Oral treatment of acute myeloid leukaemia with etoposide, thioguanine, and idarubicin (ETI) in elderly patients: a prospective randomised comparison with intravenous cytarabine, idarubicin, and thioguanine in the second and third treatment cycle.

A randomised multicentre study was conducted among patients over 65 yr of age with newly diagnosed acute myeloid leukaemia (AML) to compare oral treatment with etoposide 80 mg/m(2) and thioguanine 100 mg/m(2) twice daily on 5 d and idarubicin 15 mg/m(2) on 3 d (ETI) to a mainly i.v. combination of cytarabine 100 mg/m(2) twice daily on 5 d, idarubicin 12 mg/m(2) x 1, and thioguanine (TAI). Ninety-two patients were enrolled. Their median age was 72 yr, range 65-84 yr. Sixty-five patients had de novo AML, 21 AML subsequent to myelodysplastic syndrome, and six treatment-related AML. They received at first a 6-d i.v. treatment with cytarabine and idarubicin. After the first treatment, 68 patients were randomised to receive two cycles of ETI (n = 36) or TAI (n = 32) and thereafter maintenance with mercaptopurine and methotrexate. Of the 92 patients, 52 (57%) achieved remission at some stage. The median survival was 10 months. There were no significant differences between the patients randomised to ETI or TAI in the remission rate (67% vs. 72%), survival (12 months from randomisation in both arms), event-free survival or relapse rate. The patients randomised to receive ETI spent significantly fewer days at hospital during the two randomised cycles (20 vs. 41 d, P = 0.010), and they had fewer days with infusions, shorter neutropenias and thrombocytopenias and fewer and less severe infections. In conclusion, treatment with oral ETI resulted in a similar antileukaemic effect as obtained with mainly i.v. TAI, with less toxicity and reduced need for hospitalisation.

The predictive value of vascular risk factors and gender for the development of thrombotic complications in essential thrombocythemia.

The impact of the cardiovascular risk factors smoking, hypertension, hypercholesterolemia, and diabetes mellitus on the risk of thrombotic complications was evaluated retrospectively in 132 patients with essential thrombocythemia (ET). The median age at diagnosis was 51 years, and the median follow-up time was 65 months. Sixty-three out of 132 patients (48%) had one or more vascular risk factors, whereas 69 patients (52%) had no risk factors. Thirty-two patients were smokers, 27 had hypertension, 21 hypercholesterolemia, and four diabetes mellitus. During the follow-up, 53 patients (40%) had 98 arterial thrombotic events, half of which were disturbances of cerebral circulation. Fifteen patients (11%) experienced 27 venous thrombotic events. The presence of one or more vascular risk factors increased the risk of arterial thrombotic complications. Of the patients, 52% with one or more vascular risk factors and 29% of those without any risk factors had arterial thrombosis (P = 0.01). In multivariate analysis the only independent risk factor was smoking (P = 0.01). Male gender increased the risk of arterial thrombosis significantly. Thirty-six out of 62 men (58%) but only 17 out of 70 women (24%) had an arterial complication (P < 0.001). Smoking had a strong predictive value for the development of arterial complications in women but not in men. Among women 9/15 (60%) of the smokers and 12/82 (15%) of the non-smokers experienced arterial thrombosis (P = 0.002), whereas among men no difference between smokers and non-smokers could be found. According to the present findings, the male gender should be regarded as a risk factor when deciding about the indication for treatment. Smoking should be discouraged especially among women with ET.

Development of erythrocytosis in the course of essential thrombocythemia.

Erythrocytosis is not a feature of essential thrombocythemia (ET); this is the most important difference between ET and polycythemia vera (PV). Transformation of ET to PV has only rarely been described. We have reviewed the blood cell counts of 170 ET patients with a median follow-up of 63 months (range 11-313). Eleven of 170 patients (6.5%) developed erythrocytosis at a median of 29 months (range 12-138) after the diagnosis of ET. According to the present results, the development of erythrocytosis in patients with ET is not a rare phenomenon.

