indinavir-sulfate and Lymphoma--AIDS-Related

Lymphomas are a well-known malignancy in individuals with human immunodeficiency virus type 1 (HIV-1) infection. Most lymphomas are of B-cell lineage and cutaneous involvement is rare. Cutaneous T-cell lymphomas have been previously described in adults with HIV-1 infection but are exceptional in HIV-1 infected-children. The authors report here the extremely rare case of a large-cell cutaneous lymphoproliferation of T-cell lineage expressing Epstein-Barr virus (EBV) antigens in a 15-year-old boy with AIDS and his uncommon clinical presentation. The atypical clinical evolution with a nonaggressive treatment emphasizes that for immunosuppressed patients, the diagnosis of immunosuppression-related lymphoproliferative disorder should be considered before giving the diagnosis of malignant lymphoma when tumoral lymphoid cells express EBV antigens.

Topics: Acquired Immunodeficiency Syndrome; Adolescent; Anti-HIV Agents; Antigens, CD; Antiretroviral Therapy, Highly Active; Combined Modality Therapy; Diagnosis, Differential; Epstein-Barr Virus Infections; Gene Rearrangement, T-Lymphocyte; Herpesvirus 4, Human; HIV Protease Inhibitors; Humans; Immunophenotyping; Indinavir; Lamivudine; Lymphoma, AIDS-Related; Lymphoma, T-Cell, Cutaneous; Male; Reverse Transcriptase Inhibitors; RNA, Viral; Sarcoma, Kaposi; Skin Neoplasms; Stavudine; Transfusion Reaction; Viral Matrix Proteins

This study investigated the efficacy, toxicity, and pharmacokinetic interactions resulting from simultaneous combination chemotherapy and highly active antiretroviral therapy (HAART) for patients with human immunodeficiency virus (HIV)-associated non-Hodgkin's lymphoma (NHL). In addition, the effects on viral load, CD4 counts, and opportunistic infections were examined with the use of combination chemotherapy combined with HAART.. Sixty-five patients with previously untreated and measurable disease at any stage of HIV-associated NHL of intermediate or high grade were entered onto this study at 17 different centers. The first 40 patients entered onto the study received reduced doses of cyclophosphamide and doxorubicin, combined with vincristine and prednisone (modified CHOP [mCHOP]), whereas the subsequent 25 patients entered onto the study received full doses of CHOP combined with granulocyte colony-stimulating factor (G-CSF). All patients also received stavudine, lamivudine, and indinavir.. The complete response rates were 30% and 48% among patients who received mCHOP and full-dose CHOP combined with HAART, respectively. Grade 3 or 4 neutropenia occurred in 25% of patients receiving mCHOP and 12% of those receiving full-dose CHOP combined with G-CSF (25% v 12%). There were similar numbers of patients with grade 3 or 4 hyperbilirubinemia (12% and 17%), constipation and abdominal pain (18% and 17%), and transaminase elevation (48% and 52%) on the modified and full-dose arms of the study, respectively. Doxorubicin clearance and indinavir concentration curves were similar among patients on this study and historical controls, whereas cyclophosphamide clearance was 1.5-fold reduced as compared with control values. Human immunodeficiency virus (HIV) load declined from a median baseline value of 29,000 copies/mL to a median minimum value on therapy of 500 copies/mL.. Either modified-dose or full-dose CHOP chemotherapy for HIV-NHL, delivered with HAART, is effective and tolerable.

Topics: Adult; Anti-HIV Agents; Antineoplastic Combined Chemotherapy Protocols; Antiretroviral Therapy, Highly Active; Combined Modality Therapy; Cyclophosphamide; Dose-Response Relationship, Drug; Doxorubicin; Female; Granulocyte Colony-Stimulating Factor; HIV Infections; Humans; Indinavir; Lamivudine; Lymphoma, AIDS-Related; Lymphoma, Non-Hodgkin; Male; Middle Aged; Neutropenia; Prednisone; Stavudine; Treatment Outcome; Vincristine; Viral Load

