Effect of depression, anxiety, and distress screeners on the need, intention, and utilization of psychosocial support services among cancer patients.

PURPOSE: In clinical cancer care, distress screening is recommended to identify highly burdened patients in objective need for psychosocial support to improve psychological distress and quality of life and to enhance patient empowerment. It is however unclear whether distress screeners are suitable for psychosocial care planning and thus whether they can predict the willingness that is need, intention, and utilization, to seek psychosocial support. METHODS: In a secondary analysis of a cluster intervention study, we assessed cancer patients with three distress screeners (DT, PHQ-9, GAD-7) at baseline. The willingness to seek psychosocial support services was assessed binary for psychosocial services at 3 and 6 months. Logistic regression models were applied to examine the predictive effect of the screeners on need, intention, and utilization. We corrected all models for multiple testing. RESULTS: The 660 patients included in the study were on average 60 years, 54% were male. At the 3- and 6-month follow-up, 353 and 259 patients participated, respectively. The screeners were best in predicting the need for support (OR reaching up to 1.15, 1.20, and 1.22 for the PHQ-9, GAD-7, and DT respectively). The intention was predicted by the PHQ-9 and GAD-7, whereas utilization of psychosocial support services was not predicted by the screeners. CONCLUSION: The three distress screeners might be useful in psychosocial care planning, as they are able to predict the need and to some degree the intention to seek psychosocial support. Future research needs to examine potential barriers and supporting factors that may explain utilization of psychosocial support. TRIAL REGISTRATION: The study was retrospectively registered (2/2021) at ClinicalTrials.gov (number: NCT04749056).

[Physical long-term consequences of cancer]. / Körperliche Langzeitfolgen von Krebserkrankungen.

The number of long-term survivors of malignant diseases is steadily increasing, which is due to the further development and optimization of multimodal therapy strategies and the mechanisms of new substance classes. These can now be combined with classical treatment methods or used sequentially. At the same time the number of patients who suffer from physical and psychosocial long-term consequences of cancer therapies or have to live with chronic side effects under the long-term therapies increases. Every therapy, whether radiation, chemotherapy, targeted therapy, or operation, has undesirable long-term side effects that contribute to the decrease of one's quality of life. These affect all parts of the body. As a result, patients can be heavily burdened. In oncology and in other disciplines involved in aftercare, these consequences must therefore be increasingly addressed and clarified and treatment strategies further developed. Unfortunately, there is still a considerable need for research in this area; moreover, there is a lack of clinical studies examining the evidence of a wide variety of holistic therapy methods.

Development and preliminary psychometric investigation of the German Satisfaction with Comprehensive Cancer Care (SCCC) Questionnaire.

PURPOSE: The assessment of patient satisfaction during treatment is essential to provide patient-centered high-quality cancer care. Nevertheless, no German instrument assesses patient satisfaction with comprehensive cancer care, which not only includes oncological treatment, but also interpersonal quality of care as well as psychosocial support services. Based on the French REPERES-60, we developed the German Patient Satisfaction with Comprehensive Cancer Care (SCCC) questionnaire. METHODS: The REPERES-60 was translated and the items were adapted to make it applicable to the German healthcare system and across different tumor entities. Scales of the resulting instrument were extracted via principal axis factoring (PAF). Subsequently, we investigated the reliability (Cronbach's Alpha, CA), discriminatory power (corrected item-scale correlations) and convergent validity (pre-specified correlations of the SCCC with different outcomes). RESULTS: The SCCC consisted of 32 items which were subsequently tested among a sample of 333 patients across different tumor entities (response rate: 47%). Average age was 59 years (standard deviation: 14), 63% were male. PAF revealed four multi-item scales named Competence, Information, Access and Support accounting for 71% of the variance. Two single-items scales assess global satisfaction with medical and psychosocial care, respectively. CA across the multi-item scales ranged from .84 to .96. Discriminatory power was sufficiently high, with all r ≥ .5. Convergent validity was largely verified by negative associations of the four multi-item scales with depressive/anxious symptomatology (r ≥ - .18, p < .01) and fatigue/overall symptom burden (r ≥ - .14, p < .01). CONCLUSION: We developed a tool to assess patient satisfaction with comprehensive cancer care in Germany. The SCCC showed satisfactory psychometric properties. Further studies are needed to verify these preliminary findings.

[Basic principles of immunotherapy]. / Grundlagen der Immuntherapie.

