Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002871 (anemia)
 52,094 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Retinoids have anti-tumor activity in several malignant and premalignant conditions. Since Kaposi's sarcoma is regulated by steroid hormones both in vivo and in vitro, we hypothesized that retinoids may have anti-tumor effects in AIDS-related Kaposi's sarcoma. Thus, 27 patients with mucocutaneous, non-visceral AIDS-related Kaposi's sarcoma were treated with all-trans retinoic acid (tRA). Poor tolerance was observed at the initial starting dose of 150 mg/m2, and thus subsequent patients were treated using a weekly dose escalation, starting with 45 mg/m2 (given daily, in subdivided doses), to the target dose of 150 mg/m2 (given daily in three subdivided doses). Nearly half (46%) of the patients had extensive mucocutaneous disease with over 25 lesions. No patient had received prior cytotoxic chemotherapy. Ten patients had CD4 lymphocytes of 200/mm3 or greater (strata I); and 17 had under 200/mm3 CD4 lymphocytes (strata II). The median of the average daily tRA dose administered was 150 mg (90 mg/m2; there was no significant difference in the dose tolerance between the two strata). Adverse effects consisted of transient mild to moderate headaches in 65% of patients, mild to moderate skin dryness and cheilitis in 61%, and nausea and vomiting in 31%. Hematologic toxicities included hypertriglyceridemia in 62%, anemia in 23%, and neutropenia in 23%. Partial response to therapy was observed in 4/24 (17%) evaluable patients, occurring after 12, 20, 24, and 28 weeks of therapy, and lasting 4-24 weeks. Three responders had baseline CD4 lymphocyte counts < 200/mm3. Three additional patients experienced reduction in measured indicator lesions of greater than 25% but less than 50%, and seven patients experienced disease stabilization of 16 weeks or greater. In evaluable patients, the median time to disease progression was 22 weeks and the overall median survival in all patients was 27.3 months. No significant changes in CD4 lymphocyte counts, p24 antigen, and beta 2 microglobulin were observed over time. However, a statistically significant increase was observed in soluble IL-2 receptor levels while on tRA (p = 0.037). We conclude that tRA has activity in patients with mucocutaneous AIDS-related Kaposi's sarcoma with acceptable toxicity. tRA has immunological effects without upregulation of HIV parameters. Additional studies in combinations or with more active retinoids are warranted.
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PMID:All-trans retinoic acid for the treatment of AIDS-related Kaposi's sarcoma: results of a pilot phase II study. 780 21

Interferon-alpha (IFN-alpha) can inhibit human immunodeficiency virus (HIV-1) replication and is effective in treating Kaposi's sarcoma; interleukin-2 (IL-2) can increase circulating lymphocytes in HIV-1-infected patients. The safety of combination treatment with recombinant (r)IFN-alpha 2b and IL-2 was evaluated in HIV-1-infected patients with > 200 CD4+ T cells/mm3. A maximal tolerated dose of rIFN-alpha 2b was determined for 17 patients; then they received in combination 3, 6, or 12 x 10(6) IU/day rIL-2, given intravenously over 21 days. Twelve patients ultimately received the combination, 9 for the full 21 days. Significant toxicities included flu-like symptoms, anemia, transaminemia, and depression. Transient increases in CD4+ T cell percentages and spontaneous lymphocyte blast transformation were observed. Quantitative microcultures demonstrate a decline in HIV titers in patients receiving rIFN-alpha 2b (5/9) with a further decline on addition of rIL-2 (7/9). In summary, continuous rIL-2 at 6 x 10(6) IU/day in combination with rIFN-alpha 2b was reasonably tolerated and provided preliminary evidence of immunomodulatory and antiviral activity.
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PMID:A phase I study of interferon-alpha 2b in combination with interleukin-2 in patients with human immunodeficiency virus infection. 790 50

