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)

Of 38 patients with a Philadelphia-chromosome positive chronic myeloid leukaemia treated with recombinant interferon alpha (rIFN-alpha) 2a or 2b and monitored for emergence of IFN-antibodies in their sera 11 patients developed rIFN-alpha 2 binding and 10 rIFN-alpha 2 neutralizing antibodies. rIFN-alpha neutralizing antibody positive patients experienced significantly (P less than 0.025) more clinical relapses (6/10) than IFN-antibody negative patients (6/28) during continuous IFN-therapy. Furthermore, IFN-antibody-positive patients with titre above 400 INU/ml were more likely to relapse under rIFN-alpha-therapy than IFN-antibody-negative patients with titre below 400 INU/ml (P less than 0.05). Seven rIFN-antibody-positive patients experiencing a clinical relapse or a primary non-responsiveness were treated with two- to three-fold increased doses of rIFN-alpha 2. Only one of these seven patients developed a partial haematological remission upon intensification of the rIFN-alpha 2 therapy. Consecutively, the six patients failing high dose rIFN-alpha treatment were switched to a natural IFN-alpha preparation (3 x 9 x 10(6) I.U. weekly s.c.). Under such treatment two of the six patients achieved a long-lasting complete, one a partial haematological remission. In high-titred IFN-antibody positive patients significantly altered serum-IFN-titre and minimal IFN-inducible Mx-homologue concentrations were measured; in contrast, nIFN-alpha induced normal IFN-titre and dose-equivalent Mx-homologue amounts in these patients. The data prove that high-titred rIFN-alpha neutralizing antibodies abrogate the biological action of rIFN-alpha, but not of nIFN-alpha in vivo and explains why nIFN-alpha can be effective in the anti rIFN-alpha 2 positive patients.
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PMID:Treatment of anti-recombinant interferon-alpha 2 antibody positive CML patients with natural interferon-alpha. 206 59

A patient whose chronic myelogenous leukemia (CML) was treated with interferon alpha (IFN-alpha) is described. The disease showed karyotypic evolution during the chronic phase and the later myeloid acceleration. Both of these secondary clonal phenomena responded to IFN-alpha dose escalation. The case illustrates the dose dependence of CML responses to IFN-alpha. The phenomenon of clonal evolution is discussed in the context of this patient's disease.
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PMID:Alpha interferon dose-dependent suppression of secondary clones in a patient with Philadelphia-positive chronic myelogenous leukemia. 210 55

Three patients with hematologic relapse after bone marrow transplantation for chronic myelogenous leukemia were treated with interferon alpha and transfusion of viable donor buffy coat. All had complete hematologic and cytogenetic remission, which persisted 32 to 91 weeks after treatment. In two patients graft-versus-host disease developed and was treated by immunosuppression. These results are an example of adoptive immunotherapy without cytoreductive chemotherapy or radiotherapy in human chimeras.
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PMID:Donor leukocyte transfusions for treatment of recurrent chronic myelogenous leukemia in marrow transplant patients. 226 42

We treated 114 Ph'+ chronic myeloid leukemia (CML) patients, 105 of whom were in chronic phase (CP) and 9 in accelerated phase (AP), with interferon alpha-2b (IFN alpha-2b) at intermittent or daily doses of 2-5 MU/m2. Of 35 previously untreated CP patients, 22 (63%) showed complete hematological response (CHR). This was significantly influenced by initial risk status. In 19 of the 22 CHR patients the median of Ph'+ cells decreased from 100% to 58%. Of 36 patients pretreated for less than 12 months, 19 (53%) achieved CHR. CHR rate was significantly related to IFN dose. Cytogenetic improvement was observed in 15 of the 19 patients, the median of Ph'+ cells dropping from 100% to 76%, with complete suppression of the Ph' chromosome in 1 case. Of the 34 patients pretreated for greater than 12 months, 21 (62%) obtained CHR. Cytogenetic improvement was observed in 10 cases, the median of Ph'+ cells declining from 100% to 66%. 1 of 9 AP patients obtained CHR. After a median follow-up of 32 months for the 63 CHR patients, 49 (78%) are still in disease control: 34 on IFN therapy, 15 after bone marrow transplantation (BMT) (13 autologous and 2 allogeneic). Blastic transformation (BT) occurred in 9 of 63 (14%) CHR patients and in 24 of 51 (47%) patients with less than CHR. IFN alpha-2b has proved to be an effective treatment for CML. Its combination with other treatment modalities represents an interesting and promising approach for future studies.
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PMID:Interferon alpha-2b as therapy for patients with Ph'-positive chronic myelogenous leukemia. 227 41

