levoleucovorin and Lymphoma--AIDS-Related

Human immunodeficiency virus (HIV) infection is known to be associated with an increased risk of non-Hodgkin's lymphoma (NHL). The majority of lymphomas (>80%) occurring during immunosuppression are aggressive B-cell in origin and have a high-to-intermediate histology grade. Treatment of NHL is not standardized.. To assess the clinical effectiveness and safety of single agent or combination chemotherapy with or without immunochemotherapy (rituximab) and with or without highly active antiretroviral therapy (HAART) on overall survival (OS) and disease-free survival (DFS) for previously untreated patients with AIDS-related NHL.. The Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 1, 2009), MEDLINE (1966-March 6, 2009), EMBASE (1988-March 6, 2009), LlLACS (1982 to February 17, 2009), Gateway (March 6, 2009), and AIDSearch (2006 -February 2008) were used to identify published, potentially eligible trials. Further, we searched several electronic sources. For additional information see the Cochrane HIV/AIDS Group search strategy.. Randomized controlled trials (RCTs) assessing the effectiveness of systemic treatments for previously untreated AIDS-related NHL. There were no age or language restrictions.. Authors independently assessed relevant studies for inclusion; four RCTs were selected. No meta-analysis was attempted due to clinical heterogeneity.. Four RCTs that included 857 patients (number range: 30 to 485) met the inclusion criteria. The studies have a high risk of bias; three RCTs were conducted in the United States and one was a multi-national, multi-centre RCT performed in France and Italy. One of the trials included only men. It was impossible to pool data for any of the outcomes due to the differences in the interventions assessed in these RCTs. Overall survival did not differ significantly between treatment groups. Disease free survival (DFS) was reported in two of the four RCTs, but it was not statistically significant between treatment groups.. We found no evidence that the systemic interventions for untreated patients with AIDS-related NHL provide superior clinical effectiveness for improving OS, DSF, and tumour response rate; however, this conclusion is based on four RCTs with limited sample size and variable quality. More adequately powered RCTs that have low risk of bias are necessary to determine the real benefit or harm of interventions to treat this population. Overall survival (OS), DFS, and quality of life should be included as endpoints.

Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols; Antiretroviral Therapy, Highly Active; Bleomycin; Cyclophosphamide; Dexamethasone; Disease-Free Survival; Doxorubicin; Female; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Leucovorin; Lymphoma, AIDS-Related; Male; Methotrexate; Prednisolone; Prednisone; Randomized Controlled Trials as Topic; Rituximab; Vincristine; Vindesine

The usefulness of intensive chemotherapy with the MACOP-B protocol was evaluated in 8 patients with AIDS-related non-Hodgkin's lymphoma (NHL). Four patients had a prior AIDS diagnosis. The median CD4+ lymphocyte count was 0.079 cells x 10(9)/l (range 0.016-0.330). All patients responded to treatment. Four patients finished chemotherapy, all with complete remission, while another 3 patients deteriorated prior to finishing treatment and died. The median survival was 4 months (range 1 to 86 months). Major causes of the poor outcome were AIDS-related opportunistic infections and meningeal CNS involvement by NHL developing during or after chemotherapy. Patients with AIDS-related NHL usually do not appear to benefit from treatment with MACOP-B protocol. Advanced immunodeficiency is associated with poor tolerance to treatment and inability to finish this chemotherapy protocol. MACOP-B chemotherapy does not prevent meningeal spread of lymphoma in spite of using repeatedly systemic methotrexate crossing the blood-brain barrier. CNS prophylaxis with repeated application of intrathecal methotrexate may lower the risk of meningeal spread of lymphoma, which developed in 1 of 5 patients given CNS prophylaxis as compared to 2 of 3 patients without CNS prophylaxis.