Immunotherapy for malignant diseases is defined as a systematic therapeutic approach that aims to target the individual's immune system to prevent the development of malignancies or to combat existing tumors. Nowadays, this includes various therapeutic approaches, such as immune checkpoint inhibitors, BiTEs (bispecific T­cell engagers), CAR T­cells (CAR: chimeric antigen receptors) and oncolytic viruses, which have not only different mechanisms of action and points of attack, but also have very different efficiencies in the treatment of solid and hematological malignancies. These approaches undoubtedly enrich the therapeutic portfolio in oncology-in palliative systematic therapy and also in the interaction with operative and ablative local therapeutic approaches.

Psychosocial Impact of Personalized Therapies in Oncology.

Personalized medicine is a keyword in modern oncology summarizing biomarker-driven targeted therapies. Those novel agents enhance our therapeutic portfolio and offer new options for our patients. But the term is often misleading and implicates a tailored therapy to the individual person, but it rather means a treatment stratified on genetic characteristics of the tumor. Molecular therapies raise expectations of curability or long-term treatments making former life-threatening diseases to more chronic ones but this is true only for some patients. So we have to carefully communicate with our patients about the options and limitations of those modern therapies not to trigger disappointments.

Comprehensive cytogenetic and molecular cytogenetic analysis of 44 Burkitt lymphoma cell lines: secondary chromosomal changes characterization, karyotypic evolution, and comparison with primary samples.

Burkitt lymphoma cell lines (BL-CL) are used extensively as in vitro models in genetic studies; however, cytogenetic information is not always available or updated. We provide a comprehensive cytogenetic resource of 44 BL-CL, assessed by G-banding, multicolor-FISH, and FISH with 1q, 3p, 7q, and 13q region-specific probes, including the first cytogenetic characterization of 22 BL-CL and the revision of further 22 commonly used BL-CL. Based on these data, we determined a consensus karyotype, evaluated in detail the secondary chromosomal changes (SCC), and the karyotypic stability of these cell lines. An individual karyotype was identified in all investigated BL-CL, confirming their unique origin. Most of the BL-CL remained cytogenetically relative stable after years of intensive cultivation. The most frequent structural SCC were dup(1q), del(13q) and the most frequent numerical SCC were +7, +13. Common breakpoints were located on 1q12, 7q11, and 13q31. The most common gains were in 1q and 7q and the most common losses were in 11q and 13q. Interestingly, the frequency of 1q gains and 13q losses was significantly higher in the EBV-negative than in the EBV-positive BL-CL. Furthermore, by reviewing karyotypes of 221 primary BL listed in the Mitelman database, we observed similarities between BL-CL and primary BL regarding the frequency of numerical and structural SCC and breakpoint distribution. In BL-CL and in primary BL two SCC, dup(1q), and +12, always occurred mutually exclusive of each other. These findings validate BL-CL as appropriate model for in vitro studies on the significance of SCC in the pathogenesis of BL.

Functional autoantibodies against SSX-2 and NY-ESO-1 in multiple myeloma patients after allogeneic stem cell transplantation.

BACKGROUND: Multiple myeloma (MM) is the malignancy with the most frequent expression of the highly immunogenic cancer-testis antigens (CTA), and we have performed the first analysis of longitudinal expression, immunological properties, and fine specificity of CTA-specific antibody responses in MM. METHODS: Frequency and characteristics of antibody responses against cancer-testis antigens MAGE-A3, NY-ESO-1, PRAME, and SSX-2 were analyzed using peripheral blood (N = 1094) and bone marrow (N = 200) plasma samples from 194 MM patients. RESULTS: We found that antibody responses against CTA were surprisingly rare, only 2.6 and 3.1 % of patients evidenced NY-ESO-1- and SSX-2-specific antibodies, respectively. NY-ESO-1-specific responses were observed during disease progression, while anti-SSX-2 antibodies appeared after allogeneic stem cell transplantation and persisted during clinical remission. We found that NY-ESO-1- and SSX-2-specific antibodies were both capable of activating complement and increasing CTA uptake by antigen-presenting cells. SSX-2-specific antibodies were restricted to IgG3, NY-ESO-1 responses to IgG1 and IgG3. Remarkably, NY-ESO-1-positive sera recognized various non-contiguous regions, while SSX-2-specific responses were directed against a single 6mer epitope, SSX-2(85-90). CONCLUSIONS: We conclude that primary autoantibodies against intracellular MM-specific tumor antigens SSX-2 and NY-ESO-1 are rare but functional. While their contribution to disease control still remains unclear, our data demonstrate their theoretic ability to affect cellular anti-tumor immunity by formation and uptake of mono- and polyvalent immune complexes.

