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)

Clinical trials of natural interferon-alpha (HLBI) in the treatment of Philadelphia chromosome (Ph1) positive chronic myelogenous leukemia (CML) were carried out in a cooperative study of 22 institutions in Japan. Patients with CML in chronic and accelerated phase were given intramuscular or subcutaneous injections of HLBI at the dose of 6 X 10(6) U/body on consecutive days. Of the 47 patients in this study, forty-one were evaluable for clinical effects, and 42 could be assessed for adverse effects. Among 30 evaluable patients in the chronic phase, 9 (30.0%) achieved complete remission (CR) and 20 (66.7%) partial remission (PR). Only one patient had no response (NR), and the response rate (CR + PR) in chronic phase was 96.7% (29/30). Among 11 patients in the accelerated phase, 3 (27.3%) achieved CR and 4 (36.4%) PR. The response rate in the accelerated phase was 63.6% (7/11). In all 41 evaluable patients, the response rate was 87.8% (36/41). In 5 of 13 responding patients treated for more than 6 months, cytogenetic investigation showed the decline of Ph1 positive bone marrow cells from 100% to 92-0% (mean 46%). Adverse effects such as fever (52.4%), general fatigue (35.7%), and liver dysfunction (21.4%), were observed, but they were usually mild and reversible. No patient was taken off this study because of these toxicities. The results confirm the clinical efficacy of HLBI in patients with CML in the chronic and accelerated phase.
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PMID:[Clinical studies of natural interferon alpha (HLBI) in chronic myelogenous leukemia--a multi-institutional cooperative study in Japan]. 305 1

Recently, we reported that recombinant interferon-alpha (rIFN-alpha) can induce hematologic remissions and cytogenetic improvement in newly diagnosed Philadelphia (Ph)-positive chronic myelogenous leukemia (CML) patients. Although IFN-gamma is a structurally distinct molecule, this agent suppresses in vitro hematopoietic progenitor cells in a fashion similar to that of IFN-alpha. Therefore, we initiated a study of rIFN-gamma at doses of 0.25 to 0.5 mg/m2/d intramuscularly in patients with Ph-positive benign-phase CML. Twenty-six of 30 patients entered in the study were evaluable. Six patients have achieved a complete hematologic response; four, a partial hematologic response. The median follow-up period of patients who are in complete remission is 7.5 months (range, 5 to 12 months). No relapses have occurred among the complete responders. So far, five patients have had cytogenetic improvement with emergence of 5% to 45% diploid cells in the bone marrow. Fever and flulike symptoms were the most common side effects, with partial tolerance often developing after about 1 week. The majority of patients tolerated therapy with minimal change in performance status. In conclusion, rIFN-gamma has demonstrated clinical activity in CML. On the basis of these observations and the in vitro synergistic growth-inhibitory effects of IFN-alpha and IFN-gamma, we have started trials of combination IFN therapy in CML patients.
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PMID:Therapy of chronic myelogenous leukemia with recombinant interferon-gamma. 311 39

For palliative therapy during the chronic phase of CML busulfan has proved to be the drug of choice. During the past years hydroxyurea and also interferon-alpha have gained increasing significance since they might prolong the duration of the chronic phase. In a multicenter study it is being determined, whether the use of hydroxyurea or of interferon-alpha instead of busulfan prolongs the duration of the chronic phase of Philadelphia positive CML. Additional goals are the examination of whether the types of disease evolution and the terminal phases differ between the treatment groups, and the prospective recognition of prognostic criteria for the duration of the chronic phase of CML. By December 31, 1987, 326 CML-patients had been randomized, 150 for busulfan, 150 for hydroxyurea and 26 for interferon-alpha. The average age is 50 years. 59 patients reached the end of the chronic phase, 55 died. The mean observation time of all patients is 1.34 years. At present no significant difference in survival is recognizable between the busulfan and hydroxyurea groups. Fewer adverse effects have been observed in the hydroxyurea group. Philadelphia chromosome negative patients show a higher average age and tend to have lower white blood cell and platelet counts. The number of patients having received interferon-alpha is still too small to allow evaluation. This report intends to document organization and progress of this study which to our knowledge is, at present, the largest ongoing prospective multicenter study on the therapy of CML.
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PMID:Randomized study on the treatment of chronic myeloid leukemia (CML) in chronic phase with busulfan versus hydroxyurea versus interferon-alpha. 327 80

