Changes in the influence of lymphoma- and HIV-specific factors on outcomes in AIDS-related non-Hodgkin lymphoma.

BACKGROUND: We undertook the present analysis to examine the shifting influence of prognostic factors in HIV-positive patients diagnosed with aggressive non-Hodgkin lymphoma (NHL) over the last two decades. PATIENTS AND METHODS: We carried out a pooled analysis from an existing database of patients with AIDS-related lymphoma. Individual patient data had been obtained prior from prospective phase II or III clinical trials carried out between 1990 until 2010 in North America and Europe that studied chemo(immuno)therapy in HIV-positive patients diagnosed with AIDS-related lymphomas. Studies had been identified by a systematic review. We analyzed patient-level data for 1546 patients with AIDS-related lymphomas using logistic regression and Cox proportional hazard models to identify the association of patient-, lymphoma-, and HIV-specific variables with the outcomes complete response (CR), progression-free survival, and overall survival (OS) in different eras: pre-cART (1989-1995), early cART (1996-2000), recent cART (2001-2004), and contemporary cART era (2005-2010). RESULTS: Outcomes for patients with AIDS-related diffuse large B-cell lymphoma and Burkitt lymphoma improved significantly over time, irrespective of baseline CD4 count or age-adjusted International Prognostic Index (IPI) risk category. Two-year OS was best in the contemporary era: 67% and 75% compared with 24% and 37% in the pre-cART era (P < 0.001). While the age-adjusted IPI was a significant predictor of outcome in all time periods, the influence of other factors waxed and waned. Individual HIV-related factors such as low CD4 counts (<50/mm(3)) and prior history of AIDS were no longer associated with poor outcomes in the contemporary era. CONCLUSIONS: Our results demonstrate a significant improvement of CR rate and survival for all patients with AIDS-related lymphomas. Effective HIV-directed therapies reduce the impact of HIV-related prognostic factors on outcomes and allow curative antilymphoma therapy for the majority of patients with aggressive NHL.

Mars: new absorption bands in the spectrum.

New absorption bands have been found in the near-infrared spectrum of Mars by Fourier spectroscopy. They are tentatively identified in part as due to reduced gases in the Martian atmosphere.

Prognostic factors in the treatment of human immunodeficiency virus-associated non-Hodgkin's lymphoma: analysis of AIDS Clinical Trials Group protocol 142--low-dose versus standard-dose m-BACOD plus granulocyte-macrophage colony-stimulating factor. National Institute of Allergy and Infectious Diseases.

PURPOSE: 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. MATERIALS AND METHODS: 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). RESULTS: 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). CONCLUSION: Long-term survival can be achieved in approximately one third of patients with HIV-associated NHL with favorable characteristics.

Clinical and virologic effects of recombinant human granulocyte-macrophage colony-stimulating factor in patients receiving chemotherapy for human immunodeficiency virus-associated non-Hodgkin's lymphoma: results of a randomized trial.

Thirty patients with human immunodeficiency virus (HIV)-associated non-Hodgkin's lymphoma (NHL) receiving chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) were randomized to receive either subcutaneous recombinant human granulocyte-macrophage colony-stimulating factor (rGM-CSF) or no additional therapy. Recombinant rGM-CSF (at a dose of 10-20 micrograms/kg/d) was given on days 1 to 10 (early rGM-CSF) to the first five patients, but was changed to days 4 to 13 (delayed rGM-CSF) of each chemotherapy cycle in subsequent patients. Compared with the control group (N = 10), the delayed rGM-CSF group (N = 11) had higher mean nadirs of the absolute neutrophil count (0.36 v 0.89 x 10(9)/L; P = .009), shorter mean durations of neutropenia (4.9 v 1.3 days; P = .02), fewer chemotherapy cycles complicated by neutropenia and fever (67% v 27%; P = .001), fewer days hospitalized for fever and neutropenia (4.9 v 1.8; P = .004), fewer reductions in chemotherapy dosages, and less frequent delays in chemotherapy administration. No significant differences were observed between patients in the control group and those in the early rGM-CSF group (N = 5). Median levels of serum HIV-1 p24 antigen decreased to 18% and 17% of baseline values in control (N = 4) and rGM-CSF groups (N = 6), respectively, 1 week following administration of the first cycle of chemotherapy. In the third week after chemotherapy, median antigen levels remained below baseline in the control group, but rose to 243% of baseline values in the rGM-CSF group (P = .01), suggesting stimulation of HIV replication. The effect of this change in HIV activity on clinical outcome of treated patients could not be determined, and therefore the clinical significance of this finding remains unclear. Complete response rates of 67%, 70%, and 60% were observed in the control, delayed rGM-CSF, and early rGM-CSF groups, respectively, with corresponding survival times of 9.0, 11.4, and 8.0 months.

