Bleomycin-induced flagellate erythema in a patient with Hodgkin's lymphoma - A case report and review of literature.

Bleomycin is a glycopeptide used as a chemotherapeutic agent for lymphomas, germ cell tumors, and pleurodesis of malignant pleural effusions. The pulmonary toxicity of bleomycin is well known while the cutaneous side effects are uncommon and varies from generalized hyperpigmentation, sclerodermoid changes, erythema multiformae, and gangrene to flagellate dermatosis. Here we report a characteristic but rare side effect of flagellate erythema, which developed secondary to bleomycin in a 27-year old woman with Hodgkin's lymphoma after two cycles of treatment with adriamycin, bleomycin, vinblastine, dacarbazine regimen. The rash subsided after discontinuation of bleomycin and treatment with steroids.

Effect of parathyroid hormone and teriparatide on immune function of human adherent and non-adherent leukocytes.

Clinical data indicate that patients with hyperparathyroidism due to chronic kidney disease have abnormal immune function. We evaluated the direct effect of parathyroid hormone (PTH) and two 1-34 peptide fragments of PTH on immune function in activated leukocytes from healthy donors. IL-6 and IL-8 were measured from supernatants from phytohemagglutinin-activated non-adherent and lipopolysaccharide-activated adherent leukocytes in the presence of PTH and the two peptides using ELISA. Data showed no significant change in IL-6 and IL-8 production using PTH (0.1 - 0.8 microM) or two peptides (0.2 - 1.6 microM). Lymphocyte proliferation using 3H-thymidine was not inhibited with 0.1 - 0.4 microM of PTH. However, lymphocyte proliferation was significantly inhibited at the highest dose (0.8 microM) of PTH. There was no effect of two peptides on lymphocyte proliferation. Except for inhibition of lymphocyte proliferation at the highest dose of PTH tested, our data demonstrate no direct effect of PTH and two peptide fragment on immune function.

Drug sensitivity and cross-resistance of the 4'-(9-acridinylamino)methanesulfon-m-anisidide-resistant subline of HL-60 human leukemia.

A subline of the HL-60 leukemia resistant to 4'-(9-acridinylamino)methanesulfon-m-anisidide (HL-60/AMSA) was developed by intermittent long-term in vitro treatment. Resistance to 4'-(9-acridinylamino)methanesulfon-m-anisidide remained unchanged after 180 doublings in the absence of the drug, suggesting a stable phenotypic alteration. The pattern of cross-resistance of HL-60/AMSA was evaluated for a spectrum of antileukemic agents using the clonogenic assay. Modest cross-resistance to doxorubicin (Adriamycin) was observed in the resistant subline on continuous exposure to the drug for 8 to 9 days; however, HL-60/AMSA cells retained their sensitivity to doxorubicin following short-term exposure for 60 min. HL-60/AMSA was also sensitive to the anthracycline aclacinomycin, Vinca alkaloids, and alkylating agents. Furthermore, enhanced sensitivity to 1-beta-D-arabinofuranosylcytosine was observed. The subline was cross-resistant to etoposide.

Adoptive cellular immunotherapy for the treatment of malignant gliomas.

UNLABELLED: The median survival for adults with recurrent primary malignant gliomas is 56 weeks following surgery, radiation, and chemotherapy. Generally, reoperation can extend the median survival an additional 26-32 weeks. We have developed an aggressive treatment program that utilizes low doses of interleukin-2 (IL-2) combined with ex vivo activated killer cells (LAK) infused via an indwelling catheter placed into the surgical resection cavity. Autologous leukocytes were collected during a standard 3-4 h, outpatient leukapheresis procedure, then activated ex vivo for 4-5 days with high doses of IL-2. The treatment protocol consisted of two 2-week cycles of therapy over a 6-week period. Patients with stable disease or objective response on follow-up MRI scans were retreated at 3-month intervals. Acute and cumulative IL-2-related toxicities were observed, but limited, and included fever, headache and transient neurologic irritation. Corticosteroid levels and usage were strictly controlled during immunotherapy, although higher doses were used intermittently to mitigate toxicity. Biologic changes included lymphocytic infiltration, regional eosinophilia, tumor necrosis, and the localized production of IL-2, IFN-gamma and IL-12, demonstrated by in situ hybridization and immunohistochemistry. SUMMARY: IL-2 plus autogeneic LAK cells can be safely administered intracavitary to treat high grade primary brain tumors with limited toxicity within the central nervous system. Six out of 28 patients had long-term survival of greater than 2 years post-reoperation plus immunotherapy with 2 patients alive over 8 years. The presence of a marked regional eosinophilia appeared to correlate with increased survival and may be predictive of a biologic and therapeutic response. Regional adoptive immune therapy was well tolerated and should be considered an option for patients with high-grade tumors refractive to standard therapeutic approaches.

Fractionated stereotactic radiosurgery and concurrent taxol in recurrent glioblastoma multiforme: a preliminary report.

