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Leukemia is a type of cancer affecting the blood and bone marrow and causing uncontrolled growth of abnormal white blood cells (WBCs). Treatment with antileukemic chemotherapy (cyclophosphamide, CP) results in several side effects including hepatotoxicity and nephrotoxicity. This study aimed to investigate the therapeutic and synergistic effect of Saussurea costus ethanolic extract (SEE) against induced leukemia in adult male rats. After induction of leukemia via benzene injection, both healthy and leukemic rats were divided into six groups (8 rats each) as follows: 1) healthy control group, 2) healthy rats ingested with SEE (300mg/Kg/day) for 4 weeks, 3) untreated leukemia-modeled rats, 4) leukemic rats treated orally with SEE for 4 weeks, 5) leukemic rats treated intraperitoneally with CP (7.5 mg/kg/48 hr.) for 4 weeks, and 6) leukemic rats treated with SEE in combination with CP for 4 weeks. The obtained results revealed that treatment of leukemic rats with SEE (either alone or combined with CP) efficiently succeeded to ameliorate the leukemic and CP-complication signs; this was evidenced by the significant reduction in WBCs count; also, SEE significantly improved the nephron-hepatic function, this was monitored from the marked decrease in serum ALAT, ASAT, urea, and creatinine values. In addition, hepatic MDA and NO levels were markedly reduced coupled with a valuable raise in hepatic GSH and SOD values. It could be concluded that SEE has antileukemic potential, succeeded to ameliorate the hazardous effects of CP, and enhanced the body tolerance ability against CP giving a promising application in the treatment of leukemia. [ABSTRACT FROM AUTHOR]