[Clinical use of hematopoietic growth factors in treatment of bone marrow failure].
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Antineoplastic Combined Chemotherapy Protocols↗
Biomedical subjects
T Robak
Publications and source records attributed to T Robak.
[Apoptosis--programmed cell death].
Apoptosis is a structurally distinct programmed cell death pathway. It takes place during embryogenesis, after withdrawal of the trophic hormones and in the course of normal tissue turnover. Defective regulation of apoptosis may play a very important role in the aetiology of cancer and other diseases. In this paper these and other problems concerning with apoptosis are reviewed.
Animals↗
[Thrombocytopenia during pregnancy].
Thrombocytopenia is the most frequent cause of acquired hemorrhagic diathesis. In addition to disorders that may cause thrombocytopenia in nonpregnant women, pregnant patients are at risk for the development of thrombocytopenia caused by syndromes such as preeclampsia, which are unique to pregnancy. In this review we discuss the major causes of thrombocytopenia that occur during pregnancy. These include the immune thrombocytopenic purpura, so called "gestational" thrombocytopenia, preeclampsia-associated thrombocytopenia, HELLP syndrome, thrombotic thrombocytopenic purpura and the hemolytic uremic syndrome.
Female↗
[Biology and clinical applications of GM-CSF].
Granulocyte, macrophage colony stimulating factor (GM-CSF) and granulocyte--colony--stimulating factor (G-CSF) are two of the growing number of recognized cytokines involved in the regulation of hematopoiesis. The purification of these factors and the subsequent cloning of the DNAs which encode these proteins have led to their widespread clinical use in the setting up of therapy of disease-induced myelosuppression. GM-CSF has a broader spectrum of potential targets than G-CSF and promotes growth of progenitors of several myeloid lines and, to a lesser extent, of the megakaryocyte line. The pleiotropic effects of GM-CSF could therefore, theoretically, be an advantage compared with the more restricted activity of G-CSF. Its greatest potential use appears to be in the amelioration of neutropenia following myelosuppressive therapy. GM-CSF has demonstrated efficacy in decreasing the duration of neutropenia, decreasing the attendant infection, and enhancing the ability to deliver full doses of myelosuppressive therapy. GM-CSF can also reverse the neutropenia of myelodysplastic syndrome and aplastic anemia. It enhances recovery from bone marrow transplantation and thus reduce the attendant morbidity of this procedure. This hematopoietic growth factor may also enhance recruitment and harvest to peripheral stem cells. At clinically usefull dosages GM-CSF is generally well tolerated.
Animals↗
[Clinical applications of erythropoietin].
Erythropoietin (EPO) is a glycoprotein produced primarily by the kidney in response to tissue hypoxia, and is the principal factor regulating red blood cell production. It stimulates erythroid precursors in the bone marrow to proliferate and mature into morphologically identifiable red blood cells. This hormone acts by binding to specific high-affinity receptor on erythroid precursors. Failure to produce adequate quantities of EPO leads to severe anemia, a situation most often encountered in patients with end stage renal disease. With the application of recombinant DNA technology, the gene for this hormone has been molecularly cloned, sequenced and expressed in a biologically active form in mammalian cells. The recombinant EPO has been demonstrated to correct anemia in patients with severe end stage renal disease and alleviate their transfusion requirements. It has also been studied for anemia associated with HIV infection/zidovudine therapy, in cancer, rheumatoid arthritis, and prematurity. In addition it has been studied as a facilitator of autologous blood predeposit in patients scheduled for elective surgery and as a perisurgical adjuvant to hasten hematologic recovery and possibly avoid the need for homologous transfusion after elective surgery. When administered with the current guidelines EPO appears to be safe drug with favorable risk/benefit ratio.
Acquired Immunodeficiency Syndrome↗
[Biological properties and clinical applications of interferon gamma (IFN-gamma)].
Interferon-gamma (IFN-gamma) is produced by activated T cells and probably by NK cells. Its production can be induced by mitogens, antigens and other molecules. IFN-gamma interacts with cells by binding to specific membrane receptors. IFN-gamma--1b is an Escherichia coli--derived recombinant DNA product, which has biological activity identical to natural human IFN-gamma. This IFN type is a more potent immunomodulator than IFN-alpha and IFN-beta. Long term treatment with a therapeutic dosage of IFN-gamma--1b produces a significant reduction in the incidence of serious infections in patients with chronic granulomatous disease. This cytokine can be also useful in the treatment of patients with visceral leishmaniasis, Epstein-Barr virus infections, lepromatous leprosy and other infectious diseases. Phase I and II studies have demonstrated it to be capable of producing antitumor effects, especially in metastatic renal cell carcinoma and some hematologic malignancies. Clinical trials have suggested efficacy of IFN-gamma in the treatment of severe atopic dermatitis and rheumatoid arthritis. The most common adverse reactions are fever, headaches and erythema at the injection site.
Communicable Diseases↗
[Acute undifferentiated and minimally differentiated leukemia].
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Humans↗
Treatment of chemotherapy-induced or idiopathic bone marrow aplasia with granulocyte colony-stimulating factor (G-CSF).
