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Because of its B-cell depleting effect, rituximab has entered clinical trials in several autoimmune conditions. This study assesses the efficacy and safety of rituximab in 57 adults with chronic immune thrombocytopenic purpura (ITP). All patients had platelet counts30 x 10(9)/l, all had received two or more previous ITP treatments and 31 had undergone splenectomy. Patients received rituximab 375 mg/m(2) weekly for 4 weeks. Thirty-one patients (54%) responded, achieving a platelet count50 x 10(9)/l: 18 achieved a complete response (CR: platelet count150 x 10(9)/l) and 13 a partial response (PR: platelet count 50-150 x 10(9)/l). Twenty-nine responses occurred within 8 weeks of the first infusion. Sixteen of 18 CR patients (28% overall), including eight who had failed splenectomy, continued in CR after a median of 72.5 weeks; 15 of 16 are1 year from the first infusion. Only two of 13 maintained a PR. Thirty-three patients experienced grade 1-2 adverse events and one a grade 3 event, but they all completed treatment. Circulating B cells fell to0.03 x 10(9)/l. No changes in immunoglobulin levels or infectious complications were seen. In summary, rituximab was well tolerated with no immediate complications and induced a lasting, substantial response in 32% of adults with chronic ITP.

Multivariate analysis was used to identify which of a large number of pretreatment immunological parameters correlated with therapeutic response, subsequent development of opportunistic infection, and survival from the time of diagnosis in a group of 70 patients with Kaposi's sarcoma and acquired immunodeficiency syndrome treated with recombinant leukocyte A interferon. In a logistic regression model, delayed type hypersensitivity response to one or more recall antigens and high proliferative response to Escherichia coli were significant predictors for response to recombinant leukocyte A interferon (for the model, P = 0.01). For prediction of the development of opportunistic infection, the model selected low proliferative responses to phytohemagglutinin and E. coli (P less than 0.001). Favorable factors predicting survival in the Cox regression model were the absence of endogenous serum interferon activity and a high proliferative response to E. coli (P less than 0.001). The estimated median survival for the group with endogenous serum interferon activity and low E. coli response was 12 months; the median has not yet been reached for the group with no serum interferon and a high E. coli response. We conclude that immunological parameters may be useful in predicting prognosis in patients with Kaposi's sarcoma and acquired immunodeficiency syndrome.

Naturally produced beta-interferon was evaluated following i.m. and i.v. administration to 18 patients with advanced cancer. Fever (mean +/- S.E. = 38.1 degrees +/- 1.7 degrees), enhancement of natural killer cell cytotoxicity, and depression of the white blood cell count occurred following a single i.m. injection in the absence of detectable serum antiviral activity. Fever, rigors, and fatigue were dose-limiting toxicities following daily i.v. administration of 10 million units. Tachyphylaxis, as reported following repetitive administration of alpha-interferons, did not occur. Side effects, depression of the white blood cell count, and enhancement of natural killer cell cytotoxicity were similar when beta-interferon was administered daily as a 10-min bolus or as a 6-hr infusion. However, while natural killer cell cytotoxicity increased progressively over 10 days of bolus injections, it was maximal after the initial 6-hr infusion of beta-interferon. Administration of 10 million units of beta-interferon divided equally between a 10-min bolus injection and a 3-hr infusion was well tolerated and resulted in high initial peak and lower sustained serum interferon levels. Based on pharmacokinetic criteria, this schedule of administration can be recommended for further study in Phase II trials. However, in light of the biological activity of beta-interferon following i.m. administration, the level of beta-interferon in the serum may have limited value as a predictor of antitumor response, toxicity, or biological response modification.

It has long been suggested that malignant melanomas, cutaneous as well as uveal, are responsive to human immune-mediated host defenses. We report here 5 consecutive cases of posterior choroidal melanomas which were treated with hyperthermia generated by high-intensity focused ultrasound. Patient immune function was monitored by determination of T-cell helper/suppressor (CD4/CD8) ratios immediately before and approximately 1 week following hyperthermia treatment. All 5 patients had normal total T-cell counts as measured by the pan-T-cell marker CD3. Two patients were noted to have inverted CD4/CD8 ratios (1:1) before hyperthermia. In both these cases, the ratio reverted to normal (1:1) 1 week following treatment. One patient whose CD4/CD8 ratio was not inverted was noted to have a further increase in his CD4 T cells relative to his CD8 (37% increase). Two patients with initially normal CD4/CD8 demonstrated no significant change following hyperthermia. It appears that ultrasonic hyperthermia may induce a systemic immunomodulatory effect in patients with posterior choroidal melanoma and inverted T-cell helper/suppressor resulting in a normalization of T-cell subset ratios.