Cancer-Related Cognitive Dysfunction: A Narrative Review for Clinical Practice.

BACKGROUND: Cancer-related cognitive dysfunction (CRCD) is a major functional disorder in patients with cancer. This central nervous dysfunction is found in up to 60% of patients after tumour therapy, often significantly limits the quality of life, and significantly impedes participation in working life. For this reason, diagnosis and treatment of CRCD are of central importance. This narrative review is intended to provide an overview and support for practical clinical care with regard to diagnostics and therapeutic options. SUMMARY: In Germany, CRCD has received insufficient attention in clinical practice due to the lack of guidelines for diagnosis and therapy. The pathophysiology is complex and cannot be explained by chemotherapeutic treatment alone. In addition to the tumour disease as such and the tumour therapy, psychological factors such as anxiety and depression as well as sleep disorders also play a significant role. Today, it is known that in addition to age, molecular genetic changes also have an effect on cognitive function. Morphologically, CRCD can be located in the frontal cortex and hippocampus. In addition to easy-to-use screening instruments such as the visual analogue scale, validated questionnaires such as the Questionnaire of Subjectively Experienced Deficits in Attention (FEDA) developed in Germany are also available. These allow the suspected diagnosis to be substantiated and the patient to be referred to further neurological, neuropsychological, or psycho-oncological diagnostics. Within the framework of further neuropsychological diagnostics, the International Cognition and Cancer Task Force (ICCTF) recommends testing learning, memory, processing speed, and executive functions. From the authors' point of view, a step-by-step diagnosis is recommended in order to avoid overdiagnosis. In clinical practice, graduation according to the "Common Terminology Criteria for Adversity Events" (CTCAE Version 5.0) is suitable for assessing the degree of severity. Cognitive training should be behaviourally oriented and include regular practice of cognitive skills to restore attention, psychomotor speed, memory, and executive functions. The best evidence is currently found for web-based training programmes that can be used by the patient at home. There is also evidence for mindfulness training and physical exercises. In particular, the combination of these three therapeutic elements currently seems to be the optimal treatment strategy for CRCD. KEY MESSAGES: Cognitive dysfunction should be given much more attention in the clinical care of cancer patients. Diagnostic tools for this purpose and evidence-based therapeutic interventions are available. In the future, networks should be created that allow for better care of patients with CRCD.

Impact of high-risk cytogenetics and achievement of molecular remission on long-term freedom from disease after autologous-allogeneic tandem transplantation in patients with multiple myeloma.

Within a prospective protocol, the incidence and impact of achievement of molecular remission (mCR) and high-risk cytogenetics was investigated in 73 patients with multiple myeloma (MM) after autologous (auto)-allogeneic (allo) tandem stem cell transplantation (SCT). After induction chemotherapy, patients received melphalan 200 mg/m(2) before undergoing auto-SCT, followed 3 months later by melphalan 140 mg/m(2) and fludarabine 180 mg/m(2) before allo-SCT. Sixteen patients had high-risk cytogenetic features, defined by positive FISH for del(17p13) and/or t(4;14). Overall, 66% of the patients achieved CR or near-CR, and 41% achieved mCR, which was sustained negative (at least 4 consecutive samples negative) in 15 patients (21%), with no significant difference in incidence between the patients with high-risk cytogenetics and others (P = .70). After a median follow-up of 6 years, overall 5-year progression-free survival was 29%, with no significant difference between del 17p13/t(4;14)-harboring patients and others (24% versus 30%; P = .70). The 5-year progression-free survival differed substantially according to the achieved remission: 17% for partial remission, 41% for CR, 57% for mCR, and 85% for sustained mCR. These results suggest that auto-allo tandem SCT may overcome the negative prognostic effect of del(17p13) and/or t(4;14) and that achievement of molecular remission resulted in long-term freedom from disease.

Second autologous transplant as salvage therapy in multiple myeloma.

