Gunnel Sundström

Intestinal permeability in patients with acute myeloid leukemia

Intestinal permeability was studied in patients with acute myeloid leukemia (AML) before, during and after chemotherapy. Intestinal permeability was determined by the lactulose (La)/mannitol (Ma) absorption test in 16 adult patients with de novo AML. The hydrogen breath test was used to disclose bacterial fermentation of the test substances in the small intestine. The permeability was found significantly increased (p<0.02) in the patients before induction chemotherapy treatment. During induction treatment and throughout the cytopenic period the intestinal permeability was constantly and significantly increased, compared with controls. In patients with abnormally increased permeability, no increase in hydrogen breath test result was noted. From our results it can be concluded that increased intestinal permeability is present in AML patients before commencing chemotherapy. Factors other than chemotherapy would seem to be more important regarding the occurrence of intestinal disturbances in these patients.

Stroke in the Elderly

Clinical decision making is often difficult in very old stroke patients, partly because there is little systematic information on clinical course and outcome available. In a population-based sample of

Oral cladribine for B‐cell chronic lymphocytic leukaemia: report of a phase II trial with a 3‐d, 3‐weekly schedule in untreated and pretreated patients, and a long‐term follow‐up of 126 previously untreated patients

Summary.  A phase II study was undertaken to evaluate the efficacy and toxicity of a new schedule of cladribine administration (10 mg/m2 orally daily for 3 d every 3 weeks) in 107 patients with B‐cell chronic lymphocytic leukaemia (CLL). To minimize toxicity, treatment withdrawal criteria were defined. The results of the 63 previously untreated patients were retrospectively compared with 63 from an earlier study using a 5‐d monthly schedule. The compiled data were analysed for prognostic factors for survival. No significant difference regarding response were seen in the two cohorts of the 126 previously untreated patients. The complete response (CR), nodular partial response (nPR) and partial response (PR) rates were 15%, 21% and 41%. Quality of response had no impact on survival. The 3‐ and 5‐year overall survival for previously untreated patients was 73% and 58%, respectively, with a median follow‐up of 54 months. Pretreatment haemoglobin < 11·0 g/dl and elevated beta‐2‐microglobulin had a negative influence on survival. Major infections occurred in 21% of patients in the 3‐d study compared with 35% in the 5‐d study. The overall response (OR) and CR rates in the 40 previously treated patients were 34% and 5% respectively. Median overall survival was 24 months and median progression‐free survival for responding patients was 14 months. Cladribine used as a single agent is an effective treatment with an acceptable safety profile for pretreated and untreated B‐CLL. The achievement of complete remission was not a prerequisite for long‐term survival.

Progression of Bone Marrow Fibrosis in Patients with Essential Thrombocythemia and Polycythemia Vera During Anagrelide Treatment

Anagrelide is a second-line option for reduction of thrombocythemia in patients with chronic myeloproliferative disorders (CMPDs). A multicenter, open, phase II study of anagrelide treatment in 60 patients during 2 yr was performed by the Swedish Myeloproliferative Disorder Study Group. Adequate bone marrow biopsies were obtained from 53 of the CMPD patients [36 essential thrombocythemia (ET), 16 polycythemia vera (PV), 1 chronic idiopathic myelofibrosis (CIMF)] before treatment and compared with biopsies from 30 healthy volunteers and 34 patients with acute myeloid leukemia (AML). Higher reticulin and hyaluronan (HYA) scores were found before anagrelide therapy in the CMPD patients than in the normal controls (p<0.001 and p<0.001, respectively) and AML patients (p<0.001 and p=0.011, respectively). At the end of the study 30 CMPD patients were still on anagrelide treatment and in 19 of these patients, all diagnosed as ET (n=16) or PV (n=3), pretreatment bone marrow biopsies were compared with follow-up samples. After 2 yr of anagrelide therapy the reticulin and HYA scores were significantly higher than before treatment (p=0.02 and p=0.002, respectively). The cellularity was significantly higher (p=0.014), although the number of megakaryocytes did not change significantly. The increase of reticulin and HYA in the bone marrow after 2 yr of treatment with anagrelide indicated progression of fibrosis. Although anagrelide is a valuable drug for reduction of platelet levels, it seems unable to stop progression of bone marrow fibrosis and hypercellularity in ET and PV.

