Gene/Protein Disease Symptom Drug Enzyme Compound
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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 chemistry, biological activity, and pharmacokinetics of gamma-interferon and recombinant interferon gamma are reviewed, and the agent's clinical efficacy, adverse effects, and dosage and administration for the treatment of chronic granulomatous disease (CGD) and other disorders are described. Endogenous gamma-interferon is a 166-amino-acid protein encoded by a single gene on chromosome 12. Recombinant human interferon gamma is purified from Escherichia coli as a monomer containing 139 amino acids. Gamma-interferon has antiviral, immunomodulatory, and antiproliferative activity. Serum concentrations of recombinant interferon gamma increase in proportion to the dose. Clearance after i.m. or s.c. administration fits a two-compartment model. The half-life is 3.5-7.5 hours, and bioavailability is 89%. Evidence that recombinant interferon gamma can enhance phagocytic oxidative metabolism led to its evaluation for use in the treatment of CGD. Clinical studies showed that the agent decreases the frequency of serious infections in patients with CGD. Recombinant interferon gamma has shown only limited success in the treatment of metastatic renal cell carcinoma (RCC), both as a single agent and in combination with recombinant interferon alfa. Similarly, although interferons appear to be able to change cytogenetic abnormalities in some patients with Philadelphia chromosome-positive chronic myelogenous leukemia, therapy with recombinant interferon gamma has led to minimal success. However, the agent has produced some encouraging results in atopic dermatitis. The adverse effects of recombinant interferon gamma in patients with CGD usually consist only of fever, chills, headache, and erythema. The recommended dosage in CGD-afflicted children whose body surface area is greater than 0.5 sq m is 50 micrograms/sq m given by s.c. injection three times a week for life. Recombinant interferon gamma has given new hope to patients with CGD. Although the drug is very expensive, the cost may be offset by fewer hospitalizations to treat infection.
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PMID:Recombinant interferon gamma for treatment of chronic granulomatous disease and other disorders. 134 90

Erythromelalgia (erythermalgia) is characterized by attacks of severe burning pain, erythema, and warmth of the extremities, primarily the feet and, to a lesser extent, the hands. The distress is provoked by environmental heat, exercise, and dependency; it is relieved by exposure to cold and elevation of the extremity. Primary and secondary forms of erythromelalgia exist. Secondary erythromelalgia has been linked to a wide variety of diseases, the most common of which are certain myeloproliferative disorders: polycythemia vera and essential thrombocythemia. We describe, for the first time, a patient in whom chronic myelogenous leukemia was associated with the development of erythromelalgia, review the 60 cases in the world literature of erythromelalgia in patients with myeloproliferative syndromes, and compare the primary and secondary forms of the disease. Importantly, symptoms of erythromelalgia preceded the onset of a myeloproliferative disease by a median of 2 1/2 years. Therefore, all patients with erythromelalgia should be monitored with periodic blood cell counts. An abnormal hemoglobin level, white blood cell or platelet count, or immature cells in the differential count are not seen in idiopathic erythromelalgia and should alert the physician to the possibility of a more serious underlying disease process. Treatment of the myeloproliferative syndrome will sometimes alleviate the symptoms of erythromelalgia. Alternatively, a single daily dose of aspirin results in dramatic improvement in most patients with either primary or secondary erythromelalgia.
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PMID:Erythromelalgia and myeloproliferative disorders. 264 12

We describe the case of a 3-year-old boy who presented with typical clinical features of Lyme disease, including erythema chronicum migrans and arthritis. Over subsequent months, however, the clinical picture evolved into juvenile chronic myelocytic leukemia. To our knowledge, the combination of Lyme disease and juvenile chronic myelocytic leukemia has not been described. Dermatologic and other relevant clinical findings are presented, and the cause and effect relationship between these two rare entities is discussed.
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PMID:Erythema chronicum migrans as the presenting manifestation of juvenile chronic myelocytic leukemia. 273 38

Microscopic and medical review of twenty-six patients with skin biopsy specimens that showed granulomatous vasculitis demonstrated vascular histiocytic granulomas with fibrinoid destruction of blood vessels in the dermis and panniculus. Cultures of the biopsy specimens were nonspecific. The skin lesions varied from erythema to papulonodular and vesicular eruptions; they were usually on the extremities but also involved the trunk. Eight patients had systemic lymphoproliferative diseases: three, lymphoma; two, angioimmunoblastic lymphadenopathy; two, preleukemia; and one, chronic granulocytic leukemia. Five of these eight patients died within 2 years after the onset of skin lesions. The four patients with systemic vasculitis died within 1 year after the onset of skin lesions. Five patients with arthritis, four with gastrointestinal disease, three with systemic sarcoidosis or sarcoidlike disease, and one with tuberculosis had a more favorable prognosis. The histologic pattern of cutaneous nonlymphomatoid granulomatous vasculitis is associated with significant systemic disease, especially lymphoproliferative disorders. Patients with lymphoproliferative disorders or systemic vasculitis have a much poorer prognosis than those with inflammatory or infectious granulomatous disease.
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PMID:Cutaneous granulomatous vasculitis: its relationship to systemic disease. 395 62

