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Biomedical subjects

E Crum

Publications and source records attributed to E Crum.

10 recordsLinked to original sources

Phase I/II study of combined granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor administration for the mobilization of hematopoietic progenitor cells.

PURPOSE: To study the toxicity and efficacy of combined granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) administration for mobilization of hematopoietic progenitor cells (HPCs). MATERIALS AND METHODS: Cohorts of a minimum of five patients each were treated subcutaneously as follows: G-CSF 5 micrograms/kg on days 1 to 12 and GM-CSF at .5, 1, or 5 micrograms/kg on days 7 to 12 (cohorts 1, 2, and 3); GM-CSF 5 micrograms/kg on days 1 to 12 and G-CSF 5 micrograms/kg on days 7 to 12 (cohort 4); and G-CSF and GM-CSF 5 micrograms/kg each on days 1 to 12 (cohort 5). Ten-liter aphereses were performed on days 1 (baseline, pre-CSF), 5, 7, 11, and 13. Colony assays for granulocyte-macrophage colony-forming units (CFU-GM) and erythroid burst-forming units (BFU-E) were performed on each harvest. RESULTS: The principal toxicities were myalgias, bone pain, fever, nausea, and mild thrombocytopenia, but none was dose-limiting. Four days of treatment with either G-CSF or GM-CSF resulted in dramatic and sustained increases in the numbers of CFU-GM per kilogram collected per harvest that represented 35.6 +/- 8.9- and 33.7 +/- 13.0-fold increases over baseline, respectively. This increment was attributable both to increased numbers of mononuclear cells collected per 10-L apheresis and to increased concentrations of progenitors within each collection. The administration of G-CSF to patients already receiving GM-CSF (cohort 4) caused the HPC content to surge to nearly 80-fold the baseline (P = .024); the reverse sequence, ie, the addition of GM-CSF to G-CSF, was less effective. The CFU-GM content of the baseline aphereses correlated with the maximal mobilization achieved (r = .74, P = .001). CONCLUSION: Combined G-CSF and GM-CSF administration effectively and predictably mobilizes HPCs and facilitates apheresis.

Adolescent↗

Interleukin 2 and lymphokine-activated killer cell therapy: analysis of a bolus interleukin 2 and a continuous infusion interleukin 2 regimen.

Several groups have described the efficacy of interleukin 2 (IL-2) plus lymphokine-activated killer (LAK) cells in the treatment of cancer patients with significant response rates noted in patients with renal cell cancer and malignant melanoma; however, the optimum regimen remains undefined. The Biological Response Modifiers Program of the National Cancer Institute conducted two consecutive Phase I/II studies evaluating the toxicity and clinical efficacy of different methods of IL-2 and LAK cell therapy. In the first trial, we modified the standard Rosenberg regimen by decreasing the duration of priming in an attempt to reduce the toxicity related to this phase of the therapy and thereby administer more IL-2 doses with the LAK cells. In the second trial, we used a continuous i.v. infusion IL-2 regimen and altered both the leukapheresis procedure and the LAK cell culture techniques based on our in vitro and preclinical studies suggesting that 2-day LAK cells were superior. Thirty cancer patients received i.v. bolus IL-2 at 100,000 units/kg every 8 h for 3 days during priming and for 5 days during LAK cell administration. A second group of 22 cancer patients received IL-2 by continuous i.v. infusion at 3 x 10(6) units/m2 for 5 days during priming and an additional 5 days of IL-2 with the LAK cell phase of the treatment. The timing of the start of the leukapheresis procedures, their duration and number, and the LAK cell culture techniques differed in the two trials. Overall, 52 patients with various cancers were treated. The toxicities associated with each regimen were similar to those seen in other IL-2 plus LAK cell trials. Four patients (one each with melanoma and diffuse large cell lymphoma and two with renal cell cancer) exhibited partial responses lasting 2, 4, 10, and 15+ mo. Serial tumor biopsies from treated patients demonstrated that therapy can produce a marked mononuclear cell infiltrate and an increase in HLA-DR expression on tumor cells. There was no difference in the overall response rate between the two regimens, but toxicity was less with continuous i.v. infusion IL-2. The 5-day continuous i.v. infusion regimen resulted in significantly higher rebound lymphocytosis, cell yield from leukapheresis, and number of LAK cells harvested from culture.

