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)

This is an interim report of two National studies of human recombinant interferon-alpha 2a (ROFERON-A) in Ph+ chronic myeloid leukemia (CML). The first study (1986-1988) enrolled 322 patients who were randomized to treatment by IFN or by hydroxyurea. Karyotypic responses were more frequent and better with IFN and as of June 1992 chronic phase duration and survival of IFN treated pts are projected to be significantly longer. The second study (1989-1991) recruited 275 pts less than 56 years old, who were given ROFERON-A for 1 year with the aim of obtaining a karyotypic response, to collect and cryopreserve the responsive marrows, and intensify treatment by high dose busulfan and melphalan followed by autologous marrow infusion.
 ...
PMID:Treatment of Ph-positive chronic myeloid leukemia with alpha-interferon (ROFERON-A). The Italian Cooperative Study Group experience. The Italian Cooperative Study Group on Chronic Myeloid Leukemia. 825 89

Some patients with Philadelphia (Ph) chromosome-positive chronic myeloid leukemia (CML) may achieve partially or completely Ph-negative hemopoiesis after treatment with high doses of cytotoxic drugs or interferon-alpha at standard dosage. This observation leads to three important questions: 1) are Ph-negative myeloid cells in such patients strictly normal? 2) can such Ph-negative cells be identified in all newly diagnosed patients or only in a minority? and 3) what is the basis for the proliferative advantage manifested by CML cells and why might it be temporarily lost as a result of treatment? The mechanisms that might prevent the proliferation of normal cells in an environment of Ph-positive cells and the relevance of these questions to the design of a strategy aimed at obtaining complete remission in the majority of patients are considered. Such a strategy might incorporate autografting with Ph-negative stem cells harvested during the recovery phase of high dose chemotherapy.
 ...
PMID:Residual Ph-negative stem cells in chronic myeloid leukemia--sometimes or always? 829 77

Cytokines have been widely tested in clinical trials during recent years and beneficial responses have been observed in a variety of malignant, infectious and autoimmune diseases. Interferon-alpha induces remissions in patients with certain hematological malignancies such as hairy cell leukemia and chronic myelogenous leukemia. A proportion of patients with chronic viral hepatitis is cured upon application of interferon-alpha. Treatment with interferon-gamma reduces the number of infections in patients with chronic granulomatous disease. In addition, several chronic infections with intracellular pathogens also respond to treatment with this cytokine. With the exception of some patients with renal cell carcinoma and malignant melanoma, solid tumors are largely resistant to administration of these cytokines. Cytokine treatment has changed the outlook for a small group of patients with selected chronic diseases. However, clinical experience with cytokines is still limited and only interferons have been tested for treatment of a variety of diseases. Thus, it seems reasonable to expect that more cytokine-responsive diseases might be identified by continued research efforts.
 ...
PMID:Cytokine therapy of neoplastic and inflammatory disease. 832 83

The therapeutic efficacy of interferon-alpha (IFN-alpha) in the treatment of chronic myeloid leukemia is currently being tested in a number of institutional, interinstitutional, and international trials. There is no doubt that responses are achieved in many patients, and in a small subset complete eradication of clonogenic cells may be possible. However, it has not yet been shown that overall survival of patients treated with IFN-alpha is better than that of those treated with conventional cytoreductive drugs. There are still controversial opinions on problems such as dosages and duration of treatment, combination with cytostatic agents, definition of responses, and relevance of cytogenic and molecular data. An international workshop discussed the data on interferon therapy and attempted to define the role of interferon today in the management of chronic myeloid leukemia.
 ...
PMID:Interferon in chronic myeloid leukemia. A workshop report. 834 29

In 1983 Talpaz et al. (43) for the first time demonstrated the efficacy of interferon-alpha (IFN-alpha) for the treatment of patients with chronic myelogenous leukemia (CML). This observation has been confirmed by several study groups in the consecutive years. An overview over the 7 largest trials including more than 400 patients reveals response rates (partial and complete hematological remissions) of 55 to 91%. In contrast to conventional chemotherapy IFN-alpha treatment resulted in a decrease of Philadelphia-chromosome positive metaphases (cytogenetic remissions) in 19 to 47% of these patients. A complete disappearance of the Philadelphia chromosome was found in 5 to 10% of patients. The following factors influence the response to IFN-alpha in patients with CML: phase and duration of the disease, several well defined risk factors, and IFN-dose. Currently available data are strongly suggestive for a survival benefit of patients with cytogenetic remissions, although definitive prove by phase-III trials is lacking. Actual studies focus on combinations of IFN-alpha and cytostatics, e.g. low-dose cytosine arabinoside.
 ...
PMID:[Value of interferon-alpha in treatment of chronic myeloid leukemia]. 836 48

