Treatment of relapsed acute promyelocytic leukemia by arsenic trioxide in Iran

Although standard first line treatment of acute promyelocytic leukemia is All trans retinoic acid [ATRA] and chemotherapy, some patients relapse and need a second line of treatment. Relapsed cases of promyelocytic leukemia can be salvaged with arsenic trioxide. Between May 1999 and Jan. 2010, we treated 31 relapsed cases of promyelocytic leukemia with arsenic trioxide. These cases relapsed after previous treatment with ATRA and chemotherapy. We applied arsenic trioxide as 0.15 mg/kg iv infusion until complete remission. After achieving complete remission patients received 2-4 consolidation therapy in the same schedule as remission induction. The median age of patients was 27 years. Complete remission rate was 77.4%. We observed four mortalities during remission induction. With a median follow up of 32 months, ten more relapses occurred. Two year disease-free survival and overall survival for the entire cohort was 54.6% and 81.1%, respectively. Our result is the same as other studies. Thus, we suggest that arsenic trioxide can be used as salvage therapy in patients who relapsed. Despite a good complete remission rate, the relapse rate during the first two years of treatment is high and hematopoietic stem cell transplantation should be considered after achieving complete remission

Establishment of a doxorubicin-Resistant subline from acute myeloid leukemia cell line

In order to determine the multidrug resistance [MDR] phenotype due to P-glycoprotein expression in haematological malignancies including acute myeloblastic leukemia [AML], a well-characterized P-gp expressing cell line was required to validate and standardize flow cytometric assays and to calibrate instruments. Therefore, this resistant subline of K562 was established for the first time in Iran in order to study the MDR phenotype due to P-gp expression in some cancers. A resistant subline of K562 [KDI/20] to Doxorubicin from the same parental K562 was derived by stepwise increasing the concentration of Doxorubicin up to 20 ng/ml as a gold standard. For flow cytometric assessment of P-gp expression, 4E3 anti-P-gp was used. The resistant cell line was studied by rhodamine 123 for functional assay of P-gp. MDR1 gene expression was also confirmed using RT-PCR. P-glycoprotein was expressed in final concentration of 20 ng/ml of Doxorubicin on 70% of K562 cells after 120 passages. The Rhodamine 123 influx was 37%. The over-expression of MDR1 gene was observed in a 30-cycle PCR. P-glycoprotein is expressed in human K562 cell line [K562] by continuous exposure to anticancer drug. P-glycoprotein expression is detected by several methods including flow cytometry and RT-PCR, and the number of PCR cycles is very important