Chronic myelogenous leukemia (CML) patients in chronic phase display compromised lymphokine-activated killer (LAK) cell induction, which is partly restored after therapy with interferon alpha. However, the relative resistance of the leukemic cells from these patients to autologous or allogeneic LAK lysis is not affected by this treatment. In an attempt to render CML cells more susceptible to lysis or cytostasis, they were precultured in serum-free medium with or without recombinant growth factors. In eight patients studied, interleukin-3 (IL-3) significantly enhanced the spontaneous short-term (6-day) proliferation of CML cells, with retention of ability to form colonies in methylcellulose. Culture in either medium alone or IL-3 led to a significant enrichment of CD14+ and CD33+ cells but to a reduction in CD34+ cells. In contrast, culture of the same cells in IL-2 (to generate autologous LAK activity) resulted in a loss of CD14+ and CD33+ as well as CD34+ cells but in a significant increase in CD3+ and CD56+ cells. Despite similarities in their phenotypes, IL-3 cultured cells but not those cultured in medium alone acquired susceptibility to lysis by the IL-2-cultured autologous LAK cells. These results may have significance for the design of novel combination immunotherapy in CML.
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PMID:Susceptibility of autologous target cells to lysis by lymphokine-activated effectors from interferon-alpha-treated chronic myelogenous leukaemia patients. 228 10

We report a case of a 33-year-old woman who developed episodes of palpitation while receiving weekly alternating doses of daily intramuscular recombinant interferon alpha-2a (rIFN alpha-2a) and recombinant interferon gamma (rIFN gamma) for Philadelphia chromosome-positive chronic myelogenous leukemia. The electrocardiogram (ECG) and ambulatory Holter monitoring showed first-degree atrioventricular (A-V) block and episodes of junctional tachycardia. The ECG abnormality and palpitation disappeared after discontinuation of therapy. On rechallenge with recombinant interferon alpha-2b (rIFN alpha-2b) alone, there was recurrent palpitation and first-degree A-V block. Subsequent treatment with various doses of rIFN alpha-2b established a dose-response relationship between rIFN alpha-2b and palpitation in our patient. In view of increasing use of rIFNs in the clinical setting, this potential, albeit uncommon, toxicity requires attention and further investigation.
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PMID:Cardiac arrhythmia in a CML patient treated with interferons. 249 75

Four patients with chronic myelogenous leukemia and thrombocytosis and one patient with essential thrombocythemia were treated with purified recombinant human interferon alpha-2a (IFN-alpha 2a). Significant decline in platelet counts, from a mean ( +/- SE) of 1.396 +/- 0.265 x 10(6)/mm3 to a mean of 0.396 +/- 0.04 x 10(6)/mm3 (p less than 0.05), was observed in all patients. The platelet count remained normal for 15, 21 and 30 days after discontinuation of IFN-alpha 2a in 3 patients. In 2 patients the platelet count began to rise slowly two weeks after discontinuation of IFN-alpha 2a. Our preliminary observations suggest that purified recombinant human IFN-alpha 2a may effectively control progressive thrombocytosis in advanced chronic myelogenous leukemia and essential thrombocythemia.
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PMID:Interferon alpha-2a to control thrombocytosis in chronic myelogenous leukemia and essential thrombocythemia. 262 63

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.
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PMID:Treatment of thrombocytosis in myeloproliferative disorders with interferon alpha-2a. 264 94

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.
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PMID:Alpha interferon: progress and perspectives in the biotherapy of chronic myelogenous leukemia. 268 14

Nine previously untreated patients with Philadelphia chromosome-positive chronic myelocytic leukemia (CML) were treated with recombinant interferon alpha 2a (rIFN-alpha 2a) and hydroxyurea. Patients received 6 X 10(6) U rIFN-alpha 2a daily for the first week and 3 X 10(6) U rIFN-alpha 2a daily for the second week. As maintenance treatment starting on day 15, patients received 3 X 10(6) U rIFN-alpha 2a 3 times a week. Simultaneously, hydroxyurea was given, starting at a dose of 40 mg/kg on day one. The maintenance dosage was adjusted to the white blood cell count. Two patients responded with complete hematological remissions but without cytogenetic and molecular-genetic improvements. Seven patients responded with partial hematological remissions. Response to therapy was rapid; normal white blood cell counts were reached after a median of 12 days. The doses of rIFN-alpha 2a and hydroxyurea needed to keep the leucocyte count in the normal range were low (3 X 10(6) U rIFN-alpha 2a 3 times per week, 0.5-1.5 g hydroxyurea/day). Acute toxicity of the combination therapy consisted of fever (9 of 9 patients), flulike symptoms (7 of 9 patients), pruritus and/or rash (3 of 9 patients) and evidence of a tumor cell lysis syndrome (1 of 9 patients). The side effects were not dose-limiting. Combination therapy with rIFN-alpha 2a and hydroxyurea for CML is well tolerated and allows quick and effective hematological control of the disease.
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PMID:A phase I/II study of recombinant interferon alpha 2a and hydroxyurea for chronic myelocytic leukemia. 273 8


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