Seronegative disseminated coccidioidomycosis in patients with HIV infection.

Serologic testing for complement-fixing antibodies to Coccidioides immitis is commonly employed to assist in the diagnosis and management of this infection, but its usefulness in an HIV-coinfected population is unknown. In this study we reviewed all the mycologically or histologically proven cases of disseminated C. immitis infection after 1982. Disseminated C. immitis and proven HIV infection were present in eight patients. We performed serum complement-fixing antibody titers on all eight patients, six of whom gave positive tests, while two patients (25%) gave repeatedly negative results despite widely disseminated disease. We conclude that histopathology and culture remain the most reliable methods for the diagnosis of disseminated coccidioidomycosis in the HIV-infected host.

Treatment of acquired immunodeficiency syndrome-related Kaposi's sarcoma using bleomycin-containing combination chemotherapy regimens.

Ninety-nine patients with advanced epidemic Kaposi's sarcoma were treated with bleomycin-containing regimens: 30 received bleomycin and vincristine (BV) and 69 received doxorubicin, bleomycin, and vincristine. Treatment regimens were well tolerated, with response rates ranging from 76% to 81%. However, neutropenia developed even with the relatively nonmyelotoxic BV regimen. Twenty-eight of the 99 patients (28%) were evaluated for pulmonary function prior to, during, and after completion of combination chemotherapy to assess pulmonary toxicity commonly associated with bleomycin. The carbon monoxide diffusion capacity (DLCO) was the only measurement that showed significant changes prior to and after completion of therapy (P = .0003). Moreover, patients receiving more than 100 cumulative units of bleomycin experienced significantly greater declines in DLCO measurements than those receiving lower cumulative doses (P = .0067). No patient, however, developed clinically significant pulmonary toxicity attributable to bleomycin, with individual cumulative bleomycin doses ranging from 10 to 313 U (median, 112 U). We conclude that bleomycin is active and safe in the treatment of Kaposi's sarcoma, and close monitoring of pulmonary function is warranted with cumulative doses exceeding 100 U.

Pulmonary Kaposi's sarcoma: clinical findings and results of therapy.

PURPOSE: Kaposi's sarcoma occurs commonly in patients with the acquired immunodeficiency syndrome (AIDS). Kaposi's sarcoma may remain localized or disseminate to involve visceral organs such as the lungs. Disseminated pulmonary involvement, when it occurs, is often fatal. Effective therapy may improve survival in such patients. We herein report on 20 patients with disseminated pulmonary Kaposi's sarcoma treated with cytotoxic chemotherapy. PATIENTS AND METHODS: Twenty previously untreated patients with pulmonary Kaposi's sarcoma were identified. All were treated with cytotoxic chemotherapy consisting of either Adriamycin alone, a combination of Adriamycin, bleomycin, and vincristine (ABV), or bleomycin and vincristine (BV). The response to therapy and factors affecting prognosis were analyzed retrospectively. RESULTS: Twelve (60%) patients showed a favorable response to therapy. The median survival from the initiation of chemotherapy for the 12 responders was 10 months (range: three to 31 + months) versus six months (range: one to 17+ months) for the non-responders. Eleven of the patients showing a response received ABV or BV combination chemotherapy (p = 0.004). Survival was shortened by the presence of either pleural effusion (p = 0.002), T4 lymphopenia of less than 100/mm3 (p = 0.03), or both at study entry. CONCLUSIONS: In patients with pulmonary Kaposi's sarcoma, combination chemotherapy consisting of ABV or BV is associated with dramatic clinical and functional improvement. The median survival of 10 months demonstrates the value of combination chemotherapy in this group of patients.

Systemic treatment of AIDS-related Kaposi's sarcoma: results of a randomized trial.

PURPOSE: Patients with acquired immunodeficiency syndrome (AIDS)-related epidemic Kaposi's sarcoma generally respond well to cytotoxic chemotherapy. However, due to the associated myelosuppression, these patients are at risk for developing complicating infections that may affect survival. We therefore conducted a multi-center randomized clinical trial comparing single-agent against combination chemotherapy in advanced AIDS-related Kaposi's sarcoma. Low-dose chemotherapy was employed to evaluate its role in combination therapy for this disease and the toxicities associated with the lower intensity. PATIENTS AND METHODS: Sixty-one patients with extensive mucocutaneous Kaposi's sarcoma or visceral involvement were randomized for treatment with low-dose Adriamycin (doxorubicin, 20 mg/m2) alone (31 cases) or in combination with bleomycin and vincristine (ABV) (30 cases). Patients were randomized within strata based on prognostic features associated with shorter survival in prior studies. Both treatment arms were evenly matched at study entry. RESULTS: Complete and partial tumor remissions were significantly higher with ABV (88%) than with Adriamycin alone (48%) (p = 0.004). The median survival was 9 months in both groups. Study entry criteria significantly associated with shorter survival included CD4 lymphocyte counts less than 100/mm3, hemoglobin level less than 10 g/dL, a history of constitutional symptoms, and a prior history of opportunistic infection(s). Toxicities were similar in both arms, and the regimens were well tolerated. Neutropenia (granulocyte count less than 1,000/mm3) occurred in 34% of patients receiving Adriamycin alone and in 52% of patients receiving ABV and was progressive in successive courses of chemotherapy in both treatment arms. The development of AIDS-defined opportunistic infections was relatively infrequent during therapy (14%). CONCLUSIONS: Low-dose ABV is an effective chemotherapy regimen for the treatment of extensive Kaposi's sarcoma. ABV chemotherapy is associated with significantly higher responses than Adriamycin alone and with acceptable toxicity.

