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)

Survival times in chronic myeloid leukaemia (CML) may vary widely depending on the risk profiles of patients. This fact is frequently not, or not sufficiently, considered in evaluating survival in CML, and some studies do not report risk profiles. Therefore we analysed the relative impact of risk profile and therapy on survival using the median survival times of therapy groups and of risk groups of the three-arm randomized German CML Study I (interferon alpha v hydroxyurea v busulphan; median survival times 65 v 56 v 45 months, n = 490, median observation time 70.4 months). The impact of risk profile (Sokal) on survival as determined by the survival difference between high and low risk patients (40 months) was twice the maximum survival difference between treatment groups (20 months). A similar ratio was obtained after stratification for therapy and for risk profile. Since Sokal's index has been reported to prognostically discriminate IFN-treated patients less well than chemotherapy-treated patients, a new score with better discrimination of IFN-treated patients was also used. The results were similar for both scores. We conclude that the risk profile at diagnosis is still more important for survival of CML patients than therapy. Therefore patients should be stratified according to risk profile for comparisons of survival times between studies and treatment arms.
 ...
PMID:Comparative analysis of the impact of risk profile and of drug therapy on survival in CML using Sokal's index and a new score. German chronic myeloid leukaemia (CML)-Study Group. 913 44

The authors report the assessment of 2 patients on interferon alpha (IFN-alpha) therapy for chronic myelogenous leukemia who developed manic symptoms long after IFN-alpha therapy had been initiated. These cases suggest that chronic IFN-alpha therapy may be associated with vulnerability for developing overt psychiatric symptoms, particularly in cases where the patient is experiencing psychosocial stress, and that the current definition of persistent adverse effects of IFN-alpha should be broadened to include the occurrence of manic episodes.
 ...
PMID:Manic episodes in two patients treated with interferon alpha. 914 8

All-trans retinoic acid (ATRA) has recently been shown to synergize with the inhibitory effect of interferon alpha (IFN alpha) on the growth of malignant cells isolated from solid tumors. We investigated whether ATRA could potentiate the inhibitory effects of IFN alpha on the proliferation of leukemic progenitors in chronic myeloid leukemia (CML). CD34+ cells from chronic phase, newly diagnosed patients, were incubated in short-term liquid culture with ATRA, IFN alpha or a combination of both molecules and then plated on semi-solid cultures for colony-forming cell assay. IFN alpha was found to inhibit preferentially the generation of late progenitors. ATRA at a concentration of 10(-8) M was found strongly to inhibit CFU-M colonies. Addition of ATRA to IFN alpha dramatically potentiated the inhibitory effects of INF alpha on CFU-GM growth. In the presence of both molecules the inhibition of day 14 CFU-GM from CD34+ cells was lowered to 27 +/- 4% of control. CFU-M colonies were completely inhibited. RT-PCR analysis of the colonies resulting from the action of the combination IFN alpha plus ATRA showed the presence of an increased number of BCR-ABL-negative colonies relatively to what was observed with IFN alpha alone. FISH analysis showed a higher percentage of Ph-negative cells in the ATRA plus IFN alpha-treated samples, confirming PCR experiments. These results indicate that, in vitro, the combination of IFN alpha and ATRA effectively inhibits CFU-GM colony formation in CML and suggest that it has a potential interest for the treatment of CML.
 ...
PMID:All-trans retinoic acid potentiates the inhibitory effects of interferon alpha on chronic myeloid leukemia progenitors in vitro. 918 Feb 90

