Wilms' tumor 1 mutation accumulated during therapy in acute myeloid leukemia: Biological and clinical implications.
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Biomedical subjects
Publications and source records attributed to J Stentoft.
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Imatinib is a potent drug used in treatment of chronic myeloid leukaemia (CML). It acts by inhibition of the CML-specific p210 BCR-ABL tyrosine kinase, but also blocks other pathways such as platelet-derived growth factor (PDGF) and c-kit receptor signalling. Clinical trials have confirmed the efficacy of imatinib, which has toxic effects in cells that express BCR-ABL. Side-effects, although frequent, are generally mild and include superficial oedema and fluid retention. Here, we describe two patients with cerebral oedema, which in one patient was fatal. The pathophysiological mechanisms remain unknown, although the drug could act through inhibition of the PDGF receptor.
We have investigated a single telomere expansion in a case of acute lymphoblastic B-cell leukemia (B-ALL), where half of the cells in the bone marrow sample appeared with a Philadelphia chromosome. Comparing telomere sizes in Philadelphia-positive versus -negative cells, we found generally shorter telomeres in the Philadelphia-positive cells, but with an expansion of the telomere on the long arm of one chromosome 11 homologue. This expansion was also found in a minority of Philadelphia-negative cells. The telomeres in these cells were of the same overall size as the telomeres in the Philadelphia-negative cells without the 11q expansion. Together, these findings suggest that the order of events was: 11q telomere expansion, Philadelphia translocation, overall telomere shortening. The expanded 11q telomere contained the standard telomeric (AGGGTT)(n) repeat, but also variant repeat sequences. The single telomere expansion suggests a non-telomerase mechanism behind the expansion which may also explain the presence of variant repeats in the expanded telomere. The present case illustrates that telomere changes may occur at only some chromosome ends in a subset of cells. To reveal such changes, telomere morphology should be studied with in situ methodology.
We report the outcome of 95 patients older than 60 years with de novo acute non-lymphocytic leukaemia (ANLL), treated in two institutions during a 10 year period. Thirty-two patients, mean age 78 years, did not receive any chemotherapy, and their median survival was 38 days. Five patients in good clinical condition, aged 60-63 years, were treated conventionally with an anthracycline and cytarabine, and three patients obtained a complete remission (CR) lasting 73, 417, and 1050 days. Fifty-eight patients were treated with low-dose cytarabine (LDC) for remission-induction and maintenance. Eighteen patients obtained CR, yielding a remission rate of 31%. The median duration of remission was 380 days and median survival of the same group was 498 days. LDC is valuable in the treatment of ANLL in the elderly. Controlled studies are warranted to define the indications for LDC versus conventional therapy in the large grey zone of elderly patients.
Thirteen patients with de novo acute non-lymphocytic leukaemia (ANLL) refractory to standard chemotherapy for remission induction and 12 patients with ANLL in relapse were treated with low-dose cytosine arabinoside (LD ara-C) 10 mg/m2 subcutaneously every 12 hours for 21 days. Five of 13 patients (38%) and 6 of 12 patients (50%), respectively, obtained a complete remission (CR). Of these, 7 patients subsequently relapsed after 2-76 months, while 4 patients remain in CR after 7-131 months. Compared to standard intensive regimens treatment with LD ara-C was rather non-toxic, requiring platelet transfusions and antibiotics in only 6 and 13 cases, respectively. Three patients (12%) died during induction therapy with LD ara-C; 2 had a cerebral haemorrhage and 1 developed anuria following a staphylococcal septicaemia. In conclusion, therapy with LD ara-C may be preferable to more intensive and toxic regimens in the treatment of patients with relapsed or refractory ANLL.
All-trans retinoic acid (ATRA) was used in a case of acute promyelocytic leukemia (APL) in late pregnancy. A very prompt maternal risk reduction was achieved with subsequent complete remission and spontaneous delivery of two live children in whom no fetal damage seems to have occurred.
All-trans retinoic acid (ATRA) was used in a case of acute promyelocytic leukemia (APL) in late pregnancy. A very prompt maternal risk reduction was achieved with subsequent complete remission and spontaneous delivery of two live children in whom no fetal damage seems to have occurred.
Lupus anticoagulant (LA) and anticardiolipin antibodies (ACA) have been reported to be associated with fetal loss. OBJECTIVE. Our aim was to estimate the incidence of LA and to examine the correlation between LA and ACA in pregnant women. To investigate the clinical significance of LA and ACA in an obstetric population. STUDY DESIGN. A prospective, cross sectional study of 2856 consecutive women admitted to a department of obstetrics and gynecology for delivery or due to pregnancy complications during an 11 month period. METHODS. Activated partial thromboplastin time (APTT) was determined in all patients. LA and ACA were determined if APTT > or = 35 sec. For reference ACA was determined in a group of randomly selected patients with APTT < 35 sec. The results were analyzed in relation to the obstetrical records. RESULTS. Overall incidence of APTT > or = 35 sec.: 7.0%, significantly more frequent in patients with early spontaneous abortion (18.6%) and intrauterine growth retardation (17.5%). Incidence of LA 0.07%. The patients had undetectable ACA and no clinical condition related to LA. Incidence of ACA class IgM (IgM-ACA) in patients with APTT > or = 35: 20.4%, significantly higher than in the reference group (9.6%). Uncomplicated pregnancy in 84% of patients with IgM-ACA. No cases of ACA class IgG (IgG-ACA) in patients with APTT > or = 35 but two cases in the reference group (one normal pregnancy, one spontaneous abortion). CONCLUSION. LA is a rare manifestation with uncertain significance in otherwise healthy pregnant women. IgM-ACA in low titer occurs relatively frequently during normal pregnancy.
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In a 51-year-old man, coronary artery bypass surgery for severe angina pectoris was followed by protracted mediastinal infection. After recovery the patient had several haemoptyses. Angiography revealed aneurysm of a graft near its distal anastomosis. Upper left lobectomy and ligation of the graft were necessitated by bleeding from the aneurysm into a segmental bronchus. Angina pectoris recurred but was successfully treated with verapamil.
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A 26-year-old woman with extra-pulmonary Wegener's granulomatosis was treated with cyclophosphamide for 3.25 years, cumulated dose of 91 g. Six months before cessation of therapy discrete radiological signs of apical fibrosis appeared. The changes were progressive regardless of discontinuation of cyclophosphamide and led to severe restrictive ventilatory defect.
5 heavily pretreated patients with chronic lymphocytic leukaemia or non-Hodgkin lymphoma resistant to alkylating agents were treated with low-dose cytosine arabinoside (ARA-C). 3 of the patients showed a clinical and laboratory improvement lasting from 8 to more than 20 months. Low dose ARA-C may be therapeutically effective in terminal stages of lymphoproliferative disorders.
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The concentration of xanthine and hypoxanthine was measured in 8 portions of SAGM red cell concentrates during 4 wk storage. The concentration of xanthine increased from 4.2 to 35.1 mumol/l and the concentration of hypoxanthine increased from 16.8 to 165.2 mumol/l (mean values). Previous studies have demonstrated several important effects of purine bases--among these a reduced cytotoxicity of purine antimetabolites. It is concluded that further studies are necessary to investigate the clinical role of purines in stored blood products.