Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Splenectomy performed in a patient with polycythaemia vera and incipient osteomyelofibrosis was complicated by severe postoperative bleeding. A transient decrease of factor VIII/von Willebrand factor (VIIIR:WF) was detected as a possible cause of the bleeding tendency. As a result of this observation the VIIIR:WF system was investigated in all patients with myeloproliferative disorders who are presently followed by this laboratory. Subnormal VIIIR:WF activity was found in 5 of 9 prospectively investigated patients with polycythaemia vera and in one of 12 patients with chronic myeloid leukemia. These results suggest that acquired defects of the VIIIR:WF system are, in addition to the well known functional abnormalities of blood platelets, quite common in myeloproliferative disorders, especially polycythaemia vera, and must be reckoned with before surgery in particular. When specific antibodies directed against VIIIR:WF have been ruled out, the etiology of the VIIIR:WF defect found in our patients remains unclear.
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PMID:[Hemostasis disorders with reduced activity of the von Willebrand factor in myeloproliferative syndromes]. 660 16

Myeloid committed stem cells belong to a subpopulation of small nucleated cells, which are defined by their capacity to form colonies of mature myeloid cells in agar-medium. They are termed "Colony forming Unit, CFUC", and such cells are detectable in bone marrow and peripheral blood. Bone marrow cells from 15 control patients with regular myelopoiesis contained 86 +/- 46 CFUC/10(5) bone marrow cells and 23 +/- 14 CFUC/ml blood. In 10 patients with aplastic anemia, only 0-10, 5 CFUC/10(5) BM-cells were found and no CFUC were detectable in the peripheral blood. 17 patients with chronic myeloid leukaemia showed a moderate elevation of bone marrow CFUC (X = 105), while the circulating CFUC were markedly elevated (105-42.000/ml). The circulating CFUC were closely correlated with the number of leukocytes (p less than 0,001). In 12 patients with primary osteomyelofibrosis, the number of circulating CFUC was also (raised (325-22.199/ml) and again, a correlation with the number of leukocytes was observed (p less than 0,05). As, on the other hand, there was no difference in the leukocyte count between the control group and patients with osteomyelosclerosis, the simultaneous assessment of circulating leukocytes and CFUC proves a diagnostic tool. Pancytopenia with a hypercellular bone marrow results from either neoplastic or metabolic alterations of haemopoiesis; in pancytopenia with neoplastic infiltration or transformation, the number of CFUC was lowered, whereas it was slightly elevated in pancytopenia due to metabolic alterations. In patients with acute leukaemia, only a minority of cells was capable of proliferation in vitro. The growth of leukaemic cells in culture, their prolonged survival along with the expression of functional properties may be clinically used for a more subtle classification of blast populations. The data on patients with acute leukaemia indicate, that basic mechanisms of normal blood cell regulation operate in leukaemic haemopoiesis as well.
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PMID:[The determination of myeloid-committed stem cells in systemic disorders of myelopoiesis: implications for physiopathology, diagnosis and prognosis]. 694 36

The immune reactivity of allogeneic lymphocytes plays a major role in the control of leukemia after bone marrow transplantation. In patients with recurrent leukemia after marrow transplantation, chimerism and tolerance provide ideal conditions for adoptive immunotherapy with donor lymphocytes. We studied the effect of donor lymphocyte transfusions on acute and chronic leukemia in relapse after bone marrow transplantation. One hundred thirty-five patients with chronic myeloid leukemia (CML) (N = 84), acute myeloid leukemia (AML) (N = 23), acute lymphoblastic leukemia (ALL) (N = 22), myelodysplastic syndrome (MDS) (N = 5), and polycythemia vera with osteomyelofibrosis (PCV) (N = 1) were treated with transfusions of donor lymphocytes. Patients were monitored for response of leukemia, including in CML, the use of the polymerase chain reaction for bcr/abl mRNA transcripts and for the occurrence of graft-versus-host disease (GVHD) and myelosuppression. Complete remissions were induced by donor lymphocyte transfusions in 54 patients with CML (73%) and in the patient with PCV; complete remissions were also induced in five patients (29%) with AML and a patient with MDS. In contrast, ALL did not respond to adoptive immunotherapy with donor lymphocyte transfusions. Remissions were durable in patients treated for CML in chronic phase (probability of remission: 87% at 3 years). Lymphocyte transfusions were also given to 18 patients with ALL, AML, MDS, and transformed phase CML who were in remission after chemotherapy. These remissions were not durable. Fifty-two patients (41%) developed GVHD of grade 2 or more, and 41 patients (34%) showed signs of myelosuppression. Seventeen patients died without leukemia, 14 patients with GVHD and/or myelosuppression. Donor lymphocyte transfusions exert strong effects against myeloid forms of leukemia and induce durable remissions in CML.
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PMID:Graft-versus-leukemia effect of donor lymphocyte transfusions in marrow grafted patients. 861 35