This report describes the clinical spectrum and outcome of the hemophagocytic syndrome (HS) in 5 HIV infected patients. All 5 patients presented with fever, hepatomegaly and/or splenomegaly, confusion or coma and respiratory symptoms. Severe anemia was associated with thrombocytopenia and with neutropenia in 4 cases. Diffuse intravascular coagulopathy was present in 2 cases. Liver function tests were abnormal in three patients. The diagnosis of HS was made 2 to 12 weeks after the onset of symptoms and required in most patients repeated examinations of the bone-marrow, showing infiltration by histiocytes with prominent phagocytosis of blood cells. In one case this infiltration was not seen in the bone-marrow but only in the liver and the spleen. Varicella, mycobacterium infection, oesophageal candidiasis, Kaposi sarcoma were observed in the evolution of 3 patients. Anaplastic large cell Ki-1 lymphoma was present in one case. Four patients died as a result of complications of HS. The one patient with lymphoma survived.
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PMID:[Hemophagocytic syndrome in HIV infection]. 824 41

C57/BL/6 mice infected with LP-BM5 MuLV virus developed an AIDS-like disease (MAIDS) with splenomegaly, leukopenia, thrombocytopenia, anemia, decreased numbers of helper/inducer and suppressor/cytotoxic T-cells and decreased production of interferon alpha. We have shown previously that HIV-associated Kaposi's sarcoma tissue contains high levels of prostaglandin E2 (PgE2), and this inhibits interferon synthesis through a cAMP-dependent second-messenger process. In this study we treated groups of MAIDS-infected mice with combinations of pentoxifylline, an agent which increases cAMP and inhibits phosphodiesterases, and sodium meclofenamic acid, a PgE2 inhibitor. Treated mice showed: 1) significantly higher total leukocyte and platelet counts, 2) higher total L3T4+ (helper/inducer) and Lyt-2+ (suppressor-cytotoxic) T-cell population. Pathologic examination also showed significantly less hepatosplenomegaly and lymphadenopathy in animals treated with pentoxifylline and meclofenamic acid. Partly, PgE2-induced suppression of interferon alpha production may mediate expression of retrovirus infection in this murine model of AIDS.
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PMID:Pentoxifylline and meclofenamic acid treatment reduces clinical manifestations in a murine model of AIDS. 830 44

To assess safety, antitumor response, and immunological and virological activity of interferon-alpha 2a and zidovudine combination therapy in patients with AIDS-related Kaposi's sarcoma, we conducted an open-label, Phase II, multicenter study. Sixty-three patients with biopsy-proven Kaposi's sarcoma and no previous interferon-alpha therapy received zidovudine 600 mg/day and interferon-alpha 2a 18 x 10(6) U/day. The median duration of follow-up was 49 weeks. Of 62 evaluable patients, 25 (40%; 95% confidence interval, 0.28-0.52) showed a complete (26%) or partial (15%) antitumor response. Eight of 30 patients (27%) with < 100 CD4 cells/mm3 and 17 of 32 patients (53%) with > or = 100 CD4 cells/mm3 had a response. The median time to response was 36 weeks. Of the 25 patients with a response, four developed tumor progression. The median duration of response was 22.4 weeks. Eight patients (13%) developed another AIDS-defining event and 13 (21%) died. The major toxicities included anemia (16%), neutropenia (27%), elevated serum transaminases (16%), weight loss (16%), malaise (14%), fatigue (14%), fever (10%), and headache (6%). Therapy with intermediate-dose interferon-alpha 2a and zidovudine resulted in tumor regression in patients with AIDS-related Kaposi's sarcoma who had a wide range of CD4 cell counts; this therapy was relatively well tolerated.
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PMID:A phase II study of recombinant human interferon-alpha 2a and zidovudine in patients with AIDS-related Kaposi's sarcoma. AIDS Clinical Trials Group. 860 Dec 24

