The Role of Allogeneic Stem Cell Transplantation in Relapsed/Refractory Hodgkin's Lymphoma Patients

Despite the favorable prognosis of most patients with Hodgkin's Lymphoma (HL), 15–20% of patients remain refractory to chemoradiotherapy, and 20–40% experience relapses following autologous stem cell transplantation (SCT) being used as salvage approach in this situation. Long-term survival of only 20% was reported for patients who failed this option. As some authors suggested the presence of a graft versus HL effect, allogeneic SCT was introduced as a further option. Myeloablative strategies were reported to be able to achieve cure in some younger patients, but high nonrelapse mortality remains a problem. Reduced intensity conditioning, in turn, was found to be associated with high posttransplant relapse rates. As there is currently no standard in the management of HL patients who failed autologous SCT, we here review the literature on allogeneic stem cell transplantation in HL patients with a special focus on the outcomes and risk factors being reported in the largest studies

Molecular Diagnostics, Targeted Therapy, and the Indication for Allogeneic Stem Cell Transplantation in Acute Lymphoblastic Leukemia

In recent years, the panel of known molecular mutations in acute lymphoblastic leukemia (ALL) has been continuously increased. In Philadelphia-positive ALL, deletions of the IKZF1 gene were identified as prognostically adverse factors. These improved insights in the molecular background and the clinical heterogeneity of distinct cytogenetic subgroups may allow most differentiated therapeutic decisions, for example, with respect to the indication to allogeneic HSCT within genetically defined ALL subtypes. Quantitative real-time PCR allows highly sensitive monitoring of the minimal residual disease (MRD) load, either based on reciprocal gene fusions or immune gene rearrangements. Molecular diagnostics provided the basis for targeted therapy concepts, for example, combining the tyrosine kinase inhibitor imatinib with chemotherapy in patients with Philadelphia-positive ALL. Screening for BCR-ABL1 mutations in Philadelphia-positive ALL allows to identify patients who may benefit from second-generation tyrosine kinase inhibitors or from novel compounds targeting the T315I mutation. Considering the central role of the molecular techniques for the management of patients with ALL, efforts should be made to facilitate and harmonize immunophenotyping, cytogenetics, and molecular mutation screening. Furthermore, the potential of high-throughput sequencing should be evaluated for diagnosis and follow-up of patients with B-lineage ALL

Comparison between antithymocyte globulin and alemtuzumab and the possible impact of KIR-ligand mismatch after dose-reduced conditioning and unrelated stem cell transplantation in patients with multiple myeloma

We compared antithymocyte globulin (ATG) with alemtuzumab in 73 patients with multiple myeloma, who underwent reduced conditioning with melphalan/fludarabine, followed by allogeneic stem cell transplantation from human leucocyte antigen-matched or -mismatched unrelated donors. The ATG group had more prior high-dose chemotherapies (P < 0.001), while bone marrow was used more as the stem cell source in the alemtuzumab group (P < 0.001). Alemtuzumab resulted in faster engraftment of leucocytes (P = 0.03) and platelets (P = 0.02) and in a lower incidence of acute graft versus host disease (GvHD) grades II-IV (24% vs. 47%, P = 0.06). More cytomegalovirus (CMV) seropositive patients in the alemtuzumab group experienced CMV reactivation (100% vs. 47%, P = 0.001). The cumulative incidence of treatment-related mortality at 2 years was 26% [95% confidence interval (CI) = 12-37%] for ATG vs. 28% (95% CI = 15-55%) for alemtuzumab, P = 0.7. There was no significant difference in the estimated 2-year overall and progression-free survival between ATG and alemtuzumab: 54% (95% CI: 39-75%) vs. 45% (95% CI: 28-73%) and 30% (95% CI: 16-55%) vs. 36% (95% CI: 20-62%) respectively. In multivariate analysis, treatment with alemtuzumab had a higher risk for relapse (hazard ratio: 2.37; P = 0.05) while killer immunoglobulin-like receptor (KIR)-ligand mismatch was protective for relapse (P < 0.0001). We conclude that alemtuzumab produced less acute GvHD, but higher probability of relapse. The data implicated a major role of KIR-ligand mismatched transplantation in multiple myeloma

Operation of MSGC+GEM detectors in a High Rate environment

0info:eu-repo/semantics/publishe

Stammzellforschung : Debatte zwischen Ethik, Politik und Gesellschaft

Die biopolitische Debatte um Stammzellforschung und Reproduktionsmedizin hat heftigen Streit über biologische Sachverhalte und damit kommunizierende anthropologische Fragen provoziert. Nicht minder strittig sind die sozialen Implikationen der kontroversen Sachverhalte. Inwieweit verändern die Entwicklungen in Molekulargenetik und Reproduktionsmedizin unsere normativen Orientierungen? Welche Rolle spielen Politik und Recht gegenüber Wissenschaft und Ökonomie? Und wie prägen biotechnologische Innovationen ethische Diskurse? Die Beiträge des Bandes gehen solchen Fragen nach. Sie bieten Informationen und Einschätzungen aus medizinischen und naturwissenschaftlichen Perspektiven und sie enthalten norm- und kulturwissenschaftliche Reflexionen aus Pädagogik, Philosophie und Theologie. Der Band ist aus einer multidisziplinären Ringvorlesung hervorgegangen, die im Sommersemester 2002 an der Universität Hamburg stattgefunden hat.The biopolitical debate on stem cell research and reproductive medicine has provoked heated controversy over biological issues and related anthropological questions. The social implications of the controversial issues are no less controversial: To what extent are developments in molecular genetics and reproductive medicine changing our normative orientations? What role do politics and law play in relation to science and economics? And how do biotechnological innovations shape ethical discourses? The contributions of the volume address such questions. They offer information and assessments from medical and scientific perspectives and contain normative and cultural studies reflections from pedagogy, philosophy and theology. The volume is the result of a multidisciplinary lecture series that took place in the summer semester 2002 at the University of Hamburg