Topics: Acquired Immunodeficiency Syndrome; Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Doxorubicin; Humans; Leucovorin; Lymphoma, AIDS-Related; Lymphoma, Non-Hodgkin; Male; Methotrexate; Middle Aged; Prednisone; Survival Analysis; Vincristine

The overall results of chemotherapy in human immunodeficiency virus (HIV)-associated non-Hodgkin's lymphoma (NHL) have been poor. To define a subgroup of patients who may have a better outcome, an analysis of prognostic factors was performed of patients treated in AIDS Clinical Trials Group (ACTG) protocol 142, a phase III randomized trial of low-dose versus standard-dose methotrexate, bleomycin, doxorubicin, cyclophosphamide, vincristine, and dexamethasone (m-BACOD) plus granulocyte-macrophage colony-stimulating factor (GM-CSF) for the treatment of patients with newly diagnosed HIV-associated NHL.. The following baseline variables were included as potential predictors of survival among 192 patients who received treatment: age; intravenous drug use (IVDU); specific type of sexual contact as risk factors (homosexual, bisexual, or heterosexual contact); prior AIDS diagnosis; CD4 cell count; serum lactic acid dehydrogenase (LDH); histology; Karnofsky performance status (KPS); stage; B symptoms; race (white/nonwhite); nodal involvement; extranodal involvement; number of extranodal sites; specific sites: bone marrow, liver, kidney, lung, or gastrointestinal tract; and treatment arm (standard-dose m-BACOD/low-dose m-BACOD).. Age greater than 35 years, IVDU, stages III/IV, and CD4 cell counts less than 100/microL were adverse prognostic factors in multivariate analyses using the Cox proportional hazards model. The median overall survival for patients with none or one of the adverse factors was 46 weeks, with two was 44 weeks, and with three or four was 18 weeks. At 144 weeks, 29.5% of patients with none or one, 16.9% with two, and 0% with three or four factors were alive (P < .001).. Long-term survival can be achieved in approximately one third of patients with HIV-associated NHL with favorable characteristics.

Topics: Adolescent; Adult; Age Factors; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; CD4 Lymphocyte Count; Child; Cyclophosphamide; Dexamethasone; Doxorubicin; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Leucovorin; Lymphoma, AIDS-Related; Methotrexate; Middle Aged; Multivariate Analysis; Prognosis; Vincristine

The objective of this study was to develop and test a combined therapeutic approach for patients with AIDS-related lymphoma (ARL), employing agents with independent mechanisms of action and nonoverlapping toxicity. This study was designed to test the feasibility and tolerance of combining low dose chemotherapy with infusional immunotoxin in the treatment of ARL patients.. Previously untreated patients received low dose methotrexate, bleomycin, doxorubicin, cyclophosphamide, and vincristine (m-BACOD) on a 21- to 28-day schedule. Patients who did not have progressive disease by Cycle 3 received anti-B4-blocked ricin (anti-B4bR), a murine monoclonal antibody linked to modified ricin, 20 microg/kg/day for 7 days administered by continuous infusion on an outpatient basis. A repeat cycle of anti-B4-bR was administered during Cycle 4 of chemotherapy based on tolerance. Patients received two cycles of chemotherapy beyond complete remission up to eight cycles. Study endpoints were toxicity, development of human antimurine antibody (HAMA) and human antiricin (HARA), tumor response, and survival.. Twenty-six of 44 patients received the immunotoxin therapy. Anti-B4-bR infusion was associated with transaminase elevation (Grade 3) in 14 of 26 patients (58%), and flulike symptoms were common. HAMA or HARA was observed in 8 patients (31%). The overall response rate was 57% (13 complete responses and 12 partial responses). The median survival for all patients was 8.9 months.. This study demonstrates the safety and feasibility of using chemotherapy and immunotoxin therapies in combination and supports their further evaluation to improve the outcomes of patients with ARL.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Combined Modality Therapy; Cyclophosphamide; Dexamethasone; Doxorubicin; Female; Humans; Immunotoxins; Leucovorin; Lymphoma, AIDS-Related; Male; Methotrexate; Ricin; Vincristine

