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)

A 47-year-old woman was admitted to the hospital on March 13, 1998, because of general malaise and fever. It was determined that she had chronic myelogenous leukemia (CML) in myeloid blast crisis. Hydroxyurea was started initially, and the blasts completely disappeared from peripheral blood on day 9 of therapy. Interferon (IFN)-alpha was subsequently started, but lymphoblasts newly appeared on day 13 of administration. Treatment with adriamycin, vincristine, and prednisolone (AdVP) was immediately started, which rapidly reduced the lymphoblasts. However, the myeloblasts again began to gradually increase. Subsequent examinations showed the combined presence of myeloblasts and lymphoblasts in the marrow and peripheral blood. The ratio between myeloblasts and lymphoblasts depended on the treatment (IFN-alpha or AdVP). The patient died from respiratory failure on November 16, 1998. This patient may have had an underlying bipotential blastic clone that evolved differently in response to IFN-alpha or AdVP. In some CML patients, IFN-alpha may induce lymphoid blast crisis.
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PMID:Lymphoid blast crisis during interferon-alpha therapy in a patient with chronic myelogenous leukemia in myeloid blast crisis. 1119 15

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

Aiming to verify if insulin-like growth factor type I and its receptor (IGF-IR) are implicated on pathophysiology of chronic myelogenous leukemia (CML), we studied 35 patients with CML in chronic phase at diagnosis or during interferon-alpha (IFN-A) or hydroxyurea treatments. Cytometry flow analysis and reverse transcription PCR (RT-PCR) molecular assay for IGF-IR expression on peripheral blood cells from CML patients diagnosed didn't show statistical differences from the control group. Hydroxyurea treated patients had lower expression of IGF-IR in granulocytes, lymphocytes and monocytes (P<0.01). We found statistical higher percentage of T and B lymphocytes positive for IGF-IR on IFN-A treated patients (P<0.001). Also an increase of IGF-IR mRNA expression could be detected in this group when compared with patients in hydroxyurea therapy (P<0.05). Our study suggest that IGF-IR is not directly implicated on CML installation and that the increased expression of IGF-IR on lymphoid cells of IFN-A treated patients could contribute to the immune recognition of malignant cell clone by enhancing immunocompetent cell proliferation and action.
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PMID:Interferon-alpha therapy increases type I insulin-like growth factor receptors expression on lymphoid cells from patients with chronic myelogenous leukemia. 1139 78

Three patients, one with polycythaemia vera (PV) and two with chronic myeloid leukaemia (CML), are described who had cycling of blood counts which became apparent whilst receiving hydroxyurea therapy. Significant periodicity was confirmed with the use of the Lomb periodogram. This is Fourier power spectral analysis tailored for unevenly sampled data. The patient with PV had marked oscillations of platelet counts with a periodicity of 29 d and an amplitude of (202-588)x10(9)/L. Smaller oscillations of neutrophil, monocyte and lymphocyte numbers and Hb levels occurred with a similar periodicity. Anticipatory changes in hydroxyurea dosage or the maintenance of a constant dose did not abolish periodicity, but a change in therapy to the non-cycle-specific drug anagrelide dampened and abolished the cycling. One of the patients with CML had tremendous and clear oscillations in white cell, platelet and Hb levels, with a mean periodicity of 74 d. The other had erratic counts which were confirmed to be significantly periodic (64 d), on spectral analysis. A change in therapy to busulphan in both these patients again dampened and abolished the cycling. Hydroxyurea, which is a cell-cycle-specific agent, probably exacerbates the periodicity which may be present in some patients with myeloproliferative disease. A change in therapy to non-cycle-acting compounds such as busulphan or anagrelide results in much more stable counts in such patients.
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PMID:Hydroxyurea and periodicity in myeloproliferative disease. 1142 11

Behcet's disease (BD) is a chronic, relapsing vasculitis of unknown etiology. Its association with chronic myelogenous leukemia (CML) is extremely rare, and typical manifestations of BD were observed in a very few patients with CML, mainly under interferon-alpha (IFN-alpha) treatment. Skin pathergy test, being positive in about 50% of patients with BD, is also positive in some IFN-alpha-treated patients with CML without any evidence of BD symptoms. We describe a 62-year-old woman with CML who developed characteristic features of BD, including a positive skin hyperactivity test, during treatment with hydroxyurea. Hydroxyurea has been implicated in the appearance of skin vasculitic ulceration, but this is the first case, according to our knowledge, where the development of BD was observed during hydroxyurea maintenance in the chronic phase of CML.
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PMID:Behcet's disease in a patient with chronic myelogenous leukemia under hydroxyurea treatment: a case report and review of the literature. 1142 95

