hematologic malignancies (13 breast, five ovarian, and one testicular cancer) were enrolled. IL-3 up to 15.0 micrograms/kg/day could be administered without dose-limiting toxicities. Flu-like symptoms and headaches were common and poorly tolerated at the highest IL-3 dose. Significant increases in neutrophil counts (P = 0.018) were observed following IL-3. Overall, IL-3 administration was associated with a modest, but significant increase in CFU-GM within the bone marrow (P = 0.034). IL-3 administration had no consistent effect on CD34+ cell number within bone marrow. For the entire group, engraftment of neutrophils to greater than 0.5 x 10(9)/l occurred at a median of 21 days (range of 13-63 days) and platelet independence occurred at a median of 17 days (range 11-120 days). When IL-3 dose levels were analyzed separately, engraftment of neutrophils and platelets, blood product (platelets and packed RBCs) utilization, and discharge date were not superior in those treated with the higher dose (15.0 micrograms/kg) of IL-3. While higher doses of IL-3 were associated with more toxicity, they did not appear to enhance the stem cell pool or speed engraftment later. The effects of pre-bone marrow harvest IL-3 are modest and likely not as impressive as other approaches aimed at enhancing hematologic recovery following high-dose chemotherapy.

Bleomycin in non-Hodgkin's lymphoma.

Bleomycin is a cell-cycle--specific chemotherapeutic agent, with several interesting properties, that lends itself to use in combination chemotherapeutic protocols, especially those for malignant lymphomas. In the following article, bleomycin's use as a single agent and subsequently in three generations of combination chemotherapeutic regimens is reviewed. Bleomycin's lack of myelosuppression and its tendency to concentrate in lymphoid tissue while maintaining tolerable toxicities has been the rationale for its incorporation into more aggressive treatment regimens.

The National Institutes of Health animal handlers medical surveillance program.

The medical surveillance program for animal caretakers, technicians, and other personnel having contact with animals at the National Institutes of Health is described. The program classifies workers according to the groups of animals with which they work. It includes preplacement physical examinations, preventive immunizations, testing, and monitoring of health status. This program helps to protect the workers' health from diseases acquired from animals and to prevent ill employees from adversely affecting the health of the animals with which they work.