Seven patients suffering from hypereosinophilic syndrome with clinical and/or hematological symptoms of a myeloproliferative syndrome were treated with a combination of hydroxyurea and interferon-alpha. To date, 6 of them have been followed for more than 1 year. In all cases, this therapy decreased circulating hypereosinophilia to under 1,500/mm3 and obtained normal eosinophil levels in 5 patients with a parallel regression of visceral complications. None of the patients experienced treatment-associated side effects, particularly hematological ones. Hypereosinophilic syndrome has a poor prognosis due, for the most part, to the development of visceral, cardiac and neurological complications, and, more secondarily, to the risk of progression towards acute leukemia. Conventional treatments, corticosteroids and hydroxyurea, have greatly improved the prognosis, but failure of these therapeutics remains common in the myeloproliferative form of the disease. Because interferon-alpha was proven to effectively treat chronic myeloid leukemia, it has been proposed for the treatment of hypereosinophilic syndromes, and encouraging results have been obtained despite the high daily doses required to control the disease. In the future, its association with hydroxyurea could represent an alternative therapy capable of controlling the disease at low doses thereby limiting the risk of side effects.
 ...
PMID:[Treatment of hypereosinophilic syndromes of myeloproliferative expression with the combination of hydroxyurea and interferon alpha. Apropos of 7 cases]. 836 16

Chronic myelogenous leukemia is a lethal disease of the hematopoietic stem cell. Marrow transplant from an HLA-matched sibling donor can cure some patients with chronic myelogenous leukemia. Best results are observed when patients receive transplants early in chronic phase. The advantages of delaying marrow transplantation for a trial of interferon-alpha are questionable if a suitable matched related donor is available. The high incidence of relapse following T-lymphocyte-depleted marrow transplantation for chronic myelogenous leukemia emphasizes the existence of dormant, malignant clones that persist after ablative therapy. The presence of very small numbers of bcr-abl-positive hematopoietic cells after marrow transplantation can be detected by sensitive molecular genetic techniques and does not always predict hematologic relapse. Successful treatment of hematologic relapse after marrow transplantation can result from treatment with interferon-alpha, donor buffy coat cells, or second transplantation. HLA phenotypically matched and, in some cases, class I HLA antigen mismatched unrelated donors can be used successfully for marrow transplantation. Complications include an increased incidence of graft failure and graft-versus-host disease. Younger patients undergoing transplantation early in the disease course fare best. Preliminary results suggest that autologous marrow transplantation can induce complete hematologic and cytogenetic remission and may prolong survival in some cases. Strategies are being developed to obtain benign primitive progenitors suitable for autologous marrow transplantation by positive selection and to develop further posttransplantation antileukemic cell therapy to be used as an adjunct to autologous marrow transplantation for chronic myelogenous leukemia.
 ...
PMID:Therapy for chronic myelogenous leukemia with marrow transplantation. 845 12

Potential anti-leukemia effects mediated by T cells or by natural killer (NK) cells were investigated in chronic myelogenous leukemia (CML) patients treated with interferon-alpha. Therapy-associated modulation of T cell and NK reactivity was monitored for one year from initiation in autologous mixed lymphocyte-tumor cell reactions and cytotoxicity directed against autologous CML cells, respectively. During the course of IFN-therapy, NK activity against autologous CML cells increased steadily, whereas T cell reactivity fluctuated randomly. Despite the high level of T cell reactivity to autologous tumor cells in short-term (6 days) culture, 1) they failed to respond to synthetic peptides corresponding to the bcr/abl fusion sequence of the patient, and 2) only one proliferative T cell clone (TCC) was isolated which specifically recognized HLA-DR-matched CML cells. This TCC appeared not to recognize synthetic peptides corresponding to the bcr/abl fusion sequence of the patient; the antigen to which it responds remains unknown. To assess potential immunogenicity of bcr/abl peptides, it was attempted to sensitize T cells from normal donors in vitro. Of 109 cell lines obtained from seven different donors, eleven showed peptide-dependent proliferation. Therefore, although these results show that it is possible to isolate apparently CML-specific T cells from patients, as well as to prime T cells against tumor-specific peptide in vitro, the frequency of such T cell-mediated reactivity appears low and its relevance to anti-leukemic effects questionable. On the other hand, the strong time-dependent enhancement of natural killing of autologous CML blasts during IFN-alpha treatment, a phenomenon not observed for T cell reactivity, suggests that natural immunity may be more important in controlling disease.
 ...
PMID:Relative roles of natural killer- and T cell-mediated anti-leukemia effects in chronic myelogenous leukemia patients treated with interferon-alpha. 852 55