Use of multiagent chemotherapy has been associated with complete remission (CR) in approximately 50% of patients with newly diagnosed acquired immunodeficiency syndrome (AIDS)-lymphoma, although additional AIDS-related complications may occur. Both chemotherapy and antiretroviral therapy were employed in an attempt to ascertain if the combination was safe, and associated with changes in human immunodeficiency virus (HIV) p24 antigen levels during the course of treatment.. Low dose methotrexate, bleomycin, doxorubicin, cyclophosphamide, vincristine, and dexamethasone(M-BACOD) chemotherapy and zalcitabine (ddC) were employed in 28 patients. Since both vincristine and zalcitabine may cause peripheral neuropathy, a Phase I/II study design was employed. Serum was analyzed for immune complex dissociated (ICD) HIV p24 antigen and interleukin (IL)-6 levels during therapy.. CR was achieved in 14 of 25 patients (56%), with partial response (PR) in 5 (20%). CRs were equivalent in patients with good or poor prognostic indicators, including a history of AIDS prior to lymphoma (CR = 60%); and/or CD4 lymphocytes < 200/mm3 (CR = 53%). Five patients with a CR subsequently relapsed (36%); median survival of CR patients was 29.2 months (4.1-61+), whereas that of all of the treated patients was 8.1 months. No significant peripheral neuropathy or other toxicity was observed. Serum ICD p24 antigen levels either fell (7/14) or remained consistently negative (2/14) in 9 of 14 patients (64%), whereas 36% experienced an increase. Elevated serum IL-6 levels at diagnosis were associated with systemic "B" symptoms (P = 0.023), whereas changes in IL-6 correlated with response to therapy over time (P = 0.006).. Combination antineoplastic and zalcitabine antiretroviral therapy may be safely administered to patients with AIDS-related lymphoma, resulting in CR in 56%, lack of significant neurotoxicity, and favorable effect on HIV p24 antigen in 50%. Elevation of serum IL-6 is associated with systemic "B" symptoms, whereas changes in serum IL-6 may correlate with response.

Topics: Acquired Immunodeficiency Syndrome; Adult; Antineoplastic Combined Chemotherapy Protocols; Antiviral Agents; Bleomycin; Cyclophosphamide; Dexamethasone; Doxorubicin; HIV Core Protein p24; HIV-1; Humans; Interleukin-6; Leucovorin; Lymphoma, AIDS-Related; Male; Methotrexate; Middle Aged; Peripheral Nervous System Diseases; Remission Induction; Vincristine; Zalcitabine

The use of full-dose intensive regimens of chemotherapy in patients with HIV-associated lymphoma has often resulted in severe toxicity, treatment delay, and reduced subsequent dosing. We conducted a Phase I trial to evaluate the toxicity of the combination of m-BACOD (methotrexate, Bleomycin, doxorubicin, cyclophosphamide, vincristine, dexamethasone) with granulocyte-macrophage colony stimulating factor (GMCSF) in these patients. A total of 17 patients were entered and treated at three dose levels of m-BACOD in combination with a fixed dose of GMCSF. Eight patients received standard dose m-BACOD plus GMCSF without experiencing dose-limiting hematologic toxicity, although significant nonhematologic toxicity was seen. We conclude that it is feasible to treat patients with HIV-associated lymphoma using standard dose m-BACOD plus GMCSF, but further study is needed to determine whether full-dose regimens improve survival when compared with reduced dose regimens in these individuals.

Topics: Adult; AIDS-Related Opportunistic Infections; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Dexamethasone; Doxorubicin; Granulocyte-Macrophage Colony-Stimulating Factor; HIV Core Protein p24; Humans; Kidney; Leucovorin; Leukocyte Count; Lung; Lymphoma, AIDS-Related; Lymphoma, Non-Hodgkin; Male; Methotrexate; Neutropenia; Remission Induction; Vincristine

