Chronic lymphocytic leukemia patients with a V1-69 gene rearrangement do not have inferior survival with respect to patients that express other unmutated V(H) genes.

Recent studies indicate that V(H) gene usage in B-CLL may have prognostic impact independently of V(H) gene mutation status. The V1-69 gene is the most frequently rearranged V(H) gene in B-CLL and is almost always unmutated. We therefore investigated whether patients with a V1-69 gene rearrangement differ in clinical course and outcome with respect to patients expressing other unmutated V(H) genes. We show that V1-69 B-CLLs constitute a uniform group of patients that more often present at advanced clinical stages and require early treatment, but their survival does not differ significantly from patients with other unmutated V(H) genes.

Erythropoietin production in patients with malignant lymphoma.

Lymphomas are a heterogenous group of malignant diseases. 30-50% of patients, even before chemo- and radiotherapy are begun have anemia. The pathogenesis of this anemia is multifactorial and still not completely clear. Newer investigations refer to a causality between the anemia in patients with lymphoma and the inappropriate erythropoietin production for the degree of anemia. Based on this finding, the aim of the study was to evaluate the erythropoietin production in patients with malignant lymphoma in order to define the clinical conditions of Epo deficiency and thereby enable rational use of this expensive drug. 27 patients with malignant lymphoma were examined. The control group consisted of 25 patients with iron deficiency anemia. 14 healthy volunteers represented the so-called "normal" control. The adequacy of Epo production was estimated from the graphic representation of the linear regression between Epo and hemoglobin (Hb) in the control group, as well as from the O/PEpo ratio as a measure of the degree of adequacy of Epo production (O - observed Epo value, P-predicted Epo value from the regression equation of the control group). The erythropoietic activity was estimated from the graphic representation of the linear regression between soluble transferrin receptors (sTfR) and Hb in the control group, as well as from the O/PsTfR ratio, as a measure of the degree of adequacy of erythropoietic activity (O - observed sTfR value, P - predicted sTfR value from the regression equation of the control group). Significant inverse correlation between Epo and Hb was found in patients with malignant lymphoma (r= -0.76, p < 0.001). 33% of patients had inadequate Epo response to anemia. O/PEpo in patients with malignant lymphoma is significantly lower in comparison to the control group, which also points to the inadequacy of erythropoietin production. There was a significant negative correlation between sTfR and Hb in patients with malignant lymphoma (r= -0.056, p < 0.001). Inadequate sTfR response to anemia have 76% of patients. The positive correlation between O/PEpo and O/PsTfR (r=0.79, p < 0.001) points out to a causality between the inadequacy of erythropoietin production and the inadequate erythropoiesis. In conclusion, results from this study show unambiguously that anemia in patients with malignant lymphoma appears because of decreased erythropoiesis as a consequence of bone marrow infiltration with lymphoma cells as well as inadequate Epo production. Most probably, the inadequate Epo production in patients with malignant lymphoma is as that seen in the anemia of chronic diseases whose mechanism is not clear.

[Inadequate erythropoietin production (epo) in patients with multiple myeloma]. / Nesoodvetna produkcija na eritropoetin (Epo) kaj pacienti so multipen mielom.

Anaemia is the most common haematological complication in patients with malignant diseases. It is found in 60%-90% of cases with multiple myeloma. The pathogenesis of this hypoproliferative, normochromic, normocytic anaemia is complex. Results from clinical studies which evaluate the efficacy of recombinant human erythropoietin (rHuEpo) refer to the possibility that patients with multiple myeloma independently of renal function could have Epo deficiency. Based on this finding, the aim of the study was to evaluate the erythropoietin production in patients with multiple myeloma in order to define clinical conditions of Epo deficiency and thereby enable rational use of this expensive drug. 42 patients with multiple myeloma were examined. The control group consisted of 25 patients with iron deficiency anaemia. 14 healthy volunteers represented the so-called "normal" control. The adequacy of Epo production was estimated from the graphic representation of the linear regression between Epo and haemoglobin (Hb) in the control group, as well as from O/PEpo ratio as a measure of the degree of adequacy of Epo production (O -- observed Epo value, P -- predicted Epo value from the regression equation of the control group). The erythropoietic activity was estimated from the graphic representation of the linear regression between soluble transferin receptors (sTfR) and Hb in the control group, as well as from O/PsTfR ratio, as a measure of the degree of adequacy of erythropoietic activity (O -- observed sTfR value, P -- predicted sTfR value from the regression equation of the control group). Significant inverse correlation between Epo and Hb was found in patients with multiple myeloma but preserved renal function, which was not the case in patients with renal insufficiency. 43% of patients without renal insufficiency and 85% of patients with renal insufficiency had inadequate Epo response to anaemia. In both patient groups (with and without renal insufficiency) instead of the expected inverse relationship between Hb and sTfR as in the control group, a positive correlation was found. 76% of patients had inadequate sTfR response to anaemia. There is a positive correlation between O/PEpo and O/PsTfR which is in favour of Epo driven erythropoiesis. O/PEpo and O/PsTfR in patients with multiple myeloma are significantly lower in comparison to the control group, which also points to the inadequacy of erythropoietin production, respectively erythropoietic activity. In conclusion, the results from this study show unambiguously that anaemia in patients with multiple myeloma appears because of decreased erythropoiesis as a consequence of bone marrow infiltration with malignant plasma cells as well as inadequate Epo production. Most probably, there are two forms of inadequate Epo production: one because of the renal insufficiency and the other that found in patients with anaemia of chronic diseases the mechanism of which is not clear.