Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0854467 (myelosuppression)
 5,932 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Myelosuppression is associated with human immunodeficiency virus (HIV) infection and may also be produced by agents used for the treatment of the disease or the treatment of its complications. Didanosine (ddl; 2',3'-dideoxyinosine) is a newer purine nucleoside that has recently become available for therapy for HIV infection. The effects of didanosine on peripheral blood counts have been retrospectively evaluated in the first 170 patients treated with this new agent in four phase I trials. Patients treated with didanosine showed statistically significant improvements in hemoglobin levels, white cell counts, and granulocyte and platelet numbers as compared with baseline values. These changes were seen with or without prior therapy with zidovudine, were somewhat more pronounced at higher doses of didanosine, and persisted for up to 1 year. Reported adverse events included peripheral neuropathy, diarrhea, and most notably, pancreatitis. It is concluded that, while some toxic side effects occur, didanosine therapy in HIV infection is associated with an amelioration of HIV-induced myelosuppression.
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PMID:Effects of therapy with didanosine on hematologic parameters in patients with advanced human immunodeficiency virus disease. 146 12

As a result of a pathophysiologically unexplainable bone marrow failure, most patients with progressive stages of human immunodeficiency virus (HIV) infection develop anemia, leukopenia, and thrombocytopenia. Besides the possibility of immune-mediated cytolysis or of direct viral infection of hemopoietic progenitor cells, the inhibitory influence of cytokines, for example interferon-alpha (IFN-alpha) and IFN-gamma, on hemopoiesis of HIV-infected patients might be considered as one parameter that contributes to myelosuppression. Therefore, progenitor cells from the bone marrow of HIV+ and HIV- persons were exposed to increasing concentrations of recombinant human IFN-alpha and IFN-gamma in methylcellulose assays. The colony formation of pluripotent (CFU-GEMM), erythroid (BFU-E), and granulocyte-macrophage (CFU-GM) progenitor cells was inhibited by both interferons. The 50% inhibitory doses (ID50) of IFN-alpha were 125.6 U/mL and 131.5 U/mL for BFU-E from HIV-infected persons and normal controls, respectively; the corresponding ID50 of IFN-alpha for CFU-GM growth was 1095.8 U/ml and above 3000 U/ml. When IFN-gamma was studied the ID50 was 341.7 and 2794.6 U/ml for BFU-E from HIV-infected and healthy individuals, respectively, while the ID50 for CFU-GM was above the highest dose levels in both groups (greater than 3000 U/ml). The ID50 for CFU-GEMM was below the lowest dose levels of IFN alpha and IFN gamma tested in both groups (less than 10 U/ml). The inhibitory effects could be specifically neutralized by monoclonal antibodies against IFN-alpha and IFN-gamma, thus confirming that the suppressive effects were due to the cytokines used.
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PMID:Influence of human recombinant interferon-alpha and interferon-gamma on bone marrow progenitor cells of HIV-positive individuals. 159 59

The incidence of non-Hodgkin's lymphoma (NHL) has increased by over 50% in the United States since 1973. There is epidemiologic evidence that some of this increase is the result of AIDS-related lymphoma and that this component is increasing. Prolonged survival in the setting of a variety of immunodeficiency states is associated with an increased incidence of NHL. The development of antiretroviral therapy and improved therapy for the complications of AIDS has resulted in prolonged survival of patients with AIDS. As these patients survive longer with profound immunodeficiency, they have an increased cumulative risk of developing NHL. This may result in even more AIDS-related NHL in the future than predicted from current epidemiological studies. An increased understanding of the pathogenesis of AIDS-related NHL may lead to means of preventing their occurrence. Also, therapies that may prevent immunodeficiency from developing in HIV-infected patients may reduce the likelihood of NHL developing. Current efforts at treating these lymphomas are aimed at preventing the myelosuppression and immunosuppression associated with current regimens, lymphoma relapses within the central nervous system, and the opportunistic infections associated with treatment of these tumors. Ultimately, the best means of preventing the development of these lymphomas is by preventing infection with HIV.
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PMID:The occurrence of opportunistic non-Hodgkin's lymphomas in the setting of infection with the human immunodeficiency virus. 164 22