High-dose chemotherapy followed by autologous haematopoetic stem cell transplantation (ASCT) is a standard frontline therapy for multiple myeloma (MM). Unfortunately, there are no randomized clinical studies examining the role of a second ASCT in patients who relapse after the initial autotransplant. Analysing all available retrospective studies, it seems that salvage ASCT can safely be performed in most patients with an overall treatment-related mortality rate <5%. Approximately 65% of patients will achieve an objective response and progression-free and overall survival will be around 12 months and 32 months, respectively. Retrospective data suggest that patients with a progression-free survival of ≥18 months after initial ASCT are most likely to benefit from a salvage autotransplant. However, patients with a <12-month duration of response after initial ASCT should not be considered for a second autograft in the relapsed setting because this group will probably only experience ASCT-related toxicity without any clinical benefit. Quality of response after initial ASCT and number of therapies preceding salvage ASCT may also have a predictive value. Importantly, these findings need to be verified by randomized clinical trials in order to firmly integrate salvage ASCT into a global therapeutic concept for myeloma patients including optimized induction, consolidation, and maintenance approaches.

Cytogenetics of extramedullary manifestations in multiple myeloma.

Extramedullary disease in patients with multiple myeloma is a rare event, occurring mostly in advanced disease or relapse. Outcome is poor and prognostic factors predicting the development of extramedullary disease have not been defined. We investigated cytogenetic alterations of myeloma cells in different extramedullary manifestations by adapting the fluorescence in situ hybridization (FISH) technique in combination with cytoplasmic immunoglobulin staining to study the cytogenetics of plasma cell tumours on paraffin embedded material. Thirty six patients were investigated: 19 with extramedullary disease, 11 with skeletal extramedullary disease and six with solitary extramedullary plasmacytoma. The first two groups showed the following results: del(17p13) 32% vs. 27%, del(13q14) 35% vs. 27%, MYC-overrepresentation 28% vs. 18% and t(4;14) 37% vs. 18%. We detected an overall higher incidence of del(17p13) in both groups compared to data from bone marrow samples of multiple myeloma reported to date (range 7-16%). The solitary extramedullary plasmacytomas presented overall less cytogenetic aberrations than the other groups. Most important, three patients with extramedullary disease and one with skeletal extramedullary disease presented different FISH findings in the extramedullary tumour compared to their bone marrow plasma cells. del(17p13), occurring additional in three of four cases, seems a strong marker for extramedullary progression of myeloma.

Effectiveness of brief psychosocial support for patients with cancer and their relatives: a quasi-experimental evaluation of cancer counselling centres.

OBJECTIVES: The aim of this study was to evaluate the effectiveness of brief psychosocial support for patients with cancer and their relatives regarding their mental health. DESIGN: Quasi-experimental controlled trial with measurements at three time points (baseline, after 2 weeks and after 12 weeks). SETTING: The intervention group (IG) was recruited at two cancer counselling centres in Germany. The control group (CG) included patients with cancer or relatives who did not seek support. PARTICIPANTS: In total, n=885 participants were recruited and n=459 were eligible for the analysis (IG, n=264; CG, n=195). INTERVENTION: One to two psychosocial support sessions (approximately hour) provided by a psycho-oncologist or social worker. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was distress. The secondary outcomes were anxiety and depressive symptoms, well-being, cancer-specific and generic quality of life (QoL), self-efficacy and fatigue. RESULTS: The linear mixed model analysis showed significant differences between IG and CG at follow-up for distress (d=0.36), p=0.001), depressive (d=0.22), p=0.005) and anxiety symptoms (d=0.22), p=0.003), well-being (d=0.26, p=0.002), QoL (QoL mental; d=0.26, p=0.003), self-efficacy (d=0.21, p=0.011) and QoL (global; d=0.27, p=0.009). The changes were not significant for QoL (physical; d=0.04, p=0.618), cancer-specific QoL (symptoms; d=0.13, p=0.093), cancer-specific QoL (functional; d=0.08, p=0.274) and fatigue (d=0.04, p=0.643). CONCLUSION: The results suggest that brief psychosocial support is associated with the improvement of mental health of patients with cancer and their relatives after 3 months. TRIAL REGISTRATION NUMBER: DRKS00015516.

The t(14;18)(q32;q21)/IGH-MALT1 translocation in MALT lymphomas contains templated nucleotide insertions and a major breakpoint region similar to follicular and mantle cell lymphoma.

