Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hydroxyurea, an antineoplastic drug evaluated clinically more than 30 years ago, is still the principal drug in patients with myeloproliferative syndromes. It is suggested now that it should be used as initial therapy for chronic myelogenous leukemia. Recently hydroxyurea is used in the treatment of patients with sickle cell disease. It has been shown to augment production of fetal hemoglobin and decrease the propensity of abnormal hemoglobin to polymerize and from the sickle cells in this way.
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PMID:[Clinical pharmacology of hydroxyurea]. 774 61

Eurocord Transplant has established a registry for studying results of cord blood transplant. We have analyzed 78 patients who have received a related CBT between October 1988 and December 1996. The median follow-up time was 29 months (1-99). The median age was 5 years (0.2-20), median weight 19 kg (5-50). Forty-six patients had a malignant disease: 32 acute leukemia (AL), six chronic myeloid leukemia (CML), four myelodysplastic syndrome, two neuroblastoma and two non-Hodgkin lymphoma. Thirty-two patients were transplanted for non-malignant diseases including 17 bone marrow failure syndromes (BMFS), three sickle cell anemia, five thalassemia and seven inborn errors. The donor was an HLA-identical sibling in 60 cases and an HLA-mismatched donor in 18 cases. As conditioning, 36 patients received irradiation and 40 patients received associated busulfan-containing regimens. GVHD prophylaxis consisted of CsA alone in 36 cases, CsA associated with prednisone in eight cases, CsA, methotrexate (Mtx) with or without prednisone in 28 cases and CsA with monoclonal antibody or ATG in four cases. The median number of nucleated cells (NC) infused/kg was 3.9 x 10(7) (0.7-15). One-year survival was 63 +/- 6%. Age, weight, HLA identity and negative cytomegalovirus (CMV) serology in the recipient were significant favorable prognostic factors. Among these 78 patients, the incidence of grade > or = II GVHD was 9% in HLA-matched CBT and 50% in mismatched CBT (P < 0.001). Neutrophil engraftment was associated with age <6 years (P = 0.02) and weight <20 kg (P = 0.02). It was 73% in patients receiving <3.7 x 10(7) nucleated cells (NC) infused/kg and 85% in patients receiving more (P = 0.06). Favorable factors for platelets engraftment were age <6 years (P = 0.03), weight <20 kg (P = 0.002) and HLA identity (P < 0.0001). Related cord blood transplantation offers a good alternative to BMT. Theses results are in favor of freezing cord blood in families in whom a transplant might be indicated.
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PMID:Related cord blood transplants: the Eurocord experience from 78 transplants. Eurocord Transplant group. 971 97

Hydroxyurea is a common cancer chemotherapy agent that inhibits ribonucleotide reductase, an enzyme essential to DNA synthesis. It is considered the drug of choice in the treatment of chronic myelogenous leukemia and essential thrombocythemia. The occurrence of leg ulcers have been described in 8.5% of patients receiving continuous treatment with hydroxyurea, but the cause of this complication is unknown. We report two additional patients and suggest that macroerythrocytosis, which occurs in almost all the patients taking hydroxyurea, may be a pathogenic factor. Macroerythrocytosis can be considered as an 'acquired' blood dyscrasia, and similar leg ulcers have long been known to occur with certain hereditary blood dyscrasias, such as sickle cell anemia, thalasemia, and spherocytosis.
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PMID:Hydroxyurea-induced leg ulcers: is macroerythrocytosis a pathogenic factor? 1046 46

Hydroxyurea is classified as an S-phase antineoplastic agent (pregnancy category D). Two women became pregnant while taking hydroxyurea for sickle cell anemia and delivered live infants with no congenital anomalies. Although teratogenic effects of hydroxyurea were reported in animal studies, several case reports suggest the agent may have minimal teratogenic effects on the developing fetus. Fourteen cases of hydroxyurea therapy in pregnant patients with acute or chronic myelogenous leukemia, primary thrombocythemia, or sickle cell disease are reported in the literature. Three pregnancies were terminated by elective abortion; one woman developed eclampsia and delivered a phenotypically normal stillborn infant. All other patients delivered live, healthy infants without congenital anomalies. Further studies with larger numbers of patients receiving hydroxyurea during pregnancy, with longer follow-up of exposed children and more careful assessment of fetotoxic effects, are required before the agent can be promoted as safe in pregnancy.
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PMID:Hydroxyurea in two pregnant women with sickle cell anemia. 1060 98