For palliative therapy during the chronic phase of CML busulfan has proved to be the drug of choice. During the past years hydroxyurea and also interferon-alpha have gained increasing significance since they might prolong the duration of the chronic phase. In a multicenter study it is being determined, whether the use of hydroxyurea or of interferon-alpha instead of busulfan prolongs the duration of the chronic phase of Philadelphia-positive CML. Additional goals are the examination, whether the types of disease evolution and the terminal phases differ between the treatment groups, and the prospective recognition of prognostic criteria for the duration of the chronic phase of CML. By November 26, 1987, 321 CML-patients had been randomized, 147 for busulfan, 149 for hydroxyurea and 25 for interferon-alpha. The average age is about 50 years. 59 patients reached the end of the chronic phase, 55 died. The mean observation time of all patients is 1.34 years. At present no significant difference in survival is recognizable between the busulfan and hydroxyurea groups. Fewer adverse effects have been observed in the hydroxyurea group. Philadelphia chromosome-negative patients show a higher average age and tend to have lower white blood cell and platelet counts. The number of patients having received interferon-alpha is still too small to allow evaluation. This report intends to document organization and progress of this study which to our knowledge is, at present, the largest ongoing prospective multicenter study on the therapy of CML.
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PMID:[Chemotherapy of chronic myelocytic leukemia. Status of the German Multicenter Study on busulfan versus hydroxyurea versus alpha interferon, October 1897]. 328 22

Fourteen patients with Ph'-chromosome positive chronic myelogenous leukemia (CML) in first chronic phase were treated with recombinant interferon-alpha 2c. Interferon-alpha 2c 5 to 10 X 10(6) units s.c. was given for 12 weeks as an induction therapy. Maintenance treatment consisted of interferon-alpha 2c 5 X 10(6) units twice weekly s.c.. Two patients (14%) attained a complete clinical remission and 6 (43%) a partial remission, 3 of whom developed progressive disease during maintenance therapy. A complete disappearance of Ph'-chromosome was achieved in 1 patient. All patients had a more than 45% initial decline of the leukocyte count. Four out of ten patients with an initially enlarged spleen demonstrated reduction in spleen size. Influenza-like symptoms, anorexia, nausea, weight loss and fatigue were common side effects. Interferon-alpha is active in CML but additional clinical investigations are warranted to assess more precisely the therapeutic value of the interferons in this disease.
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PMID:Recombinant human interferon-alpha induced cytoreduction in chronic myelogenous leukemia. Results of a multicenter study. 328 12

This report aims to review briefly the current status of treatment of haematological malignancies with interferon-alpha (IFN-alpha). Overall hairy cell leukemia and chronic myelogenous leukemia appear to be most sensitive to IFN-alpha. We started to investigate, how interferon exerts its antileukemic activity and in which way interferon therapy can be optimized. Our preliminary results fail to support the view of interferon mediated enhancement of host responses. They rather indicate direct effects of IFN on leukemic cells in vitro. By means of IFN-dependent biological markers (e.g. beta-2-microglobulin, neopterin) clinically effective but atoxic doses of IFN-alpha could be defined for HCL and CML. In final conclusion, the recent studies on the clinical efficacy of IFN-alpha revealed its potent antitumoral effect in hematological malignancies. However, the further proof of the potential benefit of IFN treatment versus conventional therapeutic strategies remains to be elucidated.
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PMID:[Interferon-alpha in the treatment of hematologic neoplasms]. 352 22

Forty-two patients with multiple myeloma were allocated to two groups to receive either polychemotherapy with vincristine, melphalan, cyclophosphamide and prednisolone, or recombinant interferon-alpha 2C monotherapy. The response rate of 43% in the interferon group was significantly lower than that in the chemotherapy group (89%). Patients with stage I disease showed better response rates than those with stage II or stage III disease. Eleven patients with thrombocythaemia due to polycythaemia vera, chronic myeloid leukaemia or essential thrombocythaemia were treated with recombinant interferon-alpha 2C and complete remissions were achieved in 7 of the 8 evaluable patients. Side-effects were common on interferon therapy, but could be reduced by dose reduction and were reversed by cessation of treatment.
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PMID:Treatment with recombinant interferon-alpha-2C: multiple myeloma and thrombocythaemia in myeloproliferative diseases. 408 Feb 97