The t(14;18)(q32;q21) involving the immunoglobulin heavy chain locus (IGH) and the MALT1 gene is a recurrent abnormality in mucosa-associated lymphoid tissue (MALT) lymphomas. However, the nucleotide sequence of only one t(14;18)-positive MALT lymphoma has been reported so far. We here report the molecular characterization of the IGH-MALT1 fusion products in 5 new cases of t(14;18)-positive MALT lymphomas. Similar to the IGH-associated translocations in follicular and mantle cell lymphomas, the IGH-MALT1 junctions in MALT lymphoma showed all features of a recombination signal sequence-guided V(D)J-mediated translocation at the IGH locus. Furthermore, analogous to follicular and mantle cell lymphoma, templated nucleotides (T-nucleotides) were identified at the t(14;18)/IGH-MALT1 breakpoint junctions. On chromosome 18, we identified a novel major breakpoint region in MALT1 upstream of its coding region. Moreover, the presence of duplications of MALT1 nucleotides in one case suggests an underlying staggered DNA-break process not consistent with V(D)J-mediated recombination. The molecular characteristics of the t(14;18)/IGH-MALT1 resemble those found in the t(14;18)/IGH-BCL2 in follicular lymphoma and t(11;14)/CCND1-IGH in mantle cell lymphoma, suggesting that these translocations could be generated by common pathomechanisms involving illegitimate V(D)J-mediated recombination on IGH as well as new synthesis of T-nucleotides and nonhomologous end joining (NHEJ) or alternative NHEJ repair pathways on the IGH-translocation partner.

Evaluation of an electronic psycho-oncological adaptive screening program (EPAS) with immediate patient feedback: findings from a German cluster intervention study.

PURPOSE: Distress screening has become mandatory and essential in comprehensive cancer care. We evaluated an electronic psycho-oncological adaptive screening (EPAS) which assesses objective indicators of care needs and subjectively perceived care needs and subsequently provides patient feedback with individualized recommendations about psychosocial care services. METHODS: Patients were assessed within clusters, i.e., different oncological facilities of the competence network of the University Cancer Center Hamburg (UCCH). Patients in the intervention arm underwent the screening, controls received standard care. Patients were assessed at baseline (t0), 3-month (t1), and 6-month (t2) follow-up. Outcomes included information level and use of/access to nine psychosocial services at UCCH, well-being (GAD-7, PHQ-9, SF-8), and treatment satisfaction (SCCC). Conditional linear and logistic regressions were used to identify screening effects at t1 and t2. RESULTS: Of 1320 eligible patients across 11 clusters, 660 were included (50%). The average age was 60 years; 46% were female. The intervention was associated with increased information level for all psychosocial services at t1 and t2 (all p < .001), increased use in some of these services at t1 and t2, respectively (p ≤ .02), and better evaluation of access (e.g., more recommendations for services provided by physicians, p < .01). At t2, the intervention was associated with a lower level of satisfaction with disease-related information (p = .02). CONCLUSIONS: EPAS may improve information about psychosocial services as well as utilization of and access to these services. The effect on information level seems not to be generalizable to other aspects of oncological care. Future studies should incorporate novel technologies and condense the procedure to its core factors. IMPLICATIONS FOR CANCER SURVIVORS: The screening may help to enhance self-management competencies among cancer survivors. TRIAL REGISTRATION: The trial was retrospectively registered (2/2021) at ClinicalTrials.gov (number: NCT04749056).

Decision Conflicts in Clinical Care during COVID-19: A Patient Perspective.

(1) Background: Uncertainty is typical for a pandemic or similar healthcare crisis. This affects patients with resulting decisional conflicts and disturbed shared decision making during their treatment occurring to a very different extent. Sociodemographic factors and the individual perception of pandemic-related problems likely determine this decisional dilemma for patients and can characterize vulnerable groups with special susceptibility for decisional problems and related consequences. (2) Methods: Cross-sectional data from the OnCoVID questionnaire study were used involving 540 patients from 11 participating institutions covering all major regions in Germany. Participants were actively involved in clinical treatment in oncology or psychiatry during the COVID-19 pandemic. Questionnaires covered five decision dimensions (conflicts and uncertainty, resources, risk perception, perception of consequences for clinical processes, perception of consequences for patients) and very basic demographic data (age, gender, stage of treatment and educational background). Decision uncertainties and distress were operationalized using equidistant five-point scales. Data analysis was performed using descriptive and various multivariate approaches. (3) Results: A total of 11.5% of all patients described intensive uncertainty in their clinical decisions that was significantly correlated with anxiety, depression, loneliness and stress. Younger and female patients and those of higher educational status and treatment stage had the highest values for these stressors (p < 0.001). Only 15.3% of the patients (14.9% oncology, 16.2% psychiatry; p = 0.021) considered the additional risk of COVID-19 infections as very important for their disease-related decisions. Regression analysis identified determinants for patients at risk of a decisional dilemma, including information availability, educational level, age group and requirement of treatment decision making. (4) Conclusions: In patients, the COVID-19 pandemic induced specific decisional uncertainty and distress accompanied by intensified stress and psychological disturbances. Determinants of specific vulnerability were related to female sex, younger age, education level, disease stages and perception of pandemic-related treatment modifications, whereas availability of sufficient pandemic-related information prevented these problems. The most important decisional criteria for patients under these conditions were expected side effects/complications and treatment responses.