Hydroxyurea has been extensively used in medical practice, mainly for treating chronic myelogenous leukemia, sickle cell anemia, and other diseases. In light of its ability to inhibit DNA synthesis and to induce cell cycle arrest through inhibition of ribonucleotide reductase, the effects of hydroxyurea on replication of human immunodeficiency virus type 1 (HIV-1) have been investigated. In vitro hydroxyurea has been shown to block HIV-1 reverse transcription and/or replication in quiescent peripheral blood mononuclear cells (PBMC) and macrophages. Hydroxyurea was also found to be synergistic with the nucleoside reverse transcriptase inhibitor didanosine and to inhibit HIV-1 replication in activated PBMC; this inhibition may be due to a reduction in deoxynucleoside triphosphate pool sizes. Finally, hydroxyurea has been shown to sensitize didanosine-resistant mutants. Hydroxyurea may therefore be useful for limiting the spread of didanosine-resistant HIV-1 variants. The favorable toxicity profile of hydroxyurea and the lack of significant overlapping toxicities with some of the nucleoside reverse transcriptase inhibitors, as well as their distinct mechanisms of action, have provided further rationale for use of these agents in combination therapies.
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PMID:Rationale for the use of hydroxyurea as an anti-human immunodeficiency virus drug. 1086 Sep 5

Hydroxyurea is an antimetabolite agent used in the treatment of myeloproliferative disorders and sickle cell anaemia. Although hydroxyurea is relatively well tolerated, adverse effects often involve skin and mucous membrane during long-term therapy. A group of 510 patients affected by chronic myeloid leukaemia from 1977 to 1998 has been considered. Only 158 patients were treated with hydroxyurea and fulfilled inclusion/exclusion criteria of this study. A spectrum of severe cutaneous and mucosal changes (inflammatory and neoplastic) was seen in about 13% of patients (21 patients out of 158) and was studied in detail. Cutaneous and mucosal atrophy were observed in all 21 patients. Skin atrophy was often characterized by numerous telangiectases, especially on legs and on sun-exposed sites (16/21). Cutaneous, mucosal and nail hyperpigmentation was evident, albeit with variable extent, in 10 of the 21 patients. Severe stomatitis and glossitis with flattening of papillae were another common finding. Five patients, who received a particularly long treatment with hydroxyurea, developed squamous-cell neoplasms on sun-exposed sites (both squamous-cell carcinomas and keratoacanthomas). Acral changes were characteristic and constant, including acral erythema (21/21), dermatomyositis-like changes on the dorsa of hands (7/21), ulcers localized on acral areas of legs, on genitalia and oral mucosae (20/21). The frequency and the variety of these muco-cutaneous changes are reported and the mechanisms by which hydroxyurea may induce this muco-cutaneous syndrome-like group of changes, are proposed.
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PMID:Muco-cutaneous changes during long-term therapy with hydroxyurea in chronic myeloid leukaemia. 1129 3

Applications of nucleic acid testing in most areas of the clinical laboratory have increased rapidly. The advantages of nucleic acid testing include enhanced specificity and sensitivity, ease of sample procurement, and more rapid turnaround time compared to conventional laboratory testing methods. However, the cost of testing is usually higher due to the need for additional laboratory space, specialized equipment, safety apparel, and the need for highly trained personnel. Most nucleic acid techniques currently used in a clinical setting can be categorized as either hybridization or amplification assays. Hybridization assays, including blotting techniques and microarrays, involve the complementary binding of an oligonucleotide probe of known DNA sequence with nucleic acid derived from the patient sample. To amplify small amounts of nucleic acid, assays such as the polymerase chain reaction and branched chain DNA employ either signal amplification or exponential amplification of target nucleic acid. Clinical applications of nucleic acid testing involve the detection of genetic diseases, e.g., sickle cell anemia and Huntington disease; and identification of infectious agents, e.g., HCV and HIV; or malignancies, e.g., chronic myelogenous leukemia and Burkitt lymphoma. Quantitative molecular assays also play important roles in predicting prognosis and monitoring responsiveness to therapy.
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PMID:The new millennium laboratory: molecular diagnostics goes clinical. 1176 Aug 24

