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 efficacy of continuous oral cytarabine ocfosfate (YNK01) (300 mg/day) in combination with interferon alpha (IFNalpha, 5x10(6) IU/day) was evaluated in patients with advanced chronic myelogenous leukemia, who previously failed to respond to IFNalpha-based therapies. Dose escalations up to 900 mg YNK01 were allowed in patients who failed to respond. In view of our results, four patients developed a complete hematological response after YNK01 was started. Among those who initially responded to YNK01, one complete cytogenetic response was achieved 18 months later. Although the data are preliminary, this is the first study showing that continuous administration of YNK01 along with IFNalpha is effective in patients with advanced chronic myelogenous leukemia.
 ...
PMID:Treatment of patients with advanced chronic myelogenous leukemia with interferon-alpha-2b and continuous oral cytarabine ocfosfate (YNK01): a pilot study. 1086 32

The management of chronic myelogenous leukemia (CML) has become complex due to the availability of improved diagnostic procedures and life-prolonging or even curative treatment strategies that are more successful the earlier they are applied in the course of the disease. This is true for allogeneic bone-marrow transplantation, treatment with interferon alpha (IFN) and Philadelphia-negative stem-cell collections for autografting. Outcome differs according to risk profiles of patients at diagnosis. In addition, molecular techniques for the detection of the BCR-ABL fusion gene or its products, such as the reverse-transcriptase polymerase chain reaction (PCR), Southern blot analysis, or fluorescence in situ hybridization, facilitate accurate diagnosis and the monitoring of residual disease. They allow the individualization of treatment such as early infusion of donor lymphocytes if molecular relapse is detected after allografting, or discontinuation of IFN in the presence of very low BCR-ABL transcript levels). The availability of real-time PCR devices further improves and accelerates the diagnosis and monitoring of residual disease. This article addresses recent developments in drug therapy and allografting, including treatment intensification with low-dose ara C or intensive chemotherapy followed by autografting, introduction of new drugs (such as homoharringtonine or tyrosine kinase inhibitor STI571), progress with unrelated donor transplantations, use of peripheral blood stem cells for allografting, and transplantation without myeloablative conditioning. Tradeoffs between the treatment options will be discussed in the context of the evidence-based guidelines for treating CML, as recently published by the American Society of Hematology. Finally, the new competence network on acute and chronic leukemias will be introduced.
 ...
PMID:Current trends in the management of chronic myelogenous leukemia. 1096 82

Although interferon alpha (IFN) has been shown to prolong survival in chronic myeloid leukaemia (CML), it cannot be used in all patients. Reliable evidence on the relative benefits of busulphan and hydroxyurea is of value in treating those patients who will not receive interferon. Data for each individual patient was sought from trials which randomized patients with CML to hydroxyurea vs. busulphan. Intention-to-treat stratified log rank survival analyses were performed, reporting two-sided P-values. Data were collected on 812 patients in the three trials identified. In the group of 690 patients with confirmed Philadelphia chromosome (Ph)-positive CML, survival at 4 years was 45.1% with busulphan and 53.6% with hydroxyurea, an absolute benefit of 8.5% (95% confidence interval 0. 1-16.9; logrank P = 0.01 over 4 years). There seemed to be no further benefit for hydroxyurea in later years, but there was no apparent delayed adverse effect either. The difference between hydroxyurea and busulphan was not statistically significantly different from the overall result in any subgroup. Survival of patients with Ph-positive CML is better with hydroxyurea treatment than with busulphan.
 ...
PMID:Hydroxyurea versus busulphan for chronic myeloid leukaemia: an individual patient data meta-analysis of three randomized trials. Chronic myeloid leukemia trialists' collaborative group. 1099 66