Abuse of nitrite inhalants is widespread among male homosexuals and has been epidemiologically correlated with seropositivity to human immunodeficiency virus (HIV) and to Kaposi's sarcoma. These drugs may act as cofactors in AIDS if they compromise the ability to resist infection or tumor growth. We have previously reported that 14 daily 45-minute exposure to 900 ppm isobutyl nitrite in an inhalation chamber did compromise the immunocompetence of mice. We now report that a single 45-minute exposure produced a transient anemia. Erythrocyte counts, hemoglobin, and hematocrit levels were reduced by 7% but rebounded to above-normal levels 24 hours later. In vitro exposure of blood to isobutyl nitrite vapors did not lyse the cells but did induce Heinz body formation and increase their binding to macrophages. Thus, it is likely that the red cells were removed by phagocytic clearance not by direct lysis. Blood leukocyte numbers were also reduced following a single exposure to the inhalant, but the cell loss was delayed until 24 hours after exposure. Recovery of peripheral blood leukocytes 72 hours after exposure coincided with a reduction in spleen cellularity, suggesting that spleen cells were mobilized to replace lost blood leukocytes.
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PMID:Acute inhalation exposure to isobutyl nitrite causes nonspecific blood cell destruction. 860 63

Isobutyl nitrite is representative of a group of inhalants abused primarily by male homosexuals; abuse of this drug may be a risk factor for AIDS or Kaposi's sarcoma. Using a 14-day exposure regimen, we previously reported that inhaled isobutyl nitrite was immunotoxic to mice, severely compromising T-dependent antibody responses and cytotoxic T cell and macrophage tumoricidal activity. In addition, exposure to the inhalant dramatically reduced spleen cellularity. A single 45-minute inhalation exposure produced anemia in mice. In the present study, we examined the effects of subchronic exposure to the drug on peripheral blood cellularity and hematopoietic activity. Mice were exposed to 900 ppm isobutyl nitrite in an inhalation chamber for 45 minutes/day for 14 days. One day after the final exposure, the number of peripheral blood leukocytes was reduced by 32%; however, the number of erythrocytes was increased by 7%. This was accompanied by an apparent shift from myelopoiesis to erythropoiesis. The numbers of bone marrow and spleen burst-forming units-erythroid (BFU-E) were increased about two-fold, while the numbers of colony-forming units-granulocyte/macrophage (CFU-GM) were decreased by about half. Bone marrow stromal cells also had reductions in the production of myeloid colony-stimulating activity after subchronic exposure to the inhalant. In addition, the numbers of hematopoietic stem cells, colony-forming units-spleen (CFU-S), were reduced in both bone marrow and spleen. Peripheral blood erythrocyte and leukocyte counts returned to normal levels by 7 days after the final exposure, as did the number of BFU-E. The number of CFU-GM remained depressed, however, even after 7 days of recovery. These data suggest that repeated exposures nonspecifically depleted cells and that erythropoiesis was stimulated, apparently at the expense of myelopoiesis.
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PMID:Leukopenia and altered hematopoietic activity in mice exposed to the abused inhalant, isobutyl nitrite. 864 36

We report a 65-year-old Japanese woman with Kaposi's sarcoma (KS). The eruption first occurred on the legs while she was admitted for treatment of poorly differentiated lung cancer. Approximately eight months after the evolution, cutaneous tumors rapidly spread to the forearms, trunk, and pharynx. At that time, the patient had received systemic corticosteroid (10-40 mg/day of prednisolone) for about three months to reduce pulmonary inflammation. The laboratory data showed anemia, lymphopenia, hypogammaglobulinemia, and a decreased T cell count, although the serological test for HIV infection was negative. The patient was treated with radiation (X-ray for KS of pharynx and electron beam for KS of lower legs) and local intralesional injection of vinblastine. Although both therapies were very effective and well tolerated, she died of bacterial pneumonia and sepsis. Autopsy revealed KS tumors, unknown before death, in both lungs, the esophagus, and the stomach. The left lung cancer had disseminated and metastasized to the right lung, pleura, mediastinum, and abdominal cavity. It is suspected that chronic respiratory distress and systemic use of corticosteroids might have induced the rapid extension of KS.
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PMID:Kaposi's sarcoma associated with lung cancer and immunosuppression. 885 91

