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 is an effective agent in the treatment of chronic myelogenous leukemia. The toxic reactions have included myelosuppression and megaloblastosis. During long-term maintenance therapy, dermatologic alterations occurred in seven of 20 patients and consisted of partial alopecia, increased pigmentation, scalings, atrophy of the skin and subcutaneous tissues, nail changes, and erythema of the face and hands. The histologic changes were similar to those seen in lichen planus. These observations were a factor leading to the use of hydroxyurea in the treatment of psoriasis.
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PMID:Skin changes secondary to hydroxyurea therapy. 105 61

The effect of hydroxyurea in 35 patients with chronic granulocytic leukemia (CGL), who either had entered an accelerated phase of the disease or had experienced excessive myelosuppression following alkylating agents, was studied. By either intravenous or oral administration, the drug was successful in reducing peripheral leukocyte and blast counts in all cases and in reducing splenomegaly in 13 of 17 patients. The median duration of disease control was 75 days in myeloproliferative acceleration and 27 days in frank blastic transformation. Mild nausea and vomiting were experienced by most patients, but reversible bone marrow suppression occured in only three patients. The drug proved useful in 19 patients who demonstrated myeloproliferative acceleration, especially in controlling excessive leukocytosis and/or thrombocytosis. Rapid reduction of an elevated blast cell count was achieved in nine patients who presented in blastic crisis, in an attempt to eliminate the associated risk of cerebral vascular leukostasis. Five patients who required treatment for their disease following splenectomy in the chronic phase were also well controlled. Hydroxyurea appears to have a definite role in the management of these hematologic complications of CGL.
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PMID:Hydroxyurea in the management of the hematologic complications of chronic granulocytic leukemia. 105 10

Hydroxycarbamide (the brand name: Hydrea) was found effective to chronic myelogenous leukemia (CML) in Japan. In the preclinical study, this compound was active against mouse leukemia L 1210 and inhibited DNA synthesis. Clinically, Hydrea was given orally at the daily dose of 500-2,000 mg, dividing 1-3 times. For the maintenance therapy after remission induction, daily dose of 500-1,000 mg was given, dividing 1-2 times. As for the side effects, myelosuppression, disturbance of the gastro-intestinal tract and temporal liver and renal dysfunctions were observed. The response rate in the remission-induction therapy was as high as 92.1%.
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PMID:[Hydrea, an effective drug for chronic myelogenous leukemia]. 144 98

The evolution of hydroxyurea as a chemotherapeutic agent has been unique. Hydroxyurea inhibits synthesis of DNA, has antitumor activity, and is myelosuppressive. It has attained a significant role in the management of chronic myelogenous leukemia. A nonrandomized comparison of busulfan and hydroxyurea concluded that hydroxyurea was the preferable agent in the treatment of chronic myelogenous leukemia and was associated with less life-threatening toxicity. Because of its systemic effects, hydroxyurea is also used in the treatment of polycythemia and psoriasis.
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PMID:The evolution of hydroxyurea therapy in chronic myelogenous leukemia. 164 53

The cytotoxic effect of caracemide and hydroxyurea was compared in human chronic myeloid leukemia cells. Caracemide was found to be about twelve times more effective than hydroxyurea. The combined effect of caracemide, hydroxyurea and hydrophobic iron-chelating agents at relatively nontoxic concentrations was studied. Hydroxyurea, 2,2'-bipyridine and 1,10-phenanthroline combined with caracemide synergistically inhibited DNA synthesis, while Desferal did not show any such effect. Fe++ partially reversed the cytotoxicity of caracemide in combination with 2,2'-bipyridine, while it had no effect on the cytotoxicity of caracemide alone. Caracemide was found to have a stronger inhibitory effect on DNA synthesis in P388 lymphocytic leukemia and Ehrlich ascites carcinoma cells than hydroxyurea. However, bipyridine, phenanthroline and Desferal in combination with caracemide did not induce any synergistic inhibition. These data indicate the value of human tumor cells to predict drug responsiveness and suggest the further evaluation of caracemide and its combination with hydroxyurea and iron-chelating agents in the treatment of human leukemias.
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PMID:In vitro cytotoxicity of caracemide alone and in combination with hydroxyurea or iron-chelating agents in human chronic myeloid leukemia cells and murine tumors. 316 54

Forty-three patients with chronic myeloid leukaemia have been treated with hydroxyurea in order to be subjected to leucopheresis for white cell transfusions. Hydroxyurea decreases leucocytosis when it is administered and the blood granulocyte number increases soon after the drug is stopped. The survival of the patients is not different from the survival of the patients treated with conventional chemotherapy (busulphan, mitobronitol) and it is superior to the survival of patients treated with external radiotherapy or with (32)P. Half of the patients were subjected to splenectomy during first remission for a phase II trial. They were not randomized, but the distribution according to age was similar in the two groups. A slight difference appears in favour of splenectomy so far as survival is concerned, but there were three post-operative deaths out of 18 patients. We conclude that a phase II trial on the value of splenectomy is indicated ethically, but that the patients should be operated on and nursed in a microbiologically controlled environment.
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PMID:Hydroxyurea, leucopheresis, and splenectomy in chronic myeloid leukaemia at the problastic phase. 451 3