Localisation and distribution of hyaluronan in normal bone marrow matrix: a novel method to evaluate impending fibrosis?

Abstract: Bone marrow trephine biopsies from 30 healthy volunteers, 10 men and 20 women aged 18–60 yr were obtained for identification and localisation of hyaluronan (HYA). Fixation, decalcification and embedding were performed by two different methods, with identical results in both. For comparison bone marrow trephine biopsies from three patients with different haematological diseases and known fibrosis were studied. All bone marrow specimens were also stained for reticulin grading. HYA was found in the bone marrow specimens from healthy individuals in a pattern that was concordant with the reticulin staining, the common way of visualising bone marrow fibrosis. In bone marrow from the patients with known fibrosis the HYA and reticulin staining were both more intense and abundant. Interestingly, HYA was also found intracellularly in eosinophilic cells in normal bone marrow. HYA is a polysaccharide unique both in structural and biological properties, and in excess it may predict bone marrow fibrosis.

Bone marrow hyaluronan distribution in patients with acute myeloid leukemia.

Acute myeloid leukemia (AML) is a clonal disorder characterized by abnormal proliferation of myeloid cell precursors. Research has mainly focused on the cellular events, but the bone marrow matrix has attracted minor interest. In this study bone marrow biopsies were obtained from 35 newly diagnosed AML patients. The bone marrows were analyzed regarding the occurrence and distribution of hyaluronan (HYA) and reticulin fibers (type III collagen). The bone marrow sections were analyzed histochemically and compared with bone marrows from 30 healthy controls. The HYA staining was significantly stronger in the AML patients compared with the controls. Only one patient demonstrated abnormal reticulin staining score, but in the group of patients with antecedent myelodysplastic syndrome (MDS), the reticulin staining score was significantly higher compared with the patients with de novo AML. There was a significant correlation between the HYA staining and reticulin staining scores in the AML patients as was seen in the control group.

Comparison of Efficacies of Ondansetron and Dixyrazine for Prophylaxis of Emesis During Induction Treatment in Acute Myelogenous Leukemia: A Pilot Study

Nausea and vomiting are common and among the most distressing adverse effects of cytotoxic drugs (1). The mechanisms mediating nausea and vomiting are complex and not completely understood. Control of emesis and nausea is essential for improving the quality of life for patients with acute leukemia who are treated with highly to moderately emetogenic drugs. Tranquillizing or anxiolytic drugs such as dixyrazine and lorazepam have been used for many years for prevention of nausea and vomiting caused by cancer chemotherapy or general anaestesia (2-4).

Bone marrow hyaluronan and reticulin in patients with malignant disorders

Myelofibrosis is commonly seen in patients with chronic myeloproliferative diseases and sometimes in myelodysplastic syndrome, acute leukaemia and lymphoproliferative diseases. The fibrotic process is evaluated by grading the amount of collagen deposited in the bone marrow interstitium. The established method to evaluate bone marrow fibrosis is staining for reticulin to visualise the collagen fibres. However, the extra cellular matrix does not only contain collagens but also other components, e.g. glycosaminoglycans of which hyaluronan is the most abundant. Hyaluronan is important for structural and cellular functions. Earlier studies have shown that there is a positive correlation between hyaluronan and reticulin staining in healthy volunteers and in patients with de novo acute myeloid leukaemia. In this study bone marrow biopsies from 43 patients with a malignant disease involving the bone marrow were compared with 18 patients with a malignant disease not involving the bone marrow. The intensity of hyaluronan grading was significantly higher in the patients with disease involving the bone marrow compared to the healthy controls but not compared to the patients without disease involving the bone marrow. The staining intensity of reticulin in the bone marrow was significantly higher in the patients with disease involving the bone marrow, compared to those without disease involving the bone marrow and to the controls. In all patients and the controls there was a correlation between hyaluronan and reticulin.