Pegylated-liposomal doxorubicin versus doxorubicin, bleomycin, and vincristine in the treatment of AIDS-related Kaposi's sarcoma: results of a randomized phase III clinical trial.

PURPOSE: Kaposi's sarcoma (KS), the most common neoplasm in patients with AIDS, is a significant clinical problem for which current therapies are frequently unsatisfactory. We conducted a randomized phase III clinical trial to compare the efficacy and toxicities of a new form of therapy, pegylated-liposomal doxorubicin, with standard combination chemotherapy in patients with advanced AIDS-related KS (AIDS-KS). PATIENTS AND METHODS: Two hundred fifty-eight patients with advanced AIDS-KS were randomly assigned to receive either pegylated-liposomal doxorubicin (20 mg/m2) or the combination of doxorubicin (20 mg/m2), bleomycin (10 mg/m2) and vincristine (1 mg) (ABV) every 14 days for six cycles. Standard response criteria, toxicity criteria, and predefined indicators of clinical benefit were examined to evaluate outcomes. RESULTS: Among 133 patients randomized to receive pegylated-liposomal doxorubicin, one achieved a complete clinical response and 60 achieved a partial response for an overall response rate of 45.9% (95% confidence interval [CI], 37% to 54%). Among 125 patients randomized to receive ABV, 31 achieved a partial response (24.8%; 95% confidence interval [CI], 17% to 32%). This difference was statistically significant (P < .001). In addition to objective responses, prospectively defined clinical benefits and toxicity outcomes also favored pegylated-liposomal doxorubicin. CONCLUSION: Pegylated-liposomal doxorubicin is more effective and less toxic than the standard combination chemotherapy regimen ABV for treatment of AIDS-KS.

Delayed hematopoietic recovery after auto-SCT in patients receiving arsenic trioxide-based therapy for acute promyelocytic leukemia: a multi-center analysis.

A potential link between arsenic (ATO)-based therapy and delayed hematopoietic recovery after autologous hematopoietic SCT (HSCT) for acute promyelocytic leukemia (APL) has previously been reported. We retrospectively reviewed the clinical histories of 58 patients undergoing autologous HSCT for APL at 21 institutions in the United States and Japan. Thirty-three (56%) of the patients received ATO-based therapy prior to stem cell collection. Delayed neutrophil engraftment occurred in 10 patients (17%): 9 of the 10 patients (90%) received prior ATO (representing 27% of all ATO-treated patients), compared with 1 of the 10 patients (10%) not previously treated with ATO (representing 4% of all ATO-naïve patients; P<0.001). Compared with ATO-naïve patients, ATO-treated patients experienced significantly longer times to ANC recovery (median 12 days vs 9 days, P<0.001). In multivariate analysis, the only significant independent predictor of delayed neutrophil engraftment was prior treatment with ATO (hazard ratio 4.87; P<0.001). Of the available stem cell aliquots from APL patients, the median viable post-thaw CD34+ cell recovery was significantly lower than that of cryopreserved autologous stem cell products from patients with non-APL AML. Our findings suggest that ATO exposure prior to CD34+ cell harvest has deleterious effects on hematopoietic recovery after autologous HSCT.

