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 treatment of elderly patients, who suffer from leukemia must not be standardized. Impaired bone marrow function, cardiovascular disease and other organopathias require an individually adapted therapy. The aim of treatment should be a good quality of life and not a remission at any price. Aggressive therapy in cases of acute leukemia with little progress should be avoided in favour of symptomatic treatment. CLL are treated in the progressive state of disease. Haemolytic anaemia and recurrent infections may complicate the course of CLL. CML is not a disease of old age but when it occurs intermittent therapy with cautious dosage is preferable to a continuous therapy.
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PMID:[Treatment of leukemia in the elderly (author's transl)]. 3 67

With the advent of more effective chemotherapy an increasing incidence of central nervous system involvement in acute lymphocyte (ALL) and myelocytic leukemias (AML) and chronic myelocytic leukemia (CML) in blast crisis has become evident. Meningeal involvement in the chronic phase of CML is rare. We report two children whose initial presentation of Ph1 CML was in the central nervous system as documented by cytocentrifugation. Aggressive combination chemotherapy and cranial irradiation has resulted in prolonged survival without blastic transformation or further meningeal disease. An approach to children with CML is suggested.
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PMID:Central nervous system involvement at presentation in the chronic phase of chronic myelogenous leukemia in childhood. 27 16

Seven patients with chronic granulocytic leukaemia in transformation were treated with combination cytotoxic drugs only or cytotoxic drugs plus total body irradiation followed by transfusion of reconstituted cryopreserved autologous buffy coat cells. Four of the patients were restored to second chronic phase disease which lasted 74, 32, 26 and 12 weeks respectively. Three other patients derived little benefit from the procedure. Buffy coat cells from patients with CGL apparently contain enough pluripotential stem cells to provide effective autografts in most cases. Lymphoid as well as myeloid reconstitution can usually be achieved. Buffy coat cells may thereby be superior to bone marrow cells for this purpose. Aggressive cytoreductive treatment followed by autografting appears to be a promising approach to the palliative management of patients with CGL in transformation.
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PMID:Autografting cryopreserved buffy coat cells for chronic granulocytic leukaemia in transformation. 29 47

Histocompatible bone marrow transplantation (BMT) is the treatment of choice for pediatric patients with second remission acute lymphoblastic leukemia or acute myelogenous leukemia (AML) and has been successfully used to treat patients with first remission AML and stable-phase chronic myelogenous leukemia. The principle causes of transplantation failure are recurrent leukemia and therapeutic toxicities, including idiopathic interstitial pneumonitis and graft versus host disease (GVHD). The likelihood of leukemic relapse is related primarily to the remission status of the patient; patients in first remission have a lower relapse rate than patients in second remission, and the relapse rate of both is less than that of patients in relapse. Interstitial pneumonitis is due, in part, to the total body irradiation (TBI) that is used to cytoreduce the patients. TBI administration has been modified to reduce its toxicity. Acute and chronic GVHD are due to the immuno-aggression of donor T-lymphocytes against recipient non-HLA antigens. The in vitro removal of the T-lymphocytes from the donor bone marrow inoculum reduces the incidence of acute and chronic GVHD but may have the adverse effect of reducing hematopoietic engraftment and increasing leukemic relapse since the graft versus leukemia effect may be eliminated. The expanding role of BMT includes its use in the treatment of nonleukemic neoplasms (neuroblastoma, solid tumors) and the use of histoincompatible BMT for eligible patients without histocompatible donors.
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PMID:Current status of bone marrow transplantation in pediatric oncology. 352 38