Current treatment options for acquired-immunodeficiency syndrome (AIDS)-related non-Hodgkin's lymphoma (NHL) are unsatisfactory because of excessive toxicity rates and frequent recurrence of lymphoma. In this phase II study, we evaluated a novel 12 week chemotherapy program with respect to feasibility, toxicity and therapeutic results. Thirty HIV-seropositive patients with intermediate grade or small non-cleaved cell NHL received a 12 week program of weekly intravenous and oral chemotherapy consisting of etoposide, adriamycin, cyclophosphamide, bleomycin, vincristine, methotrexate and prednisone as well as biweekly intrathecal cytosine arabinoside. Prophylaxis against Pneumocystis carinii pneumonia (PCP) and candida were given routinely. The overall objective response rate was 73% with 33% complete responders. The time to progression for those stable or responding was 9.4 months. Five of 10 complete responders are well and free of disease 13.2 to 24.5 months from diagnosis. Median survival for the 30 patients was 8.1 months. NHL was the most common cause of death (13/22); opportunistic infection caused only one death (cryptococcal meningitis). Only 1 case of PCP occurred. The major toxicity was neutropenia. In conclusion this regimen resulted in response rates similar to other reports with acceptable toxicity and a very low incidence of PCP. Relapse of NHL remains a major challenge, however, and further studies are needed. Routine PCP prophylaxis should be incorporated into new trials of therapy for AIDS-related NHL.

Topics: Adult; Aged; AIDS-Related Opportunistic Infections; Antineoplastic Combined Chemotherapy Protocols; Bacterial Infections; Bleomycin; Cyclophosphamide; Doxorubicin; Feasibility Studies; Female; Humans; Incidence; Leucovorin; Life Tables; Lymphoma, AIDS-Related; Male; Methotrexate; Middle Aged; Neutropenia; Pentamidine; Pneumonia, Pneumocystis; Prednisone; Remission Induction; Survival Analysis; Treatment Outcome; Vincristine

To compare outcomes of patients with HIV-Burkitt's lymphoma (HIV-BL) and HIV-diffuse large-cell lymphoma (HIV-DLCL) after treatment with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) or M-BACOD (methotrexate, bleomycin, cyclophosphamide, etoposide) in pre-highly active antiretroviral therapy (HAART) versus HAART eras.. Three hundred sixty-three patients with AIDS-related lymphoma diagnosed from 1982 to 2003 were reviewed retrospectively, including 262 in the pre-HAART (HIV-BL, 117; HIV-DLCL, 145) and 101 in the HAART era (HIV-BL, 18; HIV-DLCL, 83). Pre-HAART included those who did not receive HAART, and HAART era included those diagnosed after January 1997 who received HAART.. There were no significant differences between groups in terms of age, sex, history of injection drug use, prior AIDS, lactate dehydrogenase level, and disease stage at diagnosis. Compared with HIV-BL, HIV-DLCL was associated with significantly lower CD4 counts in the pre-HAART but not the HAART era. Although the overall median survival was similar for both groups in the pre-HAART era (HIV-BL, 6.4 months v HIV-DLCL, 8.3 months; P = .43), survival was significantly worse in patients with HIV-BL in the HAART era (HIV-BL, 5.7 months v HIV-DLCL, 43.2 months; P = .0003). Failure to attain complete remission and CD4 count less than 100 cells/mm(3) independently predicted for poor survival in the pre-HAART era. In comparison, histology of HIV-BL and no attainment of complete remission were independent poor prognostic factors in the HAART era.. Survival of patients with HIV-DLCL has improved in the HAART era, along with CD4 count, whereas survival of similarly treated patients with HIV-BL remained poor. The current practice of using the same regimen for both groups of patients should be re-evaluated.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Antiretroviral Therapy, Highly Active; Bleomycin; Burkitt Lymphoma; Cyclophosphamide; Dexamethasone; Doxorubicin; Female; Humans; Leucovorin; Lymphoma, AIDS-Related; Lymphoma, Large B-Cell, Diffuse; Male; Methotrexate; Middle Aged; Prednisone; Retrospective Studies; Survival Rate; Treatment Outcome; Vincristine

Short, intensive cycles of chemotherapy have resulted in improved survival in BurkittOs lymphoma/leukemia (BL) in adults. The prognosis of patients with immunodeficiency virus (HIV)-associated BL is considered to be poor, but these patients have seldom been treated with BL-specific protocols. However, a study (PETHEMA-LAL3/97) in which patients with BL were treated regardless of their HIV status failed to find differences between HIV-infected and immunocompetent individuals. Furthermore, patients who received highly active antiretroviral therapy (HAART) seemed to have a slightly better disease-free survival than those who did not (p=0.051). We extended the follow-up analysis to elucidate the role of HAART in the survival of HIV-infected patients included in the PETHEMA-LAL3/97 protocol.

