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)

In 6 women aged 38 to 68 years with thrombocythaemia during chronic myeloid leukaemia (4 cases), myelofibrosis (1 case), and idiopathic thrombocythaemia (1 case) the effects of recombinant human alpha-interferon (Intron A, rh IFN alpha -2b, Schering) were studied. The drug was given to all patients subcutaneously in one daily dose of 3 x 10(6) u, every day for 3 weeks, and then in the same doses twice weekly for 2 weeks (5 cases) and for 14 weeks (1 case). Intron A caused in all cases a fall of peripheral blood platelet count by 37% to 65.5% (mean 50%) in relation to the initial count (532 - 1,453 x 10(9)/l). The fall of the platelet count occurred usually after 7-10 days of this treatment, and the lowest count was noted usually after 24 days (10 to 42 days). During the treatment in 4 cases the peripheral leucocyte count dropped as well by 20-70%. In no cases exacerbation of chronic myeloid leukaemia was noted, and in the patient with myelofibrosis the enlarged spleen shrunk somewhat. These results of treatment and follow-up of patients with thrombocythaemia treated with Intron A indicate a significant although short-lasting effect of platelet count fall limited, however, to the time of the treatment. Side effects of the drug included mainly febrile conditions, myalgia and arthralgia.
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PMID:[Effectiveness of interferon alfa in different stages of thrombocythemia (preliminary report)]. 182 71

A 33-year-old female was diagnosed as having chronic myelocytic leukemia (CML) with Philadelphia (Ph1) chromosome and breakpoint cluster region (bcr) rearrangement. Physical examination revealed a huge splenomegaly and laboratory data showed WBC 490 x 10(3)/microliter and NAP score 44. She was treated with hydroxyurea, alpha-interferon, or busulfan, but severe adverse reaction such as skin rash, fever, and arthralgia, which allowed the therapy discontinue was occurred. When the patient was treated with the oral form of etoposide, a semisynthetic podophillotoxin, the number of leukocyte has been successfully maintained less than 10 x 10(3)/microliters at the dose of 50-100 mg/day and splenomegaly completely disappeared. Although Ph1 chromosome was unchanged in the percentage after the therapy for 5 months, etoposide may be effective agent for a chronic or accelerated phase of CML. Alopecia which was reversible and well tolerable was the only side effect of the drug.
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PMID:[Successful therapy of Ph1 positive chronic myelocytic leukemia with oral form of etoposide]. 225 67

The present report analyzed a clinical and myopathological findings of 60 patients defined for the diagnosis of polymyositis. Patients were classified in four groups according to the system Walton and Adams. Forty five per cent were classified as Group I, 28.3 per cent as Group II, 15.0 per cent as Group III and 11.7 per cent as Group IV. Seven patients were associated with a malignant neoplasm and all of them were over fifty. The primary growth was carcinoma of the lung in 2, of the prostate, ovarium, stomach in one case each, and in one case a chronic myelogenous leukemia and in one case a malignant lymphoma. The female to male ratio was 2:1. Though cases were seen in all age groups, the largest number was in the sixth decade. The presenting symptoms and signs were essentially similar to those reported before. Proximal lower and upper limb weakness was the most frequent symptoms (91.7 and 83.3 per cent respectively). Other characteristic symptoms were skin changes, muscle pain, arthralgia and Raynaud's phenomenon. The CK was measured at the time of presentation in 58 of the 60 cases. Normal values were found in 18.3 per cent of cases. In general, muscle biopsy was performed in the first stage of the disease. A diagnostically abnormal biopsy was 55 cases (92 per cent), but 8 per cent of cases had normal biopsy. The characteristic changes in the biopsies from 60 cases were muscle fiber necrosis, inflammatory infiltration, fibrosis, basophilia and increase of internal nuclei. We could not get a significant difference between the two groups. However all of the cases of Group IV had muscle fiber necrosis, inflammatory infiltration and fibrosis.
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PMID:[Clinical and myopathological findings in polymyositis]. 367 29

A fifty-six-year old man complained of arthralgia and swelling of both feet, morning stiffness in both hands and finger joints in March 1987, and was treated with non-steroidal anti-inflammatory agents at another hospital. He has been treated for chronic myelogenous leukemia (CML) since May 1990. He was admitted to our hospital in March 1991 because of worsening of his multiple arthralgias, and a diagnosis of rheumatoid arthritis (RA) (Stage I, Class 2) was made on the basis of gait disturbance, arthralgia persisting for more than 6 weeks, the presence of subcutaneous nodules and X-ray findings. CML was confirmed by peripheral blood and bone marrow findings and the presence of the Philadelphia chromosome and bcr gene rearrangement. High fever and dyspnea developed suddenly 3 days after administration of interferon in May 1991. In addition to pneumonia, a leucostasis was suspected and he was treated with high dose steroids and antibiotics. After improvement, the steroids were tapered and he was discharged from hospital in July 1991.
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PMID:[Case report: rheumatoid arthritis complicated by chronic myelogenous leukemia treated with interferon]. 755 41