Adolescent↗

Randomized trial of recombinant alpha 2b-interferon with or without indomethacin in patients with metastatic malignant melanoma.

alpha-Interferon has antitumor activity in a variety of malignancies but is frequently associated with unacceptable toxic side-effects. The routine use of agents potentially capable of reducing these side-effects has not been recommended out of concern for possible reductions in the therapeutic activity of interferon. We conducted a prospective randomized trial of alpha-interferon given with or without indomethacin to patients with malignant melanoma to determine what effect, if any, indomethacin might have on the toxic, immunomodulatory, and therapeutic properties of interferon in this disease. 53 patients were stratified according to performance status and randomized to receive alpha 2b-interferon, 20 million units per m2 i.v., 5 days per week for 4 weeks followed by 10 million units per m2 s.c. three times per week, either with or without indomethacin, 25 mg orally three times a day. The overall major response rate was 13% (three complete responders and three partial responders among 47 evaluable patients) and was the same on both arms. The mean maximal temperature elevation induced by interferon was significantly reduced (from 102.1 to 100.7, P = 0.0002) by indomethacin, but the incidence and severity of interferon-related fatigue, reduction in performance status, headache, depression, confusion, elevations in liver function tests, and myelosuppression were no different in either arm of the study. Indomethacin did not reduce the frequency of dose reductions for toxic side-effects and did not permit the administration of higher interferon doses. Peripheral blood natural killer activity was significantly enhanced in patients during maintenance therapy whether or not they received indomethacin. Indomethacin appeared to inhibit augmentation of natural killer activity during high dose induction therapy. Immunological changes did not correlate with response status. We conclude that indomethacin can reduce the fever associated with interferon therapy in patients with malignant melanoma without interfering with its therapeutic or chronic immunomodulatory activities. Since fever is rarely the dose-limiting toxicity of interferon, indomethacin is of marginal benefit to patients with malignant melanoma receiving interferon at the doses outlined in this study.

Adult↗

Fatal radiation hepatitis: a case report and review of the literature.

A case of fatal radiation hepatitis occurring after treatment with 2200 rad given by the moving strip technique is presented. This fatality occurred in a 28-year-old woman with persistent ovarian carcinoma despite prolonged chemotherapy. Scans of the liver using computerized tomography, 99mTc sulfur colloid, and 99mTc diisopropyl iminodiacetic acid showed abnormalities only in sulfur colloid uptake and these resolved late in the course. Death was caused by progressive hepatic and renal failure. Postmortem examination showed changes typical of radiation hepatitis. Only 32 cases of radiation hepatitis have been previously reported and they are reviewed. The possible role of prolonged prior chemotherapy in enhancing sensitivity to radiotherapy is considered.

Adult↗

Sarcoidosis, Hodgkin's disease, and autoimmune hemolytic anemia.

Reported is the unique occurrence of sarcoidosis, Hodgkin's disease, and autoimmune hemolytic anemia in the same patient. Although the diagnosis of sarcoidosis preceded that of Hodgkin's disease by 29 years, massive splenomegaly had been present for 13 years before Hodgkin's disease was diagnosed following splenectomy. The known associations of sarcoidosis and Hodgkin's disease as well as each disease with autoimmune hemolytic anemia are reviewed.

Anemia, Hemolytic, Autoimmune↗

Two primary carcinomas of the lung: adenocarcinoma and a metachronous squamous cell carcinoma. A case report and review of the literature.

The case of a patient who underwent a left lower lobe lobectomy for adenocarcinoma of the lung and developed a metachronous squamous cell carcinoma of the right lung eight years later, is presented. The unusual nature of the case is emphasized utilizing a review of the literature. The criteria for diagnosing metachronous carcinomas are presented and a unified terminology for such cases is proposed. The requirement for life-long follow-up of any patient with cancer is emphasized.

Adenocarcinoma↗