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 an open prospective pilot trial, we tested the effect of recombinant interferon alpha-2 a (rIFN alpha-2 a) on thrombocytosis in myeloproliferative disorders (MPD). Since October 1986, 13 patients with MPD (4 with chronic granulocytic leukemia, 4 with polycythemia vera, 3 with essential thrombocythemia and 2 with myeloid metaplasia) were treated with rIFN alpha-2 a. Platelet counts decreased in all treated patients within 2 to 10 weeks from a median value of 1,050 x 10(9)/l (range 610-1,940 x 10(9)/l) to 340 x 10(9)/l (range 230-495 x 10(9)/l). The response was dose-dependent. In 11 patients we observed a simultaneous reduction of the white blood cell count. Six patients still continue the IFN alpha-2 a therapy. In 7 treatment was discontinued, because of chronic side effects in 3, and because of noncompliance in one. In these patients, thrombocytosis recurred after discontinuation of the therapy. These results show that rIFN alpha-2 a is effective in controlling thrombocytosis in MPD. However, the long-term benefit of interferon in these disorders remains to be established.
 ...
PMID:Treatment of thrombocytosis in myeloproliferative disorders with interferon alpha-2a. 264 94

Cytogenetic data are reported from 16 patients with Philadelphia chromosome (Ph) positive chronic myelogenous leukemia (CML) treated with bone marrow transplantation (BMT). The usefulness of cytogenetic investigations for the assessment of marrow engraftment is stressed. The significance of persistence or reappearance of Ph after BMT, possibly due to a defective leukemic clone eradication by the conditioning regimen, is also discussed. Generally, Ph-positive cells are damaged and disappear within the first year of BMT. Sometimes, however, the cells may repair the damage and proliferate again, resulting in disease relapse. Rarely, clinical and hematologic relapse does not follow Ph-positive clone expansion although leukemic cells represent more than 50% of marrow metaphases examined. Finally, the effect of interferon on Ph-positive clones after BMT and random chromosome changes, that appear transiently after BMT and are of uncertain significance, are discussed.
 ...
PMID:Cytogenetics in patients with chronic myelogenous leukemia treated with bone marrow transplantation. 267 Jan 96

Chronic myelogenous leukemia is a myeloproliferative disorder representing 20%-30% of all leukemias. The disease is characterized by a cytogenetic abnormality called the Philadelphia chromosome. Except in patients who have undergone bone marrow transplantation (BMT), the natural history of chronic myelogenous leukemia has not changed in the last 30 years. Recombinant interferon alpha controls thrombocytosis and leukocytosis, reduces the leukemic infiltrate in the bone marrow, returns the spleen size to normal, and converts some patients to a normal chromosome pattern. This review summarizes the clinical and cytogenetic responses to date. The most significant observation is that, aside from treatment with BMT, interferon is the only agent that induces cytogenetic remissions.
 ...
PMID:Alpha interferon: progress and perspectives in the biotherapy of chronic myelogenous leukemia. 268 14

Therapy of Philadelphia positive chronic myelogenous leukaemia (CML Ph1) with alpha interferon (IFN-alpha) resulted in a high frequency of haematological remissions. Effective suppression of the malignant Ph1 clone and concomitant partial or complete restoration of normal haemopoiesis is reproducibly noted in a proportion (30%-50%) of the patients. This and the low incidence of blast crisis underscore the profound effect this therapy has on the disease. Marked heterogeneity in the response to IFN-alpha was noted as well, and sensitivity or resistance to interferon was phenotypically indistinguishable. Studies of the IFN-resistant disease failed to disclose alteration in IFN receptors or in IFN-inducible genes and are suggestive, therefore, of a limited alteration in IFN-induced intracellular pathways.
 ...
PMID:Therapy of chronic myelogenous leukaemia with interferons. 270 27

The Authors report an alternative approach to treatment in CML with beta-interferon in patients in whom other traditional drugs failed. The accelerated stage of the illness was well controlled with return to chronic phase.
 ...
PMID:[Clinical experience in a case of chronic myeloid leukemia in accelerated phase treated with beta-interferon]. 271 Oct 10

We studied whether the histamine H2 receptor antagonist, cimetidine, potentiates antiproliferative effects of recombinant alpha interferon (IFN alpha) on in vitro clonal growth of certain normal and malignant hematopoietic cells. Cimetidine alone, at therapeutic serum concentrations, was not inhibitory to the cells studied. IFN alpha alone inhibited the growth of HL-60 leukemic cells only at concentrations greater than 1000 U/ml, whereas with cimetidine, inhibition was seen at greater than 1 U/ml of IFN alpha. The enhancing effect of cimetidine on IFN alpha inhibition of clonal growth was neutralized by histamine and was not seen with histamine H1 receptor antagonist. In HL-60 cells, cimetidine also increased the enzymatic activity of (2'-5')-oligoadenylate synthetase, induced by IFN alpha. The combination of cimetidine and IFN alpha had a synergistic inhibitory effect on the growth of leukemic granulocyte-macrophage colony-forming units (CFU-GM) from chronic myeloid leukemia patients, normal CFU-GM, and normal erythroid burst-forming unit (BFU-E) progenitors. These data suggest that cimetidine may play a role in overcoming resistance to IFN alpha therapy in leukemia, but may also increase IFN alpha hematopoietic toxicity.
 ...
PMID:Effect of alpha interferon on growth of leukemic and normal hematopoietic progenitors. Synergism with H2 histamine receptor antagonists. 271 24