After previous serological screening for Epstein-Barr virus (EBV), human herpesvirus-6 (HHV-6) and human cytomegalovirus (HCMV) showed elevated antibody titers against EBV and HHV-6 in more than 50% of patients with myelodysplasia and chronic myeloproliferative diseases, the present study was carried out in order to investigate viral antigen expression and distribution in bone marrow cells of these patients. Trephine biopsies were studied from 60 patients with myelodysplasia (MDS), 36 patients with chronic myelogenous leukemia (CML) and 18 patients with osteomyelofibrosis (PMF). Elevated anti-EBV EA titers were found in 62% of the MDS cases, in 33% of the CMLs and in 62% of the OMF patients. HHV-6 titers were elevated in 18% of the MDS cases, but in only one case each of CML and OMF. Antigen expression in bone marrow cells was even more frequent: EBV-EA was 76% in MDS cases, 77% in CML and 40% in OMF. HHV-6 p41 was observed in 47% of the MDS cases, in 54% of the CML cases and in 20% of the OMFs. In comparing these data with those from the literature and with our own studies in Hodgkin's disease, it is hypothesized that the reactivated herpesviruses may contribute to the pathogenesis of these hematopoietic disorders by interfering with the cytokine regulation of cell proliferation and differentiation.
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PMID:Demonstration of active and latent Epstein-Barr virus and human herpevirus-6 infections in bone marrow cells of patients with myelodysplasia and chronic myeloproliferative diseases. 789 80

A morphometric analysis has been performed on bone marrow trephine biopsies following sequential double-immunostaining with monoclonal antibodies PC10 (anti-proliferating cell nuclear antigen--PCNA) and Y2/51-CD61 (anti-platelet glycoprotein IIIa) to evaluate endoreduplicative activity of megakaryopoiesis. In addition to a control group, patients included different subtypes of chronic myeloproliferative disorders (CMPDs) like chronic myeloid leukaemia (CML), polycythaemia vera (P. vera), primary thrombocythaemia (PTH) and finally primary (idiopathic) osteomyelofibrosis (OMF). In comparison with the normal bone marrow and also with P. vera and PTH a significant increase in PCNA-labelling (late G1 and S phases) of megakaryocytes was recognizable in OMF, contrasting with a striking reduction of this marker in CML. Particularly in advanced stages of OMF, secondary folate deficiency leading to a megaloblastoid appearance of erythroid precursors is a frequent finding. In pernicious anaemia previous cytokinetic studies have demonstrated an arrest in the S phase (DNA synthesis) of the cell cycle due to vitamin B12/folate (haematinic) deficiency. A similar pathomechanism may also be effective in OMF. Consequently, a block in the S phase of the cell cycle is assumed which is in keeping with the increased numbers of PC10-positive megakaryocytes. Significant correlations were calculable between megakaryocyte sizes and PCNA-staining capacity in the normal bone marrow and CMPDs. According to morphometry small-sized (hypoploid) megakaryocytes showed a prevalence of PCNA labelling. This finding is confirmative with a hypothesis on the dynamics of endoreduplicative activity of megakaryocytes, i.e. the prolongation of G1/G2 phases in larger (polyploid) elements. On the other hand, some of the giant polyploid megakaryocytes may cease endoreduplication and enter into G0 phase, which could partially explain the predominance of PCNA-negative large-sized cells of this lineage.
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PMID:Megakaryopoiesis in chronic myeloproliferative disorders: immunohistochemical evaluation of endoreduplicative activity by PCNA-staining reaction. 798 Nov 37

