Maintenance therapy for <i>FLT3-ITD</i>-mutated acute myeloid leukemia

FLT3-ITD is a constitutively activated variant of the FLT3 tyrosine kinase receptor. Its expression in acute myeloid leukemia (AML) is associated with a poor prognosis. Due to this, the development of tyrosine kinase inhibitors (TKI) blocking FLT3-ITD became a rational therapeutic concept. This review describes key milestones in the clinical development of different FLT3-specific TKI with a particular focus on FLT3-TKI maintenance therapy in remission after allogeneic hematopoietic stem cell transplantation (HCT). Recent evidence from randomized trials using sorafenib in FLT3-ITD mutated AML provided a proof of concept that targeted post-HCT maintenance therapy could become a new treatment paradigm in AML

Safety and feasibility of stem cell boost as a salvage therapy for severe hematotoxicity after CD19 CAR T-cell therapy

Stem cell; Hematotoxicity; T-cellCélulas madre; Hematotoxicidad; Células TCèl·lules mare; Hematotoxicitat; Cèl·lules TThis work was supported by a fellowship from School of Oncology of German Cancer Consortium (DKTK) (K.R.) and was funded by the Else Kröner Forschungskolleg; a Deutsche Forschungsgemeinschaft (DFG; German Research Foundation) research grant provided within the Sonderforschungbereich (SFB-TRR 388/1 2021–452881907) and DFG research grant (451580403) (M.S.); the Bavarian Elite Graduate Training Network (M.S.), the Wilhelm-Sander Stiftung (project no. 2018.087.1) (M.S.), the Else-Kröner-Fresenius Stiftung (M.S., K.R., V. Bücklein, V. Blumenberg), and the Bavarian Center for Cancer Research (BZKF)

Effect of Cultural Adaptation of a Smartphone-Based Self-Help Programme on Its Acceptability and Efficacy: Randomized Controlled Trial

Background: Research on cultural adaptation of psychological interventions indicates that a higher level of adaptation is associated with a higher effect size of the intervention. However, direct comparisons of different levels of adaptations are scarce. Aims: This study used a smartphone-based self-help programme called Step-by-Step (Albanian: Hap-pas-Hapi) for the treatment of psychological distress among Albanian-speaking immigrants in Switzerland and Germany. Two levels of cultural adaptation (i.e., surface vs. deep structure adaptation) were compared. We hypothesised that the deep structure adaptation would enhance the acceptance and efficacy of the intervention. Method: We conducted a two-arm, single-blind randomised controlled trial. Inclusion criteria were good command of the Albanian language, age above 18, and elevated psychological distress (Kessler Psychological Distress Scale score above 15). Primary outcome measures were the total score of the Hopkins Symptom Checklist and the number of participants who completed at least three (out of five) sessions. Secondary outcomes were global functioning, well-being, post-traumatic stress, and self-defined problems. Results: Two-hundred-twenty-two participants were included, of which 18 (8%) completed the post-assessments. The number of participants who completed the third session was equal in both conditions, with N = 5 (5%) and N = 6 (6%) respectively. Discussion: Drop-out rates were high in both conditions, and no group difference was found regarding the acceptance of the intervention. The high drop-out rate stands in contrast with other trials testing Step-by-Step. Future research should examine cultural factors impacting recruitment strategies, as insights could help to reduce participant drop-out rates in clinical trials

Effect of cultural adaptation of a smartphone-based self-help programme on its acceptability and efficacy: Randomized controlled trial