Decitabine [NSC 127716, DAC, dezocitidine, Aza dC, 2'-deoxy-5-azacytidine] is a deoxycytidine and cytarabine derivative with potent antileukaemic activity, which was originated by Pharmachemie. This antimetabolite is able to induce in vitro gene activation and cellular differentiation by a mechanism involving DNA hypomethylation. SuperGen acquired worldwide rights to decitabine from Pharmachemie in the third quarter of 1999 for 4 million US dollars worth of SuperGen shares and income from manufacture upon the launch of decitabine. SuperGen announced in May 2000 that it had entered a Cooperative Research and Development Agreement (CRADA) with the US National Cancer Institute (NCI). SuperGen will supply decitabine to the NCI, which will initiate and sponsor clinical trials in patients with solid tumours and haematological malignancies. The NCI will also conduct studies on decitabine's mechanism of action. In 2002, the US FDA has granted decitabine orphan drug status for the treatment of myelodysplastic syndromes and sickle cell anaemia. In February 2003, the European Commission granted orphan drug status to decitabine for myelodysplastic syndrome. Decitabine has also received orphan drug status in the US as a host-protective agent in the treatment of AML. Decitabine has been studied in solid tumours as well as in different types of leukaemia. In several phase II studies it has been shown to have very limited efficacy against solid tumours. However, decitabine has shown better activity in the treatment of haematological malignancies such as acute myeloid leukaemia (AML), chronic myeloid leukaemia (CML) and myelodysplastic syndrome (preleukaemia). In March 2001, SuperGen announced that it had begun patient enrolment into its pivotal open-label phase III trial of decitabine in advanced myelodysplastic syndrome patients. The study, which will compare decitabine with standard care therapy, will be conducted at 15 medical centres in the US and will enrol a total of 160 patients. In March 2003, SuperGen announced that patient enrolment was complete. The study, which will compare decitabine with standard care therapy, will be conducted at 22 medical centres in the US and will enrol a total of 160 patients. A European pivotal trial is also underway for the same indication, and is aiming to enrol 220 patients. A phase I/II trial of 8 patients, designed to establish safety and efficacy in the treatment of sickle cell anaemia, has been completed at the University of Illinois, USA. Plans for additional studies of decitabine as a treatment for sickle cell anaemia are underway. Decitabine is also undergoing phase II clinical trials in Canada, for the treatment of non-small cell lung cancer, and in the US for chronic myeloid leukaemia and prostate cancer. Glasgow University in Scotland has conducted preclinical trials in chemotherapy-resistant ovarian and colon cancers. The results suggest that decitabine administration may reverse chemotherapy resistance in these cancers. SuperGen was issued a US patent (No. 6 191 119) in 2001 covering the use of decitabine in combination with rubitecan and antibiotic agents, including doxorubicin.
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PMID:Decitabine: 2'-deoxy-5-azacytidine, Aza dC, DAC, dezocitidine, NSC 127716. 1275 5

Hydroxyurea is commonly used in the treatment of various myeloproliferative disorders. In conventional pediatric clinical practice, its use is limited to benign hematologic conditions such as sickle cell disease and thalassemia. Long-term hydroxyurea use is associated with various adverse mucocutaneous effects including hyperpigmentation, alopecia, leg ulcers, and lichenoid eruptions. We report a 10-year-old boy with chronic myelogenous leukemia who presented with hyperpigmentation of the skin and nails 3 months after the start of hydroxyurea therapy. Melanonychia of all 20 nails with involvement of all three mucocutaneous areas (skin, nails, and mucosa) at presentation was a unique feature in our patient. With the recently increasing pediatric use of hydroxyurea in a variety of disorders, its benign and not so uncommon cutaneous adverse effects are emphasized here.
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PMID:Cutaneous manifestations of hydroxyurea therapy in childhood: case report and review. 1507 51

Decitabine, a potent DNA methyltransferase inhibitor, which was originally under development by Pharmachemie, is being developed by SuperGen. Pharmachemie had been studying decitabine in phase II clinical trials for several leukemia indications in Europe and the US. Preliminary results indicated that the compound was active in the treatment of myelodysplasia, relapsed leukemia, acute myeloid leukemia and postallogeneic progenitor cell transplant relapse. The compound is in phase II clinical trials with phase III trials scheduled to begin shortly. Decitabine has been used to treat myelodysplastic syndrome in a total of 125 patients, with an overall response rate of 49%. In a study using decitabine to treat chronic myelogenous leukemia in 81 patients, a response rate of 62% among patients in chronic phase of the disease was achieved. In a phase I/II trial designed to establish safety and efficacy in the treatment of sickle cell anemias treatment with decitabine generated a response in 100% of the patients tested: a total of eight patients were enrolled, each experienced elevated levels of fetal hemoglobin. Side effects were minimal and the drug was well tolerated. Plans for additional clinical studies of decitabine as a treatment for sickle cell anemia are underway. A phase II trial using a low dose of decitabine in patients with myelodysplastic syndrome has been completed. Of 66 patients entered, 62 were evaluable. The response rate was 48%, with a median response duration of 40 weeks. The mean survival from the start of therapy was 13 months. In a study with 37 CML patients, a 25% overall response rate was seen in those patients in the blastic phase of the disease, and a 52% response rate was observed in the accelerated phase patients. The most significant side effect was prolonged myelosuppression. The drug suppresses cellular growth in seven human tumor cell lines, possibly by reactivation of certain growth suppressor genes.
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PMID:Decitabine (SuperGen). 1603 61


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