We examined the effect of Eilatin, a novel marine product, on the survival of human myeloid progenitor cells (CFU-C) isolated from normal individuals and from 12 patients with Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML) in chronic phase and blastic crisis. We compared its effect to the effect of interferon-alpha (IFN-alpha) and cytosine arabinoside (Ara-C). Eilatin, IFN-alpha, and Ara-C inhibited the proliferation of CFU-C from normal individuals and CML patients in a dose-dependent manner. The percent survival of colony-forming units from bone marrow (BM) of seven CML patients in chronic phase exposed for 16 hours to Eilatin (10(-7) and 10(-6) M), IFN-alpha (500 U/mL), or Ara-C (10(-9) M and 10(-8) M) was found to be statistically lower (p < 0.05) than the percent survival of myeloid progenitors from normal individuals. A 16-hour exposure of CD34+ cells isolated from peripheral blood (PB) of three CML patients in blastic crisis and from BM of two patients in chronic phase to Eilatin 10(-7) M, IFN-alpha 500 U/mL, Ara-C 10(-9) M resulted in a marked inhibition in the ability of the cells to proliferate in liquid culture and a reduction in CFU-C content. Using fluorescent in situ hybridization (FISH), we evaluated detection of the BCR/ABL fusion product in the CD34+ cells. All five patients were 100% Ph+ at diagnosis. BCR/ABL translocations were detected in 94.6 +/- 0.6% of CD34+ cells after growth in liquid culture for 7 days. The level of BCR/ABL fusion signals detected after exposure of CD34+ cells for 16 hours to Eilatin 10(-7) M, IFN-alpha 500 U/mL, or Ara-C 10(-9) M were 54.5 +/- 5%, 63.6 +/- 5%, and 70 +/- 4%, respectively (mean +/- SE, n = 5). Our data indicate that Eilatin, a substance isolated from the Red Sea purple tunicate Eudistoma sp., has an antileukemic effect against in vitro Ph+ cells and may be used in conjunction with currently available agents for ex vivo purging of BM and/or PB of CML patients in conjunction with autologous bone marrow transplantation.
 ...
PMID:Eilatin: a novel marine alkaloid inhibits in vitro proliferation of progenitor cells in chronic myeloid leukemia patients. 854 29

Bone marrow and/or peripheral blood of patients with chronic myeloid leukemia (CML) was investigated by the following three parameters: Ph' chromosome, bcr-abl expression in fresh blood and/or bone marrow, and bcr-abl expression in single hematopoietic progenitor colonies generated from blood and/or bone marrow. Expression of bcr-abl was proven by a reverse "nested primer" polymerase chain reaction (PCR) that is able to detect 1 pg of hybrid mRNA. We performed 108 investigations on 68 patients containing all three parameters: 12 on untreated patients, seven after interferon-alpha (IFN-alpha), seven after low-dose cytosine arabinoside (Ara-C), 22 after cyclic high-dose hydroxyurea (HU), 49 after allogeneic BMT, five before and three after stem cell mobilization, and three after autologous stem cell transplantation (ASCT). In 53 cases (49%), cytogenetics and PCR gave identical results. In 40 cases (37%), PCR from single colonies gave additional information compared to cytogenetics (e.g., mosaic in colonies when all metaphases were positive or negative). Most interesting were the results of one patient after IFN, one patient after ASCT, and 10 patients after BMT (14 investigations = 13%), showing only Ph'-negative mitoses accompanied by a negative nested primer PCR from fresh blood/bone marrow but single bcr-abl-positive progenitor colonies. False-positive results could be widely excluded by repeated insertion of negative controls into the experiments. One explanation for these results could be that CML, progenitors survive in the patient's body by being inactive and not proliferating. These cells express no or very little RNA and bcr-abl is not detectable by reverse PCR. When stimulated ex vivo in a colony assay by external growth factors, cells proliferate and produce detectable amounts of hybrid mRNA. The value of these observations is not clear. A follow-up of the patients will show if such sleeping progenitors can be activated in vivo. Concluding our observations, we can say that in special cases (therapy follow-up, detection of minimal residual disease) it could be useful to perform a PCR analysis of single progenitors in parallel with the routine investigations.
 ...
PMID:Detection of bcr-abl mRNA in single progenitor colonies from patients with chronic myeloid leukemia by PCR: comparison with cytogenetics and PCR from uncultured cells. 854 60


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