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)

Most recent progress in the treatment of leukemia and choice of therapies for obtaining "cure" from leukemia are discussed. Chemotherapy can now provide about 40% long term survival in acute myeloblastic leukemia (AML) and about 20% disease-free survival in acute lymphoblastic leukemia (ALL) of adults. Bone marrow transplantation (BMT) should be applied for the patients at risk in those leukemias (Cytogenetic abnormalities for AML and prognostic factors in ALL). In CML patients, BMT offers the only cure. Update result of interferon (IFN) therapy for CML is still a matter of controversy. Ex vivo treatment of autologous cells with IFN or drugs may be beneficial for CML patients without HLA identical donor.
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PMID:[Recent advances in the chemotherapy of leukemias]. 138 49

A female patient with chronic myelocytic leukemia (CML) in chronic phase after busulfan and interferon treatment had four different cell lines in her bone marrow. In addition to cells with a normal karyotype there were cells with the Philadelphia chromosome (Ph1), cells with trisomy 8 and Ph1, and cells with trisomy 8 as the sole anomaly.
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PMID:Trisomy 8 in Philadelphia chromosome (Ph1)-negative cells in the course of Ph1-positive chronic myelocytic leukemia. 768 33

Symptoms of autoimmune disease were evaluated in 125 patients with chronic myelogenous leukemia (CML) and in 12 patients with essential thrombocythemia undergoing treatment with recombinant interferon (IFN)-alpha-2b plus/minus low-dose recombinant IFN-gamma. Twenty-seven of 137 patients (20%) developed rheumatoid symptoms. Furthermore, the incidence of antinuclear antibody (ANA) formation was studied. Elevated ANA titers were found in 5/19 (26%) of CML patients at the time of diagnosis and in 3/18 (17%) of patients treated with hydroxyurea or busulfan. During IFN treatment, 18 of 25 tested patients (72%) had elevated ANA titers. In 15 of these ANA-positive patients, clinical signs of autoimmune disease appeared. All these patients were under long-term IFN treatment and were in remission of disease. In three patients criteria for systemic lupus erythematosus were fulfilled. Severity of side effects had led to the discontinuation of IFN treatment in these patients. The data indicate that IFN-alpha and IFN-gamma can induce ANA associated with autoimmune disease in patients with myeloproliferative disorders.
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PMID:Lupus-like autoimmune disease induced by interferon therapy for myeloproliferative disorders. 138 10

Patients with Philadelphia-positive chronic-phase chronic myelogenous leukemia (CML) resistant to interferon (IFN) alpha were treated in a phase I/II study with recombinant human tumor necrosis factor alpha to overcome IFN alpha resistance. Doses of 40, 80, 120 or 160 micrograms/m2 TNF alpha were given as 2-h infusions on 5 consecutive days every 3 weeks. IFN alpha (4 x 10(6) IU/m2 s.c., daily) treatment was continued. Six patients were treated, completing 1-24 (median, 12) treatment cycles. Five of the six patients achieved partial hematological remission, while the remaining patient had to stop treatment because of WHO grade 4 thrombocytopenia following the first TNF alpha cycle. No complete hematologic remission or cytogenetic improvement was seen. Side-effects were similar to those described for both substances alone. Maximum tolerable TNF doses usually varied between 80 micrograms/m2 and 160 micrograms/m2. To examine possible pathways of TNF activity in these patients, interferon receptor status and (2'-5')-oligoadenylate synthetase levels were examined in peripheral blood mononuclear cells. Both parameters remained unchanged during TNF alpha treatment. These preliminary data point to significant clinical efficacy of additionally applied TNF alpha in IFN alpha-resistant CML patients.
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PMID:Tumor necrosis factor alpha modifies resistance to interferon alpha in vivo: first clinical data. 139 38

Eleven previously untreated patients with chronic-phase Philadelphia-chromosome-positive chronic myelogenous leukemia were treated with cytotoxic chemotherapy followed by interferon-alfa-2b (IFN-alpha) maintenance. Initial chemotherapy consisted of three cycles of mitoxantrone 10 mg/m2 on day 1 and 2, and cytarabine 100 mg/m2 daily for 5 d. Complete hematological response was obtained in 9 (82%) patients with moderately associated toxicity. However, cytogenetic responses after three cycles were poor and transient (1 partial suppression and 2 minor suppression of Ph chromosome). Maintenance therapy with IFN-alpha was started in 10 patients at 5 x 10(6) U/m2 daily with dose reduction if hematologic toxicity or severe side-effects occurred. Of 9 evaluable patients treated for more than 3 months, 6 patients maintained a complete hematological response, whereas 1 patient remained in partial remission and 2 patients showed progressive disease. Cytogenetic evaluation showed partial suppression of Ph chromosome in 1 patient, whereas 1 patient had a minor response and 5 patients had no change or evolution of new chromosome abnormalities. As the results are not superior to IFN-alpha treatment alone, it is concluded that initial cytoreduction by mitoxantrone and cytarabine has no impact on the outcome of therapy in CML.
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PMID:Initial cytoreduction by mitoxantrone and cytarabine has no impact on the outcome of interferon-alfa-2b therapy in chronic myelogenous leukemia. 139 43

