Immobilized forms of daunorubicin in patients with acute leukemia

AIM: To study pharmacokinetics of liposomal daunorubicine DaunoXome and daunorubicine (rubomycin) associated with red cells: to assess their effectiveness and toxicity in patients with acute leukemia. MATERIALS AND METHODS: 7 patients with resistant or recurrent acute leukemia entered the trial. Of them 2 patients had acute myeloid leukemia. They received DaunoXome in dose 100 mg in days 1, 2 and 3 of 7 + 3 program. 1 patient had pretreated acute promyelocytic leukemia. This patient received 5-day course of DaunoXome in a dose 100 mg in the presence of ATRA therapy. 4 patients were given single dose daunorubicin associated with autoerythrocytes in the courses RACOP and 7 + 3 in a dose 45 mg/m2. Concentrations of free, bound and liposomal daunorubicin were determined spectrofluorimetrically in chlorophorm extracts of plasm, blood, liquor and bone marrow specimens. RESULTS: Immobilization of daunorubicin on the red cells and liposomes changes pharmacokinetics of the drug: peak concentrations change and the area under the concentration curve increases. Tolerance of DaunoXome and daunorubicine associated with red cells was satisfactory in all the cases: clinical and echo-CG signs of cordiotoxicity were absent, myelotoxicity was similar to that of free daunorubicine. DaunoXome was effective in 2 of 3 patients with acute myeloblastic leukemia. CONCLUSION: The findings are of practical interest for physicians designing new programs of therapy of acute leukemia.     

Efficacy and safety of transfusion therapy in hematological patients

AIM: To determine whether probability of hepatitis B and C virus (HBV/HCV) infection of hematological patients depends on intensity of hemotransfusion therapy and to propose possible ways to diminish posttransfusion risk of virus infection with HBV/HCV. MATERIAL AND METHODS; A clinicoepidemiological prospective trial was made to monitor risk factors and indicators of HBV and HCV infection in 216 patients of a hematological department of the Hematological Research Center. A total of 447 hospitalizations (229 rehospitalizations among them) to the department of chemotherapy, depression of hemopoiesis and bone marrow transplantation for 2 years were analysed. Statistics were analysed using SAS computer programs and the "landmark method". RESULTS: Transfusions of blood components before initiation of the trial were performed in 201 (93%) patients, 120 (60%) patients received more than one transfusion (median of the number of donors was 40). Markers of virus hepatitis were initially detected 1 month after hospitalization in 103 (47.7%) patients: HCV--in 26 (12%), HBV--in 77 (35.6%); 18 (17.5%) patients were coinfected (HBV/ HCV). Probability of detection of HBV and HCV markers in patients with multiple transfusions was significantly higher than in patients with a short transfusion history (50% probability of HBV and HCV infection was 153 and 251 days, respectively, p = 0.059). CONCLUSION: Reduction of aftertreatment lethality and, finally, treatment efficacy in hematological patients depends on adequacy of replacement therapy with blood components, platelets first of all. High percentage of HBV and HCV infection confirms dependence of infection probability on the number of donors. Thus, patients with planned massive replacement therapy should be provided with specially selected donors. Blood for transfusion for them should be examined for viruses repeatedly.