The prognosis of patients with CML has improved little in the past 50 years. The relatively benign chronic phase invariably deteriorates to a refractory and rapidly fatal terminal phase. This terminal stage has been found to have two major subtypes as defined by morphologic, cytochemical, immunologic, and enzymatic criteria--myeloblastoid and lymphoblastoid. Aggressive combination chemotherapy has achieved minimal improvement in survival once the terminal phase has begun, perhaps because only Ph1-positive stem cells remain to repopulate the marrow at this stage. Bone marrow transplantation has also been unsuccessful as therapy for the terminal phase, possibly because the patients are too debilitated to tolerate transplantation once the terminal phase has begun. Combination chemotherapy has been applied in an effort to eliminate the Ph1 chromosome-containing clone during the chronic phase. This goal has not yet been consistently achieved. Chemotherapy has also not been able to delay the onset of the terminal phase nor to prolong survival. Even in those patients in whom the Ph1 chromosome-containing clone has been eliminated, relapse to the chronic phase with return of the Ph1 chromosome has generally occurred within a brief period of time. Bone marrow transplantation during the chronic phase may hold the promise of true cure for CML, with permanent elimination of the malignant clone. However, the chronic phase can be unpredictably long and patients in the chronic phase often have few, if any symptoms. Therefore, there has been a reluctance to employ drastic therapy during the chronic phase. Techniques to predict the transformation to the terminal phase prior to overt morphologic or clinical conversion are now being developed. It may be possible in the future to attempt HLA-matched sibling donor bone marrow transplantation at the earliest signs of transformation from the chronic to the terminal phase. In this manner, optimal survival might be achieved by allowing patients to be maintained in the chronic phase for as long as possible prior to the initiation of aggressive therapy. Until this is routinely possible, continued research designed to improve the therapy of the terminal phase must be pursued. These attempts are likely to include the development and evaluation of new chemotherapeutic agents, novel methods of administration of existing drugs to better exploit their pharmacokinetics (for example, continuous infusion), and the utilization of newly described treatment approaches (such as the use of "differentiating" agents in an attempt to prevent progression to blastic transformation).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Terminal-phase chronic myelogenous leukemia: approaches to treatment. 390 66

To assess the role of polyamines in the mechanism of immunosuppression in patients with chronic myeloid leukemia (CML), polyamines levels were measured in the urine and blood, polyamines reactivity was investigated in 113 CML patients in correlation with the process aggression. In patients with aggressive CML (23 subjects) and large tumor mass the above concentrations were significantly higher than in patients with less severe CML run (90 subjects). There were also parallels between polyamines concentrations in the biological media and the patient's immunoreactivity. This suggests involvement of polyamines in immunosuppression observed in CML.
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PMID:[Immunosuppressive action of polyamines in patients with chronic myeloid leukemia]. 818 35

Differentiation inhibitory factor (nm23 protein) inhibited the induction of differentiation of mouse myeloid leukemia M1 and WEHI-3BD+ and human erythroleukemia HEL, KU812, and K562 cells. Block of differentiation may be associated with the aggressive behavior of leukemia. To examine the role of nm23 in human myeloid leukemia, we investigated the relative levels of nm23-H1, nm23-H2, and c-myc transcripts in 42 patients with acute myelogenous leukemia (AML), and in 5 with chronic myelogenous leukemia at chronic phase by reverse transcriptase polymerase chain reaction. The expression of nm23-H1 and -H2 but not of c-myc in AML was significantly higher than that in normal blood cells. Among AMLs, acute monocytic leukemia (presentation with AML-M5 morphology) was especially associated with elevated nm23-H1 and -H2 mRNA levels. On the other hand, the elevated levels of c-myc expression in AML-M5 were less evident. An analysis of correlation between nm23 expression and clinicopathological parameters showed that resistance to initial chemotherapy is associated with increased nm23-H1 mRNA levels and that a high initial white blood cell count is associated with increased nm23-H2 mRNA levels. Elevated nm23-H1 mRNA levels were associated with significantly reduced the overall survival of AML, especially of AML-M5 patients. The present results indicate that nm23-H1 and -H2 are overexpressed in AML and especially nm23-H1 gene expression predicts the prognosis of AML, especially of AML-M5.
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PMID:Differentiation inhibitory factor nm23 as a new prognostic factor in acute monocytic leukemia. 889 23

Donor leukocyte infusions (DLI) are an effective therapy for patients who relapse with leukemia after bone marrow transplantation (BMT). Severe graft-versus-host disease and prolonged periods of pancytopenia compromise the success of this treatment in a substantial number of patients. We used filgrastim-mobilized peripheral blood progenitor cells (PBPCs), in some cases preceded by cytoreductive therapy, to circumvent some of the problems associated with DLI. Eleven patients (median age 41 years) received a total of 20 donor cell infusions. Their diagnosis was CML in hematological (two patients) or cytogenetic relapse (two patients), six patients suffered from acute myeloid leukemia (AM; n = 5) or Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL Ph+). One patient had multiple myeloma (MM). All six patients with acute leukemias received cytoreductive therapy prior to PBPC infusions; three patients with CML were pretreated with IFN alpha. Four of four patients with CML responded to PBPC infusions and currently are in complete clinical and molecular remission for time periods between 1 and 12 months. Six of six patients with acute leukemias achieved a complete remission. All of them relapsed after a median remission duration of 24 weeks (range 11-49 weeks). Three patients relapsed at extramedullary sites (CNS, testes, skin). Four of six acute leukemia patients received further cytoreductive therapy. All patients responded again and are in complete remission for time periods between 14 and 615 days. Two patients with acute leukemias have died due to dissemination of the disease. The patient with MM did not respond and is alive with disease. Severe (grade III) acute GVHD developed in two of 11 patients, three patients developed grade II disease, six patients did not show any signs of GVHD. Extensive chronic GVHD has developed in two cases to date. Patients with chemotherapy prior to PBPC infusion developed neutropenia and thrombocytopenia with a maximum duration of 20 and 14 days, respectively; prolonged periods of neutropenia did not occur. Two patients developed long-lasting thrombocytopenia in spite of PBPC infusion, in one case followed by leukemic relapse. Repeated courses of chemotherapy and PBPC infusion were generally tolerated well; no early deaths due to treatment-related toxicity or GVHD were observed. We conclude that the use of allogeneic PBPC instead of DLI in patients with relapse after BMT is technically feasible and safe. The efficacy of PBPC infusions seems comparable to DLI in patients with CML. Patients with acute leukemias also achieved complete albeit transient remissions. Aggressive chemotherapy followed by PBPC infusions resulted in only limited duration of cytopenia. The usage of PBPC infusion instead of non G-CSF-mobilized donor cells for treatment of relapse after BMT may reduce pancytopenia-related complications and merits further investigation.
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PMID:Allogeneic peripheral blood progenitor cells for treatment of relapse after bone marrow transplantation. 933 54