New treatments which may change the course of a disease, or which have potential carcinogenicity, may result in the development of new cytogenetic or clinical disorders. Three patients with Philadelphia chromosome-positive (Ph-positive) chronic myeloid leukemia (CML) who developed new cytogenetic abnormalities after achieving a cytogenetic complete remission (CR) of their Ph-positive disease with interferon alpha (IFN-alpha) based therapy are described. Patient 1 developed chromosomal abnormalities involving chromosomes 5 (5q13-34) and later 7 (monosomy 7) 60 months after the start of therapy and 20 months after IFN-alpha was discontinued. A myelodysplastic syndrome was noted 83 months from the start of therapy. Patient 2 developed a myeloproliferative syndrome with 18p11 chromosomal abnormalities 90 months after the start of the therapy and 60 months after IFN-alpha was discontinued. Patient 3 developed a chromosome 11 abnormality (11q21-23) 23 months after the start of therapy, without hematological manifestations. All three patients remain in cytogenetic CR of Ph-positive disease with the hypermetaphase fluorescent in situ hybridization and polymerase chain reaction studies for BCR/ABL showing minimal residual disease. The emergence of new cytogenetic or clinical disorders in patients with CML on IFN-alpha therapy needs to be monitored. These findings may be related to changing the natural course of CML, to therapy, or to the emergence of suppressed clones in a stem cell disorder.
 ...
PMID:Emergence of new clonal abnormalities following interferon-alpha induced complete cytogenetic response in patients with chronic myeloid leukemia: report of three cases. 918 Mar 6

At the present time, the combination of interferon alpha and hydroxyurea represents the standard treatment of the chronic phase of CML. Using this approach, survival can be prolonged to a median of about five years. A precondition, however, is that treatment with interferon alpha is initiated as early as possible. The sole curative treatment continues to be allogeneic bone marrow transplantation. If no donor is available, autotransplantation with subsequent maintenance treatment with interferon alpha is an alternative approach. In view of the complexity of the treatment of CML, it is recommended that patients be referred to a center at the earliest possible time following diagnosis.
 ...
PMID:[Interferon-alpha in chronic myeloid leukemia]. 920 94

The antiviral, antiproliferative and immunomodulating effect of interferon alpha (INF alpha) has led to its widespread use in malignant diseases. In hematology, the clinical effect of INF alpha has been proven empirically for several lymphoid malignancies--hairy cell leukemia, chronic lymphoid leukemia, multiple myeloma, follicular lymphoma--and also for chronic myeloproliferative diseases, particularly chronic myeloid leukemia. However, after 10 years of use, the impact of INF alpha on patient management compared with conventional treatments remains a matter of debate. Interest in cost-containment and the frequency of adverse effects after long-term treatment also raises many questions. A critical analysis of the role of INF alpha in each specific indication is thus required.
 ...
PMID:[Clinical value of interferon-alpha in the treatment of malignant hematologic diseases]. 920 87

Four randomized prospective studies on interferon alpha (IFN) in CML report varying degrees of prolongation of the chronic phase of CML and of survival as compared to conventional therapies. There is agreement that IFN prolongs survival as compared to standard busulfan. There is disagreement, however, as to which degree IFN is superior to hydroxyurea. Whereas the randomized studies of the Italian cooperative group and of the British MRC find a statistically significant survival advantage of IFN over hydroxyurea of about 20 months, this difference is only 10 months in the German randomized study and not significant. One reason for this difference might be the more intensive treatment schedule for the hydroxyurea control group in the German study. Other reasons might be differences in risk profiles between the patient groups studied and in strategies of IFN therapy. About 1% of the human genome consists of retroviral or retroviral-like sequences. By analogy to animal models, endogenous retroviruses might also have pathogenic potential in human disease. The transposon-like structure of retroviruses that enables them to integrate at almost any position in the host genome and the capability of retroviruses to serve as efficient vehicles of cellular genes are in support of a pathogenic potential. Furthermore, particles resembling retroviruses have been observed long ago in human embryonic and malignant tissues and cell lines. Sequence information and the transcriptional activity of the endogenous sequences argue against the possibility that these sequences are only fossil relics of early evolutionary periods. Most of the sequences appear to be inactivated by stop codons or frameshifts, making the genomic localization of open reading frames with biological activity difficult. Up to now, mutagenesis by insertion of retroviral-like sequences in sporadic cases of human disease appears to be the only example of pathogenic relevance of retroviruses in man.
 ...
PMID:Randomized studies with interferon in chronic myelogenous leukemia (CML) and comparative molecular aspects. German CML Study Group. 920 40