Decision Conflicts in Clinical Care during COVID-19: A Multi-Perspective Inquiry.

Background: The early COVID-19-pandemic was characterized by changes in decision making, decision-relevant value systems and the related perception of decisional uncertainties and conflicts resulting in decisional burden and stress. The vulnerability of clinical care professionals to these decisional dilemmas has not been characterized yet. Methods: A cross-sectional questionnaire study (540 patients, 322 physicians and 369 nurses in 11 institutions throughout Germany) was carried out. The inclusion criterion was active involvement in clinical treatment or decision making in oncology or psychiatry during the first year of COVID-19. The questionnaires covered five decision dimensions (conflicts and uncertainty, resources, risk perception, perception of consequences for clinical processes, and the perception of consequences for patients). Data analysis was performed using ANOVA, Pearson rank correlations, and the Chi²-test, and for inferential analysis, nominal logistic regression and tree classification were conducted. Results: Professionals reported changes in clinical management (27.5%) and a higher workload (29.2%), resulting in decisional uncertainty (19.2%) and decisional conflicts (22.7%), with significant differences between professional groups (p < 0.005), including anxiety, depression, loneliness and stress in professional subgroups (p < 0.001). Nominal regression analysis targeting "Decisional Uncertainty" provided a highly significant prediction model (LQ p < 0.001) containing eight variables, and the analysis for "Decisional Conflicts" included six items. The classification rates were 64.4% and 92.7%, respectively. Tree analysis confirmed three levels of determinants. Conclusions: Decisional uncertainty and conflicts during the COVID-19 pandemic were independent of the actual pandemic load. Vulnerable professional groups for the perception of a high number of decisional dilemmas were characterized by individual perception and the psychological framework. Coping and management strategies should target vulnerability, enable the handling of the individual perception of decisional dilemmas and ensure information availability and specific support for younger professionals.

Differences in Stakeholders' Perception of the Impact of COVID-19 on Clinical Care and Decision-Making.

Background: Pandemics are related to changes in clinical management. Factors that are associated with individual perceptions of related risks and decision-making processes focused on prevention and vaccination, but perceptions of other healthcare consequences are less investigated. Different perceptions of patients, nurses, and physicians on consequences regarding clinical management, decisional criteria, and burden were compared. Study Design: Cross-sectional OnCoVID questionnaire studies. Methods: Data that involved 1231 patients, physicians, and nurses from 11 German institutions that were actively involved in clinical treatment or decision-making in oncology or psychiatry were collected. Multivariate statistical approaches were used to analyze the stakeholder comparisons. Results: A total of 29.2% of professionals reported extensive changes in workload. Professionals in psychiatry returned severe impact of pandemic on all major aspects of their clinical care, but less changes were reported in oncology (p < 0.001). Both patient groups reported much lower recognition of treatment modifications and consequences for their own care. Decisional and pandemic burden was intensively attributed from professionals towards patients, but less in the opposite direction. Conclusions: All of the groups share concerns about the impact of the COVID-19 pandemic on healthcare management and clinical processes, but to very different extent. The perception of changes is dissociated in projection towards other stakeholders. Specific awareness should avoid the dissociated impact perception between patients and professionals potentially resulting in impaired shared decision-making.

Cancer-testis antigen expression and its epigenetic modulation in acute myeloid leukemia.