Fifty-seven patients with refractory acute leukemia were treated with high-dose cytosine arabinoside to establish the maximum tolerated dose and duration and to determine the antileukemic activity. The maximum tolerated regimen was found to be 3 g/sq m every 12 hr for 6 days. At this dose, nonhematologic toxicity was limited to conjunctivitis in approximately half of the patients, and liver toxicity (transient elevations in transaminase, alkaline phosphatase, or bilirubin) was frequently observed, but neither was dose-limiting. Extending the duration of treatment to 8 days resulted in excessive diarrhea and skin toxicity (painful erythema with bullae), while increasing the dose to 4.5 g/sq m q. 12 hr for 6 days resulted in severe cerebellar toxicity. Myelosuppression was severe, but was not related to the intensity of treatment; granulocyte recovery occurred a median of 28 days (range 22-40 days) after initiating therapy, and platelet recovery occurred after a median of 25 days (range 16-41 days). Antileukemic activity was evaluable in the 46 patients who survived at least 3 wk. Complete remissions were obtained in 1 of 6 patients with chronic myelogenous leukemia (CML) in accelerated phase and 1 of 3 acute lymphoblastic leukemia (ALL) patients. A more detailed analysis of response was possible for the 37 evaluable patients with acute nonlymphoblastic leukemia: 70% of these patients responded, with 51% complete remissions. The median unmaintained response was 4 mo (range 2-26+ mo). The complete response rate was higher in patients who received at least 12 doses of high-dose cytosine arabinoside compared to shorter regimens [17/28 (61%) versus 2/9 (22%), p less than 0.05]. Resistance to cytosine arabinoside in conventional doses was documented in 11 patients, 5 of whom responded (2 complete remissions) to high-dose regimens. We conclude that high-dose cytosine arabinoside in the maximally tolerated regimen of 3 g/sq m every 12 hr for 6 days has substantial antileukemic activity in patients refractory to standard therapy. Durable unmaintained remissions can be achieved, even in patients who fail to respond to cytosine arabinoside in conventional doses.
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PMID:High-dose cytosine arabinoside therapy for refractory leukemia. 622 74

A 45-year-old male with chronic myelocytic leukemia who received a bone marrow transplantation from a phenotypically HLA-matched unrelated donor developed chronic GVHD on day 100 post transplantation. He developed a slight fever, malaise, hepatic dysfunction and extensive itchy erythema with scaling over his entire body. The inflammatory skin lesion developed into erythroderma in about two weeks. H&E staining of a skin biopsy revealed eosinophilic bodies and a lymphocytic infiltration in the dermis and epidermis, which were compatible with the early phases of chronic GVHD. Immunohistochemistry revealed that keratinocytes expressed dense HLA-DR and ICAM-1 epitopes. Langerhans cells (CD1a+ cells) had disappeared from the epidermis. Many T cells (CD3+ cells) had migrated into the epidermis as well as into the reticular dermis. The majority of the T cells in the epidermis were CD8+ cells, while almost all the T cells in the dermis were CD4+ cells. These immunohistochemical features were similar to those previously reported for acute cutaneous GVHD. Despite the corticosteroid therapy, the eruptions did not disappear. The patient was then treated with whole body bath-methoxsalen (Oxsoralen) plus ultraviolet A (UVA). The bath-psoralen plus UVA therapy was effective in this patient.
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PMID:A case of chronic GVHD following bone marrow transplantation from a phenotypically HLA-matched unrelated donor. 805 98

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

The objective of this study was to analyze the mobilization kinetics of normal (BCR-ABL(neg)) and malignant (BCR-ABL(pos)) progenitor cells using a new, low toxic, out-patient-based mobilization regimen for Philadelphia chromosome-positive (Ph(pos)) chronic myelogenous leukemia (CML) patients. High doses of hydroxyurea (HD-HU, 3.5 g/m(2) per day, orally for 7 days) followed by granulocyte colony-stimulating factor (G-CSF) (10 microg/kg subcutaneously) were administered to 11 newly diagnosed CML patients. Each apheresis product (n = 30) was individually analyzed for the number and genotype of mature colony-forming cells (CFC) and primitive long-term culture initiating cells (LTC-IC), respectively, by reverse transcription polymerase chain reaction (RT-PCR) of individual colonies. Sufficient numbers of CD34(+) cells/kg bodyweight (BW) could easily be obtained in all patients (median, 15 x 10(6)/kg BW per patient) with a median number of three aphereses performed per patient (range 2-4). Almost each apheresis itself (25/30) contained > or =2 x 10(6) CD34(+) cells/kg BW. All patients with low and intermediate Sokal risk indices (9/11) mobilized primarily BCR-ABL(neg) LTC-IC (median 92%, range 47-100) and CFC (median 89%, range 57-100). Moreover, the mean percentage of BCR-ABL(neg) CFC and LTC-IC in the various apheresis products in these patients did not change throughout the entire time of hematopoietic regeneration. The toxicity of the mobilization procedure was low. Side effects were mild erythema in 8/11 and oral mucositis in 3/11 patients. Overall, the low toxicity of this regimen, together with the fact that sufficient BCR-ABL(neg) progenitors can be collected throughout the entire period of hematopoietic regeneration, renders this mobilization regimen particularly attractive for the collection of BCR-ABL(neg) progenitors in early chronic phase of Ph(pos) CML.
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PMID:High-dose hydroxyurea plus G-CSF mobilize BCR-ABL-negative progenitor cells (CFC, LTC-IC) into the blood of newly diagnosed CML patients at any time of hematopoietic regeneration. 1198

A 71-year-old man with chronic myelogenous leukemia received interferon therapy for 21 months, but did not have complete cytogenetic response. Imatinib was then added to the former therapy. Imatinib was prescribed for only 12 days and discontinued because of severe erythema. Since then, however, marked reduction of bcr-abl fusion chromosome positive cells was observed, and this state has been maintained to the present day even though treatment has consisted only of interferon. we discuss efficacy of the combined therapy, composed of interferon and imatinib, for chronic myelogenous leukemia and other bcr-abl fusion chromosome positive diseases.
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PMID:[Marked reduction of BCR-ABL fusion chromosome positive cells with interferon therapy combined with short-term imatinib in chronic myelogenous leukemia]. 1465 Sep 75


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