The primary thrombocytosis (thrombocythemia) associated with myeloproliferative disorders is believed to be due to autonomous platelet production. Secondary or reactive thrombocytosis can be observed in a number of clinical circumstances, and may be related to persistent overproduction of some thrombocytopoietic factors acting on megakaryocytes. Several cytokines, including IL-6, IL-1 and IL-4 have been shown to act alone or in concert, to affect various cellular stages of megakaryocytopoiesis in humans. The aim of this study is to assess the serum concentrations of these cytokines in myeloproliferative disorders (MPD) with thrombocythemia and in rheumatoid arthritis (RA) with marked reactive thrombocytosis. Twenty-two patients (14 men, 8 women) with MPD and thrombocythemia (platelet counts > 500 x 10(9)/1; range 507-996 x 10(9)/1), 33 RA patients (28 women, 5 men) with marked thrombocytosis (platelet counts > 500 x 10(9)/1; range 500-745 x 10(9)/ 1), 27 RA patients (24 women, 3 men) with normal platelet counts (range 168-399 x 10(9)/1) and 15 healthy volunteers (8 women, 7 men) with normal platelet counts (range 161-385 x 10(9)/1) enrolled in the study. Serum IL-1 alpha, IL-1 beta, IL-4 and IL-6 concentrations were measured in these four groups. Of the 22 patients with MPD, 10 had chronic myelogenous leukemia, 5 had polycythemia vera, 6 had essential thrombocytosis and 1 had osteomyelofibrosis. Serum interleukin concentrations in patients with MPD and thrombocythemia were either suppressed or similar to those of normal subjects, whereas IL-6, IL-1 beta and IL-4 levels were increased in RA patients with reactive thrombocytosis. We conclude that thrombocythemia associated with MPD is an autonomous phenomenon, and is not regulated by cytokines which affect megakaryocytopoiesis.
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PMID:Megakaryocyte-related interleukins in reactive thrombocytosis versus autonomous thrombocythemia. 863 38

Chronic myelogenous leukemia (CML) is usually treated with hydroxyurea or interferon-alpha. In some patients high platelet counts develop although leukocyte counts are well controlled with these drugs. If in such a situation cytoreductive therapy has to be intensified by a increase of the dosage, anemia and leukocytopenia as well as adverse effects of the drugs are likely to occur. In twelve CML patients we have therefore combined the basic CML treatment with anagrelide. This drug which selectively reduces platelet counts has been shown to be efficacious in the control of thrombocytosis in essential thrombocythemia. The diagnosis had been confirmed in all CML patients by cytogenetic and/or molecular biological analysis. The median age of our group was 58 years. Five were women and seven men. All patients were on treatment with hydroxyurea, some of them had previously received treatment with interferon-alpha (alone or in combination with hydroxyurea), busulfan or melphalan. Prior to the initiation of anagrelide treatment the platelet count was between 970,000 and 3,600, 000/microl (median about 2,000,000/microl). Seven patients had thrombohemorrhagic complications. All twelve patients, experienced hematologic responses, since their platelet counts decreased to less than 600,000/microl. The median platelet count after reduction was 343,000/microl. The median dosage required to achieve these responses and to maintain them for a period of at least four weeks was 1.9 mg/day. Thrombohemorrhagic complications disappeared or did not recur in all symptomatic patients. Adverse effects were seen in 3/12 patients: headache (1), tachycardia (1), palpitation (1) and fluid retention (1). Whereas these symptoms were mild and transitory they caused one patient to request discontinuation of treatment. Currently five patients are still on treatment with anagrelide (median duration of treatment 11 months) while therapy had to be discontinued in the seven others because of bone marrow transplantation, development of osteomyelofibrosis, blast crisis or on patient request. In our experience anagrelide is a useful therapeutic adjunct when thrombocytosis in patients with CML cannot properly controlled alone with traditional drugs.
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PMID:Anagrelide for treatment of patients with chronic myelogenous leukemia and a high platelet count. 951 77