Reverse transcription-polymerase chain reaction in the diagnosis of Helicobacter pylori infection in Finnish children.

BACKGROUND: The purpose of this study was to design a simplified polymerase chain reaction (PCR) technique for the detection of Helicobacter pylori and to compare it with conventional diagnostic methods-culture and histology of gastric biopsy specimens. In addition, the capability of this technique to detect H. pylori in the gastric mucosal biopsies of originally H. pylori-negative children with gastritis or recurrent abdominal pain was investigated. METHODS: Reverse transcriptase polymerase chain reaction (RT-PCR) using polymerase from Thermus thermophilus was applied to detect H. pylori 16S rRNA. Twenty-five children H. pylori-positive by culture and/or histology were used as positive control subjects. Sixteen healthy H. pylori-negative children served as negative control subjects. Biopsy specimens from gastric antrum and corpus from 81 children were examined by RT-PCR. Altogether, 30 had histologic gastritis and 51 had nonspecific abdominal pain only, with no disease in histologic specimens. Histology and culture of H. pylori were negative in both patient groups. RESULTS: Reverse transcription-polymerase chain reaction detected 24 of 25 tissue-positive and 0 of 16 tissue-negative cases, indicating 96% sensitivity and 100% specificity for the test. None of the culturally and histologically H. pylori-negative samples showed H. pylori colonization when analyzed by RT-PCR. CONCLUSIONS: RT-PCR using Thermus thermophilus polymerase is a fast and simple means of detecting H. pylori in gastric biopsy specimens. It is at least as specific and sensitive as conventional methods. In pediatric patients it may be necessary to take more than two biopsy specimens to increase sensitivity in cases of local or patchy colonization.

Essential thrombocythemia at diagnosis: causes of diagnostic evaluation and presence of positive diagnostic findings.

The reasons for diagnostic evaluation and the clinical and laboratory data at diagnosis of 170 patients with essential thrombocythemia (ET) were studied retrospectively. The age distribution was 19-88 years (median 52 years), and 52 patients were under the age of 45 years. In 111 patients (65%) thrombocytosis was a chance finding, but the past history of 37 of these patients revealed symptoms known to be related to ET. The diagnosis was based on a chance finding in a significantly higher proportion of female (74%) than male (53%) patients. The diagnosis of ET is based mostly on negative findings, i.e., on the exclusion of other causes of thrombocytosis, and positive diagnostic tests would be useful. We evaluated the presence of positive diagnostic findings of myeloproliferative disorders in ET. Splenomegaly was seen in 26% and an abnormal karyotype in 5% of the patients. Abnormal megakaryocyte morphology was seen in 80%, abnormal in vitro growth of hematopoietic progenitors in 74%, and abnormal platelet function in 83% of the patients. Both in vitro cultures of hematopoietic progenitors and platelet functions were studied in 36 patients, and in only two of these were both tests normal. We conclude that in most patients with ET the diagnosis can be strongly supported by positive findings, especially by in vitro cultures of hematopoietic progenitors and studies of platelet function.

Intensive chemotherapy of poor prognosis myelodysplastic syndromes (MDS) and acute myeloid leukemia following MDS with idarubicin and cytarabine.

Forty patients with high risk myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) preceded by MDS were treated with intensive induction and consolidation chemotherapy in a prospective multicenter pilot study. They were given two cycles of cytarabine 100 mg/m with 12-h intervals on days 1-7 and idarubicin 12 mg/m2 on days 5-7, both intravenously. Patients who were in remission after these two cycles were given two further cycles of cytarabine on days 1-5 and idarubicin on day 5. No maintenance treatment was given. Eleven out of 19 MDS patients (58%) and 10 out of 21 AML patients (48%), in total 21 out of 40 patients (53%), entered remission. Eight patients underwent allogeneic bone marrow transplantation. The follow-up time was 13-48 (median 33) months. At the time of the analysis, seven patients survived, four patients with MDS all of whom had been treated with bone marrow transplantation (three in continuous remission), and three patients with AML treated with chemotherapy only (two in continuous remission). The median survival of the patients treated with chemotherapy only was 12 months, with the median progression-free survival being 8 months. In view of the poor prognostic factors of the patients, the remission rate was satisfactory, but the responses as well as the survival were short. The post-remission treatment needs to be improved.

