Significance of Multidrug Resistance (MDR) Activity in Remission Induction & Survival of Acute Myeloid Leukemia

Kim, Ho Young; Lee, Mark H; Kim, Jung Han; Lee, Se Hoon; Park, Jinny; Kim, Kihyun; Park, Qu Ehn; Kim, Won Seog; Jung, Chul Won; Park, Keunchil

Abstract

BACKGROUND
The significant improvement in the treatment of adults with acute myeloid leukemia (AML) has been achieved in recent years. However, many patients still fail to achieve a complete remission and long term survival because of either toxic death during aplasia periods of induction chemotherapy or resistance to induction chemotherapy. The P-glycoprotein (Pgp) associated with Multidrug Resisitance (MDR) gene is the best characterized mechanism of resistance to induction chemotherapy. In this study, the authors effort to examine the functional activity of Pgp using the rhodamine123 functional efflux assay and discuss for the predictive value of MDR functional assay for treatment outcomes of AML.
METHODS
Between January 1996 and June 2003, 45 patients with AML were enrolled in this study. For evaluation of functional MDR activity using the rhodamine123 functional efflux assay, mononuclear cells isolated from bone marrow aspirates of 45 patients were used. All patients were received induction chemotherapy and consolidation therapy with high dose chemotherapy or stem cell transplantation.
RESULTS
Among the 45 AML patients, 30 (66.7%) patients showed positive functional MDR activity and 15 (33.3%) patients negative functional MDR activity. Complete remission rate was lower in the group with positive functional MDR activity than negative, but no statistical significance was observed (P=0.453). Survival time in both groups was investigated. Leukemia free survival was 40.9 months in negative group and 18.7 months in positive group (P=0.336). Overall survival was 48.5 months and 26.6 months respectively (P=0.513).
CONCLUSION
The functional MDR activity using the rhodamine123 functional efflux assay does not significantly affect induction rate and survival rate of AML patients.