Pathogenesis of AIDS lymphomas.

The AIDS-associated lymphomas represent a heterogeneous set of disease processes. The largest histologic subset of lymphomas is the large-cell lymphomas, which represent a spectrum of disease processes ranging from monomorphic monoclonal B-cell proliferations to very polymorphic and polyclonal mixtures of B cells, T cells and macrophages. The next most frequent class of systemic lymphoma are the small non-cleaved cell or Burkitt's-like lymphomas. These are relatively monomorphic, monoclonal malignant B-cell proliferations. The final subset of lymphomas, which are likely to become more common as the AIDS epidemic progresses, are the primary CNS lymphomas, which are expansions of EBV-immortalized B cells. The high incidence of tumor-associated EBV in the CNS lymphomas makes these lesions somewhat analogous to an opportunistic EBV infection. In HIV disease there is a long lag after infection before the appearance of clinical manifestations of impaired T-cell immunity. During this period, both appropriate B-cell proliferation in response to antigen (including the ubiquitous HIV) and abnormal B-cell proliferation (autoimmune, dysregulated) occur as the follicular architecture is disrupted by the virus and potential APC are exposed and/or infected with HIV. The destruction of FDC or the involution of their processes could interfere with the elimination by apoptosis of low-avidity B-cell clones. Antigen-competent B cells with pre-existing chromosomal translocations such as the t(8;14) (c-myc, IgH) would have a selective growth advantage in this setting. Figure 9 shows a schematic representation of prelymphomatous and lymphomagenic events as they are projected to occur. A similar pathogenetic scheme has been postulated for follicular B-cell lymphomas: PCR studies have demonstrated that a pool of t(14;18) (IgH;bcl-2) B-cells are present in lymph nodes featuring follicular hyperplasia. In response to antigen (the evidence favoring antigen drive is extensive hypersomatic mutation in sequences related to binding sites), B cells with the t(14;18) translocation have a selective advantage because the bcl-2 oncogene confers a resistance to apoptosis. Burkitt's lymphomas, particularly sporadic or HIV variants, fulfill at least the key criteria for antigen competence, mainly the presence of surface Ig. The c-myc-associated chromosomal translocational events are likely to occur early during the enzymatic machinations of gene rearrangement. Such B cells would be in the dysregulated cytokine and antigen milieu of HIV disease and ultimately could have a selective advantage. EBV infection of B cells probably requires activation and expression of the CD21 receptor. Furthermore, CD5+ B cells of CLL are refractory to EBV infection.(ABSTRACT TRUNCATED AT 400 WORDS)

The safety and pharmacokinetics of GLQ223 in subjects with AIDS and AIDS-related complex: a phase I study.

A phase I dose-escalation study was performed to evaluate the safety and pharmacokinetics of a single intravenous infusion of GLQ223 in subjects with AIDS and AIDS-related complex (ARC). The active ingredient in GLQ223 is trichosanthin. Trichosanthin, imported from China, is the active drug in community-initiated treatment programs for patients with HIV infection. Eighteen subjects were enrolled, 10 with AIDS and eight with ARC. All subjects were monitored for tolerance and toxicity. Immunological and virological parameters were also followed. GLQ223 administration was not associated with notable toxicity with the exception of one subject who experienced a severe neurological adverse reaction. No consistent or sustained changes in CD4+ lymphocyte populations or HIV antigen levels were observed. Serum concentrations of GLQ223 that were comparable to concentrations shown to have antiviral activity in vitro were achieved transiently but may not have been maintained for a sufficient duration to exert antiretroviral effects. Further studies are indicated to determine pharmacodynamic properties of GLQ223, its optimal dosing schedule, and whether GLQ223 or related molecules will be useful in the treatment of HIV infection.