Tolerability and kinetics of a solvent-detergent-treated intravenous immunoglobulin preparation in hypogammaglobulinaemia patients.

The tolerability and kinetics of a solvent-detergent-treated 6% intravenous immunoglobulin (IVIG) preparation were studied in 15 hypogammaglobulinaemia patients during 3-4 regular substitution infusions of 9-48 g, the mean dose being 359 mg/kg. The infusions were well tolerated, and the trough serum IgG levels achieved were comparable to two commercial IVIG preparations. The stepwise increase of the infusion rate up to 5 mg/kg/min and the use of this IVIG as a 12% solution were possible without serious adverse events in all the 6 studied hypogammaglobulinaemia patients. This greatly reduced the time needed for the infusions.

Leukocyte-depleted blood components prevent platelet refractoriness in patients with acute myeloid leukemia.

Platelet refractoriness arising from HLA immunization develops in 20-50% of multitransfused patients with hematologic malignancies. We retrospectively analyzed the efficiency of leukocyte-depleted blood components in preventing refractoriness in 140 adult patients with acute myeloid leukemia (AML), treated according to a standardized cytostatic protocol. Sixty-eight patients received leukocyte-depleted (L-D) platelet concentrates (PCs) and red cells (RBCs), with fewer than 10(6) leukocytes per unit, and 72 patients received standard (STD) blood components. Two of 67 (3%) evaluable patients in the leukocyte-depleted group and 14 of 68 (21%) in the standard group became refractory during the median follow-up time of 229 days. Nine of 24 (37%) previously pregnant women in the STD group but none of 17 in the L-D group became refractory. Twenty patients were shifted during later treatment from L-D to STD PCs; none became refractory. Corrected platelet increments (CI) at 18 hours were higher after STD PCs (6.50 than L-D PCs (5.2), but more PCs and RBCs were transfused per patient in the STD group. It is concluded that effective leukocyte depletion prevents platelet refractoriness in patients with AML, even in those with previous immunization, and reduces the consumption of blood components.

Adverse reactions to platelet transfusions are reduced by use of platelet concentrates derived from buffy coat.

We closely observed 86 transfusions to multitransfused hematologic patients with leukocyte-depleted platelet concentrates (PCs) prepared from buffy coats (BC PCs), filtered either prior to storage (BC1) or after 3-4 days' storage (BC3). The patients were first given, randomly, either BC1 or BC3, and were thereafter used as their own controls by giving them the two BC types alternately. The results were compared with an earlier study on standard platelet-rich plasma (PRP) PCs (46 transfusions to 23 patients) and leukocyte-depleted PRP PCs (23 transfusions to 12 patients). There was no difference in adverse reactions between BC1 and BC3 PCs, but BC PCs caused significantly fewer and milder adverse reactions than PRP PCs. Febrile reactions (FTR) occurred in 4.6%, urticarial skin reactions in 21%, and pulmonary reactions in 0% of BC PC transfusions (17, 29 and 0% of patients). The mean corrected increments (CI) at 16-18 h were higher after BC1 PCs than BC3 PCs (10.3 vs. 8.0, p = 0.046). We conclude that adverse reactions are reduced by use of BC PCs. Prestorage leukocyte depletion may improve platelet increments.

Hepatitis C antibodies in dialysis patients and patients with leukaemia.