Topics: Acquired Immunodeficiency Syndrome; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Antiretroviral Therapy, Highly Active; Cyclophosphamide; Cytarabine; Dexamethasone; Disease-Free Survival; Etoposide; Female; Follow-Up Studies; Humans; Ifosfamide; Leucovorin; Leukemia; Lymphoma, AIDS-Related; Male; Methotrexate; Middle Aged; Prednisone; Treatment Outcome; Vincristine

P-glycoprotein is a product of the multidrug resistance (MDR-1) gene. In non-Hodgkin's lymphoma, less than 20% of untreated de novo lymphomas express MDR-1 compared with approximately 50% after failure of chemotherapy. We wished to study the expression of MDR-1 in AIDS-related non-Hodgkin's lymphoma (AIDS-NHL). Tissue biopsies from 50 patients with newly diagnosed AIDS-NHL were studied by immunohistochemical analysis using C494, a monoclonal antibody specific for the MDR-1 isoform of P-gp. MDR-1 expression was correlated with patient demographics, lymphoma characteristics, response to chemotherapy, and survival. Forty-six males and four females with a median age of 38 years (range 26-63) were studied. A prior AIDS-defining opportunistic infection was reported in 35 patients (70%). The median CD4+ lymphocyte count was 69/mm(3) (range 0-920). Thirty-two patients (63%) had received prior anti-HIV therapy, including a protease inhibitor in five (10%). Pathologic types consisted of diffuse large cell in 13 (26%), immunoblastic in 13 (26%), small non-cleaved in 22 (44%), and high grade not otherwise specified in two (4%). The majority of patients (76%) had stage III/IV disease. Pre-treatment lymphoma tissues from 33 patients (66%) stained positively for MDR-1. MDR-1 positive patients had a significantly lower complete remission rate compared to MDR-1 negative patients (33 versus 65%, P=0.042). Duration of complete response was significantly longer in MDR-1 negative patients compared with MDR-1 positive patients (not reached versus 9.9 months, P=0.003). Strategies to overcome MDR-1 expression may be important for initial treatment in patients with AIDS-NHL.

Topics: Acquired Immunodeficiency Syndrome; Adult; Anti-HIV Agents; Antineoplastic Combined Chemotherapy Protocols; ATP Binding Cassette Transporter, Subfamily B, Member 1; Bleomycin; Cyclophosphamide; Dexamethasone; Disease-Free Survival; Doxorubicin; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Female; Gene Expression Regulation, Leukemic; Humans; Leucovorin; Lymphoma, AIDS-Related; Male; Methotrexate; Middle Aged; Neoplasm Proteins; Prednisone; Remission Induction; Retrospective Studies; Survival Analysis; Vincristine

The introduction of triple antiretroviral therapy has led to reductions in opportunistic diseases in HIV-infected patients. However, little is known of the effect of this therapy on the clinical and pathological features and the outcome of patients with AIDS-related systemic non-Hodgkin's lymphoma (NHL). We examined the incidence and clinical manifestations of HIV-infected patients with systemic NHL at the Harris County Hospital District and Veterans Affairs Medical Center (Houston, TX). Between January 1996 and December 2000, 76 cases of systemic NHL were diagnosed in 3655 HIV-infected patients. Three groups of patients diagnosed with systemic NHL were identified according to their history of antiretroviral therapy: treatment naive (n = 20), dual nucleoside (n = 22), and triple antiretroviral drug-treated patients (n = 34). The median duration of antiretroviral therapy before the diagnosis of systemic NHL in the triple antiretroviral and dual nucleoside treatment groups was 12 versus 8 months (p < 0.0004). Thirty-five percent of patients (12 of 34) in the triple treatment group had an HIV RNA viral load of <400 copies/ml and their median CD4+ cell count was 301 cells/mm(3) (range, 46 to 667 cells/mm(3)) at the time of diagnosis of systemic NHL. More patients treated with triple antiretroviral therapy received complete courses of chemotherapy as compared with the other two groups (p = 0.013). However, the overall survival did not differ significantly among the three groups of patients. These data suggest that AIDS-related systemic NHL continues to occur even in patients treated with triple antiretroviral therapy. In addition, this opportunistic malignancy is associated with significant mortality. Therefore, it is necessary to develop a better understanding of the pathogenesis of this disease.