Treatment with interferon-alpha (IFN-alpha) adequately controls the leukemic cell mass in the majority of newly diagnosed patients with chronic myeloid leukemia (CML). However, the degree of response ranges from no 'hematologic' response to complete suppression of the leukemic clone. The mechanism(s) by which IFN-alpha elicits these responses is unknown, but in vitro studies have indicated that IFN-alpha might function by (1) selective toxicity against the leukemic clone, (2) enhancement of 'immune' regulation, and (3) modulation of bone marrow microenvironmental regulation of hematopoiesis. Using in vitro clonogenic assays we were unable to demonstrate that IFN-alpha selectively inhibited the proliferation of CML progenitor cells. We also found no difference in the expression of LFA-3 on normal or CML CD34+ cells. However, by panning and co-culturing hematopoietic cells on monolayers of bone marrow stromal cells, grown with and without IFN-alpha, we found that IFN-alpha enhanced the adhesion of CML progenitors to stromal cells, whereas adhesion by normal progenitor cells was essentially unaffected. This enhanced adhesion by CML progenitor cells was associated with a reduction in neuraminic acid levels in the extracellular matrix overlying stromal cells. Therefore, it is possible that one of the mechanisms by which IFN-alpha exerts its regulatory effect on the leukemic clone is through enhancement of hematopoietic cell-microenvironmental cell interactions.
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PMID:Potential mechanisms of action of interferon-alpha in CML. 750 44

Treatment of chronic myelogenous leukemia (CML) with interferon-alpha frequently results in normalization of peripheral blood counts and, in up to 20% of patients, reestablishment of normal hematopoiesis. We hypothesize that interferon-alpha may restore normal adhesive interactions between CML progenitors and the bone marrow microenvironment and restore normal growth regulatory effects resulting from these progenitor-stroma interactions. We demonstrate that treatment with interferon-alpha induces a significant, dose-dependent increase in the adhesion of primitive long-term culture initiating cells and committed colony-forming cells (CFC) from CML bone marrow to normal stroma. Adhesion of CFC seen after interferon-alpha treatment could be inhibited by blocking antibodies directed at the alpha 4, alpha 5, and beta 1 integrins and vascular cell adhesion molecule, but not CD44 or intracellular adhesion molecule, suggesting that interferon-alpha induces normalization of progenitor-stroma interactions in CML. Because FACS analysis showed that the level of alpha 4, alpha 5, and beta 1 integrin expression after interferon-alpha treatment is unchanged, this suggests that interferon-alpha may restore normal beta 1 integrin function. Normalization of interactions between CML progenitors and the bone marrow microenvironment may then result in the restoration of normal regulation of CML progenitor proliferation, and explain, at least in part, the therapeutic efficacy of interferon-alpha in CML.
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PMID:Interferon-alpha restores normal adhesion of chronic myelogenous leukemia hematopoietic progenitors to bone marrow stroma by correcting impaired beta 1 integrin receptor function. 804 Feb 70

A group of 46 patients with chronic myelogenous leukemia (CML) [chronic phase (CP), 24 patients; accelerated phase (AP), 22 patients] ineligible for allogeneic bone marrow transplantation were given an intensive chemotherapy regimen consisting of idarubicin, intermediate-dose cytarabine, and etoposide. All patients had previously received interferon-alpha and only 2 had shown a partial cytogenetic response. During early recovery from chemotherapy-induced aplasia, peripheral blood progenitor cells (PBPC) were harvested by leukapheresis. All metaphases were found to be Philadelphia chromosome (Ph) negative in the collection from 17 of 46 (37%) patients [CP, 12 of 24 (50%); AP, 5 of 22 (23%)], and a decrease to less than 50% Ph-positive metaphases was seen in an additional 6 (CP, 3 patients; AP, 3 patients). The percentage of patients showing complete Ph disappearance was 64% in those receiving this procedure within the first year of diagnosis. In vitro studies were performed to assess the behavior of the Ph-negative PBPC. In clonogenic cultures they responded to stem cell factor and were able to grow as mixed colonies. Moreover, long-term culture initiating cells (LTCIC) were present in many Ph-negative collections but rarely in Ph-positive PBPC. In 4 females, clonality was studied by analyzing X chromosome inactivation and methylation patterns of the DXS255 locus with the probe M27 beta. Hematopoiesis was polyclonal in all 4 patients tested. Thus far, the Ph-negative collections have been used for autografting in 16 patients (CP, 11 patients; PA, 5 patients) after conditioning with total-body irradiation, etoposide, and cyclophosphamide or idarubicin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Idarubicin, intermediate-dose cytarabine, etoposide, and granulocyte-colony-stimulating factor are able to recruit CD34+/HLA-DR- cells during early hematopoietic recovery in accelerated and chronic phases of chronic myeloid leukemia. 753 Jan 35


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