The prevalence of hepatitis C antibodies (anti-HCV) among multitransfused patients was studied and compared with predicted values obtained from a post-transfusion hepatitis study and from data on the prevalence of anti-HCV among blood donors. The prevalence of hepatitis B core antibodies (anti-HBc) was also studied to determine the routes of transmission of hepatitis C virus. The patients consisted of 65 dialysis patients (57 on haemodialysis and 8 on continuous ambulatory peritoneal dialysis) and 71 leukaemia patients in long-term remission [49 with acute myeloid leukaemia (AML) and 22 with acute lymphatic leukaemia (ALL)]. The presence of anti-HCV was investigated using a second generation enzyme-linked immunosorbent assay. Reactive samples were confirmed by a second generation recombinant immunoblot assay. Anti-HBc was studied in the 65 dialysis patients and in 40 of the leukaemia patients. Three (4.6%) of the 65 dialysis patients and 12 (24.5%) of the 49 AML patients were anti-HCV positive whereas all of the ALL patients were seronegative. The total number of blood units transfused to 134 patients (data on two dialysis patients were not available) was 18,148, out of which 17,575 units had been transfused prior to the initiation of anti-HCV screening of blood donors. On the basis of the anti-HCV prevalence among blood donors and the incidence of post-transfusion hepatitis, the predicted number of seropositive patients was 11 and 18, respectively. Five of the 65 dialysis patients were anti-HBc positive, compared with only one of the 40 leukaemia patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Impact of leucocyte-depleted blood components on the haematological recovery and prognosis of patients with acute myeloid leukaemia. Finnish Leukemia Group.

Use of leucocyte-depleted blood components reduces refractoriness to platelet transfusions, but the cost-effectiveness of this policy has been in doubt. We retrospectively analysed data of 115 patients with acute myeloid leukaemia (AML), treated according to a standardized cytostatic protocol. Fifty patients had received standard (STD) platelet concentrates (PCs) and red blood cell concentrates (RBCs). Sixty-five patients had received leucocyte-depleted (L-D) components, with fewer than one million leucocytes per unit. Refractory patients (22% of the STD group and 3% of the L-D group) were excluded from further observations. There were no differences between the groups during the first cytostatic treatment period. Thereafter, significantly fewer PCs and RBCs were transfused to the L-D group. In the L-D group, granulocytopenia (< 0.5 x 10(9)/l) and thrombocytopenia (< 50 x 10(9)/l) were shorter, the lowest leucocyte counts were higher, serious infections were less common (44% v 59%), and the patients spent fewer days in hospital. The median relapse-free survival (RFS) was longer in the L-D group than in the STD group. We conclude that leucocyte depletion of blood components has favourable effects on the recovery of haematopoiesis, consumption of blood components, occurrence of serious infections, and relapse-free survival in AML.

Megakaryocyte and erythroid colony formation in essential thrombocythaemia and reactive thrombocytosis: diagnostic value and correlation to complications.

Megakaryocyte and erythroid colony formation in vitro by progenitors from the bone marrow and/or blood was studied in 61 patients with essential thrombocythaemia (ET) and 22 patients with reactive thrombocytosis (RT) using the methyl cellulose assay. 47 (77%) of the patients with ET showed megakaryocyte and/or erythroid spontaneous colony formation while 14 (23%) patients did not have any kind of spontaneous colonies. Spontaneous megakaryocyte colony formation was seen in 42 (69%) of the patients and 36 (59%) ET patients showed spontaneous erythroid growth. 31 patients had both types of spontaneous colonies. 11 patients showed only spontaneous megakaryocyte colony formation, and five patients only spontaneous erythroid growth. None of the patients with RT or of the normal controls showed either type of spontaneous growth. Neither the presence of spontaneous megakaryocyte colony formation nor the number of spontaneous colonies correlated with the platelet count. Patients with spontaneous megakaryocyte growth had significantly more often thromboembolic or haemorrhagic problems than those without spontaneous colony formation. In conclusion, it was found that a great majority of patients with ET but none of those with RT grow spontaneous megakaryocyte and/or erythroid colonies. Spontaneous colony formation is strong evidence for a myeloproliferative disorder. The presence of spontaneous colony growth is associated with an increased risk of thromboembolic or haemorrhagic complications regardless of the platelet count, particularly among young patients.

Prevention of alloimmunization in patients with acute leukemia by use of white cell-reduced blood components--a randomized trial.