We report on our experience with the application of recombinant human granulocyte colony-stimulating factor (G-CSF, Neupogen, Hoffmann La Roche) in patients with various types of hematological malignancies, who had chemotherapy-induced myelosuppression, and in patients with idiopathic aplastic anemia. The administration of G-CSF was associated with marked increase in white blood cells counts (WBC) in twelve out of 14 treated patients. In one patient with aplastic anemia the WBC decreased rapidly to the initial value after the cessation of cytokine therapy. Significant increase of platelet number was observed in 6 patients. No toxicity was encountered with the hematopoietic growth factor therapy. Our study points to the fact that G-CSF have a stimulating effect on the regeneration of hematopoiesis, particularly within the granulopoietic compartment. The effect can be obtained both in a case of idiopathic- and cytostatic-dependent marrow aplasia.
Adolescent↗
[Biological properties and clinical application of filgrastim (G-CSF)].
Granulocyte--colony stimulating factor (G-CSF, filgrastim) is a glycoprotein hormone of the hematopoietin family that primarily influences the proliferation and differentiation of neutrophilic granulocytic precursors. As with all glyco-protein hormones, G-CSF interacts with target cells by binding to specific cell-surface receptors. It stimulates proliferation, differentiation and activation of cells of the neutrophil--granulocyte lineage and has been investigated as therapy for patients with various neutropenic conditions. A major use for recombinant G-CSF therapy will be in ameliorating the neutropenia which follows cytoreductive chemotherapy. The increase in neutrophils produced by this factor render it a useful treatment for conditions such as congenital, acquired and cyclic neutropenias. It may be an effective therapy in myelodysplasia and aplastic anaemia. G-CSF is also useful in accelerating the recovery of transplanted bone marrow in patients with leukaemia, lymphoma and solid tumors. G-CSF is well tolerated. The most frequently reported adverse effect is mild to moderate bone pain.
Acquired Immunodeficiency Syndrome↗
Application of hematopoietic growth factors (G-CSF and GM-CSF) in the treatment of chemotherapy-induced or idiopathic bone marrow failure.
Fifteen patients with various myeloid and lymphoid neoplasias after receiving highly myelotoxic chemotherapy were treated with a single daily dose of 5 micrograms/kg of GM-CSF. G-CSF at a daily dose of 5-8 micrograms/kg was used in four patients with severe pancytopenia in the course of acute or chronic lymphoid leukemia treated with cytotoxic agents, and in two patients with idiopathic aplastic anemia. The administration of cytokines was provided for 4-10 days GM-CSF increased the WBC in twelve out of fifteen patients, mainly because of an increase in the number of neutrophils. Six patients receiving GM-CSF demonstrated rapid platelet recoveries. The rapid increase of the WBC was observed in all G-CSF treated patients. In one patient with aplastic anemia the WBC/ANC decreased rapidly to the initial values after the cessation of the G-CSF therapy. Fast platelet recovery was seen in three patients treated with G-CSF.
Adolescent↗
The influence of 2-chlorodeoxyadenosine alone and in combination with cyclophosphamide or methotrexate on normal hematopoiesis in mice.
The influence of 2-chlorodeoxyadenosine (2-CDA) administered alone or in combination with cyclophosphamide (CY) or methotrexate (MTX) on normal hematopoiesis in mice was investigated. The peripheral blood counts such as the number of leukocytes, platelets, and erythrocytes, hematocrit values and hemoglobin concentration were measured. The number of mononuclear cells and multipotential stem cells (CFU-S) in bone marrow was also checked. 2-CDA caused both the decrease in white cell count (granulocytes, monocytes, lymphocytes) and the suppression of mononuclear cells and multipotential stem cells in the bone marrow. The addition of CY significantly enhanced the suppression of these parameters. In contrast to CY, MTX did not augment myelotoxic effect of 2-CDA. 2-Chlorodeoxyadenosine administered singly and in combination with CY or MTX had no influence on the number of erythrocytes, hemoglobin concentration, hematocrit values and number of platelets.
Animals↗
Synergistic action of 2-chlorodeoxyadenosine and cyclophosphamide on murine leukemias L1210 and P388.
The influence of 2-chlorodeoxyadenosine (2-CDA) administered alone and in combination with cyclophosphamide (CY) or methotrexate (MTX) on the survival time of mice bearing L1210 or P388 leukemia was investigated. 2-CDA given alone significantly prolonged survival time of mice bearing L1210 leukemia and caused only a slight prolongation of survival time in mice bearing P388 leukemia. Survival times of mice bearing both kinds of leukemia, receiving combined therapy of 2-CDA and MTX were not significantly prolonged as compared with mice treated with these agents separately. The groups of mice with both leukemia L1210 and P388 treated with 2-CDA and CY lived significantly longer as compared with the control group and with mice receiving only single cytostatic.
Animals↗
[Biology and therapy of hairy cell leukemia].