Kaposi's sarcoma involving the lung in patients with the acquired immunodeficiency syndrome.

To determine the distinguishing features of pulmonary Kaposi's sarcoma (KS) in patients with the acquired immunodeficiency syndrome (AIDS), we compared three groups of patients, 16 with endobronchial KS, 15 with endobronchial KS and an opportunistic lung infection, and 40 with Pneumocystis carinii pneumonia (PCP) without concomitant pulmonary KS. The majority of pulmonary KS patients had extensive cutaneous disease at the time of pulmonary diagnosis, and the diagnosis of pulmonary KS was easily established by the characteristic appearance of the endobronchial lesions. Dyspnea, fever, and cough were common presenting symptoms, but occurred more commonly in association with accompanying opportunistic infection. Diffuse interstitial infiltrates were observed in most patients in both groups, but the findings of nodular parenchymal densities or pleural effusion were more commonly observed in patients with pulmonary KS than in those with PCP alone. Pulmonary uptake of gallium-67 citrate or a diffusing capacity less than 80% were unusual in patients with pulmonary KS alone, but common in those with accompanying opportunistic infection or with PCP alone. Median survival in patients with pulmonary KS was only 2 months, and most patients had complicating opportunistic infections at the time of death. Pulmonary KS is generally a late and often preterminal manifestation of AIDS. Chest radiographs, gallium lung scans, and pulmonary function testing may provide diagnostic information that is helpful in distinguishing pulmonary KS from opportunistic lung infections.

Cryotherapy for cutaneous Kaposi's sarcoma (KS) associated with acquired immune deficiency syndrome (AIDS): a phase II trial.

To assess the response and toxicity of liquid nitrogen cryotherapy for cutaneous lesions of Kaposi's sarcoma (KS) associated with AIDS, we evaluated 20 subjects with biopsy-proven KS in a phase II clinical trial. Subjects had two to four cutaneous KS indicator lesions treated with liquid nitrogen cyrotherapy. Treatment was repeated at 3 week intervals, allowing adequate healing time. On average, subjects received three treatments per lesion with a mean follow-up time of 11 weeks (range of 6-25 weeks). One treatment consisted of two freeze-thaw cycles, with thaw times ranging from 11 to 60 s per cycle. A complete response was observed in 80% of treated KS lesions and lasted a minimum of 6 weeks following the completion of therapy. Greater than 50% cosmetic improvement of KS was observed. Histopathology of treated lesions correlated poorly with cosmetic improvement. Response was not predicted by tolerance to zidovudine therapy, CD4+ cell count, presence of B symptoms, or previous chemotherapy. Subjects without prior history of opportunistic infection (OI) were more likely to have a better response than those with a prior history of OI. Subjects tolerated cryotherapy well. Blistering occurred frequently, but local pain was limited and relieved by acetaminophen. Secondary infection did not occur. Based on this study, we recommend cryotherapy to subjects with cutaneous KS lesions. Liquid nitrogen cryotherapy is easily applied as a primary therapy, and may also have a role in the treatment of cutaneous KS lesions that respond slowly or show incomplete cosmetic improvement with systemic therapies.

AIDS-associated polyclonal lymphoma: identification of a new HIV-associated disease process.