Platelet refractoriness arising from HLA alloimmunization is a serious complication of transfusion therapy. In a prospective randomized trial, white cell (WBC)-reduced blood components were compared to standard platelet and red cell concentrates with respect to alloimmunization, refractoriness, and platelet increments after transfusion. Sixteen of 31 adult acute leukemia patients received only WBC-reduced platelet concentrates (PCs) and red cells (RBCs), with fewer than 10(6) WBCs per unit. Fifteen control patients received standard blood components with a mean of 0.1 x 10(9) (PCs) and 1 x 10(9) (RBCs) WBCs per unit. Platelet loss during cotton-wool filtration averaged 14 percent (range, 3-32%) from fresh PCs and 24 percent (range, 9-62%) from stored PCs. Filtration did not change corrected increments (CI) measured after transfusion of fresh PCs. The Cl 1 hour after filtration of stored PCs diminished by 27 percent, but the difference was smaller after 18 hours, which suggests better survival of WBC-reduced platelets. The number of platelet units transfused did not differ in the two groups. No patient in the WBC-reduced group developed permanent platelet refractoriness; transient HLA antibodies of low titer developed in two patients. In the control group, one patient became refractory because of immunization and two developed transient HLA antibodies. It can be concluded that the reduction of WBCs in blood components can effectively prevent alloimmunization.

Chest radiography and computed tomography in the evaluation of mediastinal adenopathy in lymphoma.

Thoracic computed tomography (CT) in 232 patients with either primary staging of new or suggested relapsing lymphoma was compared with conventional chest radiography and both were correlated with clinical staging. Particular attention was given to the possibility of reducing routine thoracic CT, which is the current method used in this hospital in all patients with suggested lymphoma. Mediastinal lymphoma was detected by CT in 95 per cent of patients with clinically active mediastinal lymphoma, and by conventional chest radiography in 56 per cent. CT was found to be less reliable in evaluation of the hilar region than in that of other mediastinal areas. No areas of particular difficulty were found with chest radiography. CT also provided additional information concerning extra-mediastinal lymph adenopathy and involvement of the thoracic wall and pericardium. Routine thoracic CT examination was considered justifiable in all patients with suggested lymphoma.

Primary infection with HIV in a severely immunosuppressed patient with acute leukemia.

A 47-year-old female with acute myeloid leukemia received HIV positive platelets during induction chemotherapy. 18 days later, coincident with the recovery of the bone marrow function, she developed an erythematous rash, mild lymphadenopathy, and nausea which disappeared within 10 days. A week later mild CSF pleocytosis consisting of mature lymphocytes and macrophages together with elevated CSF protein levels (1,080 mg/l) were observed suggesting mild aseptic meningitis, and the HIV was concomitantly isolated from CSF. The CSF abnormalities have improved and the patient is well and in remission after 3 cycles of chemotherapy. This case expands the clinical spectrum of HIV infection to include a primary syndrome during immunosuppression from an unrelated cause.

The pharmacokinetics of disopyramide in patients with acute myocardial infarction.

The effects of acute myocardial infarction on the pharmacokinetics of disopyramide were studied. Disopyramide (200 mg) was given orally to nine patients with left-sided cardiac failure due to acute myocardial infarction within 24 h after the onset (phase I). In seven patients the study was repeated 7-14 days later at discharge from the hospital (phase II). Serum concentrations and the 24-h area under the serum concentration-time curve of disopyramide were significantly lower during phase I than during phase II (p less than 0.05 and p less than 0.001, respectively). The peak serum concentrations and the 24-h area under the pulmonary capillary wedge pressure (less than 0.05) in phase I. Rates of absorption and elimination of disopyramide were similar during both phases. Renal clearance of disopyramide showed concentrations and the decrease of 24-h area under the serum concentration-time curve are most probably due to decreased gastrointestinal absorption and are related to the degree of left ventricular failure. Thus, the dosage of oral disopyramide obviously needs to be increased in these patients to achieve therapeutic concentrations in the acute phase.