Topics: Adult; Anti-HIV Agents; Antineoplastic Combined Chemotherapy Protocols; Base Sequence; Bleomycin; CD4 Lymphocyte Count; Cyclophosphamide; Dexamethasone; DNA Primers; Doxorubicin; Female; HIV Infections; Humans; Incidence; Leucovorin; Lymphoma, AIDS-Related; Male; Methotrexate; Middle Aged; Prednisone; Texas; Treatment Outcome; Vincristine; Viral Load

Bone marrow involvement is reported in approximately 25% of patients with newly diagnosed acquired immunodeficiency syndrome-related lymphoma (ARL). Studied were 291 patients with ARL, diagnosed and treated at one medical center between 1984 and 1998. Clinical, immunologic, and pathologic characteristics of patients with bone marrow involvement were compared with those of patients without marrow involvement. Bone marrow involvement was present in 55 patients (19%). Small noncleaved lymphoma was diagnosed in 38% of the entire group and was the most common pathologic subtype in patients with bone marrow involvement (55% versus 34%; P =.008). Analysis of complete blood counts revealed a median hemoglobin level of 10.6 g/dL in both marrow-positive and marrow-negative groups. In contrast, a platelet count lower than 100 000/microL was more common in patients with bone marrow involvement (27% versus 11%; P =.02). Patients with marrow involvement were more likely to have leptomeningeal (cerebrospinal fluid [CSF]) lymphoma than patients whose marrows were uninvolved (24% versus 7%; P <.001) and were also more likely to have high lactate dehydrogenase (LDH) (P =.002), bone involvement (P <.001), and/or systemic B symptoms including fever, night sweats, and/or weight loss (P =.05). Median survival did not differ between marrow-positive and marrow-negative groups. On multivariate analysis, factors associated with decreased survival of marrow-positive patients included greater than 50% involvement (P =.002), systemic B symptoms (P =.008), and high-grade histologic type (P =.035). Marrow involvement in ARL correlates with small noncleaved pathology, thrombocytopenia lower than 100 000 mm(3), high LDH, and lymphomatous involvement of the CSF. Survival is statistically shorter in patients with greater than 50% marrow involvement, high-grade pathology, and/or systemic B symptoms.

Topics: Adult; Aged; Antibodies, Monoclonal; Antigens, CD; Antineoplastic Combined Chemotherapy Protocols; Biopsy; Bleomycin; Bone Marrow; Chi-Square Distribution; Cyclophosphamide; Dexamethasone; Doxorubicin; Female; Humans; Immunohistochemistry; Leucovorin; Lymphoma, AIDS-Related; Male; Methotrexate; Middle Aged; Prednisolone; Prognosis; Retrospective Studies; Survival Rate; Vincristine