High-grade non-Hodgkins B-cell lymphoma is one of the principle malignancies that occurs in individuals infected with the human immunodeficiency virus (HIV-1). Immunoblastic lymphomas that arise in immunosuppressed transplant patients have been described as both monoclonal and polyclonal, and occur in association with Epstein-Barr virus (EBV) infection. To test whether polyclonal lymphoma occurred in patients with AIDS we studied tumors from multiple sites in three patients who died with widespread AIDS-associated large cell or large cell immunoblastic lymphoma. All biopsy specimens contained invasive lymphoma. Tumor cells were mature IgM-positive immunoblasts by immunohistochemical analysis, with the same B-cell phenotype observed in all tumor sites. Only a minority of sites from all patients analyzed were monoclonal as measured by immunoglobulin gene rearrangements, with one case having several foci of monoclonal disease with other histologically identical metastases showing no evidence of monoclonal proliferation. Similar to the transplant-associated polyclonal B-cell proliferations. EBV gene sequences were present in multiple sites from one autopsy. In the other two autopsies, polyclonal B-cell proliferations occurred in the absence of EBV involvement except at one site, where a minor clone of EBV-infected cells was found. In contrast to HIV-associated Burkitt's lymphoma, no c-myc rearrangements were found at any site. These studies describe the occurrence of polyclonal lymphoma in AIDS and suggest that EBV-negative polyclonal lymphoma may be a distinct disease entity unique to HIV-infected individuals.

Intralesional recombinant tumor necrosis factor-alpha for AIDS-associated Kaposi's sarcoma: a randomized, double-blind trial.

The effect of recombinant tumor necrosis factor-alpha (rTNF), injected directly into the tumor, was evaluated in a Phase I/II study of 27 patients with AIDS-associated Kaposi's sarcoma (KS). The maximally tolerated intralesional dose was less than 100 micrograms/m2 and the recommended intralesional dose was 25 micrograms/m2. In a double-blind, randomized, placebo-controlled study, rTNF reduced the cross-sectional area of 15 of 16 (94%) of the injected KS lesions and caused complete disappearance of 3 of 16 (19%) lesions. Only injected lesions showed a response. Rigors and fever were common dose-dependent side effects and were attenuated by meperidine. There were no changes in human immunodeficiency virus (HIV) activity as determined by serum p24 antigen levels. While biologically active, the systemic toxicity of rTNF as well as the lack of distant antitumor effects in noninjected lesions limits its clinical usefulness under the conditions employed in this trial.

The usefulness of diagnostic bone marrow examination in patients with human immunodeficiency virus (HIV) infection.

To determine the utility of bone marrow examination for the diagnosis of opportunistic infections and lymphoma in patients with known or suspected human immunodeficiency virus (HIV) infection, we retrospectively reviewed the medical and laboratory records of all patients undergoing diagnostic bone marrow examinations at San Francisco General Hospital between January 1, 1988 and December 31, 1989. All marrow examinations of patients with known or suspected HIV infection in which specimens were examined histopathologically and/or microbiologically for opportunistic pathogens or lymphoma were analyzed. Bone marrow examination resulted in the diagnosis of mycobacterial infection in 16% of the patients studied. Blood culture was 77% sensitive and bone marrow culture was 86% sensitive for detecting disseminated mycobacterial infection. This difference was not statistically significant (p greater than 0.05). Disseminated fungal infections occurred in less than 5% of the patients studied, and most were rapidly and accurately detected by examination of stained bone marrow samples. No case of lymphoma was diagnosed by bone marrow examination. Bone marrow examination may be useful for diagnosing opportunistic infections in patients with HIV infection. Mycobacterial blood cultures have a sensitivity comparable to bone marrow cultures in detecting disseminated mycobacterial infections, are less invasive, and may be less costly. Marrow examination is not useful for diagnosing lymphoma but can determine the extent of lymphoma that has been diagnosed by other means.

Lack of response to suramin in patients with AIDS and AIDS-related complex.

Forty-one homosexual men with the acquired immune deficiency syndrome (AIDS) or AIDS-related complex were treated with 0.5, 1.0, or 1.5 g of suramin weekly for up to six months. In no patient was evidence of symptomatic improvement or regression of Kaposi's sarcoma shown. Opportunistic infections developed in 16 patients during therapy. Only six patients (15 percent) became human immunodeficiency virus (HIV) culture-negative during treatment, despite documentation of adequate serum suramin levels. All but one of these six have had disease progression. Decreases in the numbers of total T4 cells with time were observed in both AIDS and AIDS-related complex subgroups. Toxicity was significant and consisted of fatigue, fever, and hepatic and renal dysfunction, all of which were observed most frequently with the 1.0 or 1.5 g dosages. Fatal hepatic failure developed in two patients, and adrenal insufficiency was documented in eight patients. Suramin is a toxic agent that shows no virologic, immunologic, or clinical benefit in patients with HIV-related disease.

