To assess the applicability of the National Institutes of Health (NIH) consensus criteria (NCC) for chronic graft-versus-host disease (cGVHD), 211 patients who developed GVHD more than 100 days after allogeneic transplantation were reclassified using NCC. Classifications were: late acute GVHD (44 patients, 21%), overlap syndrome (64 patients, 30%) and classic cGVHD (103 patients, 49%). Classic cGVHD and overlap syndrome patients (n ¼ 167) were graded using both the revised Seattle criteria (RSC) and NIH global scoring (NGS). Twenty-three patients (14%) had mild, 81 (48%) had moderate and 63 (38%) had severe cGVHD. After a median follow-up of 46 months (range 5-71 months), the 4-year GVHD-specific survival was not significantly different among the different subtypes of NCC. Among patients with late acute GVHD, however, the pattern of acute GVHD onset (late, persistent or recurrent) was significantly different with respect to GVHD-specific survival. Among patients with overlap syndrome and classic cGVHD, multivariate analysis showed that NGS as well as RSC were useful in predicting survival and discontinuation of immunosuppressive therapy despite of more detailed grouping. Our study indicates that NCC is applicable. The clinical impact of NIH types and NGS should be verified through prospective studies.

We conducted a systemic evaluation to describe the effect of minimal residual disease (MRD) kinetics on long-term allogeneic transplantation outcome by analyzing 95 adult transplants with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-positive ALL) who received first-line two courses of imatinib-based chemotherapy (median follow-up 5 years). MRD monitoring was centrally evaluated by real-time quantitative PCR (4.5 log sensitivity). After the first course of imatinib-based chemotherapy, 33 patients (34.7%) achieved at least major molecular response. On the basis of MRD kinetics by the end of two courses of imatinibbased chemotherapy, we stratified entire patients into four subgroups: early-stable molecular responders (EMRs, n ¼ 33), late molecular responders (LMRs, n ¼ 35), intermediate molecular responders (IMRs, n ¼ 9) and poor molecular responders (PMRs, n ¼ 18). Multivariate analysis showed that the most powerful factor affecting long-term transplantation outcome was MRD kinetics. Compared with EMRs, IMRs or PMRs had significantly higher risk of treatment failure in terms of relapse and disease-free survival (DFS). LMRs had a tendency toward a lower DFS. Quantitative monitoring of MRD kinetics during the first-line imatinib-based chemotherapy course is useful in identifying subgroups of Ph-positive ALL transplants at a high risk of relapse.

The aim of this prospective study was to investigate the feasibility of reduced-intensity conditioning (RIC) allogeneic stem cell transplantation (SCT) in 37 adults with high-risk acute lymphoblastic leukemia (ALL) in first (n ¼ 30) or second (n ¼ 7) complete remission (CR). All patients were treated with fludarabine (150 mg/m 2 ) and melphalan (140 mg/m 2 ) followed by transplantation from matched sibling (n ¼ 27) or unrelated (n ¼ 10) donors. The indications for reduced-intensity conditioning allogeneic SCT (RIC-SCT) were as follows: (1) X50 years, 16 (43.2%) and (2) decreased organ function or active infections, 21 (56.8%). Graft-versus-host disease (GVHD) prophylaxis consisted of calcineurin inhibitor (cyclosporine for sibling and tacrolimus for unrelated transplants) and methotrexate. The cumulative incidence of acute (grades II-IV) and chronic GVHD was 43.2 and 65.6%, respectively. After a median follow-up of 36 months for surviving transplants, the 3-year relapse, non-relapse mortality, disease-free survival and overall survival rates were 19.7, 17.7, 62.6 and 64.1%, respectively. Transplants in first CR showed better transplantation outcomes than those in second CR. The potential of antileukemic activity of chronic GVHD was also found. This study suggests that RIC-SCT is a potential therapeutic approach for adults with high-risk ALL in remission who are ineligible for myeloablative transplantation.

To investigate the risk factors for acute GVHD (aGVHD), based on NIH consensus criteria (NCC), we evaluated 775 patients who underwent allogeneic transplantation. Of them, 346 patients developed aGVHD by NCC, in whom we also analyzed factors affecting aGVHD-specific survival. The cumulative incidence of aGVHD was 44.7%, consisting of classic aGVHD (n ¼ 320) and late-onset (n ¼ 26). Multivariate analyses revealed that younger age (P ¼ 0.015), unrelated donors (P ¼ 0.004) and acute leukemia compared with other hematologic malignancies (P ¼ 0.005) were significant risk factors for aGVHD, whereas PBSCs showed no association (P ¼ 0.720). Multivariate analyses, with only aGVHD patients, revealed that late-onset aGVHD had superior aGVHD-specific survival to classic aGVHD (P ¼ 0.044), and identified the association of visceral organ involvement (P ¼ 0.002), severity of aGVHD at onset (P ¼ 0.035) and advanced disease status (Po0.001) with inferior aGVHD-specific survival. In conclusion, this study demonstrates the risk and prognostic factors for aGVHD by NCC with some differences with the previous reports that were based on old criteria. The difference in the risk factors according to different criteria will give insights about the pathophysiology of GVHD. The better prognosis of late-onset aGVHD than of classic aGVHD raises the necessity for prospective trials with a large cohort focusing on the onset time.