In this article, the rationale for autografting in chronic myeloid leukemia is reviewed, and alternative therapeutic approaches to the use of granulocyte-colony stimulating factor and chemotherapy-mobilized peripheral blood stem cells are discussed. The data from patients treated using the original ICE (idarubicin, cytarabine, etoposide), or the shorter course mini-ICE protocols are considered, with special emphasis on those patients who received their chemotherapy regimens soon after diagnosis and prior to any treatment with interferon alpha. The appropriate design of a trial to test the value of autografting in chronic myeloid leukemia is discussed, as is the optimal timing of collections to achieve the maximal yield and purity of Ph-negative peripheral blood stem cells.
 ...
PMID:Stem-cell mobilization for autografting in chronic myeloid leukemia. 937 46

Treatment of recurrent leukemia after bone marrow transplantation with the transfusion of lymphocytes from the marrow donor has been successful in a majority of patients with chronic myelogenous leukemia and a minority of patients with acute myeloid leukemia and myelodysplastic syndrome. It has been disappointing in patients with acute lymphoblastic leukemia and in advanced stages of chronic myelogenous leukemia. In chronic-phase chronic myelogenous leukemia remissions were of good quality and the actuarial relapse rate was less than 20% at 3 years. In acute leukemias remissions were less durable. Graft-versus-host disease and marrow aplasia were the major complications of this form of treatment. In patients with marrow aplasia hematopoiesis could be restored by infusion of donor marrow without further conditioning treatment. Preceding or concomitant treatment with interferon alpha is not essential for a response, but the exact role of interferon alpha remains to be determined in a randomized study. Similarly, the best time for treatment remains to be defined. Treatment of cytogenetic and molecular recurrence of chronic myelogenous leukemia is most effective in preventing marrow aplasia, but a few patients may be treated unnecessarily, for some cytogenetic recurrences may remit spontaneously. The mechanism of the graft-versus-leukemia reaction is still not clear. Effector cells and target antigens remain to be defined. Observations are compatible with a graft-versus-host reaction directed against minor histocompatibility antigens presented at the cell surface of hematopoietic cells, but reactions against leukemia-specific antigens are possible. Future studies will focus on differences of reactions against possible leukemia-specific antigens and histocompatibility antigens on hematopoietic cells and cells of other organs.
 ...
PMID:Donor leukocyte transfusions for leukemic relapse. 937 31

Chronic myelogenous leukemia involves clonal expansion of hematopoietic progenitor cells associated with the characteristic translocation between chromosomes 9 and 22, resulting in the generation of an aberrant bcr-abl protein with enhanced tyrosine kinase activity. The bcr-abl protein can induce cell proliferation, induce transformation of immature hematopoietic cells, and suppress apoptosis in vitro. Abnormalities of stromal cell and progenitor cell interaction may be central to the pathogenesis of the abnormal hematopoiesis in chronic myelogenous leukemia. Therapy with interferon alpha in chronic-phase chronic myelogenous leukemia can result in hematologic responses in up to 70% to 80% of patients and partial or complete cytogenetic responses in up to 50%; many studies show a significant overall survival advantage for patients treated with interferon. Allogeneic marrow transplantation can result in long-term survival for patients with chronic myelogenous leukemia, particularly younger patients undergoing transplantation early in the course of disease, and unrelated donor or autologous marrow transplantation may be an option for patients without a matched sibling donor. Future therapy will likely involve selection and expansion ex vivo of Ph- stem cells for reinfusion as part of a strategy for autologous marrow transplantation. Other areas of current investigation include in vitro assessment of the activity of antisense oligonucleotides and of the immunologic responses to chronic myelogenous leukemia cells.
 ...
PMID:Chronic myelogenous leukemia. 937 92


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