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L D Kaplan

Publications and source records attributed to L D Kaplan.

At least 37 records · Page 2Linked to original sources
PubMed1991

Clinical manifestations and treatment of HIV related non-Hodgkin lymphoma.

Non-Hodgkin lymphoma developing in patients with HIV infection fulfills diagnostic criteria for AIDS. Clinical manifestations of AIDS-NHL are similar to those of malignant lymphoma arising in other acquired and congenital immunodeficiency states. AIDS related NHLs therefore consist primarily of tumours with B cell phenotype, intermediate or high grade histological subtype and rapid clinical progression with a high frequency of unusual extranodal involvement. Treatment of AIDS-NHL has been much less rewarding than treatment of lymphoma in non-HIV infected individuals. Complete response rates are lower than the corresponding rates seen in the non-HIV infected population, and responses that do occur tend to be of short duration. Improvements in treatment for AIDS-NHL will require the use of new therapies, designed to cause less myelosuppression, in conjunction with aggressive efforts to prevent opportunistic infections.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

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.

Acquired Immunodeficiency Syndrome↗
PubMed1991

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.

Acquired Immunodeficiency Syndrome↗
PubMed1991

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.

Bone Marrow Examination↗
PubMed1990

The safety and pharmacokinetics of recombinant soluble CD4 (rCD4) in subjects with the acquired immunodeficiency syndrome (AIDS) and AIDS-related complex. A phase 1 study.

STUDY OBJECTIVE: To evaluate the safety and pharmacokinetics of recombinant, soluble human CD4 (rCD4) in subjects with the acquired immunodeficiency syndrome (AIDS) and AIDS-related complex. The protein rCD4 binds to envelope protein, gp120, of the human immunodeficiency virus (HIV) and blocks HIV infection of CD4 lymphocytes in vitro. DESIGN: Phase 1 trial with dose escalation. SETTING: Two university-affiliated hospital clinics. SUBJECTS: Of 42 subjects enrolled, 29 had AIDS and 13 had AIDS-related complex. INTERVENTIONS: The rCD4 was administered by rapid intravenous infusion on day 1, followed by a 3-day washout, then once a day for 10 days, followed by a 7-day washout, and then three times a week for 8 weeks. Doses of 1, 10, 30, 100, and 300 micrograms/kg body weight per day of rCD4 were administered intravenously to 6 subjects at each dose level. Twelve additional patients received 300 micrograms/kg.d of rCD4: 6 by intramuscular and 6 by subcutaneous injection. All subjects were monitored for toxicity. Immunologic and virologic variables were also monitored. MEASUREMENTS AND MAIN RESULTS: Administration of rCD4 was not associated with important toxicity as determined by clinical monitoring or by serum chemistry, hematologic, or immunologic variables. No subjects required dose reduction or discontinuation of therapy due to rCD4-related toxicity. No consistent or sustained changes in CD4 lymphocyte populations or HIV antigen levels were observed. The volume of distribution of rCD4 was small, and clearance remained constant over the dose range studied. The bioavailability of intramuscular injection and subcutaneous injection was 51% and 45%, respectively. CONCLUSIONS: At the dose levels used in this study, rCD4 appears safe and well tolerated. Serum concentrations of rCD4 were achieved that were comparable to concentrations shown to have antiviral activity in vitro. Further studies are indicated to determine whether rCD4 or related molecules will be useful in treating HIV infection.

AIDS-Related Complex↗
PubMed1990

AIDS-associated lymphoma.

Like other immunodeficient populations, HIV-infected individuals are at risk for developing high grade B-cell malignancies. The aetiology of these lymphomas remains unknown. While the tumours share many of the features of B-cell lymphomas seen in immunosuppressed transplant recipients, unlike transplant recipients, Epstein-Barr virus genomic sequences are identified in only a small minority of peripheral lymphomas from HIV-infected individuals. The majority of lymphomas are classified as diffuse, large-cell tumours of either the intermediate grade type or the high grade immunoblastic type. However, approximately one-third of patients present with high grade, small, non-cleaved cell lymphomas. Patients typically present with widespread extranodal disease, often at unusual sites. Lymphoma confined to the central nervous system has been observed in approximately 25% of HIV-infected patients with non-Hodgkin's lymphoma. The therapeutic outcome and survival in these patients has been disappointing. Complete response is achieved less frequently, relapse rates are higher and survival generally shorter than those observed in non-HIV-infected patients with non-Hodgkin's lymphoma. Prognosis is better for those patients without a prior AIDS diagnosis, who have higher total CD4 cell counts, good performance score, absence of an extranodal site of disease, and treatment with more moderate doses of chemotherapy. Hodgkin's disease, while not causally linked to the presence of immunodeficiency, appears to have a more aggressive natural history in the patient with HIV infection. Advanced disease at presentation is the rule, and the response to therapy has been poor with associated short survivals. Poor bone marrow reserve and the occurrence of intercurrent opportunistic infections has made it difficult to administer many of the standard chemotherapeutic regimens now used for the treatment of Hodgkin's disease.

Acquired Immunodeficiency Syndrome↗
PubMed1990

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.