Cancer-testis antigens (CTA) represent attractive targets for tumor immunotherapy. However, a broad picture of CTA expression in acute myeloid leukemia (AML) is missing. CTA expression was analyzed in normal bone marrow (BM) as well as in AML cell lines before and after treatment with demethylating agents and/or histone acetylase inhibitors. Presence of selected CTA with a strictly tumor-restricted expression was then determined in samples of patients with AML before and after demethylating therapy. Screening AML cell lines for the expression of 20 CTA, we identified six genes (MAGE-A3, PRAME, ROPN1, SCP-1, SLLP1, and SPO11) with an AML-restricted expression. Analyzing the expression of these CTA in blast-containing samples from AML patients (N = 64), we found all samples to be negative for MAGE-A3 and SPO11 while a minority of patients expressed ROPN1 (1.6%), SCP-1 (3.1%), or SLLP1 (9.4%). The only CTA expressed in substantial proportion of patients (53.1%) was PRAME. Following demethylating treatment with 5'-aza-2'-deoxycytidine, we observed an increased or de novo expression of CTA, in particular of SSX-2, in AML cell lines. In AML patients, we detected increased expression of PRAME and induction of SSX-2 after demethylating therapy with 5-azacytidine. With the exception of PRAME, CTA are mostly absent from AML blasts. However, demethylating treatment induces strong expression of CTA, particularly of SSX-2, in vitro and in vivo. Therefore, we propose that CTA-specific immunotherapy for AML should preferentially target PRAME and/or should be combined with the application of demethylating agents opening the perspective for alternative targets like CTA SSX-2.

Clinical and Biological Characteristics of Medullary and Extramedullary Plasma Cell Dyscrasias.

Background: Extramedullary plasma cell (PC) disorders may occur as extramedullary disease in multiple myeloma (MM-EMD) or as primary extramedullary plasmocytoma (pEMP)/solitary osseous plasmocytoma (SOP). In this study, we aimed to obtain insights into the molecular mechanisms of extramedullary spread of clonal PC. Methods: Clinical and biological characteristics of 87 patients with MM-EMD (n = 49), pEMP/SOP (n = 20) and classical MM (n = 18) were analyzed by using immunohistochemistry (CXCR4, CD31, CD44 and CD81 staining) and cytoplasmic immunoglobulin staining combined with fluorescence in situ hybridization (cIg-FISH). Results: High expression of CD44, a cell-surface glycoprotein involved in cell-cell interactions, was significantly enriched in MM-EMD (90%) vs. pEMP/SOP (27%) or classical MM (33%) (p < 0.001). In addition, 1q21 amplification by clonal PC occurred at a similar frequency of MM-EMD (33%), pEMP/SOP (57%) and classical MM (44%). Conversely, del(17p13), t(4;14) and t(14;16) were completely absent in pEMP/SOP. Besides this, 1q21 amplification was identified in 64% of not paraskeletal samples from MM-EMD or pEMP compared to 9% of SOP or paraskeletal MM-EMD/pEMP and 44% of classical MM samples, respectively (p = 0.02). Conclusion: Expression of molecules involved in homing and cytogenetic aberrations differ between MM with or without EMD and pEMP/SOP.

Unrelated stem cell transplantation after reduced intensity conditioning for patients with multiple myeloma relapsing after autologous transplantation.

From 2002 to 2007, 49 myeloma patients who relapsed following autologous SCT were included in a prospective multicenter trial to determine the efficacy of a reduced melphalan/fludarabine regimen followed by allogeneic SCT from unrelated donors. All patients showed leucocyte and platelet engraftment after a median of 15 and 19 d, respectively. Grade II-IV acute graft-versus-host disease (GvHD) occurred in 25% of patients and 35% had chronic GvHD. Overall response rate at day 100 was 95% including 46% complete remission (CR). Cumulative incidence of non-relapse mortality at 1 year was 25% [95% confidence interval (CI): 13-37%] and was significantly lower for human leucocyte antigen (HLA)-matched compared to -mismatched SCT (10% vs. 53%, P = 0.001). The cumulative incidence of relapse at 3 years was 55% (95% CI: 40-70%). After a median follow up of 43 months, the estimated 5-year progression-free and overall survival rates were 20% and 26% respectively and were significantly better for matched in CR at day 100 (41% vs. 7%, P = 0.04 and 56% vs. 16%, P = 0.02). We conclude that optimal donor selection is mandatory for a low non-relapse mortality and high relapse incidence, which remains a major concern, should be improved by including post-transplant strategies to upgrade remission status.