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 first allogenic bone marrow transplantation (TKD), when for the preparation whole body irradiation was used, was implemented in the Institute of Haematology and Blood Transfusion (UHKT) in Prague in 1986. Before June 1992 36 TKD were performed incl. 28 allogenic, 2 syngenic and 6 autologous. For the first time bone marrow from a non-related donor was transplanted. Of 30 allogenic and syngenic TKD to the present time 17 patients survive, i.e. 56.6% of the whole group. According to individual diagnoses 8 patients with the diagnosis of chronic myeloid leukaemia (CML) survive, 5 of 10 patients with the diagnosis of acute leukaemia (AL) and 3 of 4 patients with the diagnosis of severe aplastic anaemia (SAA) or with Fancon's anaemia (FA) resp. The survival period of the whole group is from 1-62 months since the transplantation. The main cause of death of 8 from 13 patients who died were infections associated with acute or chronic disease of the graft against the host (GVHD). In autologous TKD the bone marrow was treated with etoposide. Of the six transplanted patients with AL five survive 1.5-30 months after transplantation. The authors present some general information of pretransplantation preparation, prevention of GVHD, its incidence and results of TKD.
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PMID:[Results of bone marrow transplantation at the Institute of Hematology and Blood Transfusion in Prague]. 128 83

Platelet function and the clinical course of the disease were prospectively investigated in 29 patients with myeloproliferative disorders. Serial determinations (median: 5 investigations per patient within 17 months) of platelet aggregation, plasma and intraplatelet concentrations of beta-thromboglobulin (beta TG) and platelet factor 4 (PF4), and of fibrinopeptide A (FPA) plasma levels were carried out. In the chronic phase of polycythaemia vera, patients with thrombohaemorrhagic complications during the study period had higher platelet count, more severe platelet aggregation defects, and increased plasma levels of beta TG and FPA compared to patients without complications. However, thrombohaemorrhagic complications were not predicted by changes in these parameters in the individual patient during the chronic disease phase. When patients with chronic myelogenous leukaemia entered blast crisis, bleeding complications were related to thrombocytopenia, impaired platelet function and low intraplatelet concentrations of beta TG and PF4. Cytoreduction by chemotherapy in the chronic phase of CML did not alter beta TG and PF4 plasma levels, whereas treatment of polycythaemia rubra vera by venesection favourably influenced platelet alpha-granule secretion and increased intraplatelet concentrations of beta TG and PF4.
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PMID:A prospective study of haemostatic parameters in relation to the clinical course of myeloproliferative disorders. 214 44

Chronic myelogenous leukemia (CML) cell growth may be inhibited by exposure to antisense (AS) oligodeoxynucleotides (ODN). Our initial studies targeted the c-myb protooncogene and were carried out on cells derived from patients in CML blast crisis. Subsequently, we extended these studies to cells isolated from patients in chronic disease phase. We found that c-myb AS ODN inhibited growth of CML CFU-GM in a dose dependent, sequence specific manner in approximately 75% of cases evaluated. Bcr-abl expression was either greatly decreased or nondetectable in the residual colonies and no residual leukemic CFU were demonstrable upon re-plating of treated cells. AS ODN that target the c-kit protooncogene also inhibit CML CFU and lead to downregulation of bcr-abl in responding cells in approximately 50% of cases. Therefore, AS ODN may prove to be useful purging agents. Most recently, we have treated SCID mice engrafted with bcr-abl expressing human K562 cell leukemia with phosphorothioate modified AS ODN. We have found that treated mice survive three to eight times longer than their untreated or sense treated controls. In aggregate, these results suggest that AS ODN may prove useful for both ex vivo and in vivo treatment of patients with CML.
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PMID:Potential therapeutic applications of antisense oligodeoxynucleotides in the treatment of chronic myelogenous leukemia. 750 43