In the paper recent advances in etiology and pathogenesis of hairy cell leukaemia (HCL) are reviewed. Role of human T-cell leukaemia virus II (HTLV-II) and Epstein-Barr virus as well as benzene and other environmental factors in the etiology of this leukaemia is presented. The new achievements in diagnosis including electron microscopic, cytogenetic and immunologic studies are discussed. A rare variants of HCL are described. The special attention is paid to the modern approach in treatment including alfa-interferon, 2'-deoxycoformycin and 2-chlorodeoxyadenosine.
HTLV-I Infections↗
[Clinical pharmacology of idarubicin].
Idarubicin (IDA,4-demethoxydaunorubicin) is a new antineoplastic agent that is structurally related to daunorubicin (DNR) and has the same mechanism of action as DNR and doxorubicin (ADR). Unlike the other currently available anthracyclines, IDA has significant oral bioavailability (about 30%). Animal tumor studies have shown that it has greater antitumor activity at lower drug concentration than DNR. IDA is an effective agent for the management of acute myelogenous leukemia (AML). It has achieved greater response rates than the standard anthracycline, DNR, when it is administered with cytarabine in newly diagnosed patients. IDA is also an effective agent in acute lymphoblastic leukemia, lymphomas, breast cancer and some other tumors. Adverse effects are similar to those seen with other anthracyclines, although IDA may be associated with less cardiotoxicity than ADR or DNR.
Animals↗
[Clinical pharmacology of ondansetron].
Ondansetron (ODS) is a new carbazole which exerts selective and potent antagonism on serotoninergic neurotransmission at serotonin 3 (5-HT3) receptors. Animal and clinical studies show that ODS reduces the incidence and severity of nausea and vomiting induced by cytotoxic drugs and radiotherapy. The antiemetic properties of this agent have been determined in ferrets against the nausea and vomiting induced by cisplatin, cyclophosphamide and whole-body radiation. The current hypothesis is that there may be both a peripheral and a central site of action for ODS. The lack of antagonist activity on dopamine and other non 5-HT3 receptors indicates that, unlike metoclopramide, ODS will not cause extrapyramidal or other dose-limiting side effects. ODS is rapidly and completely absorbed when administered as a tablet. Preliminary data show that ondansetron can be combined with dexamethasone safely with enhanced antiemetic results.
Animals↗
[Therapeutic problems during pregnancy and delivery in two women with aplastic anemia].
We have observed two cases of aplastic anaemia diagnosed during the second trimester of pregnancy. In both patients a cesarean section was performed (in 32 and 37 week of gestation). During the course of pregnancy the patients received transfusions of erythrocytes and platelets. In one case high doses of methylprednisolone were administered. The same patient was given immunoglobulins IV prior to the delivery and the number of platelets increased to 100 x 10(9)/L. One baby had respiratory distress syndrome and died 3 months after birth. The second baby is 9 months old now and is in good health. Haematological improvement did not occur post partum and immunosuppressive treatment with antithymocyte globulin and cyclosporine was performed in both patients. Despite of that remissions did not occur and one patient died 7 months after delivery. The second patient still has haematological problems and is red cell and platelet transfusion dependent. We discuss the pathogenetic aspects of aplastic anaemia occurring during pregnancy, as well as the therapeutic problems before and after delivery.
Adult↗
[Progress in biology and the treatment of acute promyelocytic leukemia].
Acute promyelocytic leukaemia (APL) is a distinct subtype of acute myeloid leukaemia distinguished by the presence of a balanced chromosomal translocation: t(15; 17). The most characteristic clinical manifestation of this disease is the presence of a haemorrhagic syndrome associated with an abnormal coagulation profile. In the last few years significant progress in the understanding of the biology of this leukaemia and its treatment has been done. In particular, the breakpoint on chromosome 17 has been localized within the retinoic acid receptor alpha locus while the breakpoint on chromosome 15 has been localized within a new gene named PML. In contrast to the other acute myeloid leukaemia subtypes APL shows high response rate to induction monochemotherapy with anthracycline drugs and with all-trans retinoic acid.
Chromosomes, Human, Pair 15↗
Effect of recombinant human granulocyte-macrophage colony-stimulating factor on chemotherapy-induced myelosuppression.
We have studied the efficacy of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) in stimulating haematopoiesis of patients with chemotherapy-induced myelosuppression. Ten patients with various myeloid and lymphoid neoplasias were treated daily with a single subcutaneous dose of rhGM-CSF (5 micrograms/kg/day), for a period of 5-10 days, after receiving highly myelotoxic chemotherapy. The treatment increased the white blood cell count (WBC) in nine of ten patients, primarily because of an increase in the number of neutrophils. Increase in bone marrow myeloid precursor cells, and myeloid to erythroid cell rations accompanied the white-cell response. In spite of this, five patients demonstrated rapid platelet recoveries, and in two patients erythrocyte levels increased after GM-CSF treatment. No toxicity was encountered with the cytokine therapy. Although rhGM-CSF was shown to stimulate haematopoiesis in patients with chemotherapy-induced myelosuppression, additional studies are needed to assess whether the use of GM-CSF will reduce chemotherapy-associated morbidity and improve response rates and survival among patients with neoplasias.
Adolescent↗