Since STI571, a BCR-ABL tyrosine kinase inhibitor, has made a great therapeutic advance in the management of CML, we have to reconsider the treatment protocol for chronic phase CML. Interferon-alpha (IFN-alpha) will be replaced with STI571 therapy. However, some patients are reported to become refractory to STI571, and it is unclear whether STI571 therapy alone may be sufficient to induce long-term survival in CML. There are also important progress in the field of allogeneic hematopoietic stem cell transplantation (SCT); i.e. minitransplant(non-myeloablative SCT) and cord blood stem cell transplantation. Currently, newly-diagnosed CML patients in chronic phase should be initially treated with STI571. If the patients are appropriate candidates for allogeneic SCT and have HLA-indentical sibling donors, allogeneic SCT should be conducted within one year. The other patients should also receive related or unrelated allogeneic SCT if Ph suppression is insufficient with STI571 therapy for several months. The patients who are not candidates for allogeneic SCT may be treated with IFN-alpha and/or Hydrea(or cytosine arabinoside) in addition to STI571 if they become refractory to STI571. Since each therapeutic modality has different risk and benefits, informed consent is very important to determine the treatment plan for individual patients.
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PMID:[Treatment plan and informed consent]. 1176 45

Chronic myeloid leukemia (CML) is a myeloproliferative disease arising from abnormal stem cells and associated with splenomegaly and leukocytosis. Hydroxyurea and interferon alpha are used in treatment very frequently. Behcet's disease (BD) is a chronic, repetitive disease of unknown etiology and associated with mucocutaneous, ocular, vascular and central nervous system involvement. Cases with symptoms of BD have been reported during interferon alpha treatment of CML. However, similar symptoms due to hydroxyurea treatment have been reported in only one case until now. A 32-year-old female patient under follow up because of CML and BD, developed a large genital ulcer during hydroxyurea treatment. Ulcers due to hydroxyurea treatment and the co-existence of these two diseases has been reported in only one case in the literature while large genital ulcers have not been reported previously.
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PMID:Development of large genital ulcer due to hydroxyurea treatment in a patient with chronic myeloid leukemia and Behcet's disease. 1285 11

Hydroxyurea is a ribonucleotide diphosphate reductase inhibitor used in the treatment of patients with myeloproliferative disorders. Hydroxyurea has some dermatological side-effects. It has recently been recognized that hydroxyurea can induce squamous cell and basal cell carcinomas of skin. We present the case of an elderly man with chronic myeloid leukaemia who was treated with hydroxyurea for 4 years, with good control of his disease. However, in addition to the appearance of various skin lesions and cutaneous squamous cell carcinoma after 3 years of therapy, he was found to have a metastatic squamous cell carcinoma after 4 years. Hydroxyurea was discontinued, and he underwent surgery and radiotherapy. The patient subsequently died of ventricular fibrillation. We present this case to draw attention to the association between hydroxyurea and secondary skin cancers and to emphasize the need for dermatological examination before and during the course of hydroxyurea therapy.
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PMID:Metastatic squamous cell carcinoma of the skin in chronic myeloid leukaemia: complication of hydroxyurea therapy. 1297 26

Interferon-alpha (IFN-alpha) is a therapy of unquestionable efficacy in chronic myeloid leukemia (CML) patients. The best dose of IFN-alpha in the treatment of CML still remains controversial. Our primary objective was to compare cytogenetic responses in patients treated with intermediate versus high doses of IFN-alpha. A multicenter randomized controlled trial was conducted involving 109 patients with untreated CML in chronic phase from 26 Spanish hospitals. Patients were assigned to receive either an intermediate (2.5 MU/m(2) per day) or high (5 MU/m(2) per day) target dose of IFN-alpha. Hydroxyurea was allowed in both groups. In total, 108 patients were analyzed, 53 in the intermediate- and 55 in the high-dose group. Median follow-up was 47.5 months. The dose of IFN-alpha actually given was lower in the intermediate-dose group (3.83 MU/day) than in the high-dose group (6.6 MU/day) ( p<0.001). The rate of complete cytogenetic response was 24.5% in the intermediate- and 12.7% in the high-dose group (NS). A partial cytogenetic response was obtained in 7.5% and 10.9%, respectively. Cox analysis did not reveal any influence of the randomization arm on cytogenetic response rate. Ten patients in each group discontinued IFN-alpha because of toxicity. Albeit not our primary objective, no differences were found in terms of survival or transformation rate between both groups. Median survival was 73 months; 64% of patients remained free of transformation at 5 years. In terms of cytogenetic response, intermediate doses of IFN-alpha are as effective as high doses in the treatment of CML.
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PMID:A randomized study of intermediate as compared with high doses of interferon-alpha for chronic myeloid leukemia: no differences in cytogenetic responses. 1451 91

Chronic myeloproliferative disorders (CMPD) are neoplastic disorders of the hematopoietic stem cell. Four different entities are defined: chronic myeloid leukemia (CML), polycythemia vers, essential thrombocythaemia, and idiopathic myelofibrosis. In addition, overlapping entities within the CMPDs and between CMPDs and myelodysplastic syndrome have been described. Diagnostic measures are performed to classify the subtype exactly and to assess risk factors and prognosis. Cytogenetic and molecular analyses are mandatory for the characterization of the malignant clone. Hydroxyurea and interferon-alpha have proven effective in all CMPE. In CML, specific inhibition of the elevated ABL tyrosine kinase activity with imatinib is associated with high response rates. Allogeneic stem cell transplantation is the only curative treatment option for all entities. In CML, the decision-making analysis should be based on established scores. In BCR-ABL negative CMPDs an allogeneic stem cell transplantation should only be performed in patients with unfavorable prognosis.
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PMID:[Chronic myeloproliferative diseases. Diagnosis and therapy]. 1467 16


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