Anthracycline drugs and MDR expression in human leukemia.

We investigated the expression of P-glycoprotein (P-gp) in 50 adults with de novo acute myeloid leukemia (AML) at the initial diagnosis in order to further define the relationship between the presence of P-gp on leukemic cells and the efficacy of two different anthracycline drugs, Daunorubicin (DNR) and Idarubicin (IRR), in terms of remission, induction and survival. We found that 30 (60%) of the 50 patients were negative for P-gp expression (group 1) and 20 patients (40%) were positive (group 2) for P-gp expression by MRK16MoAb using a cut of 10% positive cells. Among the 50 patients, 35 (70%) obtained complete remission (CR); depending on P-gp expression the CR rate was 80% for group 1 and 45% for group 2 (p < 0.005). The median duration of overall survival (OS) was 20 months for patients in group 1, compared to 10 months for patients in group 2 (p < 0.005). Regarding the anthracycline used, no difference in CR has been observed in patients of group 1 (75% CTR with DNR versus 90% CR with IDR); on the contrary in group 2 we observed 40% CR with DNR versus 70% CR with IDR (p < 0.005). No significant difference has been achieved in group 1 terms of median duration of overall survival between DNR and IDR regimen; on the contrary the median duration of OS in patients of group 2 treated with IDR regimen was significantly longer than DNR regimen (p < 0.005). These results confirm the prognostic value of P-gp expression in AML at diagnosis and we suggest that Idarubicin could be a valid anthracycline drug for reversing multidrug resistance.

Lymphocyte subsets in patients with idiopathic thrombocytopenic purpura during high-dose gamma globulin therapy.

Peripheral lymphocyte subsets (OKT3+, OKT4+, OKT8+) were studied by monoclonal antibodies in 10 patients with chronic idiopathic thrombocytopenic purpura (ITP), before and after high-dose intravenous gamma globulin therapy at a daily dose of 0.4 g/kg/body weight for 5 consecutive days followed by several boosters every 10-15 days. A stable increase of platelet count was obtained in 5 patients, whereas the other 5 showed a transient improvement of platelet count but then became refractory to the treatment. Phenotypic analysis of T cell subsets showed a decrease of the OKT4+/OKT8+ ratio following therapy, with non change in the percentage of OKT3+ cells. A significant decrease of lymphocyte count and platelet associated IgG was shown in 80% of our patients. These data suggest the possible long term efficacy of repeated iv IgG inchronic ITP patients through a mechanism of specific enhancement of suppressor T cell function.