A retrospective analysis of 67 patients with chronic myelogenous leukemia treated with hydroxyurea (41 patients) and busulfan (26 patients) compared the effectiveness of treatment and resulting survival. After 4 days of treatment, the white blood count in the hydroxyurea group fell at a rate of 31% +/- 10% per day compared to 10% +/- 8% for the busulfan group. At 6 months, the hemoglobin was similar, but in the busulfan group, the white blood count was significantly lower (12,500 vs. 29,900) (p = greater than 0.03). The platelet count was lower (311,000 vs. 481,000) in the busulfan group; however, the difference was not significant. When treatment was discontinued because of progression of the disease, the hemoglobin and white blood counts for both groups were similar. The platelet count was higher in the hydroxyurea group (762,000 vs. 269,000) (p greater than 0.02). The duration of therapy for both groups was similar. The median survival was also similar (hydroxyurea = 51 months; busulfan = 45 months). Hydroxyurea was associated with less life-threatening toxicity. Hydroxyurea is as effective as busulfan in treating chronic myelogenous leukemia.
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PMID:Hydroxyurea versus busulfan in the treatment of chronic myelogenous leukemia. 695 59

Survival of patients with chronic myeloid leukemia seen in the University of Colorado Leukemia Clinic were reviewed with respect to therapy. A total of 55 patients seen consecutively through mid 1980 were included in this study. Of these patients 30 were treated with busulfan, 14 were treated with hydroxyurea and 11 received under modalities. Busulfan treated patients who are now deceased, have had a median survival of 35 months (range, 13-108) and actuarial analysis shows the total busulfan treated population to have an expected median survival of 48 months. Hydroxyurea treated patients who are still alive have been followed for a median period of 69 months (range, 25-136 months) and a projected median survival for periods of 56 and 90 months, respectively. These data suggest that hydroxyurea may be an important treatment modality in the treatment of chronic myelogeous leukemia.
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PMID:Busulfan versus hydroxyurea in long-term therapy of chronic myelogenous leukemia. 695 30

Hydroxyurea is a cytotoxic agent used in the management of chronic granulocytic leukemia. This compound is teratogenic and embryolethal in various animal species, and has been widely used in experimental studies aimed at understanding the possible mechanisms of drug-induced malformations. Previous studies from our laboratory have demonstrated that maternal subcutaneous injections of hydroxyurea produce immediate circulatory alterations in rabbit embryos similar to those observed subsequent to uterine artery occlusion. The present study was designed to investigate the possibility that the embryolethal and teratogenic properties of hydroxyurea might be due to alterations in maternal hemodynamics, i.e., constriction of the uterine vasculature, resulting in exposure of the embryo to uterine ischemia at critical stage of in utero development. This study demonstrates that hydroxyurea significantly alters blood pressure and heart rate and produces significant uterine vasoconstriction. The resulting reductions in uterine blood flow (77%) elicited by hydroxyurea may be associated with its immediate embryotoxicity.
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PMID:Effects of hydroxyurea on hemodynamics of pregnant rabbits: a maternally mediated mechanism of embryotoxicity. 719 56

Hydroxyurea (HU) is currently used in the clinic for the treatment of chronic myelogenous leukemia, head and neck carcinoma, and sarcoma. One of its drawbacks, however, is the development of HU resistance. To study this problem, we developed a HU-resistant human KB cell line which exhibits a 15-fold resistance to HU. The characterization of this HU-resistant phenotype revealed a gene amplification of the M2 subunit of ribonucleotide reductase (RR), increased levels of M2 mRNA and protein, and a 3-fold increase of RR activity. This HU-resistant cell line also expressed a "collateral sensitivity" to 6-thioguanine (6-TG), with a 10-fold decrease in the dose inhibiting cell growth by 50% as compared to the KB parental line. The mechanism responsible for this supersensitivity to 6-TG is believed to be related to an increasingly efficient conversion of 6-TG to its triphosphate form, which is subsequently incorporated into DNA. After passage of the resistant cells in the absence of HU, the cell line reverts. The revertant cells lose their resistance to HU and concomitantly their sensitivity to 6-TG. This phenomenon is due to the return of RR to levels comparable to that of the KB parental cell line. These observations and their relevance to cancer chemotherapy will be discussed in this paper. Our results suggest that a clinical protocol could be designed which would allow for a lower dose of 6-TG to be used by taking advantage of the increased RR activity in HU-refractory cancer patients. Two drugs which display collateral sensitivity are known as a "Ying-Yang" pair. Alternate treatment with two different Ying-Yang pairs is the rationale for the "Ying-Yang Ping-Pong" theory in cancer treatment. This rationale allows for effective cancer chemotherapy with reduced toxicity.
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PMID:Characterization of a hydroxyurea-resistant human KB cell line with supersensitivity to 6-thioguanine. 751 43


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