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

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

Abnormal Behavior of ZrO[2]-MgO Porous Ceramic Composite under Compression

In this work ZrO[2]-MgO porous ceramic composite fine crystalline structure was studied, its microstructure and mechanical properties after sintering at 1600°С. Pores had a bimodal size distribution with the mean sizes of about 30 and 100 [mu]m. It was shown that the introduction of organic pore-forming particles into the initial powder composition of ZrO[2]-MgO allows producing ceramics with a bimodal pore structure, the material strength is mainly determined by microstresses, and in general, such porous ceramics show uncharacteristic behavior under compression, which is confirmed by plot of the Hall-Petch dependence of microstresses on the average crystallite size with the coefficient K=0.38 MPa m{1/2}, corresponding to plastic materials

Toward high-resolution population genomics using archaeological samples

The term ‘ancient DNA’ (aDNA) is coming of age, with over 1,200 hits in the PubMed database, beginning in the early 1980s with the studies of ‘molecular paleontology’. Rooted in cloning and limited sequencing of DNA from ancient remains during the pre-PCR era, the field has made incredible progress since the introduction of PCR and next-generation sequencing. Over the last decade, aDNA analysis ushered in a new era in genomics and became the method of choice for reconstructing the history of organisms, their biogeography, and migration routes, with applications in evolutionary biology, population genetics, archaeogenetics, paleoepidemiology, and many other areas. This change was brought by development of new strategies for coping with the challenges in studying aDNA due to damage and fragmentation, scarce samples, significant historical gaps, and limited applicability of population genetics methods. In this review, we describe the state-of-the-art achievements in aDNA studies, with particular focus on human evolution and demographic history. We present the current experimental and theoretical procedures for handling and analysing highly degraded aDNA. We also review the challenges in the rapidly growing field of ancient epigenomics. Advancement of aDNA tools and methods signifies a new era in population genetics and evolutionary medicine research

Reduced-Intensity Allografting as First Transplantation Approach in Relapsed/Refractory Grades One and Two Follicular Lymphoma Provides Improved Outcomes in Long-Term Survivors

Comparison of long-term outcomes in patients with refractory/relapsed grade 1-2 follicular lymphoma (FL) after allogeneic (allo-HCT) vs. autologous hematopoietic cell transplantation (auto-HCT) in the rituximab-era

Stellenwert der MRD-Diagnostik vor und nach allogener Stammzelltransplantation bei akuten Leukämien

Die prognostische Relevanz der MRD (measurable residual disease)-Diagnostik bei Patient:innen mit akuten Leukämien nimmt in den letzten Jahren kontinuierlich zu. Wenngleich die MRD-Bestimmung bereits (u.a. bei der akuten lymphatischen Leukämie, ALL) den Weg in die Routinediagnostik zur verbesserten individualisierten Risikostratifizierung gefunden hat, stellt die Biologie der Erkrankung (u.a. Polyklonalität und klonale Evolution) zusammen mit technischen Aspekten (Standardisierung, Qualitätssicherung) eine Herausforderung dar. Komplementäre technische Methoden (z.B. next generation sequencing, NGS/Durchflusszytometrie (multicolored flow cytometry, MFC)) können in dieser Hinsicht von Bedeutung sein. Die MRD-getriggerten peri- (z.B. optimale Spenderauswahl und Konditionierung) und post-transplantären Strategien (z.B. zielgerichtete Erhaltungstherapien, Spenderlymphozyten/Donorlymphozyten-Infusionen, DLI) sind zwar mit vielen offenen Fragen verbunden, werden aber sicherlich an Bedeutung zunehmen und eine weitere Optimierung der Ergebnisse der allogenen Stammzelltransplantation (alloSCT) erlauben