Germline assessment for alloHSCT candidates over 50 years: A 'Fast-Track' screening in myeloid neoplasms.

Patients aged 50 or above diagnosed with myeloid neoplasms (MNs) are typically not candidates for germline testing. However, approximately 8% carry pathogenic germline variants. Allogeneic haematopoietic stem cell transplantation (alloHSCT) remains an option for those aged over 50; neglecting germline testing could mask the risk for relative donor cell-derived MN. We propose a germline-augmented somatic panel (GASP), combining MN predisposition genes with a myeloid somatic panel for timely germline variant identification when initial testing is not indicated. Out of our 133 whole-exome-sequenced MN cases aged over 50 years, 9% had pathogenic/likely variants. GASP detected 92%, compared to 50% with somatic-only panel. Our study highlights the relevance of germline screening in MN, particularly for alloHSCT candidates without established germline-testing recommendations.

Access to assisted human reproduction techniques in Colombia: Disparity between the recognition of reproductive rights and their effective implementation.

Public funding of assisted reproduction technologies (ARTs) is a controversial issue. Some health systems have proposed public funding of ARTs. In recent years, there has been evidence of a change in the line of jurisprudence and legislation in Colombia about this topic. This article analyzes the tension between the recognition of individual sexual and reproductive rights and the common good, in terms of the sustainability of the health system and the reasonable use of limited resources to meet the health needs of the population. This article concludes that, despite regulatory progress, there has been a lack of corresponding progress in their effective implementation and the recognition of reproductive rights.

Cytogenetic Assessment and Risk Stratification in Myelofibrosis with Optical Genome Mapping.

Cytogenetic assessment in myelofibrosis is essential for risk stratification and patient management. However, an informative karyotype is unavailable in a significant proportion of patients. Optical genome mapping (OGM) is a promising technique that allows for a high-resolution assessment of chromosomal aberrations (structural variants, copy number variants, and loss of heterozygosity) in a single workflow. In this study, peripheral blood samples from a series of 21 myelofibrosis patients were analyzed via OGM. We assessed the clinical impact of the application of OGM for disease risk stratification using the DIPSS-plus, GIPSS, and MIPSS70+v2 prognostic scores compared with the standard-of-care approach. OGM, in combination with NGS, allowed for risk classification in all cases, compared to only 52% when conventional techniques were used. Cases with unsuccessful karyotypes (n = 10) using conventional techniques were fully characterized using OGM. In total, 19 additional cryptic aberrations were identified in 9 out of 21 patients (43%). No alterations were found via OGM in 4/21 patients with previously normal karyotypes. OGM upgraded the risk category for three patients with available karyotypes. This is the first study using OGM in myelofibrosis. Our data support that OGM is a valuable tool that can greatly contribute to improve disease risk stratification in myelofibrosis patients.

Healthcare resource utilization in adult patients with relapsed/refractory FLT3 mutated acute myeloid leukemia: A retrospective chart review from Spain.

BACKGROUND: Information regarding impact on healthcare systems of relapsed or refractory (R/R) FLT3 mutated (FLT3mut) acute myeloid leukemia (AML) is scarce. OBJECTIVE: To assess the time and reimbursement associated with hospitalizations of patients with R/R FLT3mut AML in a tertiary Spanish hospital. METHODS: Retrospective review of medical charts identified patients aged ≥ 18 years with R/R FLT3mut AML between 1998 and 2018. Data were collected from the date of first diagnosis of R/R FLT3mut AML (index) until death or loss to follow-up. The primary end point was duration and frequency of hospitalization, use of outpatient resources and transfusion burden. Reimbursement associated with hospitalizations (including associated chemotherapy) was also assessed. RESULTS: Thirty-eight patients were eligible for inclusion. Their median age was 52 years, and 30 (79%) received intensive salvage chemotherapy; FLAG-IDA-based regimens were the most frequent (24 patients, 63%). Overall, there were 150 hospitalizations (mean 3.9/patient; mean duration 21 days). Patients spent a mean of 24% of the study period in hospital. Total mean reimbursement was €108 293 per patient; the majority (€89 834) attributable to inpatient stays (€22 576 /hospitalization). During chemotherapy period (prior to first alloHSCT), there were 73 hospitalizations (mean duration 22 days); mean reimbursement was €19 776 per hospitalization and €49 819 per patient. AlloHSCT (n = 16) involved 77 hospitalizations (mean duration 21 days), mean reimbursement €25 231/hospitalization and €131 515 per patient. CONCLUSION: Data from this study suggest that there is a substantial healthcare resource utilization and cost burden on R/R FLT3mut AML patients in Spain receiving active treatments.