The pulmonary manifestations of AIDS-related non-Hodgkin's lymphoma.

STUDY OBJECTIVE: To describe the clinical, radiographic, and autopsy features of AIDS-related non-Hodgkin's Iymphoma (NHL) with pulmonary involvement. DESIGN: Retrospective series of patients with HIV infection and NHL with pathologically documented lung or pleural involvement. SETTING: A university and a county hospital in San Francisco. PATIENTS: Thirty-eight patients with HIV infection and NHL involving the lungs or pleura. RESULTS: Most patients had respiratory symptoms (87%) and signs (84%). The majority of patients had advanced HIV infection, with a mean CD4 count of 67 (+/- 65). The most common laboratory abnormalities were elevated lactate dehydrogenase value (89%), elevated erythrocyte sedimentation rate (94%), hematologic abnormalities (95%), and widened alveolar-arterial gradient (89%). Thoracic CT revealed pulmonary nodules (50%), lobar infiltrates (27%), and lung mass (19%) as the most common parenchymal abnormalities. Pleural effusion (68%) and thoracic lymphadenopathy (54%) were unexpectedly common. Autopsy confirmed the high prevalence of pulmonary nodules (30%), airspace disease (35%), and lung mass (25%). Pleural effusions (65%) and thoracic lymphadenopathy (60%) were also common at autopsy. The respiratory system was the most common extranodal site (71%) in patients with AIDS-related NHL undergoing autopsy. Of the bronchoscopic procedures performed, transbronchial biopsy had the highest diagnostic yield (58%) for lymphoma. BAL and bronchial brushing were never diagnostic. Pleural fluid cytologic study and open lung biopsy specimens also had high diagnostic yields (75% each). CONCLUSIONS: The lung is a common extranodal site in AIDS-related NHL. NHL with pulmonary involvement occurs primarily in patients with advanced HIV infection. Most patients have nodules, infiltrates, or masses by thoracic imaging and autopsy. Thoracic lymphadenopathy is much more common than previously believed. Transbronchial biopsy, pleural fluid cytologic study, and open lung biopsy are the most useful diagnostic procedures.

AIDS-associated lymphomas.

Patients with HIV infection, like immunosuppressed transplant recipients, are at high risk for the development of non-Hodgkin's lymphoma. These are high-grade lymphomas of B cell origin. Most patients present with advanced extralymphatic disease, and primary lymphoma of the central nervous system has frequently been reported. The cause of the non-Hodgkin's lymphomas in the setting of HIV infection remains unclear. In contrast to those lymphomas observed in transplant recipients, Epstein-Barr virus DNA sequences have been identified in a minority of AIDS-associated lymphomas. Response to therapy in these patients has been disappointing. Response rates to chemotherapy have been lower than those observed in other lymphoma patients, and treatment has been complicated by lack of adequate bone marrow reserve and the occurrence of frequent opportunistic infections. Survivals have been short. Good performance status and absence of a prior AIDS diagnosis are important predictors of response and survival. Although Hodgkin's disease has been observed in HIV-infected patients, epidemiologic data are not suggestive of a direct causal relationship. Hodgkin's disease in this setting is characterized by poor prognosis histologic pattern, advanced disease, and median survivals of less than 1 year.

Doxorubicin encapsulated in liposomes containing surface-bound polyethylene glycol: pharmacokinetics, tumor localization, and safety in patients with AIDS-related Kaposi's sarcoma.