Between October 1988 and December 1992, 167 patients with leukemia receiving marrow transplants from HLA-identical donors and conditioned with cyclophosphamide (120 mg/kg) were randomized to additional treatment with either busulfan (16 mg/kg, n = 88) or total body irradiation (TBI; n = 79). The busulfan-treated patients had an increased cumulative incidence of veno-occlusive disease of the liver, ie, 12% compared with 1% in the TBI group (P = .009). Furthermore, hemorrhagic cystitis occurred in 24% of the busulfan patients versus 8% in the TBI patients (P = .003). In patients with advanced disease beyond first remission or first chronic phase, transplantation-related mortality was 62% among the busulfan-treated patients compared with 12% among the TBI recipients (P = .002). These differences between the two groups were statistically significant in multivariate analysis. Seizures were seen in 6% of the busulfan-treated patients and were absent in the TBI group (P = .03). Grade II-IV of acute graft-versus-host disease (GVHD) was similar in the two groups, but grade III-IV and chronic disease was more common in the busulfan-treated group (P = .04). Death associated with GVHD occurred in 17% of the busulfan-treated group and 2% of the TBI group (P = .003). Patients treated with busulfan had a 3-year actuarial survival of 62%, which was worse than the 76% among those treated with TBI (P < .03). In multivariate analysis, poor survival was associated with advanced disease (P < .0001), no posttransplant septicemia (P = .0006), grade II-IV GVHD (P = .006), and busulfan treatment (P < .02). The incidence of relapse did not differ between the two groups. Relapse-free survival was also similar in the two treatment groups on analysis of data from all patients, children, patients with early disease, and those with acute myeloid leukemia, acute lymphoblastic leukemia, and chronic myeloid leukemia. However, in adults (P = .05) and patients with advanced disease (P = .005), leukemia-free survival was significantly better in those treated with TBI. We conclude that patients treated with busulfan have more early toxicity and an increased transplant-related mortality in patients with advanced disease. TBI is therefore the treatment of choice, especially in adults and patients with advanced disease. However, busulfan is an acceptable alternative for patients with early disease and for those in whom TBI is not feasible.
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PMID:A randomized trial comparing busulfan with total body irradiation as conditioning in allogeneic marrow transplant recipients with leukemia: a report from the Nordic Bone Marrow Transplantation Group. 816 51

The effectiveness of reapherone administration for treatment of chronic myeloid leukemia has been studied using sonography of the liver and spleen as well as morphometry of histological patterns of the bone marrow. The study group included 17 patients (chronic disease-16; progressing disease-1). Ten patients received reapherone and 7-myelosan. Dynamic evaluation of scanning evidence for liver and spleen proved instrumental in assessing the effect of reapherone therapy of chronic myeloid leukemia. Similar tendencies were identified by sonography and morphometry applications: reapherone-treated patients revealed decreased liver and spleen, foci of fibrosis dissolving while the morphometric findings pointed to the decreasing indices of collagenous fibrosis and megacariocytic source of the bone marrow. It is suggested that reapherone acts upon the hemopoietic tissue indirectly-via endosal cells of the bone marrow stroma.
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PMID:[The effectiveness of reaferone in chronic myeloid leukemia assessed with ultrasonic and histomorphologic examination]. 880 42

Interferon-alpha (IFN-alpha) remains the only viable alternative to bone marrow transplantation for patients with chronic myeloid leukemia (CML) and is the treatment of choice in many circumstances. IFN-alpha can induce hematologic remissions in most patients with CML and suppresses the Philadelphia chromosome-positive cell clone in 30%-40% of hematologically responsive patients. IFN-alpha can also prolong the length of the chronic disease phase and survival time in patients who achieve a karyotypic response. A third of patients, however, never respond to IFN-alpha, and a proportion of the initial responders will later become resistant. It has been suggested that the induction of anti-IFN-alpha antibodies might be one of the reasons for resistance to IFN-alpha. It is difficult to evaluate the factors that influence antibody induction and the effects of these antibodies on clinical results. The source of IFN-alpha product, trial design, and differences in the sensitivity of the assays used to measure antibodies are all factors that need to be considered.
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PMID:Clinical experience of antibodies to interferon-alpha during treatment of chronic myeloid leukemia. 924 16