The Philadelphia (Ph') chromosome in chronic myelogenous leukemia (CML) results in fusion of the bcr gene and c-abl oncogene, which transcribes into two types of chimeric bcr/abl mRNAs: the L-6 junction and the K-28 junction. By means of a highly sensitive assay, combination of reverse transcription and polymerase chain reaction (RT/PCR), we analyzed 38 blood samples obtained from 31 patients with Ph'-positive CML and two patients with Ph'-negative bcr rearranged CML. Among the 21 samples obtained in chronic phase, eight patients had the L-6 mRNA, 11 had the K-28 mRNA, and two had both the L-6 and K-28 mRNAs. Among the nine samples obtained in blast crisis, four contained the L-6 mRNA, two contained the K-28 mRNA, and three contained both the K-28 and L-6 mRNAs. This finding supports the concept of alternative splicing of bcr/abl mRNAs transcribed in Ph'-positive CML. However, it appears to be a rare event. Of the eight samples obtained from eight patients who had achieved complete cytogenetic remission and negativity for bcr region rearrangement for 6 months to 3 years after recombinant alpha interferon (r alpha-IFN) therapy, all of them showed evidence of minimal residual Ph'-positive clones as detected by the RT/PCR assay. This finding suggests that interferon therapy suppresses the proliferation of the Ph'-positive clones, but it does not completely eradicate the Ph'-positive stem cells.
 ...
PMID:Detection of two alternative bcr/abl mRNA junctions and minimal residual disease in Philadelphia chromosome positive chronic myelogenous leukemia by polymerase chain reaction. 273 Sep 54

Twenty-seven patients with Philadelphia chromosome positive chronic myelogenous leukaemia in the chronic phase were treated with low doses of recombinant interferon (IFN) alpha-2b. Ten patients entered a complete and six a partial haematologic remission with a median duration of 5.8 and 9.1 months respectively. Five minor cytogenetic responses were observed. These results are inferior compared to other studies with higher interferon-doses. Fever was an acute side effect after injection of IFN, limb pains and fatigue occurred protractedly. Haematologic side effects, nonspecific EEG changes, weight loss, and development of pulmonary infiltrates were observed in later periods of the treatment. Eight patients developed neutralizing anti-IFN antibodies after 4.2-20.4 months (median 12.8 months). Anti-IFN antibodies were associated with relapse or refractoriness to IFN treatment: five out of nine patients with rising WBC after initial fall had antibodies, while four did not. Two out of four patients with primary non-response had IFN-antibodies. These results may indicate a serious problem in the long-term treatment of CML with recombinant interferon.
 ...
PMID:Recombinant human interferon (IFN) alpha-2b in chronic myelogenous leukaemia: dose dependency of response and frequency of neutralizing anti-interferon antibodies. 276 3

Our earlier studies demonstrated that about 55% of chronic myeloid leukemia (CML) patients in remission exhibited impaired natural killer (NK) cytotoxicity (low NK responders) while antibody-dependent cellular cytotoxicity (ADCC) of these patients, on chicken red blood cells as targets, was within normal range. In this paper, we have attempted to modulate the NK cytotoxicity of CML patients in remission with interferon (IFN) and interleukin-2 (IL-2) singly or together. ADCC using K562 target-directed monoclonal antibody (MAb) 4.6E10 was also modulated by treating the effectors with IFN or IL-2. Pretreatment of nonadherent mononuclear cells from peripheral blood (NAPBMNC) with IFN or IL-2 was found to result in 20 and 21% increase in target cell lysis in case of healthy donors, 79 and 98% increase in case of CML normal NK responders, and 164 and 159% increase in case of CML low NK responders. Combined use of IFN and IL-2 potentiated further the lymphocytotoxicity to 25% in healthy donors, 135% in normal NK responder CML patients and 283% in low NK responder CML patients. This treatment resulted in restoration of cytotoxicity of the latter group of patients to a normal level. The augmentation was seen in 80-100% CML patients. Although ADCC with chicken red blood cells as targets was within normal range, ADCC mediated with MAb to K562 cells was significantly lower in CML low NK responders (24.5%) than CML normal NK responders (42.4%) and healthy donors (65.9%).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Modulation of natural killer and antibody-dependent cellular cytotoxicity by interferon and interleukin-2 in chronic myeloid leukemia patients in remission. 278 54

The paper gives a brief account of alpha interferon (IFN) production employed for clinical use in oncology. In onco-haematology, in particular, the alpha IFN effect in hairy-cell leukaemia and chronic myeloid leukaemia is surprisingly favorable. This study analyzes the IFN therapeutical results in 11 patients with hairy-cell leukaemia during the first six months of treatment. For various reasons, four patients were not treated with IFN long enough to attain a therapeutic effect. One female patient with splenomegaly failed to respond to the treatment. In six patients the treatment was successful. Satisfactory partial remission was induced in five of these patients, in one--a complete remission. The paper briefly discusses the present knowledge of how IFN works. The effect is three-fold: anti-viral, immunomodulatory, and anti-proliferative. In hairy-cell leukaemia, the IFN anti-proliferative effect on the leukaemic cell population was observed in most cases. In conclusion, the authors, drawing on their own experience and literary data, propose indications, dosage, length of IFN therapy and describe side-effects in hairy-cell leukaemia, treated with alpha IFN. In natural and recombination forms, the alpha IFN can be considered important addition to the limited therapeutical options of hairy-cell leukaemia treatment.
 ...
PMID:[Treatment of hairy-cell leukemia using interferon alfa]. 279 Sep 14


<< Previous 1 2 3 4 5 6 7 8 9 10