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The cure rate of pediatric acute lymphoblastic leukemia (ALL) has dramatically improved after the introduction of maintenance therapy. But many Korean patients could not tolerate the planned dose of methotrexate (MTX) and 6-mercaptopurine (MP) from Western protocols. Recently, tailored therapy based on individual pharmacogenetic background is introduced to improve the survival with the reduction of complication. To establish the basis for the tailored therapy, genes associated with MTX and MP metabolism were analyzed in Korean children with ALL. The dose percent to the planned dose of MTX (20 mg/m2) and MP (50 mg/m2) at final maintenance cycle were analyzed with the 7 polymorphism site (MTHFR 677 C>T, MTHFR 1298 A>C, RFC 80 G>A, TYMS enhancer repeat, TPMT 238 G>C, TPMT 460 G>A, TPMT 719 A>G) in 96 ALL patient using TotalPlex PCR method (except TYMS). The median dose percent of MTX and MP of all patients were 57.5% and 49%, respectively. Only 31/96 and 22/96 patients tolerated more than 75% of planned MTX and MP doses, respectively. Variant TPMT was found in 6 patients (one *1/*3B and five *1/*3C). The mean dose percent of MP in patients with variant TPMT (33.2%) was lower than that of others (53.5%), significantly (P=0.04). MTHFR 677, MTHFR 1298, RFC 80, and TYMS enhancer repeat were not associated with the dose percent of MTX. But the dose percent of MTX was correlated with the dose percent of MP significantly (R2=0.64, P=0.00). The 5 year event free survival of all patients was 93.7%. Although 16/96 patients received less than 25% of full MP dose, there was no event in these patients. Dose reduction of MP is recommended for the patients with 3 major variant types of TPMT but many others with wild type could not tolerate the planned dose of MP. Study of novel polymorphism is necessary for the basis of tailored therapy in Korean pediatric ALL patients.

Cord blood transplantation (CBT) is a promising alternative means of allogeneic stem cell transplantation. However, limited cell doses may compromise outcome. To enhance engraftment, CBT has been conducted using two units with promising results. Our preliminary results showed the dominance of one unit which occurred early after CBT (Bone Marrow Transplant. 38:197). However, little is known about the mechanism of engraftment and factors influencing the dominancy. To improve the outcomes, CBT was performed with 2 partially HLA-matched units in pediatric acute leukemia with the analysis of factors that affect the determination of dominancy. The median age and body weight of patients (M:11, F:4) were 13 years (3–17) and 45.0 kg (10.5–62.9), respectively. Patients received various conditioning regimens according to the disease status. The median number of the infused nucleated cells by the sum of 2 units after thawing was 5.28×107/kg (0.72–15.09×107/kg). Engraftment achieved in 14/15 Patients. The median number of days required for ANC of more than 0.5×109 or 1.0×109/l were 18 days (13–31 days) and 21 days (14–34 days), respectively. Spontaneous platelet recovery to more than 20×109/l required a median 50 days (19–93 days). The early engraftment kinetics reveals that dominancy of one of two units determined from the day of engraftment (ANC > 0.5×109/l). The numbers of total nucleated cells, CD34+ cells, CD3+ cells, CFU-GM, order of infusion, and donor-recipient HLA disparities of the UCB units were viewed as factors that potentially influence dominancy. Among them infused CFU-GM per patient body weight was associated with the dominancy (P = 0.017). Interestingly, CFU-GM could not be found from each cord blood units in patient failed engraftment. Multiple factors associated with outcomes of CBT could influence the determination of dominancy, such as those factors that affect the recipient environment (underlying disease, previous treatment, conditioning regimen, use of ATG and the method of GVHD prophylaxis), the characteristics of each UCB unit and HLA disparity. For this reason, the selection of the two units requires consideration of the above factors. However optimal selection guidelines that take into account influencing factors are unavailable. CFU-GM was associated with the dominancy in our preliminary result but this kind of data is hard to get before CBT practically. Introducing the analysis of new parameters such as CFU-GM before freezing could help the selection of optimal cord blood unit and improve the outcomes with the consideration of cost-benefit.