Small-noncleaved-cell (SNC) lymphoma is a high-grade, biologically aggressive neoplasm notable for poor response to therapy, high relapse rate, and less than a 20% long-term survival. We treated 20 patients with SNC lymphoma with a novel chemotherapeutic regimen using intensive doses of chemotherapy at frequent intervals in the inpatient setting. All patients were previously untreated. Sixteen patients (80%) had stage IV disease. Most patients (95%) had at least one other characteristic associated with poor prognosis (bulky [greater than 10 cm] disease, multiple extranodal sites, poor performance status), and 85% had two or more characteristics associated with poor prognosis. Seventeen patients (85%) achieved a complete response (CR) to therapy, including all three patients with human immunodeficiency virus (HIV)-associated disease. There have been three relapses, all occurring less than 18 months after treatment, and two of three relapses occurred in patients who were unable to complete therapy. At a median follow-up of 29 months, 13 patients (65%) remain disease-free; the calculated 5-year actuarial disease-free survival is 60%. Toxicity, chiefly myelosuppression, was severe but manageable. There were two treatment-related deaths, both in elderly patients with poor performance status and advanced-stage disease. These data suggest that such a dose-intensive approach improves the response and survival of patients with SNC lymphoma.
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PMID:Effective treatment of small-noncleaved-cell lymphoma with high-intensity, brief-duration chemotherapy. 170 85

Human immunodeficiency virus (HIV) infection is associated with multiple defects in immune regulation and hematopoiesis. These defects include decreased proliferation of hematopoietic progenitor cells and increased destruction of mature cells. There are also disturbances of regulatory cytokines. As a result, hematopoietic cytopenias are common and the tolerance of myelosuppressive therapy is poor. One successful approach to the management of these clinical problems is the use of hematopoietic growth factors. To date, three agents have been studied in patients with HIV infection. In a Phase I trial, granulocyte macrophage-colony stimulating factor (GM-CSF) corrected leukopenia and pre-existing neutrophil defects in patients with HIV infection. In uncontrolled trials, GM-CSF also appears to reduce toxicity from zidovudine, ganciclovir, alpha-interferon, and antineoplastic therapy. In a placebo-controlled trial, erythropoietin (EPO) decreased transfusion requirements and corrected anemia in the majority of patients receiving zidovudine. In a Phase I/II trial, granulocyte colony-stimulating factor (G-CSF) also corrected leukopenia and neutrophil defects in patients with AIDS without altering HIV expression. Combined G-CSF and EPO treatment corrected both anemia and leukopenia and reduced zidovudine toxicity. New combinations of hematopoietic stimulants are being used to decrease the toxicity from cytotoxic chemotherapy in the treatment of AIDS-related malignancies. Future treatments with other recombinant cytokines may result in both reduction in myelosuppression from drug therapy and, possibly, reconstitution of the immune and hematopoietic systems of HIV-infected patients.
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PMID:The use of hematopoietic growth factors in HIV infection and AIDS-related malignancies. 171 6

Cytomegalovirus (CMV), a major opportunistic viral pathogen frequently causing disease in immunocompromised patients such as organ transplant recipients and people with AIDS, may present as pneumonitis, gastrointestinal disease, or encephalitis. Its most common manifestation in patients with AIDS is retinitis which, if left untreated, invariably progresses to extensive retinal necrosis and ultimately to blindness. Ganciclovir sodium, currently the only licensed antiviral agent for the treatment of CMV retinitis, effectively controls this infection in a majority of AIDS patients, but significant granulocytopenia or thrombocytopenia related to ganciclovir therapy often limit its clinical application. Myelosuppression may be further exacerbated in AIDS patients by such other agents as zidovudine or trimethoprim/sulfamethoxazole, often necessitating dosage reductions or discontinuation of these agents in patients receiving ganciclovir. Foscarnet sodium, a pyrophosphate analog active against both cytomegalovirus and the human immunodeficiency virus type 1 (HIV), may be an effective alternative to ganciclovir in the management of CMV retinitis. Trials with intravenous foscarnet in CMV retinitis have reported favorable results using initial daily doses of 180-230 mg/kg/d given as intermittent infusions every eight hours, followed by maintenance regimens of 60-90 mg/kg/d given as single daily one- or two-hour infusions. Foscarnet therapy may result in renal impairment, and indefinite intravenous maintenance therapy may be required to prevent recurrence of CMV infection. Despite these drawbacks, foscarnet's lack of major myelosuppressive toxicity, and its activity in suppressing HIV replication, make this a potentially safe and effective alternative agent for the management of CMV infection, especially in AIDS patients.
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PMID:Foscarnet sodium. 184 59

