Autologous bone marrow transplantation in the therapy of small cell carcinoma of the lung.

Ten patients with small cell carcinoma of the lung were entered into a chemotherapeutic treatment program consisting of cyclophosphamide, vincristine, Adriamycin, and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea. Two courses of combination chemotherapy were administered to each patient followed by a third course with the same doses of drugs used on Course 2 but with autologous bone marrow transplantation given 24 to 48 hr after drug infusion. No differences could be detected between Courses 2 and 3 in terms of the magnitude, timing, or degree of myelosuppression. Serial bone marrow biopsies documented a progressive decline in granulocyte-macrophage colony-forming units in culture per mg bone marrow medullary core from 138 +/- 179 (S.D.) prior to chemotherapy to 7 +/- 11 after the marrow transplant recovery (p = 0.05). These data suggest that autologous bone marrow transplantation does not reduce the myelosuppression seen following the drugs used in this study at the dosages used. Autologous bone marrow transplantation may be useful only in the setting of marrow lethal therapy. Its usefulness in shortening recovery time from nonlethal therapy appears questionable.

Regulation of granulopoiesis and distribution of granulocytes in early phase of bacterial infection.

Studies have been carried out to determine the effect of bacterial infection on CSF production, CFU-C activation, and bacterial clearance by mature granulocytes in mice infected with Escherichia coli. These studies have shown that immediately after bacterial infection (5 minutes), serum colony-stimulating factor (CSF) levels and bone marrow colony-forming units in culture (CFU-C) levels are elevated. This is followed by oscillatory rises in both of these parameters and the appearance of granulocytes in the infected site. With clearance of bacteria, CSF and CFU-C levels return to normal. These studies have indicated further that bacterial infection is a major stimulus for granulocyte production through the CSF-CFU-C system and that clearance of bacteria by mature granulocytes may serve as a negative feedback regulatory arm.

High-dose nitrogen mustard (HN2) with autologous nonfrozen bone marrow transplantation in advanced malignant melanoma. A phase I trial.

In a Phase I trial patients with advanced malignant melanoma were treated with high-dose nitrogen mustard (HN2) and autologous bone marrow transplantation. Three patients were entered into the protocol. After procurement of 1.1--5.5 x 10(5) committed stem cells (CFU-C) per kg body wt, 33 mg/m2 of HN2 was administered i.v. as a bolus. Forty-eight hours later the noncryopreserved bone marrow was reinfused i.v. Side effects consisted of nausea, vomiting, anorexia, alopecia, phlebitis, hepatotoxicity, and neurotoxicity. Cardiotoxicity and hypocalcemia were encountered as unanticipated side effects not described so far by using lower dosages of HN2. Granulocytopenia of less than 10 x 10(9)/l and thrombocytopenia of less than 50.0 x 10(9)/l lasted for a mean of 10 and 8 days, respectively. Measureable disease present in two of three patients did not respond to the dose of HN2 used in this protocol. This study shows that hematologic recovery was shorter than previously reported in studies using HN2 without autologous bone marrow transplantation. The nonhematologic side effects of this dose of HN2, however, were severe and preclude the use of higher doses.

Autologous nonfrozen bone marrow transplantation after intensive chemotherapy: a pilot study.

15 patients with metastatic, nonhematopoietic neoplasms refractory to conventional means of treatment were given intensive chemotherapy followed by infusion of autologous noncryopreserved bone marrow which had been stored at 10 degrees C. This study has shown that the procurement of bone marrow from patients with advanced disease and reinfusion 12 h after high dose chemotherapy is tolerated without significant patient morbidity. The use of marrow stored at 10 degrees C leads to adequate recovery of granulocyte stem cells. The present data also suggest that autologous bone marrow transplantation is beneficial in shortening hematopoietic recovery time in patients receiving high dose chemotherapy and may improve response rates in patients with refractory neoplasms.