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Summary. Allogeneic stem cell transplantation from an HLA-identical sibling donor is a curative treatment option for a young patient with myelodysplastic syndrome, limited by age and lack of sibling donors. Alternative stem cell sources have been used more recently, such as unrelated donors, non-identical family members or autologous transplants. This analysis of 1378 transplants reported to the European Group for Blood and Marrow Transplantation (EBMT) addresses the outcome of the varying procedures according to the known risk factors. The estimated diseasefree survival (DFS) and estimated relapse risk at 3 years were both 36% for 885 patients transplanted with stem cells from matched siblings. In the multivariate analysis, age and stage of disease had independent prognostic significance for DFS, survival and treatment-related mortality. Patients transplanted at an early stage of disease had a significantly lower risk of relapse than patients transplanted at more advanced stages. The estimated DFS at 3 years was 25% for the 198 patients with voluntary unrelated donors, 28% for the 91 patients with alternative family donors and 33% for the 126 patients autografted in first complete remission. The nonrelapse mortality was 58% for patients with unrelated donors, 66% for patients with non-identical family donors and 25% for autografted patients. The relapse rate of 18% was relatively low for patients with non-identical family donors, 41% for patients with unrelated donors and 55% for patients treated with autologous stem cell transplantation. Both allogeneic and autologous stem cell transplantation have emerged as treatment options for patients with myelodysplastic syndromes. Transplantation with an HLA-identical sibling donor is the preferred treatment option. Patients without an HLA-identical sibling donor may be treated with either autologous stem cell transplantation or an alternative donor transplantation. Patients younger than 20 years may be treated with an unrelated donor transplantation. Patients older than 40 years, and probably also patients between 20 and 40 years, may benefit most from an autologous stem cell transplantation.

Key Points• DNMT3A mutations are frequent in younger adults with AML and have no significant impact on survival end points.• Only moderate effects on outcome, depending on molecular subgroup and DNMT3A mutation type, could be observed.In this study, we evaluated the frequency and prognostic impact of DNMT3A mutations (DNMT3A mut ) in 1770 younger adult patients with acute myeloid leukemia (AML) in the context of other genetic alterations and the European LeukemiaNet (ELN) classification. DNMT3A mut were found in 20.9% of AMLs and were associated with older age (P < .0001), higher white blood cell counts (P < .0001), cytogenetically normal AML (CN-AML; P < .0001), NPM1 mutations (P < .0001), FLT3 internal tandem duplications (P < .0001), and IDH1/2 mutations (P < .0001). In univariable and multivariable analyses, DNMT3A mut did not impact event-free, relapse-free (RFS), or overall survival (OS) in either the entire cohort or in CN-AML; a negative prognostic effect was found only in the ELN unfavorable CN-AML subset (OS, P 5 .011).

Summary:The incidence of adenovirus (AV) infections following SCT was determined in a prospective multicenter trial. Over 1 year, 130 consecutive patients undergoing allogeneic SCT at Essen University Hospital were included and followed for 6 months. Source of stem cells was blood in 68 cases. Fifty-eight patients had HLA-identical sibling donors. Throat swabs, urine and stool samples were screened weekly for AV antigen and DNA by ELISA and nested PCR, respectively. In 35 cases adenovirus infection was detected. There was no seasonal variation. Throat swabs were positive in 24, urine in 12, and stool in 11 cases, resulting in a cumulative risk of infection of 29%. The incidences of AV infection of the respiratory, gastrointestinal and urinary tract were 19%, 10%, and 9%, respectively, and infections were diagnosed after a median (range) interval of 44 (−2-179), 37 (−2-168), and 53 (17-153) days after transplantation. On multivariate analysis, presence of AV antibody in the donor and acute graft-versus-host disease grade IV were found to be independent risk factors for AV infection. Eleven patients had AV isolated from more than one site and five patients had probable AV disease. We were not able to identify patients in whom AV infection was the leading cause of death. The majority of patients infected with AV suffered from severe acute graft-versus-host disease often accompanied by other opportunistic infections, such as aspergillosis or CMV reactivation. Nineteen out of 36 patients who died during the observation period had AV infection. In summary, AV infection after allogeneic SCT was observed in a substantial number of patients. In addition to well-known risk factors for viral infection after SCT we were able to demonstrate that a positive AV antibody test in the donor is an important risk factor for AV infection. Further studies are needed, how- Hemopoietic stem cell transplantation has been used with increasing success for treatment of patients with various hematological neoplasms, but the procedure itself is associated with significant morbidity and mortality. Infectious complications are major factors contributing to transplantrelated mortality. In the past, the most common viral infections following marrow transplantation were caused by herpes simplex virus (HSV), cytomegalovirus (CMV), and varicella zoster virus (VZV). With the introduction of acyclovir for HSV and VZV and ganciclovir treatment for CMV, fatalities caused by these viruses have decreased dramatically. Over the same period of time, reports on fatal viral infections caused by adenovirus (AV) have been published by several groups. [1][2][3] The most common clinical manifestation of AV infection is hemorrhagic cystitis, 4 followed by gastroenteritis, pneumonitis, and liver failure. 5 In addition, AV can cause pancreatitis, nephritis, and disseminated disease leading to mortality rates ranging from 18 to 60%. The outcome of AV disease depends on patient age, type of immunosuppression, and AV serotype. 6 An increasing incidence of AV infection...