Background: Research on cultural adaptation of psychological interventions indicates that a higher level of adaptation is associated with a higher effect size of the intervention. However, direct comparisons of different levels of adaptations are scarce. Aims: This study used a smartphone-based self-help programme called Step-by-Step (Albanian: Hap-pas-Hapi) for the treatment of psychological distress among Albanian-speaking immigrants in Switzerland and Germany. Two levels of cultural adaptation (i.e., surface vs. deep structure adaptation) were compared. We hypothesised that the deep structure adaptation would enhance the acceptance and efficacy of the intervention. Method: We conducted a two-arm, single-blind randomised controlled trial. Inclusion criteria were good command of the Albanian language, age above 18, and elevated psychological distress (Kessler Psychological Distress Scale score above 15). Primary outcome measures were the total score of the Hopkins Symptom Checklist and the number of participants who completed at least three (out of five) sessions. Secondary outcomes were global functioning, well-being, post-traumatic stress, and self-defined problems. Results: Two-hundred-twenty-two participants were included, of which 18 (8%) completed the post-assessments. The number of participants who completed the third session was equal in both conditions, with N = 5 (5%) and N = 6 (6%) respectively. Discussion: Drop-out rates were high in both conditions, and no group difference was found regarding the acceptance of the intervention. The high drop-out rate stands in contrast with other trials testing Step-by-Step. Future research should examine cultural factors impacting recruitment strategies, as insights could help to reduce participant drop-out rates in clinical trials

Cultural adaptation of Hap-pas-Hapi, an internet and mobile-based intervention for the treatment of psychological distress among Albanian migrants in Switzerland and Germany.

BACKGROUND: Internet- and mobile-based mental health interventions have the potential to narrow the treatment gap in ethnic groups. Little evidence exists on the cultural adaptation of such interventions. Cultural adaptation of evidence-based interventions distinguishes between surface and deep structure adaptation. Surface refers to matching materials (e.g., illustrations, language) or methods of treatment delivery to the target population, whereas deep structure adaptation considers cultural concepts of distress (CCD). So far, CCD have only been considered to a limited extent in cultural adaptation of psychological interventions, and there is a lack of well documented adaptation procedures. AIMS: With a cross-disciplinary and mixed-method approach, following a new conceptual framework for cultural adaptation of scalable psychological interventions, this study aimed to develop both surface and deep structure adaptations of an internet- and mobile-based intervention called Hap-pas-Hapi for the treatment of psychological distress among Albanian migrants in Switzerland and Germany. METHODS: A qualitative ethnopsychological study was conducted to examine the target group's CCD. Focus group discussions, an online survey, and individual key informant interviews were utilised to evaluate the original intervention, adaptation drafts and the final adapted intervention. A reporting system was developed to support the decision-making process and to report all adaptations in a transparent and replicable way. RESULTS: The ongoing involvement of target population key informants provided valuable feedback for the development of a more person-centred intervention, which might enhance treatment acceptance, motivation and adherence. DISCUSSION: This study provides empirical and theory-based considerations and suggestions for future implementation that may foster acceptability and effectiveness of culturally adapted evidence-based interventions

ASXL1 mutations predict inferior molecular response to nilotinib treatment in chronic myeloid leukemia

Gene mutations independent of BCR::ABL1 have been identified in newly diagnosed patients with chronic myeloid leukemia (CML) in chronic phase, whereby mutations in epigenetic modifier genes were most common. These findings prompted the systematic analysis of prevalence, dynamics, and prognostic significance of such mutations, in a clinically well-characterized patient population of 222 CML patients from the TIGER study (CML-V) by targeted next-generation sequencing covering 54 myeloid leukemia-associated genes. In total, 53/222 CML patients (24%) carried 60 mutations at diagnosis with ASXL1 being most commonly affected (n = 20). To study mutation dynamics, longitudinal deep sequencing analysis of serial samples was performed in 100 patients after 12, 24, and 36 months of therapy. Typical patterns of clonal evolution included eradication, persistence, and emergence of mutated clones. Patients carrying an ASXL1 mutation at diagnosis showed a less favorable molecular response to nilotinib treatment, as a major molecular response (MMR) was achieved less frequently at month 12, 18, and 24 compared to all other patients. Patients with ASXL1 mutations were also younger and more frequently found in the high risk category, suggesting a central role of clonal evolution associated with ASXL1 mutations in CML pathogenesis

Sefalet

Emine Semiye'nin Mütalaa'da tefrika edilen Sefalet adlı romanıArşivdeki eksikler nedeniyle tefrika yarım kalmıştır. Ancak tefrikanın tamamlandığı bilinmektedir