The effects on survival in patients with chronic myelogenous leukemia (CML) treated with natural interferon alpha (Sumiferon) were analyzed. The subjects were 131 patients with CML who underwent treatment with Sumiferon between August 1991 and December 1992. Sumiferon was administered more than 8 weeks, and patients were followed for 5 years. In the end, 101 patients were analyzed after 30 patients were dropped from the study because they had received bone marrow transplantation. Survivals from the start of Sumiferon administration were 63.4% at 3 years, 52.5% at 4 years, and 42.6% at 5 years, respectively. Survivals were compared between the 74 patients who received Sumiferon administration with 1 year of diagnosis, and the 27 patients who received Sumiferon administration after more than 1 year from diagnosis. The 50% survivals were 2,089 days and 868 days, respectively (p = 0.0011). It was concluded that early administration of interferon alpha results in a prolonged survival of CML patients.
 ...
PMID:[Long-term follow up of chronic myelogenous leukemia patients treated with natural interferon alpha--multi-institutional cooperative study]. 1101 99

Although interferon alpha (IFN-alpha) is able to induce haematological remission in 60-80% of patients with chronic myeloid leukaemia (CML) in early chronic phase, major cytogenetic remissions are only achievable in 30-40%. Recent clinical data suggest that the addition of granulocyte-macrophage colony-stimulating factor (GM-CSF) to IFN-alpha therapy can significantly improve the cytogenetic response in some patients, although the mechanism remains unknown. We hypothesized that the combination of GM-CSF and IFN-alpha induces the differentiation of dendritic cells, which subsequently stimulates a specific anti-leukaemic response. Monocytes from CML patients were cultured in GM-CSF and interleukin (IL)-4 (GM/IL-4)or in GM-CSF and IFN-alpha (GM/IFN-alpha). After 7 d, the number of cells exhibiting typical antigen-presenting cell (APC) morphology was equal in both groups, and fluorescence in situ hybridization (FISH) analysis confirmed that the APCs generated with GM/IFN-alpha were of leukaemic origin. Phenotypically, both sets of APCs expressed typical surface markers; however, CD86, CD83, CD11c, HLA-ABC and HLA-DR expression was significantly higher in the GM/IFN-alpha APCs, whereas CD1a expression was significantly lower. In mixed lymphocyte reactions (MLR), GM/IFN-alpha APCs stimulated the proliferation of allogeneic T cells significantly better than GM/IL-4 APCs. However, both groups of APCs stimulated autologous T-cell proliferation equally. Finally, we assessed the ability of GM/IFN-alpha APCs to induce a leukaemia-specific cytotoxic T-cell response. Some samples generated cytotoxic T lymphocytes (CTLs) that specifically lysed bcr-abl-positive target cells. These data show that the combination of GM-CSF and IFN-alpha, when used in vitro, induces the differentiation of malignant APCs with potent T-cell stimulatory capacity. Although there is no in vivo evidence to support these findings, it is possible that, when administered to CML patients, GM-CSF in combination with IFN-alpha results in the generation of highly stimulatory leukaemic APCs.
 ...
PMID:Interferon alpha in combination with GM-CSF induces the differentiation of leukaemic antigen-presenting cells that have the capacity to stimulate a specific anti-leukaemic cytotoxic T-cell response from patients with chronic myeloid leukaemia. 1112 8

