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)

Interferon alfa has been used in the treatment of myeloproliferative disorders, particularly chronic myeloid leukemia, polycythemia vera, and idiopathic thrombocythemia. The effectiveness of interferon alfa in agnogenic myeloid metaplasia needs additional evaluation, although preliminary evidence suggests that it may be more efficacious when used in the cellular (ie, proliferative) phase than when the marrow is fibrotic or osteosclerotic. Cytogenetic and molecular changes after interferon alfa therapy are apparent in patients with chronic myeloid leukemia, as manifested by change in the Philadelphia chromosome and BCR-ABL gene, respectively. The exact role of interferon in prolonging the life of chronic myeloid leukemia patients, however, remains to be determined in larger studies of longer duration. Interferon treatment seems to be well tolerated, and the frequency of treatment-limiting toxicity is low. Data to date suggest that interferon alfa may be a new and effective drug for the treatment of the myeloproliferative disorders.
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PMID:Interferon in the treatment of myeloproliferative diseases. 211 94

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

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

Although chronic myeloid leukemia is an incurable disease for the majority of patients, striking advances in our understanding of cell biology, molecular genetics, and new treatment programs involving interferon and bone marrow transplantation have led to clinical improvement for a small number of patients afflicted with this disease. Nevertheless, hope exists that such basic and clinical information will be expanded to a larger number of patients in the near future.
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PMID:Chronic myeloid leukemia. A perspective of the clinical and biologic issues of the chronic phase. 218 94

Chronic myelogenous leukemia (CML) is a myeloproliferative disorder triggered by a chromosomally induced mutation in a pluripotent stem cell. Its progressive clinical course consists of a chronic or benign phase, which terminates in blast crisis. Historically, treatment has been limited: conventional chemotherapy yields a median survival of approximately 36 to 42 months, and bone marrow transplantation, while achieving success in more than half of patients treated, is limited to younger patients with HLA-matched siblings. Treatment with interferon alfa in CML was initiated in 1981. The first studies were performed using partially pure interferon alfa; these studies were followed by treatment regimens employing interferon alfa-2a.
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PMID:Update on therapeutic options for chronic myelogenous leukemia. 219 31

A 53-year-old woman was admitted to our hospital on Nov. 16, 1987, because of general fatigue. On admission, she had hepatosplenomegaly and her peripheral blood profile showed a white blood cell count (WBC) of 309 x 10(3)/microliters with immature neutrophils, a hemoglobin level (Hb) of 7.6 g/dl, platelet count (PLT) of 536 x 10(3)/microliters, neutrophilic alkaline phosphatase (NAP) score of 44. Both Vitamin B12 and LDH levels were high. The bone marrow showed marked myeloid hyperplasia. In a cytogenetic study, Ph1 was found in 3 of 8 metaphases and Ph1 with an additional abnormality of 8 trisomy was noted in 5 of 8 metaphases. She was diagnosed as having chronic myelogenous leukemia (CML) and treated by i.m. injection of interferon (IFN)-alpha at a daily dose of 6 x 10(6) U. Administration of IFN-alpha induced fever for a few days. WBC, PLT count and LDH level gradually decreased, and the NAP score and hepatosplenomegaly improved. She achieved remission in February, 1988. Administration of IFN-alpha was stopped in April, 1988, when the bone marrow showed hypocellularity and normal karyotype. She was treated with 20 mg of prednisolone daily from May until August, because of progressive pancytopenia. She had received no treatment until July, 1989. In May, 1989, the bone marrow again showed myeloid hyperplasia and Ph1 was found in all cells analyzed. Therefore, we resumed IFN-alpha treatment. It is interesting that remission of CML continues for more than one year after discontinuation of IFN-alpha in this case.
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PMID:[One-year remission of chronic myelogenous leukemia (CML) after discontinuation of interferon-alpha]. 221 81