This report describes a single institution's recent experience with six patients fulfilling the diagnostic criteria of chronic neutrophilic leukemia. No patient had the Philadelphia chromosome or the BCR/ABL fusion gene. None of the common cytogenetic abnormalities characteristic of myeloid disorders were detected. Two patients demonstrated clonal evolution during the course of the disease. All responded initially to therapy with hydroxyurea with control of leukocytosis and reduction in splenomegaly. Three patients eventually became refractory to hydroxyurea, manifesting progressive neutrophilia without blastic transformation. Aggressive chemotherapy to control progressive leukocytosis resulted in death due to cytopenias in two of these patients. The third patient received less intensive chemotherapy and died of progressive disease. One patient died after transformation of the disease into undifferentiated acute myeloid leukemia. Two patients remain alive with stable disease on hydroxyurea therapy, 12 and 54 months after initial diagnosis. Chronic neutrophilic leukemia is a rare clinicopathologic entity that can be distinguished from chronic myelogenous leukemia, the recently described neutrophilic-chronic myelogenous leukemia, and myelodysplastic syndrome. The clinical course is heterogeneous, with a definite risk of death from either blastic transformation or progressive neutrophilic leukocytosis. Continued study and reporting of these cases must be encouraged.
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PMID:Chronic neutrophilic leukemia (CNL): a clinical, pathologic and cytogenetic study. 1124 96

Wild-type Wilms' tumor gene WT1 is expressed at high levels not only in most of acute myelocytic, acute lymphocytic, and chronic myelocytic leukemia, but also in various types of solid tumors including lung cancer. We tested the ability of the gene product (WT1) to serve as a target antigen for tumor specific immunotherapy both in human in vitro system and mouse in vivo system. In the latter, we can evaluate the efficacy and the side effects of WT1 vaccination in vivo. In the human in vitro system, two WT1 peptides that contain HLA-A2.1 binding anchor motifs were determined to bind to HLA-A2.1 molecules. Peripheral blood mononuclear cells (PBMC) from an HLA-A2.1-psitive donor were repeatedly stimulated in vitro with TAP-deficient T2 cells pulsed with each of these two peptides, and CD8-positive cytotoxic T lymphocytes (CTLs) that specifically lyse WT1-expressing, HLA-A2.1-positive tumor cells were induced. Other groups also have succeeded in generating CTLs which specifically lyse WT1-expressing leukemia cells, and which do not inhibit colony-formation of normal hematopoietic cells that express WT1 at physiological levels. In the mouse in vivo system, immunization of C57BL/6 mice with one WT1 peptide with relatively high binding affinity for H-2D(b) molecules, which contain H-2D(b) binding anchor motifs, induced CTLs, which specifically lysed WT1-expressing tumor cells in an H-2D(b)-restricted manner. Furthermore, mice immunized with the WT1 peptide (peptide vaccination) or WT1 cDNA (DNA vaccination) rejected challenges by WT1-expressing tumor cells and survived with no signs of auto-aggression to WT1-expressing normal organs by the induced CTLs. The WT1 protein has been identified as a novel tumor antigen and recent investigations provide a rationale for developing WT1-based adoptive T cell therapy and vaccination against various kinds of malignant neoplasms.
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PMID:WT1 as a novel target antigen for cancer immunotherapy. 1218 20


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