Sarcoidosis and lymphoma: an unusual association.

The coexistence of sarcoidosis and malignant lymphoma is uncommon. Here we report four patients with histologically proven sarcoidosis; one developed Hodgkin's Lymphoma of the pleura; another, B cell lymphoma involving the cervical nodes; the third Gastric B cell lymphoma, and the last an aggressive widespread B cell lymphoma.

Advanced acquired immune deficiency syndrome-related Kaposi's sarcoma. Results of pilot studies using combination chemotherapy.

Pilot studies were conducted to evaluate the toxicity and efficacy of two relatively marrow-sparing chemotherapy regimens in the treatment of advanced or progressive epidemic Kaposi's sarcoma. Chemotherapy regimens consisted of bleomycin (10 mg/m2), vincristine (1.4 mg/m2, 2 mg maximum) and Adriamycin (doxorubicin) at either 10 mg/m2 (Group I) or 20 mg/m2 (Group II). The therapy was given intravenously, every 2 weeks, until intolerable toxicity or maximum antitumor response. Thirty-three patients were treated. Although the patient populations were similar regarding pretreatment prognostic factors, the patients were not assigned randomly to these two treatment regimens. Major responses (complete or partial remission) were attained in 79% of the cases. The treatment-related toxicities consisted of mild to moderate nausea, hair loss, and peripheral sensory neuropathy. Bone marrow suppression consisted primarily of neutropenia (less than 1000/mm3) which occurred in a third of the patients. Variables significantly associated with shorter survival included hemoglobin (less than 10 g/dl), low Karnofsky performance status (less than 70%), and weight loss. Opportunistic infections occurred in the majority of cases during administration of chemotherapy, and were most likely related to severe cell-mediated immune dysfunction and low CD4-positive lymphocyte counts.

Clindamycin and primaquine therapy for mild-to-moderate episodes of Pneumocystis carinii pneumonia in patients with AIDS: AIDS Clinical Trials Group 044.

The objective of this prospective, noncomparative study was to assess the safety and efficacy of clindamycin and primaquine therapy for mild-to-moderate pneumocystis pneumonia (defined as a difference of < 40 mm Hg between the alveolar and the arterial oxygen determinations) in patients with AIDS. In the first part of the study, 22 patients were treated with iv clindamycin (900 mg every 8 hours) for the first 10 days, and then their therapy was switched to oral clindamycin (450 mg every 6 hours) for an additional 11 days. In the second part of the study, 38 patients were treated entirely with oral clindamycin (600 mg every 8 hours). All patients were treated with oral primaquine base (30 mg once daily). Fifty-five (92%) of 60 patients responded to the study treatment. Forty-six (77%) of 60 patients completed a full course of therapy. Of the nine patients with treatment-limiting toxic effects, four had only a mild rash. This study indicates that the combination of clindamycin and primaquine is an effective and well-tolerated therapy for mild-to-moderate pneumocystis pneumonia in patients with AIDS. Entirely oral therapy appears to be as effective as initial therapy with iv clindamycin.

Trimetrexate with leucovorin versus trimethoprim-sulfamethoxazole for moderate to severe episodes of Pneumocystis carinii pneumonia in patients with AIDS: a prospective, controlled multicenter investigation of the AIDS Clinical Trials Group Protocol 029/031.

Trimetrexate is a powerful inhibitor of the dihydrofolate reductase of Pneumocystis carinii. AIDS patients (n = 215) with moderate to severe P. carinii pneumonia were enrolled in a double-blind study of trimetrexate plus leucovorin versus trimethoprim-sulfamethoxazole (TMP-SMZ) for 21 days. By study day 10, study therapy failed because of lack of efficacy in 16% of patients assigned to TMP-SMZ and 27% assigned to trimetrexate (P = .064), and the PAO2-PaO2 improved significantly faster with TMP-SMZ. By study day 21, failure rates were 20% with TMP-SMZ and 38% with trimetrexate (P = .008), with respective mortality rates of 12% and 20% (P = .088). By study day 49, the difference in mortality (16% vs. 31%) was significant (P = .028). The cumulative incidence of serious and treatment-terminating adverse events including hematologic toxicities was less with trimetrexate (P < .001). Thus, trimetrexate plus leucovorin was effective, albeit inferior to TMP-SMZ, for moderately severe P. carinii pneumonia but was better tolerated than TMP-SMZ.

Trimetrexate-leucovorin dosage evaluation study for treatment of Pneumocystis carinii pneumonia.

To determine the maximal tolerable dosage of trimetrexate for treatment of pneumocystis pneumonia, 25 patients were treated each day with 45 mg/m2 of trimetrexate and 80 mg/m2 of leucovorin; 10 received 60 mg/m2 and 80 mg/m2; 12 received 60 mg/m2 and 160 mg/m2; and 6 received 90 mg/m2 and 160 mg/m2, respectively. Leucovorin was increased twofold and trimetrexate reduced by 50% or suspended briefly for various levels of neutropenia and thrombocytopenia until blood counts increased. Dosage-modifying hematologic toxicity occurred in 12 (46%), 8 (80%), 9 (75%), and 4 (67%) patients with the respective groups. Cytopenias were in each case reversible and other toxicities were well tolerated. All survivors but one were able to receive a full 21 doses of trimetrexate. Twenty-four (92%), 10 (100%), 7 (58%), and 4 (80%) of patients in the respective groups survived. Thus, the 45 mg/m2/day dosage of trimetrexate with 80 mg/m2/day of leucovorin resulted in the least dosage-modifying toxicity and excellent efficacy. This combination should be selected for studies to compare trimetrexate with other therapies for pneumocystis pneumonia.