Thirty patients with chronic myeloid leukemia from 11 Israeli medical centers entered this study. Their ages ranged from 16-65 (median 41) and time from diagnosis to treatment was 1-16 months (median 4 months). After cytoreductive therapy with hydroxyurea (22 patients) or busulphan (8 patients), patients received 9 million units/day of recombinant interferon alpha-2 alpha (Roferon A) subcutaneously. Side effects included arthralgia or low back pain in 7 patients, thrombocytopenia in 9, weight loss in four, neurologic disturbances in 4 and leukopenia in 3 cases. Seventeen patients achieved complete hematologic remission (CHR) and 6 partial hematologic remission (PHR). Six patients achieved major cytogenetic response, 4 of them lost all Ph1 chromosome positive cells and 4 had minimal cytogenetic response. Frequency of relapse was high: 8 patients with CHR and 6 with PHR relapsed, but patients with major cytogenetic response did not relapse. Patients who had received prior therapy with busulphan had a higher remission rate but a lower quality of cytogenetic response. Escalation of Roferon to 12 million units per day in relapsing or nonresponding patients induced PHR in 2/7. Neutralizing anti-interferon antibodies occurred in 7 relapsing or nonresponding patients. The cytoreductive induction with hydroxyurea enhanced the hematologic remissions to a median of 6 weeks. Further studies should define the role of combination therapy in order to improve response and prevent relapses.
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PMID:Treatment of chronic myeloid leukemia with interferon alpha (Roferon): results of the Israeli Study Group on CML. 825 95

Avascular femoral head necrosis was identified in 15 patients treated at a major pediatric oncology center from 1974 to 1991. The predominant underlying diagnosis was acute leukemia (lymphoblastic, n = 6; non-lymphoblastic, n = 2); two patients had chronic myeloid leukemia, two Hodgkin's disease, and three other solid tumors. Patients ranged from 7 to 27 years of age at diagnosis of this complication, with a median interval of 25 months (range, 0-11 years) from primary diagnosis. Both steroids and radiation therapy appear implicated in the pathogenesis of avascular necrosis: nine patients had received high cumulative doses of prednisone (3.4-14 g/m2), four had received 35-64.8 Gy local irradiation involving the femoral head, and one underwent total body irradiation (12 Gy). Of the 11 surviving patients, six are asymptomatic and fully active. Two patients have joint pain that is responsive to conservative measures. Severe pain and joint deterioration necessitated arthroplasty in two cases, and a third child is undergoing orthopedic evaluation because of worsening symptoms. Thus, like adult cancer patients, children who receive high doses of steroids or local irradiation involving femoral heads are at risk for avascular necrosis. In patients with chronic myeloid leukemia, the complication may be disease related. Although outcomes in our series are better than those reported in adults, the long period of risk for these children and young adults precludes definitive conclusions.
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PMID:Avascular femoral head necrosis in pediatric cancer patients. 841 99

(1) Chronic myeloid leukaemia goes through three clinical phases: a chronic phase, an acceleration phase, and a terminal blast crisis. In the chronic phase, interferon alfa-2 is more effective than cytotoxic chemotherapies but it also has more adverse effects. (2) Imatinib inhibits tyrosine kinase, an enzyme encoded by the pathological gene BCR-ABL, which is created during a reverse translocation between chromosomes 9 and 22 (characteristic of chronic myeloid leukaemia). This translocation almost always creates the pathological chromosome Philadelphia in blood cell lines. (3) 1 027 patients were recruited to three non comparative trials of imatinib, each focusing on a different phase of chronic myeloid leukaemia. Efficacy was evaluated largely on the basis of blood cell count and clearance of cells harbouring the Philadelphia chromosome. (4) During the chronic phase, in patients in whom interferon alfa-2 had failed or been poorly tolerated, a major cytogenetic response, lasting at least one month, occurred in 35% of patients on imatinib, compared to 20% of patients on interferon alfa-2 + cytarabine (historical comparison). It is not known whether this translated into longer survival. (5) Preliminary results from a randomised but unblinded trial comparing imatinib with interferon + cytarabine seem to favour imatinib. Some patients developed relapses resistant to imatinib, owing to mutations in the BCR-ABL gene. (6) In patients going through the acceleration phase or blast crisis, imatinib did not improve survival compared with standard treatments. (7) The main adverse effects so far described with imatinib are gastrointestinal problems, oedema and fluid retention, and muscle and joint pain, which prompted patients to stop treatment in no more than 5% of cases. (8) Imatinib has a strong potential to interact with other drugs, including paracetamol, but few specific studies have been done. (9) In practice imatinib may be a useful option during the chronic phase, after interferon alfa-2 has failed or been stopped because of adverse effects, provided that its benefits, so far shown only in surrogate endpoints, translate into longer survival. During the acceleration phase and blast crisis imatinib may cause fewer side effects than existing treatments.
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PMID:Imatinib: new preparation. For Chronic myeloid leukaemia: further assessment required. 1266 27