PURPOSE: Surgery and systemic chemotherapy offer modest benefit to patients with recurrent glioblastoma multiforme. These tumors are associated with rapid growth and progressive neurological deterioration. Radiosurgery offers a rational alternative treatment, delivering intensive local therapy. A pilot protocol to treat recurrent glioblastoma was developed using fractionated stereotactic radiosurgery with concurrent intravenous (i.v.) Taxol as a radiation sensitizer. METHODS AND MATERIALS: The treatment outcome was analyzed in 14 patients with recurrent glioblastoma treated with fractionated stereotactic radiosurgery and concurrent Taxol. Median tumor volume was 15.7 cc and patients received a mean radiation dose of 6.2 Gy at 90% isodose line, 4 times weekly. The median dose of Taxol was 120 mg/m2. RESULTS: The median survival was 14.2 months, 1-year survival was 50%. CONCLUSIONS: Survival for this small group of patients was similar to or better than historical controls or patients treated with single-fraction radiosurgery alone. This data should stimulate the investigation of both fractionated radiosurgery and the development of radiation sensitizers to further enhance treatment.

High-dose chemotherapy. Concepts and strategies.

In experimental tumors, a steep dose-response curve has been demonstrated for chemosensitive malignancies. In clinical practice, increasing dose over the conventional dose results in higher responses. These observations have prompted efforts to use chemotherapy in higher doses. Initial empiricism lends itself to more rational use of high-dose chemotherapy. Strategies are based on alteration in drug schedules [e.g., high-dose cytosine arabinoside (Ara-C)], drug-to-drug interaction [e.g., high-dose methotrexate (MTX) with citrovorum rescue], and drug pharmacokinetics (e.g., regional chemotherapy). In general, increasing the dose of cytotoxic agents leads to increasing toxicity. Methods to circumvent unacceptable toxicity have been explored. Autologous bone marrow transplant is one such method that provides new avenues of therapy and has resulted in the emergence of a new spectrum of dose-limiting toxicity. Despite the improved response rate, high-dose chemotherapy has resulted in short response durations and no significant impact on the survival of cancer patients as yet. The greater benefit of such a modality may be in the consolidation of drug-sensitive tumors (e.g., lymphoma and small cell carcinoma) with minimal residual disease after minimal conventional therapy. We review various factors and concepts as they relate to the current use of high-dose chemotherapy. We conclude that drug resistance is multifactorial, and one variable that can be manipulated by clinicians is drug dose. The drug concentration appears crucial in enhancing cytotoxicity. All frontiers examining this approach in clinical practice deserve continued enthusiasm and cautious exploration while other factors are being fully understood and exploited.

Treatment of recurrent glioblastoma multiforme using fractionated stereotactic radiosurgery and concurrent paclitaxel.

Despite the progress in neurosurgery and radiotherapy, almost all patients treated with malignant gliomas develop recurrent tumors and die of their disease. Eighty-eight patients (median age 56 years) with recurrent glioblastoma (median tumor volume 32.7 cm3) were treated with noninvasive fractionated stereotactic radiosurgery and concurrent paclitaxel used as a sensitizer. The median interval between diagnosis of primary glioblastoma and salvage radiosurgery was 7.8 months. Four weekly treatments (median dose: 6.0 Gy) were delivered after the 3-hour paclitaxel infusion (median dose: 120 mg/m2). Survival was calculated by the Kaplan-Meier method from radiosurgery treatment. Overall median survival was 7.0 months, and the 1-year and 2-year actuarial survival rates were 17% and 3.4%, respectively. When grouped by performance status, there was no difference in survival between the patients with low and high Karnofsky score. Patients with tumor volume less than 30 cm3 survived significantly longer than those with tumor greater than 30 cm3 (9.4 vs. 5.7 months, p = 0.0001). Their 1-year survival rate was 40% and 8%, respectively. Eleven patients (11%) had reoperation because of expanding mass. Stable disease was seen in 40% of patients (n = 34), and increase in radiographically detected mass was observed in 41 patients (48.8%). Although the treatment of recurrent GBM is mostly palliative, the fractionated radiosurgery offers a chance for prolonged survival, especially in patients with a smaller tumor volume.

Brain metastases and elevated alpha-fetoprotein level in a patient with esophageal carcinoma.

Carcinoma of the esophagus rarely metastasizes to the brain. We have reported a case of esophageal cancer in a patient with early central nervous system metastasis and an exceptionally high level of serum alpha-fetoprotein, a finding not previously described with this neoplasm.

Recurrent glioblastoma multiforme: potential benefits using fractionated stereotactic radiotherapy and concurrent taxol.

UNLABELLED: A pilot protocol to treat recurrent glioblastoma was developed using fractionated stereotactic radiosurgery with concurrent intravenous Taxol as a radiation sensitizer. METHODS: The treatment outcome was analyzed in two groups of patients with recurrent glioblastoma. Group 1 was analyzed retrospectively, and consisted of 9 patients with a median tumor volume of 9.2 cm3 treated with single-fraction stereotactic radiosurgery alone (mean radiation dose of 19.2 Gy). In group 2, prospectively analyzed, were 14 patients treated with fractionated stereotactic radiotherapy and concurrent Taxol. RESULTS: The median survival in group 2 was 14.2 months versus 6.3 months in group 1 (p < 0.04). One-year survival for patients who received fractionated radiotherapy with Taxol was 50% compared to 11% for those treated with single-fraction radiotherapy only (p = 0.05). CONCLUSIONS: Survival for group 2 patients was significantly better compared to those treated with single-fraction radiotherapy alone. These data should stimulate the investigation of both fractionated stereotactic radiotherapy and the development of radiation sensitizers to further enhance treatment.