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on behalf of the European Working Group on Childhood MDS (EWOG-MDS) and the European Blood and Marrow Transplantation (EBMT) GroupAllogeneic hematopoietic stem cell transplantation (HSCT) is the only proven curative therapy for juvenile myelomonocytic leukemia (JMML). We, the European Working Group on Childhood MDS (EWOG-MDS) and the European Blood and Marrow Transplantation (EBMT) Group, report the outcome of 100 children (67 boys and 33 girls) with JMML given unmanipulated HSCT after a preparative regimen including busulfan, cyclophosphamide, and melphalan. Forty-eight and 52 children received transplants from an HLA-identical relative or an unrelated donor (UD), respectively. The source of hematopoietic stem cells was bone marrow, peripheral blood, and cord blood in 79, 14, and 7 children, respectively. Splenectomy had been performed before HSCT in 24 children. The 5-year cumulative incidence of transplantation-related mortality and leukemia recurrence was 13% and 35%, respectively. Age older than 4 years predicted an increased risk of disease recurrence. The 5-year probability of event-free survival for children given HSCT from either a relative or a UD was 55% and 49%, respectively (P ‫؍‬ NS), with median observation time of patients alive being 40 months (range, 6 to 144

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and *4501, but not other alleles. Based on these findings, we developed an algorithm for prediction of nonpermissive HLA-DPB1 mismatches. Retrospective evaluation of 118 transplantations showed that the presence of nonpermissive HLA-DPB1 mismatches was correlated with significantly increased hazards of acute grade II to IV graftversus-host disease (HR ‫؍‬ 1.87, P ‫؍‬ .046) and transplantation-related mortality (HR ‫؍‬ 2.69, P ‫؍‬ .027) but not relapse (HR ‫؍‬ 0.98, P ‫؍‬ .939), as compared with the permissive group. There was also a marked but statistically not significant increase in the hazards of overall mortality (HR ‫؍‬ 1.64, P ‫؍‬ .1). These data suggest that biologic characterization of in vivo alloreactivity can be a tool for definition of clinically relevant nonpermissive HLA mismatches for unrelated HSC transplantation.

Summary. This study aimed to ascertain whether extracorporeal photochemotherapy (ECP) is an effective treatment for paediatric patients with refractory graft-versus-host disease (GVHD). From January 1992 to December 2000, 77 children (median age 8AE6 years) with either acute (n ¼ 33) or chronic (n ¼ 44) GVHD, resistant to conventional immunosuppressive therapy, were treated with ECP in four Italian paediatric hospitals. After ECP, acute GVHD involving skin, liver and gut responded completely in 76%, 60% and 75% of patients respectively. The 5-year overall survival was 69% for responding patients vs 12% for nonresponders (P ¼ 0AE001). Among the 44 children with chronic GVHD, 15 (44%) showed a complete response and 10 (29%) a significant improvement after ECP. The 5-year overall survival was 96% for responders vs 58% for nonresponders (P ¼ 0AE04). Our results suggest that ECP is an effective treatment that may be useful in paediatric patients with either acute or chronic GVHD who have failed to respond to standard immunosuppressive therapy.

The study underlines the possibility of finding out which patients are more prone to developing post-HSCT TMA, and identifies which risk factors are more frequently associated with a dismal outcome after TMA.

BackgroundWe analyzed the outcome of 100 patients with acquired severe aplastic anemia undergoing an alternative donor transplant, after immune suppressive therapy had failed. Design and MethodsAs a conditioning regimen, patients received either a combination of fludarabine, cyclophosphamide, and antithymocyte globulin (n=52, median age 13 years) or this combination with the addition of low dose (2 Gy) total body irradiation (n=48, median age 27 years). ResultsWith a median follow-up of 1665 and 765 days, the actuarial 5-year survival was 73% for the group that received fludarabine, cyclophosphamide, and antithymocyte globulin and 79% for the group given the conditioning regimen including total body irradiation. Acute graft-versushost disease grade III-IV was seen in 18% and 7% of the groups, respectively. Graft failure was seen in 17 patients with an overall cumulative incidence of 17% in patients receiving conditioning with or without total body irradiation: 9 of these 17 patients survive in the long-term. The most significant predictor of survival was the interval between diagnosis and transplantation, with 5-year survival rates of 87% and 55% for patients grafted within 2 years of diagnosis and more than 2 years after diagnosis, respectively (P=0.0004). Major causes of death were graft failure (n=7), post-transplant-lymphoproliferative-disease (n=4) and graft-versus-host disease (n=4). ConclusionsThis study confirms positive results of alternative donor transplants in patients with severe aplastic anemia, the best outcomes being achieved in patients grafted within 2 years of diagnosis. Prevention of rejection and Epstein-Barr virus reactivation may further improve these results.Key words: aplastic anemia, unrelated transplants, graft failure, graft versus host disease, fludarabine. Citation: Bacigalupo A, Socie' G, Lanino E, Prete A, Locatelli F, Locasciulli A, Cesaro S, Shimoni A, Marsh J, Brune M, Van Lint MT, Oneto R, and Passweg J for the Severe Aplastic Anemia Working Party of the European Group for Blood and Marrow Transplantation, (SAA WP-EBMT).Fludarabine, cyclophosphamide, antithymocyte globulin, with or without low dose total body irradiation, for alternative donor transplants, in acquired severe aplastic anemia: a retrospective study from the EBMT-SAA working party. Haematologica 2010;95:976-982. doi:10.3324/haematol.2009 This is an open-access paper.Fludarabine, cyclophosphamide, antithymocyte globulin, with or without low dose total body irradiation, for alternative donor transplants, in acquired severe aplastic anemia: a retrospective study from the EBMT-SAA working party

on behalf of the AIEOP-BMT Group Chronic graft-versus-host disease (cGVHD) remains the major cause of late morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). However, only a few studies specifically focused on children, and little information is available on the antileukemic effect of cGVHD and its impact on diseasefree survival (DFS) in children. We retrospectively analyzed 696 children given allogeneic HSCT for malignant (n ‫؍‬ 450) or nonmalignant (n ‫؍‬ 246) diseases. The donor was an HLA-identical sibling in 461 cases and an alternative donor in 235. Bone marrow was the stem cell source in 647 cases, peripheral blood in 17, and cord blood (CB) in 32. cGVHD developed in 173 children (25%) at a median of 116 days after HSCT. Three-year cGVHD probability was 27%. In multivariate analysis, variables predicting cGVHD were donor and recipient age, grade II to IV acute GVHD, female donor for male recipient, diagnosis of malignancy, and use of total body irradiation; CB transplants had a very low risk of cGVHD (RR ‫؍‬ 0.07, P ‫؍‬ .0001). cGVHD occurrence increased transplant-related mortality (P < .05). Nevertheless, in hematologic malignancies, patients with cGVHD had a reduced relapse probability compared with children without cGVHD (16% ؎ 3% versus 39% ؎ 3%, P ‫؍‬ .0001) and a better DFS (68% ؎ 4% versus 54% ؎ 3%, P ‫؍‬ .01). The antileukemic effect of cGVHD was observed mainly in patients with acute lymphoblastic leukemia (ALL). This study provides novel data on cGVHD in childhood. Use of CB stem cells and preparative regimens without radiotherapy may prevent its development. In patients affected by ALL, cGVHD was associated with a strong graft-versusleukemia effect, improving DFS. (Blood.