Expression of the signal transduction molecule zeta in peripheral and tumour-associated lymphocytes in Hodgkin's disease in relation to the Epstein-Barr virus status of the tumour cells.

We investigated whether the described immune evasion of Epstein-Barr virus (EBV)-infected malignant Hodgkin and Reed-Sternberg (HRS) cells in Hodgkin's disease (HD) is paralleled by a disturbed expression of the signal transduction molecule zeta associated with CD3 and CD16 in tumour-associated T lymphocytes (TAL). Flow cytometric analysis revealed a significantly lower zeta expression in CD3+/4+, CD3+/8+ and CD16+ patient peripheral blood lymphocytes (PBL; n = 10) compared with normal donor PBLs (n = 11). When patient PBLs were compared with the corresponding TAL, the latter showed a significantly higher (CD3+/4+) or equal (CD3+/8+) zeta expression. The EBV status of the tumours did not correlate with zeta expression in the TAL. Immunohistochemical staining revealed zeta-positive lymphocytes among the adjacent bystander cells of the HRS cells in all analysed tumours (n = 8), irrespective of tumour EBV status. In conclusion, these results do not support downregulation of zeta in TAL as a critical mechanism contributing specifically to the immune escape of EBV+ HRS cells.

A validated decision model for treating the anaemia of myelodysplastic syndromes with erythropoietin + granulocyte colony-stimulating factor: significant effects on quality of life.

We have published previously a prototype of a decision model for anaemic patients with myelodysplastic syndromes (MDS), in which transfusion need and serum erythropoietin (S-Epo) were used to define three groups with different probabilities of erythroid response to treatment with granulocyte colony-stimulating factor (G-CSF) + Epo. S-Epo 500 U/l and >/= 2 units/month for a poor response, whereas the presence of only one negative prognostic marker predicted an intermediate response. A total of 53 patients from a prospective study were included in our evaluation sample. Patients with good or intermediate probability of response were treated with G-CSF + Epo. The overall response rate was 42% with 28.3% achieving a complete and 13.2% a partial response to treatment. The response rates were 61% and 14% in the good and intermediate predictive groups respectively. The model retained a significant predictive value in the evaluation sample (P < 0.001). Median duration of response was 23 months. Scores for global health and quality of life (QOL) were significantly lower in MDS patients than in a reference population, and fatigue and dyspnoea was significantly more prominent. Global QOL improved in patients responding to treatment (P = 0.01). The validated decision model defined a subgroup of patients with a response rate of 61% (95% confidence interval 48-74%) to treatment with G-CSF + Epo. The majority of these patients have shown complete and durable responses.