Summary:the diagnosis of MDS may improve prognosis due to a lower treatment-related mortality and a lower relapse risk. Allogeneic bone marrow transplantation (BMT) offers a potential cure for younger patients with myelodysplasticKeywords: allogeneic bone marrow transplantation; HLA-identical sibling; first-line treatment; myelodysplastic syndromes (MDS) or secondary acute myeloid leukemia (sAML). More than 600 patients from 50 European censyndrome; secondary acute myelogenous leukemia ters have now been reported to the European Group for Blood and Marrow Transplantation (EBMT). We retrospectively analyzed 131 patients reported to the Myelodysplastic syndromes (MDS) comprise a heteroChronic Leukemia Working Party of the EBMT who geneous group of hematopoietic stem cell disorders with underwent BMT from HLA-identical siblings without varying clinical, laboratory and morphological features. prior remission induction chemotherapy. At the time ofAccording to the proposals of the French-American-British BMT 46 patients had refractory anemia (RA) or RA Cooperative Group (FAB) five morphological entities can with ringed sideroblasts, 67 patients had more advanced be distinguished, including refractory anaemia (RA), refrac-MDS subtypes and 18 patients had progressed to sAML.tory anaemia with ring sideroblasts (RARS), refractory aneThe 5-year disease-free (DFS) and overall survival (OS) mia with excess of blasts (RAEB), refractory anemia with for the entire group of patients was 34 and 41%, excess of blasts in transformation (RAEB/T), and chronic respectively. Fifty patients died from transplant-related myelomonocytic leukemia (CMML). 1 Treatment of MDS complications, most commonly graft-versus-host disease and secondary acute myelogenous leukemia (sAML) has and/or infections. Relapse occurred in 28 patients generally been unsatisfactory. Because of their advanced between 1 and 33 months after BMT, resulting in an age most patients have been treated solely with supportive actuarial probability of relapse of 39% at 5 years. DFS measures. Limited success has been reported with low-dose and OS were dependent on pretransplant bone marrow cytosine arabinoside, 2 retinoic acid, 3 corticosteroids, 4 and blast counts. Patients with RA/RARS, RAEB, RAEB/T hematopoietic growth factors. 5 Young patients with and sAML had a 5-year DFS of 52, 34, 19 and 26%, advanced MDS may achieve prolonged, disease-free surrespectively. The 5-year OS for the respective patient vival when treated with intensive antileukemic chemogroups was 57, 42, 24 and 28%. In a multivariate analytherapy. 6 However, remission duration has generally been sis, younger age, shorter disease duration, and absence short. 7 Nowadays, allogeneic BMT is considered the treatof excess of blasts were associated with improved outment of choice for younger patients with histocompatible come. From these data we conclude that patients with siblings. The timing of transplant in the management of myelodysplasia who have appropriate marrow donors, the disease remains controversial....