Chronic myelogenous leukemia (CML) is a malignant clonal disorder of hemopoietic stem cells characterized by abnormal proliferation and accumulation of immature granulocyte. Leukostasis is one of the complications of CML and is characterized by partial or total occlusion of microcirculation by aggregation of leukemic cells and thrombi leading to respiratory, ophthalmic or neurologic symptoms. We experienced a rare case of avascular necrosis of the femoral head as the initial presentation of chronic myelogenous leukemia. A 24-year-old male patient was admitted to our hospital with pain in the right hip joint. The patient was diagnosed to be suffering from chronic myelogenous leukemia by packed marrow with granulocytic and megakaryocytic hyperplasia and the presence of Philadelphia chromosome. The right hip joint pain was attributed to avascular necrosis of the femoral head. And the avascular necrosis could be considered as the complication of chronic myelogenous leukemia due to microcirculatory obstruction of the femoral head. The avascular necrosis of the right femoral head was treated with bipolar hemiarthoplasty.
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PMID:A case of avascular necrosis of the femoral head as initial presentation of chronic myelogenous leukemia. 1629 87

Targeting constitutively activated tyrosine kinases, such as BCR-ABL, in chronic myeloid leukaemia (CML) and c-KIT in gastrointestinal stromal tumours (GIST) has substantially changed the clinical management of both diseases. The introduction of imatinib, a tyrosine kinase inhibitor mainly targeting BCR-ABL, c-KIT and PDGFR, has profoundly improved the prognosis of both entities, while being surprisingly well tolerated. This article summarizes recent data on clinical efficacy as well as safety aspects of imatinib for treatment of CML and GIST, including a final benefit-risk assessment. Imatinib induces high rates of cytogenetic and molecular responses in all phases of CML and also has substantial activity in GIST patients. In both diseases, only a few adverse effects, such as musculoskeletal and joint pain, muscle cramps, oedema and gastrointestinal symptoms, occur. Most of these are grade I or II toxicities and generally occur during the early phase of treatment (i.e. within the first 2 years). Thus, in view of the low rates of severe toxicities and the extraordinary efficacy of the drug in both diseases, imatinib represents an oral drug with a high benefit-risk ratio for the treatment of CML and GIST.
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PMID:A benefit-risk assessment of imatinib in chronic myeloid leukaemia and gastrointestinal stromal tumours. 1981 Jul 74

As chronic myeloid leukemia is rare in children, most data on imatinib mesylate therapy is derived from adult studies. We retrospectively evaluated pediatric (<14 years) patients with Ph+ chronic myeloid leukemia treated with imatinib mesylate, from January 2003 through June 2008. Of the 12 chronic myeloid leukemia patients (2% of all leukemias) 11 were in chronic phase while one had myeloid blast crisis. Six subsequently underwent stem cell transplantation. Five patients had grade 3-4 arthralgia requiring therapy alteration. None achieved complete molecular remission (MR) with imatinib mesylate alone. In contrast 3/6 patients post stem cell transplantation have undetectable BCR-ABL. Three patients relapsed to chronic phase (1 imatinib mesylate; 2 stem cell transplantation). Relapse free survival is 65.6% at four years and all are alive. Imatinib mesylate is effective therapy for children with chronic myeloid leukemia. However, cure probably requires stem cell transplantation. Acute toxicity of imatinib mesylate is tolerable, but long-term effects on growing children are unknown. Pediatric patients with chronic myeloid leukemia should undergo stem cell transplantation when appropriate related donors are available.
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PMID:Clinical characteristics and treatment outcome of pediatric patients with chronic myeloid leukemia. 2041 Jan 82


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