AIDS-Related Complex↗
PubMed1989

AIDS-associated non-Hodgkin's lymphoma in San Francisco.

The characteristics of acquired immunodeficiency syndrome-associated non-Hodgkin's lymphoma in 84 patients diagnosed and treated at San Francisco General Hospital are presented herein. While the majority were high-grade B-cell lymphomas, one cutaneous T-cell and one peripheral T-cell lymphoma were observed. In addition, three other tumors were suspicious for T-cell lymphoma. Sixty-seven percent of patients had stage IV disease, often at unusual sites. Epstein-Barr virus DNA sequences were identified in only five of 15 tumors by dot-blot analysis. Patients were treated with a variety of standard chemotherapeutic regimens, with radiation therapy alone, or with a novel chemotherapy protocol (COMET-A). No significant differences in complete response rates were observed. The most important predictor of survival was the total number of CD4-positive lymphocytes. Other predictors of survival included history of a diagnosis of acquired immunodeficiency syndrome, Karnofsky performance score, and the presence of extranodal disease. Survival was shorter among patients who received higher doses of cyclophosphamide (greater than 1 g/m2), including those treated with the COMET-A regimen. Implications for therapeutic decision making are discussed.

Acquired Immunodeficiency Syndrome↗
PubMed1989

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.

Acquired Immunodeficiency Syndrome↗
PubMed1988

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.

Acquired Immunodeficiency Syndrome↗
PubMed1988

High titer anti-HIV antibody reactivity associated with a paraprotein spike in a homosexual male with AIDS related complex.

We observed a human immunodeficiency virus (HIV)-infected homosexual male with AIDS related complex (ARC) who had a serum globulin level of 80 g/L. Serum protein electrophoresis revealed a gamma globulin fraction of 40 g/L, of which 50% (20 g/L) was contained within a paraprotein spike, comprised predominantly of IgG kappa. This patient also had high titer anti-HIV antibodies in his serum, which were Western blot reactive at a final dilution of 1:500,000, and recognized gp120env, p66pol, p55gag, p53pol, p41gag, and p24gag. Because paraproteins in the past have been shown to be directed against specific antigens, we purified this patient's paraprotein using a modified high performance liquid chromatography (HPLC)-hydroxylapatite procedure and tested the purified paraprotein for anti-HIV antibody activity. The purified paraprotein retained anti-HIV antibody activity to a final dilution of 1:100,000, and recognized p66pol, p55gag, p53pol, p41gag, and p24gag. The recognition of both "gag" and "pol" gene products suggested that the purified paraprotein might not be monoclonal in origin. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) demonstrated that the purified paraprotein contained at least two immunoglobulin light chain species (Mol wt 30 to 33 Kd). Affinity chromatography of the purified paraprotein using a p24-Sepharose 4B matrix separated the "gag" and "pol" antibody activities. Immunoglobulin gene rearrangement analysis of a bone marrow aspirate (which contained 15% plasma cells) failed to reveal a clonal population of immunoglobulin producing cells. We conclude that this patient's paraprotein accounted for most of the anti-HIV activity present in whole serum, and that this paraprotein was not monoclonal in origin.

AIDS-Related Complex↗
PubMed1988

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.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Suramin therapy in AIDS and related disorders. Report of the US Suramin Working Group.

Suramin sodium is a reverse transcriptase inhibitor with in vitro activity against the human immunodeficiency virus (HIV), the causative agent of acquired immunodeficiency syndrome (AIDS). Ninety-eight patients with AIDS manifest as opportunistic infections (n = 38), AIDS with Kaposi's sarcoma (n = 38), AIDS-related complex (n = 20), or AIDS-associated non-Hodgkin's lymphoma (NHL) (n = 2) were treated with suramin sodium at 0.5, 1.0, or 1.5 g/wk for six weeks followed by maintenance therapy with 0.5 or 1.0 g/wk. Of 72 patients who were HIV culture positive before therapy and were assessable for subsequent HIV culture 40% became culture negative during treatment, with no apparent correlation between virus recovery and serum suramin concentration. No immunologic improvement was noted. One complete clinical remission was noted in a patient with Kaposi's sarcoma and stage IV NHL. Seven minor clinical responses were also noted. Toxic reactions were generally reversible, and included fever (78%), rash (48%), malaise (43%), nausea (34%), neurologic symptoms (33%), and vomiting (20%). Suramin-induced neutropenia was noted in 26%, thrombocytopenia in 12%, a serum creatinine level of 180 mumol/L or higher (greater than or equal to 2.1 mg/dL) in 12%, liver dysfunction in 14%, and clinical and/or laboratory evidence of adrenal insufficiency in 23%. Sixteen patients died while receiving suramin or within three weeks of discontinuation of drug therapy due to infection (n = 6), hepatic failure (n = 3), pulmonary Kaposi's sarcoma (n = 2), AIDS encephalitis (n = 2), AIDS-associated NHL (n = 1), iatrogenic hemo-pneumothorax (n = 1), or pulmonary disease of uncertain etiology. Suramin as currently administered cannot be recommended as effective therapy for AIDS.

AIDS-Related Complex↗