A patient with chronic myeloid leukaemia was treated with interferon without using conventional cytotoxic agents. Bone marrow necrosis developed at the onset of blast transformation. It is suggested that cytotoxic drugs should be given before treatment with interferon for chronic myeloid leukaemia. Cytotoxic drugs may also be needed to prevent rapid bone marrow growth once interferon has been withdrawn.
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PMID:Bone marrow necrosis at transformation of chronic granulocytic leukaemia treated with interferon. 140 Dec 21

We report the occurrence of autoimmune hepatitis after treatment with interferon-alpha in a patient with Philadelphia chromosome-positive chronic myeloid leukemia. Cytogenetic and molecular genetic studies of the T lymphocytes in this patient demonstrated that the T lymphocytes were not part of the leukemic clone. The role of interferon in the production of autoimmune abnormalities is reviewed.
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PMID:Interferon-alpha induced autoimmune hepatitis in a patient with Philadelphia chromosome-positive chronic myeloid leukemia with cytogenetically normal T lymphocytes. 144 68

Patients with chronic myelogenous leukemia (CML) have been treated with interferon (IFN) alpha-2b alone or in combination with IFN gamma. In order to predict clinical response to IFN, bone marrow samples from 15 CML patients were incubated with serial dilutions of IFN alpha-2b to obtain the IC50 values for erythroid burst forming units (BFU-E) and granulocyte-macrophage colony forming units (CFU-GM). A dose-dependent inhibition of at least one lineage was observed in all but one sample. An inhibitory effect of greater than 50% was reached for BFU-E in 8/14 patients and for CFU-GM in 10/14 patients. All three patients with no response (NR) to IFN treatment had IFN-sensitive BFU-E and CFU-GM. In four patients with hematologic remission (HR) or partial hematologic remission (PHR), BFU-E or CFU-GM were affected very little by the inhibitory effect of IFN. These observations suggest no predictive value for pretesting IFN sensitivity in vitro. The in vivo effect of IFN on the hemopoietic progenitor cells BFU-E and CFU-GM was evaluated in patients treated with either IFN alpha-2b alone (n = 11), or in combination with low dose IFN gamma (n = 10). All patients were newly diagnosed and not pretreated. After a median treatment duration of 11 months (range 3-25) a significant decrease in BFU-E and CFU-GM was observed in both groups of patients. We conclude that in vitro colony growth reflects the therapeutic efficacy of IFN.
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PMID:Clonogenic assay is not predictive but reflects therapeutic efficacy of interferons in the treatment of chronic myelogenous leukemia. 145 16

The place of alpha interferon (IFN) therapy in the treatment of chronic myeloid leukaemia (CML) is under intensive investigation at present. It is now established that as a single agent it can provide good disease control in the chronic phase and that cytogenetic responses will occur in a minority of patients. However its impact on long term survival has been less certain. Optimal haematological and cytogenetic results have to date been seen when IFN is used in the early phase of the disease, i.e. within one year of diagnosis. We have performed a prospective single arm study on the effect on survival of the addition of low dose IFN (9 mU/week) to conventional oral chemotherapy in patients who were at a median of 19 months from the initial diagnosis at the time of study entry. Comparison of this cohort with a control group of CML patients treated with oral chemotherapy only at the same participating institutions gave an estimated 72% reduction in the risk of death as a result of IFN therapy. Median survival for the IFN group has not been reached at 43 months compared with a median survival of 33 months for the chemotherapy alone group. These results suggest that the introduction of low dose IFN at any stage in the chronic phase may produce a worthwhile improvement in survival.
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PMID:Recombinant alpha 2B interferon in combination with oral chemotherapy in late chronic phase chronic myeloid leukaemia. 147 37

Clinical trials have shown that interferon (IFN) have myelosuppressive effects that can help reduce the uncontrolled clonal growth of hematopoietic cells in myeloproliferative disease. There are at least four diseases that are considered to be myeloproliferative disorders: chronic myelogenous leukemia, myelofibrosis polycythemia vera and idiopathic thrombocythemia. Recombinant IFN alpha has shown promise in inducing haematological and cytogenetic remission in some patients with chronic myelogenous leukemia. The exact role of IFN in prolonging the life of CML patients, however, remains to be determined in larger studies of longer duration. Preliminary evidence suggests that in myelofibrosis it may be more efficacious in the cellular than in fibrotic or osteosclerotic phase. IFN alpha has been reported to be of value in controlling excess platelet production in chronic myelogenous leukemia and idiopathic thrombocythemia as well as in reducing of red cell mas in polycythemia vera.
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PMID:[Use of interferon in the treatment of chronic myeloproliferative disorders]. 148 70


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