A 33-year-old female was diagnosed as having chronic myelocytic leukemia (CML) with Philadelphia (Ph1) chromosome and breakpoint cluster region (bcr) rearrangement. Physical examination revealed a huge splenomegaly and laboratory data showed WBC 490 x 10(3)/microliter and NAP score 44. She was treated with hydroxyurea, alpha-interferon, or busulfan, but severe adverse reaction such as skin rash, fever, and arthralgia, which allowed the therapy discontinue was occurred. When the patient was treated with the oral form of etoposide, a semisynthetic podophillotoxin, the number of leukocyte has been successfully maintained less than 10 x 10(3)/microliters at the dose of 50-100 mg/day and splenomegaly completely disappeared. Although Ph1 chromosome was unchanged in the percentage after the therapy for 5 months, etoposide may be effective agent for a chronic or accelerated phase of CML. Alopecia which was reversible and well tolerable was the only side effect of the drug.
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PMID:[Successful therapy of Ph1 positive chronic myelocytic leukemia with oral form of etoposide]. 225 67

Cell cycle distribution in bone marrow and peripheral blood mononucleated cells was studied in patients with chronic myelogenous leukemia (CML) before and during treatment with interferon (IFN) alpha-2b. DNA-flow cytometry with ethidium bromide fluorescence was used. Highly significant differences between mononucleated cells from CML patients and normal controls were seen in peripheral blood but not in bone marrow specimens. Patients achieving hematologic remission during IFN treatment showed a cell cycle distribution in bone marrow cells and peripheral blood cells similar to normal controls.
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PMID:DNA-flow cytometry studies in blood and marrow cells from chronic myelogenous leukemia patients treated with interferon alpha-2b. 225 27

20 CML patients with hematological (5 pts) or only cytogenetic (15 pts) relapse occurring after allogeneic BMT have been treated with alpha-2b-interferon (IFN) at a starting dose of 5 x 10(6) IU/m2, subcutaneously, three times a week. All 5 patients with hematological relapse achieved hematological remission without reduction of bone marrow Ph1-positive cells. With a median follow-up of 43 months (range 6-48) from the hematological relapse, 3 patients are alive and 2 patients died from non-lymphoid blast crisis. 7 out of 15 patients with only cytogenetic relapse remain in hematological remission at a median of 37 months (range 3-45) from cytogenetic relapse, with 2 patients achieving complete cytogenetic remission confirmed at the molecular level by disappearance of the bcr rearranged band. With a median follow-up of 21 months (range 6-46), 8 patients progressed from cytogenetic to hematological relapse: 4 patients died from blast crisis and the other 4 patients are currently alive in chronic phase. For the 15 patients, the actuarial survival from BMT is 71% at 5 years.
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PMID:Alpha-2b-interferon as single therapy for patients with chronic myeloid leukemia relapsing after T-cell depleted allogeneic bone marrow transplantation. 227 45

Serial cytogenetic studies were carried out on 36 patients with Ph1-positive chronic myelogenous leukemia treated with allogeneic bone-marrow transplantation from unlike sex (21 patients) or like sex (15 patients) donors. Fourteen of the 21 sex-mismatched and 12 of the 15 sex-matched donor marrows were T cell depleted. Disease relapse was documented in 19 of the 26 patients who received T cell-depleted marrow, and in none of the 10 patients who received non-T cell-depleted marrow. In the group of patients with unlike sex donor, a triple donor/normal recipient/Ph1-positive recipient or a double donor/Ph1-positive recipient chimerism was documented during the subsequent months, while on alpha-interferon treatment for relapse. Two of these patients subsequently showed a complete disappearance of the Ph1 chromosome. Unstable and/or stable, clonal or non-clonal chromosome changes were detected in Ph1-positive cells from 12 of the 19 patients who relapsed. Analysis of the identified stable changes showed a non-random distribution of breakpoints with clustering to chromosome nos. 1, 4, 7 and 12.
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PMID:Cytogenetic follow-up after allogeneic bone-marrow transplantation for Ph1-positive chronic myelogenous leukemia. 231 Aug 76


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