104 1.0 0.8 la 0.6 v i v r Su 0.4 0.2 EJ Lee, et al. • Outcome of HSCT for childhood ALL in second CR P=0.014 MSD=68±9.3% MUD=38.5±13.5% MMUD=14.3±9.4% 0 12 24 36 48 60 Time (mo) Fig. 1. Estimated 5-year disease-free survival curves by donor type considering human leukocyte antigen compatibility. MSD, matched sibling donor; MUD, matched unrelated donor (high or low resolution); MMUD, mismatched unrelated donor (high or low resolution). initial WBC count ≥50,000/mm3 more likely to relapse than those with lower counts (P =0.082). However, no one variable had a definite significant impact on rate of relapse, as determined by univariate analysis. All patients with BM relapse, except 2 who were lost to follow-up within 1 year of relapse, died. The patient with isolated testicular relapse underwent localized radiotherapy and chemotherapy and has survived for 89 months post-HSCT at last follow-up. Another 15 patients died during the initial year post-transplantation due to causes other than relapse for a 1-year cumulative TRM incidence of 26.4±6.1%. Although univariate study of prognostic factors for TRM revealed donor type (P =0.002) and HLA compatibility (P =0.022) to be significant variables, none proved to maintain significance on multivariate study. Causes of TRM were as follows: pneumonia and acute respiratory distress syndrome 5, acute GvHD 3, thrombotic microangiopathy 2, pulmonary hemorrhage 2, veno- occlusive disease 1, sepsis 1, and acute renal failure 1. Nearly all non- relapse deaths occurred during the first year post-transplantation, with only 1 patient dying of chronic GvHD beyond this period. 5. Analysis of overall survival The estimated 5-year OS for the entire cohort was 48.3±7%, showing a rate similar to the DFS. Reanalysis according to donor type with consideration of HLA compatibility resulted in the following OS rates: 75±8.9% for MSD, 38.5±13.5% for MUD, and 14.3±9.4% for MMUD. Significant differences were noted when comparing the OS for MSD to that for either MUD (P =0.018) or MMUD (P<0.001). Discussion In this study, we report the outcomes of allogeneic HSCT undertaken in children with ALL in second CR at a single institution during a lengthy period spanning more than 17 years. As far as we know, this is the first such report to derive from a Korean pediatric population. The overall 45.3±6.9% incidence of grade II to IV acute GvHD was considerably higher than reported rates in similar studies6,7). The lack of routinein vivo T cell depletion with the use of ATG in the conditioning regimen for unrelated HSCTs done in the early period of the study may have had a role in increasing acute GvHD incidence. Cumulative incidence of 28.5±6.3% for chronic GvHD was similar to the 22 to 27% reported from large cohort studies comprising both matched sibling and alternative donor HSCTs13,14). Overall, less than half the patients of the cohort survived disease-free. Also of note, the DFS and OS were similar emphasizing once more the extremely poor prognosis once a patient relapsed after HSCT. Excluding patients lost to follow-up, only 1 patient with isolated testicular relapse survived after relapse. In comparison, the DFS of 45.2% for the overall cohort is similar to previous reports based on HSCTs from heterogenous donor types7,15), but is considerably lower than the 67.1% 3-year DFS reported by one study6) which also included patients transplanted in first CR. Sub-analysis according to donor type lends some evidence for this discrepancy; although the estimated DFS of 68% for MSD HSCT was superior or comparable to previous results, the 38.5% DFS for MUD HSCT was much lower6,7). Hence, unlike these reports which conclude on similar results for MSD and alternative donor HSCT, there was at least a trend towards a significant difference when comparing MSD and MUD HSCT (P =0.051). Akin to the survival analyses, the regression modeling revealed that donor type, sibling versus unrelated donor, was the only significant prognostic factor for DFS. As all sibling donors were fully HLA- matched except for 1 donor who showed 1 allele mismatch with a sibling patient, how much of the prognostic significance of a sibling donor pertains to HLA compatibility, and how much is based on the potential benefits of a sibling donor beyond standard HLA typing would require further comparative study of a cohort consisting of MSD and high resolution-typed MUD HSCTs only. Our study also revealed the lack of a survival benefit for patients who underwent HSCT after a lengthy period of first remission compared to those who relapsed early on during treatment. This is an important finding considering that nearly half the patients (45%) in our cohort relapsed after at least 3 years of CR status. Previous studies indicate either a survival advantage for late relapse patients7), or are inconclusive as to whether HSCT improves upon the approximately 50% survival rate based on chemotherapy only16), and our results underscore the impor- tant question of whether patients with late relapse may benefit from HSCT.