Outpatient combination chemoimmunotherapy for patients with metastatic melanoma. Results of a phase I/II trial.

BACKGROUND: Few studies have examined the feasibility, safety, and efficacy of an outpatient biochemotherapy regimen of low dose, subcutaneously administered interleukin-2 (IL-2) for patients with metastatic (Stage IV) melanoma. METHODS: Nineteen patients were treated with intravenous cisplatin and dacarbazine (DTIC), oral tamoxifen, and subcutaneous IL-2 and interferon-alpha-2b (IFN). Eligibility requirements included bidimensionally measurable metastatic melanoma, a Karnofsky performance score of 60 or higher, absence of significant cardiac or pulmonary dysfunction, no prior DTIC or cisplatin chemotherapy, and no evidence of central nervous system involvement. Patients were given a minimum of 2 6-week cycles. Treatment was continued in the absence of progressive disease, and patients were monitored for response at two-cycle intervals. RESULTS: Of the 19 patients, 1 (5%) achieved a complete response; 6 (32%) a partial response; 3 (16%) stable disease; and 9 (47%) progressive disease, for an overall response proportion of 37% (95% confidence interval, 16-61%). The median survival of the treated cohort was 10.6 months. The mean time to disease progression for patients with stable disease or better was 8.4 months, with a mean response duration of 5.1 months. The most common toxicities noted were constitutional symptoms, weight loss, nausea, neutropenia, and fatigue. The 19 patients received a total of 59 cycles of treatment, and IL-2, IFN, or both were held in 14 of these cycles secondary to Grade 3 or 4 toxicities. In addition, six patients required dose reduction of IL-2 and/or IFN. CONCLUSIONS: Chemoimmunotherapy consisting of cisplatin, DTIC, and tamoxifen combined with subcutaneous IL-2 and IFN can be safely administered in an outpatient setting. The described regimen yields moderate activity in metastatic melanoma, and efforts to improve its efficacy merit further examination.

Recombinant human granulocyte macrophage-colony stimulating factor (rhGM-CSF) and autologous melanoma vaccine mediate tumor regression in patients with metastatic melanoma.

In mice, significant immunoprotection was achieved using B16 melanoma cells transfected with granulocyte-macrophage colony-stimulating factor (GM-CSF) as vaccines (Dranoff G, Jaffee E, Lazenby A, et al. Vaccination with irradiated tumor cells engineered to secrete murine granulocyte-macrophage colony-stimulating factor stimulates potent, specific, and long-lasting anti-tumor immunity. Proc Natl Acad Sci USA 1993;90:3539-43). The aim of this study is to test the hypothesis that recombinant human GM-CSF (rhGM-CSF) injected with autologous melanoma vaccine may result in tumor rejection in melanoma patients. Twenty stage IV melanoma patients were treated as outpatients with multiple cycles of autologous melanoma vaccine and bacillus Calmette-Guérin (BCG) plus rhGM-CSF injection in the vaccine sites. Two patients (10%) showed a complete response, with one patient showing resolution of subcutaneous, hepatic, and splenic metastases. In the second patient, buccal, subcutaneous, pulmonary, paraaortic, hepatic, splenic, and retroperitoneal metastases regressed completely. Two patients (10%) showed partial response, with regression of a paraaortic metastasis in one patient. In the second patient, there was shrinkage (> 75%) of a large hepatic lesion. One patient has been rendered free of disease after resection of a single pulmonary metastatic nodule. Three patients (15%) had stable disease during treatment but subsequently developed progression of disease. In 12 patients (60%), the disease progressed. Side effects were minimal. In a separate pilot study, 15 stage IV melanoma patients were also treated with autologous melanoma vaccine with BCG but not with rhGM-CSF; none responded. The fact that four patients showed objective responses to active specific immunotherapy with rhGM-CSF demonstrates that melanoma patients bearing a significant tumor burden may respond specifically to their autologous melanoma.

A case of composite Hodgkin's disease and chronic lymphocytic leukemia in bone marrow. Lack of Epstein-Barr virus.

We report Hodgkin's disease arising in a 68-year-old patient with a history of chronic lymphocytic leukemia for 8 years. The patient presented with a 4-month history of weakness, loss of appetite, and a 15-pound weight loss. A bone marrow biopsy showed two distinct histologic types of lymphoma: chronic lymphocytic leukemia and Hodgkin's disease. Immunohistochemical studies showed that chronic lymphocytic leukemia cells were composed of kappa-light chain-restricted monoclonal B cells. The Reed-Sternberg cells expressed CD15. Epstein-Barr virus RNA was not identified in either the Reed-Sternberg cells or cells of chronic lymphocytic leukemia by in situ hybridization. To our knowledge, this is the second reported case of composite Hodgkin's disease and chronic lymphocytic leukemia involving the bone marrow.

Lymphomatoid papulosis followed by Hodgkin's lymphoma. Differential response to therapy.

BACKGROUND: The association of lymphomatoid papulosis (LyP) with Hodgkin's lymphoma or other lymphomas is well recognized. However, the issue as to whether this represents an independent association or a transformation of one proliferative process to the other remains unresolved. OBSERVATION: A woman with LyP subsequently developed Hodgkin's lymphoma. Combination chemotherapy resulted in apparent cure of the lymphoma but had only a transient effect on the LyP. A literature review revealed a similar difference in response to chemotherapy or radiation therapy in most patients who had LyP and associated lymphoma. CONCLUSIONS: The differential response to therapy in patients with LyP and associated lymphoma suggests that there are biological differences between LyP cells and associated lymphoma cells even though in some patients the immunophenotype and genotype were reported to be identical. However, alternative explanations are possible. In this article we also review studies on other cases of LyP associated with Hodgkin's lymphoma.

Adjuvant immunotherapy of high risk stage I melanoma with transfer factor.

Following conventional surgical management, 100 patients with high risk Stage I melanoma were treated with transfer factor to reduce the incidence of disease recurrence. All patients had primary lesions invasive to Clark's level III or deeper and exceeding 1.0 mm in measured thickness. Ninety-six patients are available for analysis at 15 to 67 months (median: 30 months) after diagnosis. Nine patients have had a recurrence of disease (treatment failure), and one has died. Actuarial non-failure rate is 90%, and survival rate is 99% at five years. A nonrandomized but contemporary control group of 46 patients displaying comparable risk factors was treated with surgery alone. The non-failure rate of this group is 63%, and the survival rate is 69%, data consistent with the results of several published studies. These results suggest that transfer factor immunotherapy may be a valuable adjunct in the treatment of patients with high risk Stage I melanoma.

Priapism and multiple myeloma. Successful treatment with plasmapheresis.

Priapism was associated with multiple myeloma and hyperviscosity in a sixty-year-old black male. Plasmapheresis treatment of the hyperviscosity corrected his priapism, and chemotherapy for the underlying multiple myeloma prevented the recurrence of priapism after a chronic intermittent history of seventeen years.

Post-transfusion thrombocytopenic purpura: a case report.

Post-transfusion thrombocytopenic purpura (PTTP) is a rare syndrome which was first brought to widespread attention by Shulman et al. Eighteen cases have been reported. The present report describes an additional patient, a multiparous female who developed petechia 7 days after blood transfusion. The patient's serum contained anti-P1A1 antibodies and her own platelets were P1A1-negative. She was treated with prednisone and recovered spontaneously without exchange transfusion of whole blood or plasma.