Human immunodeficiency virus (HIV) carrier patients experience several secondary effects with drugs, being mainly skin reactions and myelosuppression. Owing to this, close observation of patients is necessary with regard to therapeutic and prophylactic schedules. In this paper, we describe the secondary effects of zidovudine in 60 patients of groups III and IV from CDC. The main toxicity was found in bone marrow; with anemia in 50% and leukopenia in 53% of patients. Finally, the more frequent secondary effects of therapy for opportunist infections are analysed. A guide for identifying the drugs' secondary effects is also included, based on our experience and on a wide range of literature reviews.
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PMID:[Drug surveillance for adverse reactions in patients with human immunodeficiency virus infection]. 210 16

A girl with non-Hodgkin's lymphoma and immunodeficiency based on absence of the purine salvage pathway enzyme purine nucleoside phosphorylase experienced profound neutropenia while receiving combination chemotherapy with cyclophosphamide, vincristine, methotrexate, and prednisone (COMP). Neutropenia was most severe following courses that included either systemic or intrathecal methotrexate, even in the face of major dose reductions. Delays in the development of neutropenia-during periods of leucovorin administration also implicate methotrexate as the primary responsible agent. This case suggests that certain immunodeficiency states predispose patients to extensive chemotherapy-induced myelosuppression and supports the concept that purine salvage is a clinically important mechanism for modulating methotrexate toxicity.
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PMID:Excessive chemotherapy-related granulocytopenia in a child with non-Hodgkin's lymphoma and a congenital abnormality of purine salvage. 211 61

Myelosuppression is a major symptom in the acquired immunodeficiency syndrome (AIDS). Moreover zidovudine, an anti-retroviral drug used to treat AIDS patients has myelosuppressive side effects. Therefore treatment with IL-3, a multi-lineage hemopoietic growth factor may be beneficial for zidovudine-treated individuals. In this study we examined the effect of IL-3 on human immunodeficiency virus (HIV) expression. The proliferative response to rIL-3 and the effects on the replication of the monocytotropic HIV variant, HTLV-III Ba-L, in the absence or presence of the anti-retroviral drug zidovudine was studied in purified human peripheral blood monocytes. Zidovudine concentrations sufficient for complete inhibition of HIV replication did not affect rIL-3 induced monocyte proliferation. Although rIL-3, like rGM-CSF, was able to augment HIV expression in monocytes, it did not interfere with the anti-retroviral activity of zidovudine. These data indicate that rIL-3 is a potential candidate for use in myelosupportive therapy in AIDS patients treated with anti-retroviral drugs.
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PMID:Induction of monocyte proliferation and HIV expression by IL-3 does not interfere with anti-viral activity of zidovudine. 220 24

Since 1978 we have treated 26 patients with testicular cancer in stage IV with the following chemotherapy regimen: Vinblastine 6 mg/m2 (day 1 and 2) and bleomycin 30 mg given over 24 hour period (day 1 to day 5). After two cycles this therapy was changed and patients received the combination adriamycin 60 mg/m2 (day 1) and cis-DDP 20 mg/m2 (day 1 to 5) for further two cycles. We achieved 69% (18 of 26 patients) complete remissions. Patients without response or no change received as second treatment modality vincristine 0,8 mg/m2 (day 1) and ifosfamide 1500 mg/m2 (day 1 to 5). Before each chemotherapy in an interval of two days 1 Unit (= 1 KE) of OK-432 (Streptococcus pyogenes) preparation, an immunomodulating agent, was given intravenously. In the therapyfree interval of chemotherapy 2 KE of OK-432 were applied. The maintenance therapy for 1 year consisted of vinblastine and trofosfamide and also OK 432. For the achievement of complete remissions 4 courses of chemotherapy seemed to be sufficient. The inclusion of OK 432 immunotherapy in an already established chemotherapy regimen seems to be qualified due to the reduction of chemotherapy induced side effects (myelosuppression, immunodeficiency) and the immunorestoration achieved before chemotherapy.
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PMID:[Chemo-immunotherapy in disseminated malignant testicular tumors]. 618 83


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