Chronic disease duration and survival have been investigated in three groups of patients suffering chronic myeloid leukemia (CML). The first group included 13 patients on alpha-interferons 6-9 mln MU/24 h (mean dose--48 mln MU/week). 31 patients received 2 mln MU/m2/24 h; mean weekly dose--15 x 10(6) MU. Standard chemotherapy was given to another 79 patients (group III). Actual survival and chronic disease duration were computed after Kaplan-Meyer: 4-year survival in group I--88%; group II--85.6% and group III--54%. Five-year survival in patients who had received standard or lower doses of alpha-interferon was 78.7%; chemotherapy alone--28.9%. Median survival in alpha-interferon-treated patients was 66 months; chemotherapy--48 months. After standard alpha-interferon, chronic disease three years after CML diagnosis was in 87% of those treated with standard alpha-interferon, 89% of those receiving lower doses of the drug and 53.4% of chemotherapy-treated patients. After 4 years, chronic disease was registered in 75.5% (alpha-interferon)--74.8% in group I and 72.9% in group II, and in 34.4% of patients treated with myelosan or hydroxyurea. Median chronic stage duration after interferon was 51 months and 39 months in group III, hence, both standard and lower doses of alpha-interferon prolong chronic disease and improve survival in CML patients.
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PMID:[Alpha-interferons in the treatment of patients with chronic myeloid leukemia]. 1053 97

The effects of low doses of cytosine-arabinoside (Ara-C) were studied in 17 patients with chronic myeloid leukemia: chronic, resistant to IFN and hydroxyurea therapy (including 4 cases of advanced chronic disease)--7, and tumor progression--10. Hematologic effect was recorded in 7 chronic patients tolerant to hydroxyurea and alpha-interferon therapy. Among 10 cases of tumor progression, chronic stage II was observed in 3, stabilization (tumor progression short of blastic crisis)--5, and without effect--1. Low-dose Ara-C treatment was considered effective in 15 (88%) out of 17 patients.
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PMID:[Low-dose cytosine-arabinoside (Ara-C) therapy for chronic myeloid leukemia]. 1131 37

This year the Lasker DeBakey Clinical Research Award will be shared by Brian Druker, Nicholas Lydon, and Charles Sawyers for their development of a targeted molecular therapy for treating chronic myeloid leukemia. Their work demonstrated the ability of drugs directed against cancer-causing oncogenes to turn a rapidly fatal malignancy into a manageable chronic disease.
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PMID:Attacking cancer at its root. 1976 56

In the last decade, cancer research has been a highly active and rapidly evolving scientific area. The ultimate goal of all efforts is a better understanding of the mechanisms that discriminate malignant from normal cell biology in order to allow the design of molecular targeted treatment strategies. In individual cases of malignant model diseases addicted to a specific, ideally single oncogene, e.g. Chronic myeloid leukemia (CML), specific tyrosine kinase inhibitors (TKI) have indeed been able to convert the disease from a ultimately life-threatening into a chronic disease with individual patients staying in remission even without treatment suggestive of operational cure. These developments have been raising hopes to transfer this concept to other cancer types. Unfortunately, cancer cells tend to develop both primary and secondary resistance to targeted drugs in a substantially higher frequency often leading to a failure of treatment clinically. Therefore, a detailed understanding of how cells can bypass targeted inhibition of signaling cascades crucial for malignant growths is necessary. Here, we have performed an in vitro experiment that investigates kinetics and mechanisms underlying resistance development in former drug sensitive cancer cells over time in vitro. We show that the dynamics observed in these experiments can be described by a simple mathematical model. By comparing these experimental data with the mathematical model, important parameters such as mutation rates, cellular fitness and the impact of individual drugs on these processes can be assessed. Excitingly, the experiment and the model suggest two fundamentally different ways of resistance evolution, i.e. acquisition of mutations and phenotype switching, each subject to different parameters. Most importantly, this complementary approach allows to assess the risk of resistance development in the different phases of treatment and thus helps to identify the critical periods where resistance development is most likely to occur.
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PMID:Dynamics of resistance development to imatinib under increasing selection pressure: a combination of mathematical models and in vitro data. 2221 47


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