The reported outcome of hematopoietic stem cell transplantation (HSCT) from HLA-mismatched family members has been inconsistent. The object of this study was to evaluate the true impact of HLAmismatch by using recent data from a homogenous population, excluding HSCT procedures that used graft manipulations, and by considering genotypic matching. Clinical data of 2947 patients who underwent allogeneic HSCT for leukemia or myelodysplastic syndrome were extracted from the database of the Japan Society for Hematopoietic Cell Transplantation. The main outcome measures were survival and the incidence of graft-versushost disease (GVHD). The presence of serologic HLA-mismatch, higher age, and high-risk disease were identified as independent risk factors for both shorter survival and the development of grade III to IV acute GVHD. The impact of HLAmismatch on survival was more relevant in standard-risk patients. These findings persisted when we used genotypic HLA matching. Survival after one-locusmismatched HSCT was equivalent to that after HLA-matched unrelated HSCT. We concluded that when a one-locusmismatched family donor is available for high-risk patients, immediate HSCT using this donor is warranted. In standard-risk patients, however, survival after onelocus-mismatched HSCT is significantly shorter than that after HLA-matched HSCT, and the indications for HSCT should be considered carefully. (Blood. 2003;102:1541-1547)

Summary The efficacy of allogeneic haematopoietic stem‐cell transplantation (allo‐HSCT) for natural killer (NK)‐cell neoplasms is unknown. We investigated the results of allo‐HSCT for NK‐cell neoplasms between 1990 and 2003 through questionnaires. After reclassification by a haematopathologist, of 345 patients who underwent allo‐HSCT for malignant lymphoma, 28 had NK‐cell neoplasms (World Health Organization classification): extranodal NK/T‐cell lymphoma (n = 22), blastic NK‐cell lymphoma (n = 3), and aggressive NK‐cell leukaemia (n = 3). Twelve were chemosensitive and 16 chemorefractory. Twenty‐two had matched‐related donors. Stem‐cell source was bone marrow in eight and mobilised peripheral blood in 20. Conditioning regimens were myeloablative (n = 23) and non‐myeloablative (n = 5). Grade 2–4 acute graft‐versus‐host disease (GVHD) and chronic GVHD developed in 12 and 8 respectively. Eight died of disease progression, three of infection, two of acute GVHD, one of veno‐occlusive disease, one of interstitial pneumonitis, and one of thrombotic microangiopathy. Two‐year progression‐free and overall survivals were 34% and 40% respectively (median follow‐up, 34 months). All patients who did not relapse/progress within 10 months achieved progression‐free survival (PFS) during the follow‐up. In multivariate analysis, stem cell source (BM versus peripheral blood; relative risk 3·03), age (≥40 years vs. <40 years; relative risk 2·85), and diagnoses (extranodal NK/T‐cell lymphoma versus others; relative risk 3·94) significantly affected PFS. Allo‐HSCT is a promising treatment for NK‐cell neoplasms.

Summary:published 1,2 regarding leukemia relapse after BMT which summarize strategies for prevention and treatment of leukemia relapse after BMT. In these articles, treatment for leuTo assess the consequence of second BMT (BMT2) for leukemia relapse after allogeneic BMT, we analyzed the kemia relapse was analyzed in four parts; reinduction chemoradiotherapy, cytokine therapy, donor leukocyte clinical course of 66 recipients who were treated by BMT2 in Japan. Diagnoses included 29 ANLL, 27 ALL, transfusion, and second allogeneic BMT (BMT2). The rate of achieving complete remission by reinduction chemosix CML and four MDS. Durations between the first BMT (BMT1) to relapse and BMT1 to BMT2 were therapy ranged from 30 to 50% in acute leukemias and the median duration of remission was very short, between 6 13.5 ± ± ± 13.7 months and 17.4 ± ± ± 13.9 months, respectively. Donors for BMT2 were replaced in 11 cases. Thirty-one and 14 months. 3 The response to interferon-␣ and donor leukocyte transfusion was good only for chronic phase patients were in CR (or CP) at BMT2. Earlier deaths were observed in those who received BMT2 within 12 CML and poor during the acute phase of CML and acute leukemia. 4 Therefore, BMT2 may be the only hopeful treatmonths after BMT1, mostly caused by regimen-related toxicity and infections. Overall leukemia-free survival ment for leukemia relapsing after BMT. There are many reports 5-8 concerning BMT2 which show rate was 28% at 2 years and 16% at 4 years. Factors influencing the poor prognosis after BMT2 were early 8-76% disease-free survival depending on the diagnosis, disease status, and many other factors which may affect (Ͻ6 months) relapse, early (Ͻ12 months) BMT2, not in remission at BMT2, and ALL. Intensified conditioningoutcome. In order to analyze the current status of second BMT in Japan, we performed a retrospective survey of did not affect either remission duration or LFS. Among the 39 cases observed for more than 100 days, 18 BMT2 for leukemia relapse in BMT units in Japan. We report the results from analysis of multi-institutional experideveloped chronic GVHD (cGVHD) and showed longer remission duration than those without cGVHD. Our ences of repeated BMT. analysis indicates that BMT2 as treatment for leukemia relapse is effective in selected cases, and exploration of pre-BMT treatment and post-BMT immunotherapy is Materials and methods warranted.

Among these matched pairs, 1829 unrelated bone marrow transplants (UR-BMT) were performed. The initial 500 UR-BMT transplanted from January 1993 to October 1995 were analyzed as of July 1998. Engraftment was achieved in 95% of cases. Probability of the occurrence of grade III and IV acute GVHD was 18.4%. The rate of disease-free survival (DFS) of the patients who had standard-risk leukemia and did not suffer from grade III or IV acute GVHD (n = 154) was 60-71% and the rate of survival of patients with aplastic anemia was 56%. It can be stated that UR-BMT is a modality of treatment which is as effective as related BMT if the occurrence of grade III or IV acute GVHD is predicted and prevented.