A study of the plasma pharmacokinetics, tumor localization, and safety of a single dose of doxorubicin encapsulated in liposomes containing surface-bound polyethylene glycol (PEG-liposomal doxorubicin) was conducted in patients with Kaposi's sarcoma (KS) as a manifestation of acquired immune deficiency syndrome (AIDS). Eighteen patients with AIDS-KS diagnosed by examination of biopsy specimens were randomly assigned to receive either standard doxorubicin or PEG-liposomal doxorubicin. Consecutive participants were entered at three dose levels (10, 20, and 40 mg/m2) in ascending fashion. Clearance of PEG-liposomal doxorubicin was 0.034 L/h/m2 to 0.108 L/h/m2, volume of distribution (Vd) was 2.2 L/m2 to 4.4 L/m2, and half-lives (t1/2) of the initial decline in the plasma concentration-time curve and of the terminal decline were 3.77 hours and 41.3 hours, respectively. Seventy-two hours after administration, doxorubicin levels observed in lesions of patients receiving PEG-liposomal doxorubicin were 5.2 to 11.4 times greater than those found in patients given comparable doses of standard doxorubicin. PEG-liposomal doxorubicin and standard doxorubicin were roughly equipotent in producing toxicity. Encapsulation in liposomes containing surface-bound PEG significantly limits the distribution and elimination of doxorubicin, results in greater accumulation of the drug in KS lesions 72 hours after dosing than does standard doxorubicin, and may improve drug efficacy and therapeutic index in the treatment of AIDS-KS.

Diagnosis and management of systemic non-Hodgkin's lymphoma in HIV disease.

Persons with HIV infection are at an increased risk of developing intermediate and high-grade non-Hodgkin's lymphomas. Patients present with wide-spread extranodal disease at the time of initial presentation, with unusual sites of disease common. Factors predictive of a poor prognosis are low performance status, history of AIDS prior to the diagnosis of lymphoma, bone marrow involvement, and low CD4 count. Experience suggests that in some patients, more aggressive chemotherapy may be associated with shortened survival time. Recent clinical trials have demonstrated that the use of either myeloid growth factors or reduced-dosage chemotherapeutic regimens can reduce the morbidity associated with chemotherapy. A number of new and exciting experimental treatments are now in clinical development. These include new chemotherapy-based regimens, immune modulators immunotoxin therapy, and cellular therapy. It is hoped that as we continue to learn more about the biology of the HIV-associated lymphomas, we can develop more rational and effective treatment modlities that take advantage of the unique molecular characteristics of these tumors.

Cutaneous presentations of lymphoma in human immunodeficiency virus disease. Predominance of T cell lineage.

BACKGROUND AND DESIGN: Most non-Hodgkin's lymphomas in patients with human immunodeficiency virus infection are of B-cell lineage. Cutaneous lymphoma in the human immunodeficiency virus disease has not been systematically reviewed. We studied 25 patients with both human immunodeficiency virus infection and cutaneous presentations of lymphoma, using immunohistochemistry and in situ hybridization for Epstein-Barr virus. RESULTS: Two groups of patients were discerned: (1) those with conditions similar to mycosis fungoides or Sézary syndrome with an indolent course (n = 8) and (2) those with nodules or papules, greater immunosuppression, a rapid clinical course, and large cell lymphoma seen on biopsy specimens (n = 17). The epidermotropic lymphomas were T-cell lineage and CD30-. Thirteen of the large cell lymphomas were also of the T-cell type, and 71% were CD30+. Epstein-Barr virus was absent in the epidermotropic lymphomas, but it was present in 73% of the nonepidermotropic cases. CONCLUSIONS: Two forms of human immunodeficiency virus-associated cutaneous lymphoma were found: indolent disease resembling mycosis fungoides or Sézary syndrome and large cell lymphomas with a poor prognosis, whose cells often had a CD30+ T-cell phenotype and harbored the Epstein-Barr virus.