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)

The breakpoint localization was analyzed in 61 patients with Philadelphia chromosome (Ph) positive chronic myelogenous leukemia to compare the breakpoint localization and clinical course. All patients were treated with interferon alfa (IFN alpha) or IFN alpha plus IFN gamma at the time of the study. Thirty-three of the patients had been pretreated with other cytostatic drugs. Sixty-nine per cent of the breakpoints were located in the 5' region of the major breakpoint cluster region (M-bcr), 29% in the 3' part. There was no significant difference between these two groups with respect to response to IFN(s), clinical course or conversion to blast crisis, nor survival.
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PMID:Breakpoint localization within the M-bcr and clinical course do not correlate in patients with chronic myelogenous leukemia undergoing alfa interferon therapy. 205 69

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

Introduction of interferon-alpha therapy to chronic myelogenous leukemia (CML) has improved the survival rate of CML patients compared with conventional busulfan therapy. There still, however, are some IFN-resistant cases. To improve the survival rate of these IFN-resistant cases, bone marrow transplantation (BMT) has been tried at the world wide level. In cases without any allogeneic donors, autologous BMT is another choice. We recently have proposed the flow chart therapy system to select the auto-BMT candidates in CML patients. This system, briefly, consists of (1) bone marrow collection as early stage of CML as possible, (2) IFN-alpha treatment with administration of weekly methotrexate or occasional use of hydroxyurea, (3) early detection of accelerated or blastic phase of CML by using scoring system, (4) conditioning regimens of auto-BMT for CML and (5) post-BMT follow-up with IFN-alpha. Following this system, we have initiated the treatment of CML cases. Our tentative results on one case favorable outcome including complete disappearance of Ph1 positive clone. However, there are several questions to be answered in the auto-BMT for CML, namely, (1) do we need to purge Ph1 progenitor cells or not, if yes, how? (2) does the long term use of IFN affect the bone marrow microenvironment resulting in graft failure? Although our preliminary results gave some answers on these questions, further clinical and basic studies are required to obtain higher survival rates in CML treatment.
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PMID:[Autologous bone marrow transplantation in chronic myelogenous leukemia]. 206 83

Acute lymphoblastic leukemia (ALL) patients with a Philadelphia chromosome (Ph+ ALL) were treated with a combination of antineoplastic drugs recommended for both myeloid and lymphoid leukemia (BHAC-DMPV: behenoylcytosine arabinoside, daunorubicin, 6-mercaptopurine, prednisolone, and vincristine). Ph+ ALL patients with chromosome breaks which occur within the major breakpoint cluster region (M-BCR rearranged Ph+ ALL) were treated with natural interferon-alpha (IFN-alpha) after entering complete remission. In this study, four of seven patients with Ph+ ALL had M-BCR rearrangement, and all achieved complete remission with karyotypic normalization. Subsequent cytogenetic analysis during complete remission in two ALL patients with M-BCR rearrangement revealed that the percentage of bone marrow cells with the Ph chromosome increased, while the bone marrow maintained remission status. This cytogenetic-hematological discrepancy led us to consider that M-BCR rearranged Ph+ ALL might be a variant of chronic myelogenous leukemia, therefore, three Ph+ ALL patients with M-BCR rearrangement were treated with IFN-alpha after achieving complete remission. In contrast, only one of three patients with M-BCR non-rearranged Ph+ ALL obtained complete remission.
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PMID:Treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia: a pilot study which raises important questions. 207 47

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

PTT-119, a new synthetic alkylating compound, has shown a marked "in vitro" inhibitory effect on chronic myeloid leukemia (CML) granulo-monocytic precursors (CFU-GM) at doses greater than 5 micrograms/ml. Based on previous experiences of synergistic associations between alkylating drugs and biological modifiers, we tested the effects of low doses of PTT-119 (from 0.1 to 1 microgram/ml) in concert with alpha, gamma, or alpha + gamma interferons and compared to IFNs alone, in order to investigate an alternative choice for treatment of CML patients in chronic phase. Our results showed a significantly higher CFU-GM cloning inhibition after addition of 100 or 1,000 U/ml of alpha IFN to 0.1 microgram/ml PTT-119 (from 39.6% +/- 26.6 SD to 80.7% +/- 10 SD and 91.5% +/- 8 SD, respectively), while gamma IFN resulted in only a slight increase in colony growth inhibition when compared to the drug used alone. The association of alpha plus gamma IFN coupled with PTT-119 treatment did not significantly improve the results observed after exposure of leukemic progenitors to PTT-119 and alpha IFN alone. We conclude that a combined treatment with PTT-119 and IFN is probably worth testing both for purging methods before autologous bone marrow transplantation and for in vivo administration in chronic myeloid leukemia.
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PMID:Sensitivity of chronic myeloid leukemia hemopoietic progenitors to PTT-119 in combination with human recombinant interferon alpha and gamma. 211 14

