ALBERT

Description: In the connective tissues the two major structural components are collagens and glycosaminoglycans (GAGs). When assessing pathological processes in the extracellular matrix, e.g. fibrosis, attention is primarily directed to the collagens. Hyaluronan (HYA) is a GAG of great interest not only as a tentative marker of early fibrosis but also of importance for the disease process in various malignancies. Acute myeloid leukaemia (AML) is a clonal disorder characterised 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 and 30 healthy individuals. The bone marrow sections were analysed histochemically for HYA and reticulin (type III collagen). The HYA staining was significantly stronger, p=0.003, in the AML patients compared to the healthy controls. Only one patient demonstrated abnormal reticulin staining score, but in the group of 8 patients with antecedent myelodysplastic syndrome (MDS), the reticulin staining score was significantly higher, p=0.003, compared to the patients with de novo AML. There was a significant correlation between the HYA and reticulin staining scores, p=0.005, in the AML patients as was seen in the control group, p=0.0005, indicating that the variables HYA and reticulin are not independent. No correlation was found between HYA grading and lactate dehydrogenase (LDH), number of blast cells, sex, age or antecedent blood disease before AML diagnosis. In the control group there was a significant correlation, p=0.042, between HYA and age. Our findings establish that there is a deposition of HYA in bone marrow in healthy individuals and that HYA is increased in AML patients. It is discussed whether HYA could be an early marker of impending fibrosis and also exert important effects on cellular events in the disease process.

Description: We introduced a risk-adapted treatment program for non-APL AML in four Swedish health regions. The aim was to optimise treatment results by the use of risk group stratification, mainly based on cytogenetic findings at diagnosis. All patients received induction therapy with idarubicin-cytarabine 3+7 and consolidation cycles containing high-dose cytarabine. Stem cell transplantation was done in CR1 in selected patients, sparing patients with low/intermediate risk of relapse the risks associated with transplantation. 279 patients, 77% of all AML patients 18–60 years (median 51 yrs), in the population were included in the program. Cytogenetics was performed in 98%. Excluding APL, 19 patients had low-risk. The intermediate-risk group consisted of 165 patients, 96 with a normal karyotype. 95 patients were allocated to the high-risk group. 6% died 〈 30 days after diagnosis. CR rate was 80%. 111 transplants, 78 allogeneic/URD and 33 autologous, were performed in CR1. 40% of all patients were alive after five years. Median overall survival time was 887 days in low-risk, 611 days in intermediate risk, 345 days in high-risk patients. Relapse-free survival times were also significantly (p

Description: Follicular lymphoma (FL) is characterized by a highly variable clinical course, with survival after diagnosis ranging from less than one year, to more than 20 years. The prognosis for the individual patient is difficult to assess. Sporadic reports have suggested that a high number of T-cells in FL lymph nodes may cause spontaneous regression of the lymphoma. To gain more knowledge of the prognostic importance of T-cells, a flow cytometric analysis of FL biopsy samples was performed. A total of 231 patients diagnosed with FL between 1 January 1994 and 31 December 2003 were identified in the pathology archives at Karolinska University Hospital, Huddinge. 121 of these patients had been diagnosed at the Department of Hematology, and for 87 patients out of the 121, complete data have been found, including clinical data from patient files and complete flow cytometric assays on diagnostic FL lymph nodes. The flow cytometry T- and B-cell markers included CD3, CD4, CD8, CD16/56, CD20, CD19 and CD25. The median age at diagnosis was 58.9 years (range 34.9—87.6 years). The median follow-up after FL diagnosis was 4.3 years (range 0.6—10.5 years). 49.4% of the patients were male. The patients received a variety of standard treatments. Information on disease stage was available for all 87 patients: stage I 15%, stage II 20%, stage III 22% and stage IV 44%. The histopathological diagnoses of the lymph nodes were FL grade 1 or grade 2 in 84% of the cases, and FL grade 3 in 16%. LDH-values were available for 98% of the patients. Median number of lymphocyte T- and NK-cell subsets in the lymph nodes were: CD3+: 29% (range 4—83%), CD4+CD3+: 22% (2—69%), CD8+CD3+: 6% (2—26%), CD25+CD3+: 6% (1—31%) and CD56+ and/or CD16+: 1% (0—2%). The CD4/CD8 ratio had a median of 3.6 (0.7—15). The median number of total B-cells was 69% (15—94%), and the median number of clonal B-cells was 65% (13—94%). Only cells within flow cytometric lymphocyte gate have been counted. For statistical grouping, the patients were divided by median values from the flow cytometry results. Kaplan-Meier analyses of the preliminary data have been performed. Comparison has been made, for each CD, between the group with higher-than-median counts and the group with median-and-lower counts. It seems that patients with a high CD3+ count might have a prolonged overall survival and event-free survival, compared to the patients with low CD3+ numbers. The group with high counts of activated (CD25+) T-cells showed a significantly better overall survival (p