Qualitative Analysis by Experts of the Essential Elements of the Nursing Practice Environments Proposed by the TOP10 Questionnaire of Assessment of Environments in Primary Health Care.

Background: A short TOP10 scale based on the Practice Environment Scale-Nursing Work Index questionnaire measures the characteristics of nursing work environments. Positive environments result in better quality care and health outcomes. Objective: To identify a small number of core elements that would facilitate more effective interventions by nurse managers, and compare them with the essential elements proposed by the TOP10. Method: Qualitative research by a nominal group of eight experts. The content analysis was combined with descriptive data. Results: Ten most important items were selected and analyzed by the expert group. A high level of consensus in four items (2, 15, 20, 31) and an acceptable consensus in five items was reached (6, 11, 14, 18, 26). The tenth item in the top ten was selected from content analysis (19). The expert group agreed 90% with the elements selected as essential to the TOP10. Conclusion: The expert group achieved a high level of consensus that supports 90% of the essential elements of primary care settings proposed by the TOP10 questionnaire. Organizational changes implemented by managers to improve working environments must be prioritized following our results, so care delivery and health outcomes can be further improved.

Dexamethasone does not prevent malignant cell reintroduction in leukemia patients undergoing ovarian transplant: risk assessment of leukemic cell transmission by a xenograft model.

STUDY QUESTION: Does dexamethasone (DXM) incubation avoid the reintroduction of leukemic malignant cells after ovarian tissue retransplantation in vivo? SUMMARY ANSWER: DXM incubation prior to retransplantation of ovarian tissue does not prevent reintroduction of leukemic cells. WHAT IS KNOWN ALREADY: Retransplantation of cryopreserved ovarian cortex from patients diagnosed with acute lymphoblastic leukemia (ALL) involves a risk of reintroducing malignant cells. DXM treatment is effective at inducing leukemic cell death in vitro. STUDY DESIGN, SIZE, DURATION: This was an experimental study where ovarian cortex fragments from patients with ALL were randomly allocated to incubation with or without DXM (n = 11/group) and grafted to 22 immunodeficient mice for 6 months. In a parallel experiment, 22 immunodeficient mice were injected i.p. with varying amounts of RCH-ACV ALL cells (human leukemia cell line) and maintained for 4 months. PARTICIPANTS/MATERIALS, SETTING, METHODS: Cryopreserved ovarian fragments from patients with ALL were exposed in vitro to 0.4 µM DXM or basal media (control) prior to xenograft into ovariectomized severe combined immunodeficiency (SCID) mice (experiment 1). After 6 months of monitoring, leukemia cell contamination was assessed in ovarian grafts and mouse organs by histology, PCR (presence of mouse mtDNA and absence of p53 were together considered a negative result for the presence of human cells) and detection of immunoglobulin monoclonality and specific ALL markers if present in the patient.In experiment 2, a series of 22 immunodeficient female mice was injected with specific doses of the leukemia cell line RCH-ACV (103 - 5 × 106, n = 4/group) to assess the engraftment competence of the SCID model. MAIN RESULTS AND THE ROLE OF CHANCE: ALL metastatic cells were detected, by PCR, in five DXM-treated and one control human ovarian tissue graft as well as in a control mouse liver, although malignant cell infiltration was not detected by histology in any sample after 6 months. In total, minimal residual disease was present in three DXM-treated and three control mice.RCH-ACV cells were detected in liver and spleen samples after the injection of as little as 103 cells, although only animals receiving 5 × 106 cells developed clinical signs of disease and metastases. LIMITATIONS, REASONS FOR CAUTION: This is an experimental study where the malignant potential of leukemic cells contained in human ovarian tissues has been assessed in immunodeficient mice. WIDER IMPLICATIONS OF THE FINDINGS: These results indicate that DXM incubation prior to retransplantation of ovarian tissue does not prevent reintroduction of leukemic cells. Therefore, caution should be taken in retransplanting ovarian tissue from patients with leukemia until safer systems are developed, as leukemic cells present in ovarian grafts were able to survive, proliferate and migrate after cryopreservation and xenograft. STUDY FUNDING/COMPETING INTEREST(S): Funded by the Regional Valencian Ministry of Education (PROMETEO/2018/137) and by the Spanish Ministry of Economy and Competitiveness (PI16/FIS PI16/01664 and PTQ-16-08222 for S.H. participation). There are no competing interests.

Time and Cost of Hospitalisation for Salvage Therapy in Adults with Philadelphia Chromosome-Negative B Cell Precursor Relapsed or Refractory Acute Lymphoblastic Leukaemia in Spain.