A 23-year-old male patient with Philadelphia chromosome (Ph) positive chronic myelogenous leukemia (CML) was treated with both IFN alpha and IFN gamma. Normalization of leukocyte counts was reached after 3 months of treatment. Southern blot analysis failed to detect the neoplastic cell clone after 19 months of therapy. Cytogenetically, complete suppression of Ph positive cells in the patient's bone marrow and blood was observed after 20 months and 25 months, respectively. This response was achieved with doses of IFN alpha and IFN gamma which were considerably lower than the dosage of IFN used in single agent therapy of CML.
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PMID:Treatment of chronic myelogenous leukemia with interferons alpha and gamma. 211 76

Alpha- and gamma-interferons have been shown to actively suppress hematopoiesis in patients in the chronic phase of chronic myelogenous leukemia in vitro and in vivo. Since both interferons act through different receptors on their hematopoietic target cells, they are expected to be capable of independently inhibiting abnormal blood cell development in patients with chronic myelogenous leukemia. We have utilized recombinant human interferon alfa-2c to treat 11 patients with Philadelphia chromosome positive chronic myelogenous leukemia in chronic phase, who were resistant to previous interferon gamma therapy. Ten of the patients were evaluable for hematologic, cytogenetic and molecular-genetic response following interferon alfa-2c therapy for 6 to 30 months. In 5 patients, IFN alfa-2c treatment failed due to lack of hematologic response. A complete hematologic or partial hematologic response was achieved in the remaining 5 patients. Three of these experienced cytogenetic improvement with reappearence of 100% diploid hematopoietic cells and disappearence of c-abl/bcr rearrangement in one patient. In two patients interferon alfa-2c did not prevent transformation of the disease into an accelerated state or blast crisis, respectively. We conclude that recombinant human interferon alfa-2c may also control hematopoiesis in interferon-gamma resistant chronic myelogenous leukemia patients, although the long-term response will need to be elucidated in further studies.
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PMID:Interferon alfa-2c in chronic myelogenous leukemia (CML): hematologic, cytogenetic and molecular-genetic response of patients with chronic phase CML previously resistant to therapy with interferon gamma. 212 Dec 99

Several clinical observations have shown that alpha-IFN is presently the most interesting investigational agent for the treatment of Ph+ chronic myeloid leukemia (CML). Gamma-IFN is also effective, and experimental data as well as preliminary clinical observations suggest that the combination of the two IFNs is worth investigating. No comparative data are available on the effects of the two IFNs, given alone, in the same patients. In this study 11 patients with PH+ CML were first treated with gamma-IFN, up to a maximum period of 35 weeks, and after a short rest period were retreated with alpha-IFN. Both IFNs were ineffective in 3 patients in accelerated or instable chronic phase. Both IFNs were equally effective in 8 patients in stable chronic phase, but none of these patients achieved a karyotypic conversion with either IFN. This study did not show any measurable differences in the therapeutic response to gamma-IFN and alpha-IFN given consecutively to the same patients.
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PMID:Sequential treatment of Ph-positive chronic myeloid leukemia with interferon gamma and interferon alpha. 212 66

Long-term parenteral administration of human alpha-interferon (HuIFN-alpha) is effective in the treatment of several malignancies, including chronic myelocytic leukemia. In the present study, a model for fibroblast-mediated HuIFN-alpha gene therapy for the treatment of chronic myelocytic leukemia is described. Human IFN-alpha 5 complementary DNA was inserted into a bovine papilloma virus plasmid vector (BMGNeo) containing a neomycin resistance gene. The recombinant plasmid (BMGNeo-IFN) was transfected into NIH/3T3 fibroblasts by the calcium phosphate coprecipitation method, and stably transformed cells were isolated by G418 selection. A fibroblast clone secreting a large amount of HuIFN into the culture supernatant was selected by radioimmunoassay using anti-HuIFN-alpha monoclonal antibodies. Southern blot analysis revealed that the transformed cells contained approximately ten copies of the BMGNeo-IFN plasmid per cell, and Northern blot analysis demonstrated high expression of HuIFN-alpha mRNA in the cells. This fibroblast clone strongly suppressed proliferation of a HuIFN-alpha-sensitive chronic myelocytic leukemia cell line (KU812) during cocultivation in vitro. When the HuIFN-alpha-producing fibroblasts were implanted into nude mice bearing KU812 tumors by the subcutaneous diffusion chamber method, tumor growth in vivo was also significantly suppressed. This study suggests the clinical potential of fibroblast-mediated gene therapy in the future.
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PMID:Implantation of genetically manipulated fibroblasts into mice as antitumor alpha-interferon therapy. 216 55


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