Clinical, morphological and cytogenetic investigations were done in those patients with leukocytosis having become victims of the Chernobyl catastrophe. Of these (n = 10), six patients demonstrated chromosomal abnormalities. In the study made at a later date in six patients with cytogenetic abnormalities, five patients were found to have chronic myeloproliferative disorders, with four cases presenting with chronic myeloid leukemia and one patient having osteomyelofibrosis.
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PMID:[The characteristics of the pre- and leukemic stages of chronic myeloproliferative diseases in persons suffering as a result of the Chernobyl catastrophe]. 1087 66

In chronic myeloproliferative disorders other than CML (CMPD) recurrent cytogenetic abnormalities occur, but specific patterns of chromosomal aberrations in the specific entities have so far not been detected. Thus, the value of conventional cytogenetics in the routine diagnostic setting of CMPD remains to be clarified. We performed a cytogenetic study on 409 patients with different CMPD [polycythemia vera, essential thrombocytosis (ET), idiopathic osteomyelofibrosis, chronic myelomonocytic leukemia (proliferative subtype), idiopathic hypereosinophilic syndrome (HES), myeloproliferative syndrome (unclassifiable)] and on 102 patients with suspected CMPD. Cytogenetic abnormalities occurred in different frequencies ranging from 3 to 40% depending on the subtype, and showed some specific differences with respect to their type. The highest frequency and the most complex pattern of clonal aberrations were observed in idiopathic osteomyelofibrosis. However, clonal aberrations were also found in 10% of patients with suspected CMPD establishing the diagnosis of a malignant disease. In conclusion, cytogenetics are essential in the routine diagnostic setting of CMPD or cases suspicious for CMPD. In ET and in HES the aberration rate was only 3 and 7%, respectively. Thus, cytogenetics can be omitted. However, in some of these cases molecular procedures should be integrated into the routine diagnostic process.
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PMID:Conventional cytogenetics of myeloproliferative diseases other than CML contribute valid information. 1569 38

Donor lymphocyte infusion (DLI) is used to prevent or treat haematological malignancies relapse after allogeneic stem cell transplantation (allo-SCT). Recombinant human granulocyte colony-stimulated factor primed DLI (gDLI) is derived from frozen aliquots of the peripheral blood stem cell collection. We compared the efficacy and safety of gDLI and classical DLI after allo-SCT. We excluded haploidentical allo-SCT. Initial diseases were acute myeloblastic leukaemia (n = 45), myeloma (n = 38), acute lymphoblastic leukaemia (n = 20), non-Hodgkin lymphoma (n = 10), myelodysplasia (n = 8), Hodgkin lymphoma (n = 8), chronic lymphocytic leukaemia (n = 7), chronic myeloid leukaemia (n = 2) and osteomyelofibrosis (n = 1). Indications for DLI were relapse (n = 96) or pre-emptive treatment (n = 43). Sixty-eight patients had classical DLI and 71 had gDLI. The response rate was 38.2%, the 5-year progression-free survival (PFS) rate was 38% (29-48) and the 5-year overall survival (OS) rate was 37% (29-47). Graft versus host disease rate was 46.7% and 10.1% of patients died from toxicity. There were no differences between classical DLI and gDLI in terms of response (p = 0.28), 5-year PFS (p = 0.90), 5-year OS (p. 0.50), GvHD (p = 0.86), treated GvHD (p = 0.81) and cause of mortality (p. 0.14). In conclusion, this study points out no major effectiveness or toxicity of gDLI compared to classical DLI.
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PMID:A Retrospective Comparison of DLI and gDLI for Post-Transplant Treatment. 3266 88


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