Doxorubicin is an antineoplastic drug which has in vitro and in vivo activity against a number of malignancies including Kaposi's sarcoma. Incorporation of doxorubicin into polyethylene glycol-coated (pegylated) liposomes alters the pharmacokinetics of the drug. Liposomal doxorubicin has a smaller volume of distribution and slower plasma clearance than standard free doxorubicin. The liposomal formulation achieves higher concentrations in the highly vascularised lesions of Kaposi's sarcoma than in normal tissue. Liposomal doxorubicin monotherapy in patients with AIDS-related Kaposi's sarcoma produced overall response rates (complete plus partial) of 43 and 59% in large comparative studies and 67 to 100% in noncomparative studies which included > or = 20 patients. In comparative studies, liposomal doxorubicin was significantly more effective than the combination of standard doxorubicin, bleomycin and vincristine (overall response rates of 43 and 25%, respectively) and bleomycin and vincristine (BV) [overall response rates of 59 and 23%, respectively]. In addition, overall response rates to the liposomal drug were higher in both treatment arms of 2 smaller comparative studies which compared liposomal doxorubicin with BV, but significant between-treatment differences were not detected. Patient numbers in these 2 studies, however, may have been too small to detect significant differences. Liposomal doxorubicin is generally well tolerated. Myelosuppression is the most common dose-limiting adverse effect in patients with AIDS and Kaposi's sarcoma. Neutropenia occurs most often; anaemia and thrombocytopenia occur less frequently, as do nausea and vomiting and stomatitis. Palmar-plantar erythrodysaesthesia occurs in some patients, most commonly after 6 to 8 weeks of chemotherapy. Although symptoms may occasionally be severe, the syndrome usually does not require dosage reduction or treatment delay. Limited data suggest that the incidence of cardiotoxicity may be lower after liposomal doxorubicin than after equivalent doses of standard doxorubicin. Overall, liposomal doxorubicin appears to be one of the most active single agents available for treating patients with AIDS-related Kaposi's sarcoma. The therapeutic potential of liposomal doxorubicin administered in combination with other active agents to patients with Kaposi's sarcoma is, as yet, unknown. However, administered alone, the drug seems to be more effective than the best available combination chemotherapy regimens.
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PMID:Polyethylene glycol-liposomal doxorubicin. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in the management of AIDS-related Kaposi's sarcoma. 907 48

Chronic oral VP-16 (Etoposide) is a chemotherapy regimen with wide application in oncology and documented efficacy against germ cell tumors, lymphomas, Kaposi sarcoma, and glial brain tumors. Eight patients ranging in age from 4 to 36 years (median 7.5 years) with locally recurrent medulloblastoma were treated with VP-16. No patient displayed evidence of cerebrospinal fluid dissemination, distant brain or spine parenchymal metastases, or extraneural metastatic disease. All patients had previously been treated with surgery (gross total resection, 5; subtotal resection, 3), craniospinal radiotherapy, and platinum-based chemotherapy (adjuvant, 3; salvage, 8). Each cycle of therapy consisted of 21 days of VP-16 (50 mg/m2/day) followed by a 7 to 14 day rest followed by an additional 21 days of VP-16 (50 mg/m2/day). Complete blood counts were obtained weekly. Neurologic examination and brain magnetic resonance imaging scan with contrast were performed prior to each cycle of therapy. Treatment-related complications included: partial alopecia (5 patients); diarrhea (4); weight loss (3); anemia (2); neutropenia (4); and thrombocytopenia (4). Two patients required transfusion and 1 patient received antibiotics for neutropenic fever. All patients were evaluable for response: 3 demonstrated progressive disease after the first cycle of VP-16, 3 had stable disease (range 4 to 6 months) and 2 had partial neuroradiographic responses (8 and 10 months). Median duration of response and stable disease was 6 months (range: 4 to 10 months) in 5 of 8 (62.5%) patients. Chronic oral VP-16 is a well-tolerated and relatively non-toxic chemotherapeutic agent with demonstrated activity in locally recurrent medulloblastoma.
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PMID:Chronic oral VP-16 for recurrent medulloblastoma. 939 Jun 99


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