The relationship between clinical and molecular characteristics of 45 treated individuals with histologically-documented human immunodeficiency virus (HIV)-associated B-cell non-Hodgkin's lymphoma was examined to determine whether differences in molecular features of lymphoma were associated with differences in clinical outcome. Tissue specimens from these tumors were evaluated for evidence of Ig heavy-chain gene rearrangements using both Southern blot analysis and reverse transcriptase polymerase chain reaction (RT-PCR). Lymphomas were also evaluated for the presence of Epstein-Barr virus (EBV) DNA sequences and c-myc gene rearrangements. Twenty-five lymphomas were characterized as polyclonal and 20 as monoclonal. PCR amplification of expressed Ig variable (V)-region genes confirmed polyclonality in three extensively studied polyclonal lymphomas. The median CD4 count was significantly higher in the group with polyclonal disease (277/microL) than in the group with monoclonal disease (123/microL), P = .04. The complete response rate to therapy was significantly higher in patients with polyclonal disease (78%) and CD4 greater than 200/microL (81%) than in those with monoclonal disease (31%) and CD4 less than 200/microL (33%). CD4 count, clonality, and presence of EBV DNA sequences were the most important predictors of survival. Both Kaplan-Meier and Cox proportional hazards analyses showed a markedly prolonged survival in those patients with both CD4 > or = 200/microL and polyclonal disease. Histologically the polyclonal lymphomas were high grade in appearance and contained prominent macrophages. All seven surviving patients were in this group. Median survival for those individuals whose tumors contained EBV sequences was only 3.2 months (range, 0.4 to 19.5), whereas those with EBV- tumors survived for a median of 9.0 months (range, 0.7 to 65.2), P = .0007. These data indicate that molecular features of HIV-associated lymphomas may be important predictors of clinical outcome. These characteristics define a distinct subset of patients with polyclonal EBV- tumors and CD4 counts greater than 200/microL that appear to have a less aggressive clinical course.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Blotting, Southern; CD4 Lymphocyte Count; Clone Cells; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Dexamethasone; DNA, Neoplasm; DNA, Viral; Doxorubicin; Etoposide; Gene Rearrangement, B-Lymphocyte, Heavy Chain; Genes, Immunoglobulin; Genes, myc; Granulocyte-Macrophage Colony-Stimulating Factor; Herpesvirus 4, Human; Humans; Immunoglobulin Variable Region; Immunologic Factors; Leucovorin; Life Tables; Lymphoma, AIDS-Related; Lymphoma, Non-Hodgkin; Methotrexate; Polymerase Chain Reaction; Prednisone; Proportional Hazards Models; Radiotherapy, Adjuvant; Recombinant Proteins; RNA, Messenger; RNA, Neoplasm; Survival Analysis; Treatment Outcome; Vincristine

Recent studies showed that patients with non-Hodgkin's lymphoma (NHL) with human immunodeficiency virus type 1 (HIV-1) infection may benefit from an intensive chemotherapeutic regimen. We report on our experience in the treatment of NHL-associated HIV-1 infection, with excellent prognostic factors, with MACOP-B regimen.

Topics: Acquired Immunodeficiency Syndrome; Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Doxorubicin; HIV-1; Humans; Leucovorin; Lymphoma, AIDS-Related; Methotrexate; Middle Aged; Prednisone; Prognosis; Remission Induction; Survival Rate; Vincristine

The occurrence of HIV associated non-Hodgkin's lymphoma (NHL) is a well recognized event. HIV associated Hodgkin's disease (HD) has also been observed. A unique patient with both entities is described. The patient was a 29 year old homosexual male who developed clinical IIA nodular sclerosis HD in 1985. He was HIV + with CD4/CD8 = 0.2 and his sister had HD 20 years earlier. He received MOPP and had a complete response. In October 1988 he developed weight loss with an abdominal mass and biopsy revealed diffuse small non-cleaved NHL, with bone marrow involvement. This was his first AIDS associated illness. Probes identified clonally rearranged DNA fragments in the J region of IgH chains and clonal rearrangements in the c-myc gene were also observed but EBV sequences could not be demonstrated. He was treated with m-BACOD but died in March 1989. His course was not complicated by opportunistic infection. Possible etiologies for the HD include his HIV status or shared sibling environment. The development of the NHL may have resulted from HIV infection and/or secondary to his treatment for HD. The relationship between the two lymphomas is uncertain and factors other than HIV exposure and its immune dysfunction may have been causal.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Child; Cyclophosphamide; Dexamethasone; DNA, Neoplasm; Doxorubicin; Environmental Exposure; Female; Gene Rearrangement, B-Lymphocyte, Heavy Chain; Herpesvirus 4, Human; HIV Infections; Hodgkin Disease; Humans; Incidence; Leucovorin; Lymphoma, AIDS-Related; Lymphoma, Non-Hodgkin; Male; Mechlorethamine; Methotrexate; Neoplasms, Multiple Primary; Neoplasms, Second Primary; Prednisone; Procarbazine; Remission Induction; Vincristine