The purpose of the present study was to evaluate the impact of modern antiretroviral therapy in patients with acquired immunodeficiency syndrome (AIDS)-related lymphoma who were treated with standard chemotherapy. Twenty-nine patients with AIDS were treated with triple antiretroviral therapy, including protease inhibitors, were treated with a chemotherapy regimen involving cyclophosphamide 750 mg/m2, i.v. day 1; vincristine 1.4 mg/m2, i.v. day 1; mitoxantrone 10 mg/m2, i.v. day 1; and bleomycin 10 mg/m2, i.v. day 14. Granulocyte colony stimulating factor 5 ug/kg/day, started on day 5 of every cycle was administered to ameliorate the presence of severe myelosuppression. Complete response (CR) was observed in 21 cases (72%, 95% confidence interval; 63% to 83%). At three years the time to treatment failure (TTF) was 85%; disease free survival (DFS) 62%; and overall survival 55%. Eleven patients died secondary to tumor progression and only three patients died secondary to opportunistic infections. Chemotherapy was well tolerated, only 12% of the cycles developed granulocytopenia grade 3 and eleven episodes of infection-related granulocytopenia were observed. Delay on treatment was observed on 39 cycles (22%) N. death secondary to chemotherapy were recorded.. The use of modern antiretroviral therapy improved the prognosis of patients with AIDS-related lymphoma, because patients could receive adequate dose intensity of chemotherapy and the presence of opportunistic infections secondary to AIDS declines with the use of protease inhibitors. Future studies will consider the use of more intensive chemotherapy in an aim to improve the CR rate and overall survival.

Topics: Acquired Immunodeficiency Syndrome; Adult; Anti-HIV Agents; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Disease-Free Survival; Drug Therapy, Combination; Female; Granulocyte-Macrophage Colony-Stimulating Factor; HIV Protease Inhibitors; Humans; Indinavir; Lamivudine; Lymphoma, AIDS-Related; Male; Middle Aged; Mitoxantrone; Prognosis; Survival Rate; Vincristine; Zidovudine

A 36-year-old HIV-seropositive man developed progressive confusion and unilateral tremor of the hand. His medical history included cryptococcal meningitis and CMV colitis. CT scan revealed a single hyperdense mass with minimal peripheral enhancement at the region of the cerebral peduncle and pons, causing obstructive hydrocephalus. He was treated with ventriculo-peritoneal shunt and cranial radiotherapy. He also received treatment with highly active antiretroviral therapy (HAART). A CD4+ cell count was increased from 2 to 345 cells/mm3. He returned to normal function for about 32 months after treatment.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Antiretroviral Therapy, Highly Active; Brain Neoplasms; HIV Seropositivity; Humans; Indinavir; Lamivudine; Lymphoma, AIDS-Related; Male; Radiography; Stavudine; Ventriculoperitoneal Shunt

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; CD4 Lymphocyte Count; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Female; HIV Infections; HIV Protease Inhibitors; Humans; Immunocompromised Host; Immunosuppression Therapy; Indinavir; Lamivudine; Lymphoma, AIDS-Related; Male; Methotrexate; Middle Aged; Prednisone; Reverse Transcriptase Inhibitors; Stavudine; T-Lymphocyte Subsets; Vincristine

Combination therapy with protease inhibitors and nucleoside analogues dramatically suppresses plasma HIV-1 RNA and delays progression to AIDS, but the impact on HIV-associated malignancy remains to be established. We therefore examined incidence trends of Kaposi's sarcoma and non-Hodgkin's lymphoma in patients with advanced HIV infection in nine AIDS Clinical Trial Group studies of antiviral therapies for HIV and cytomegalovirus infections. Among a total of 6587 patients enrolled between November 1987 and February 1997, there were 280 cases of Kaposi's sarcoma and 68 cases of non-Hodgkin's lymphoma. Incidence rates per 100 person-years of both malignancies declined in concert with decreases in mortality, but the decreases in Kaposi's sarcoma were more profound and consistent than the decreases in non-Hodgkin's lymphoma. These data suggest that current therapies have ameliorated the incidence of Kaposi's sarcoma, but may not have had an equal effect on non-Hodgkin's lymphoma.

Topics: AIDS-Related Opportunistic Infections; Anti-HIV Agents; Antiviral Agents; Clinical Trials as Topic; Cytomegalovirus Retinitis; Foscarnet; Ganciclovir; HIV Infections; Humans; Incidence; Indinavir; Lymphoma, AIDS-Related; Lymphoma, Non-Hodgkin; Retrospective Studies; Sarcoma, Kaposi