In chronic myelogenous leukemia (CML), autologous stem cell transplantation could be a promising new approach for patients with no cytogenetic response after interferon alpha (IFN-alpha) therapy. We report data on 28 CML patients autotransplanted in chronic phase with peripheral blood progenitor cells mobilized with G-CSF (5 microg/kg/day x 5 days) given subcutaneously while continuing IFN-alpha therapy. At mobilization, 23 patients (82%) were in complete hematological remission (CHR), 16 (57%) achieved a minor cytogenetic response (mcr). We obtained, after stimulation, a median of 37.4 x 10(9)/l (6.9-108) white blood cells, 7.2 x 10(8)/kg (2.2-16.6) mononuclear cells, 39 x 10(4)/kg (4.8-403.5) CFU-GM and 4.2 x 10(6)/kg (0-58.6) CD34+ cells. Six patients received GM-CSF after transplantation. All patients engrafted, with no significant influence stemming from the Sokal index score and pretransplantation IFN-alpha therapy duration. The first cytogenetic evaluation after transplantation showed 11 (39%) major cytogenetic response (Mcr), and nine (32%) mcr with no significant correlation between these responses, the Sokal index score, and pretransplantation IFN-alpha therapy duration, although there was a significant impact from GM-CSF administration (P=0.01). After transplantation, 26 patients received IFN-alpha alone or associated with hydroxyurea. The median follow-up was 12 months after transplantation and 57 months after diagnosis. At the time of follow-up, nine patients were in CHR, six remained stable in chronic phase, three presented an mcr and one remained in Mcr. At the last follow-up, 22 patients were alive. We conclude that the results of this strategy are encouraging in poor IFN-alpha responders but that other prospective studies that try to maintain the cytogenetic responses obtained immediately after transplantation are needed.
 ...
PMID:Late autologous transplantation in chronic myelogenous leukemia with peripheral blood progenitor cells mobilized by G-CSF and interferon-alpha. 1118 94

A patient with essential thrombocythemia was diagnosed with pulmonary sarcoidosis after interferon alpha therapy. Following interferon treatment the miliary pulmonary dissemination has appeared and after disruption of this therapy it resolved during two months. Few cases of sarcoidosis associated with interferon alpha treatment have been reported. These patients were treated for chronic myelogenous leukemia, chronic hepatitis C, and renal cell carcinoma. We report the first case of interferon-related sarcoidosis in an essential thrombocythemia patient.
 ...
PMID:Pulmonary sarcoidosis in a patient with essential thrombocythemia treated with interferon alpha: a short case report. 1120 42

We report a 54-year-old woman who received interferon alpha for haematological relapse of Ph-positive CML, 7 years after allogeneic BMT from an HLA-identical brother. Eighteen months after relapse, cytogenetic and molecular remission was achieved. She received interferon therapy for 25 months and it was discontinued when she developed skin lesions on her face and trunk, dysphagia and fever with respiratory failure and bilateral patchy airspace consolidation of the lung without microbiologic findings. Histologic features showed discoid lupus erythematosis, oesophagitis with pseudomembranes and a mixed pattern of lymphocytic bronchiolitis involving the alveoli and interstitial spaces all compatible with chronic GVHD. The patient was commenced on immunosuppressive therapy with complete clinical and radiological resolution. The available evidence supports an atypical presentation of chronic GVHD and suggests a role for interferon alpha in the pathogenesis of GVHD. To the best of our knowledge, this is the first case reported of severe chronic GVHD occurring during the course of interferon therapy for relapsed CML.
 ...
PMID:Atypical chronic graft-versus-host disease following interferon therapy for chronic myeloid leukaemia relapsing after allogeneic BMT. 1124 42

Thrombocytosis is a common clinical condition. Drugs used for thrombocytosis are hydroxy urea, alkylating agents and interferon alpha. We are reporting a case of chronic myeloid leukemia with thrombocytosis who did not respond to hydroxy urea but was controlled with the addition of a new drug anagrelide. Anagrelide is a platelet reducing agent with no serious side effects. It may be the main weapon against thrombocytosis associated with chronic myeloid leukaemia (CML) and essential thrombocytosis in the coming years.
 ...
PMID:Thrombocytosis--report of a case. 1127 86

Acute pancreatitis related to interferon alpha therapy is very rare. We report two patients with chronic myelogenous leukemia (CML) who developed acute pancreatitis following treatment with interferon alpha. A review of the literature on the association of pancreatitis and interferon alpha is provided. Possible pathophysiologic mechanisms are also discussed.
 ...
PMID:Acute pancreatitis associated with interferon alpha therapy for chronic myelogenous leukemia. 1134 49


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