BACKGROUND: Philadelphia chromosome-negative (Ph-) relapsed or refractory (R/R) B-cell precursor acute lymphoblastic leukaemia (ALL) is rare, and information on its impact on healthcare systems is scarce. OBJECTIVE: To quantify the time and reimbursement associated with hospitalisations of patients with R/R ALL in a Spanish hospital. METHODS: Retrospective review of medical charts identified patients aged ≥ 18 years with Ph- R/R ALL hospitalised between 1998 and 2014. Data were collected from the date of first diagnosis of R/R ALL (index) until death or loss to follow-up. The primary endpoint was the proportion of time hospitalised during chemotherapy. Reimbursement associated with hospitalisations (including associated chemotherapy) was also assessed. RESULTS: Thirty-two patients were eligible for inclusion. Their median age was 41 years, and 50% had a first remission duration of ≤ 1 year; 34% had undergone allogeneic haematological stem-cell transplantation (alloHSCT). Overall, 31 patients had received intensive salvage chemotherapy, during which there were 42 hospitalisations (mean 1.4/patient; mean duration 26 days). Patients spent a mean of 71% of the chemotherapy period in hospital. Total mean reimbursement was €26,417 per patient, almost all (€25,723) attributable to inpatient stays (€18,986/hospitalisation). From the index date to death or loss to follow-up (excluding alloHSCT-related hospitalisations), there were 80 hospitalisations (mean duration 24 days); mean reimbursement was €16,692 per hospitalisation and €41,730 per patient. AlloHSCT (n = 8) involved 18 hospitalisations (mean reimbursement €39,782/hospitalisation; €89,510/patient). CONCLUSION: Data from this sample of patients suggest that hospitalisations in R/R ALL are lengthy and associated with high costs in Spain.

Integrating clinical features and genetic lesions in the risk assessment of patients with chronic myelomonocytic leukemia.

Chronic myelomonocytic leukemia (CMML) is a myelodysplastic/myeloproliferative neoplasm with variable clinical course. To predict the clinical outcome, we previously developed a CMML-specific prognostic scoring system (CPSS) based on clinical parameters and cytogenetics. In this work, we tested the hypothesis that accounting for gene mutations would further improve risk stratification of CMML patients. We therefore sequenced 38 genes to explore the role of somatic mutations in disease phenotype and clinical outcome. Overall, 199 of 214 (93%) CMML patients carried at least 1 somatic mutation. Stepwise linear regression models showed that these mutations accounted for 15% to 24% of variability of clinical phenotype. Based on multivariable Cox regression analyses, cytogenetic abnormalities and mutations in RUNX1, NRAS, SETBP1, and ASXL1 were independently associated with overall survival (OS). Using these parameters, we defined a genetic score that identified 4 categories with significantly different OS and cumulative incidence of leukemic evolution. In multivariable analyses, genetic score, red blood cell transfusion dependency, white blood cell count, and marrow blasts retained independent prognostic value. These parameters were included into a clinical/molecular CPSS (CPSS-Mol) model that identified 4 risk groups with markedly different median OS (from >144 to 18 months, hazard ratio [HR] = 2.69) and cumulative incidence of leukemic evolution (from 0% to 48% at 4 years, HR = 3.84) (P < .001). The CPSS-Mol fully retained its ability to risk stratify in an independent validation cohort of 260 CMML patients. In conclusion, integrating conventional parameters and gene mutations significantly improves risk stratification of CMML patients, providing a robust basis for clinical decision-making and a reliable tool for clinical trials.

Promotion of emotional wellbeing in oncology inpatients using VR.

INTRODUCTION: In Psycho-oncology, VR has been utilized mainly to manage pain and distress associated to medical procedures and chemotherapy, with very few applications aimed at promotion of wellbeing in hospitalized patients. Considering this, it was implemented a psychological intervention that uses VR to induce positive emotions on adult oncology inpatients with the purpose of evaluating its utility to improve emotional wellbeing in this population. METHOD: Sample was composed of 33 patients (69.7% men, aged from 41 to 85 years old; X=62.1; SD=10.77). Intervention lasted 4 sessions of 30 minutes, along one week. In these sessions, two virtual environments designed to induce joy or relaxation were used. Symptoms of depression and anxiety (Hospital Anxiety and Depression Scale, HADS) and level of happiness (Fordyce Scale) were assessed before and after the VR intervention. Also, Visual Analogue Scales (VAS) were used to assess emotional state and physical discomfort before and after each session. RESULTS: There were significant improvements in distress and level of happiness after the VR intervention. Also, it was detected an increment in positive emotions and a decrease in negative emotions after sessions. CONCLUSIONS: Results emphasize the potential of VR as a positive technology that can be used to promote wellbeing during hospitalization, especially considering the shortness of the intervention and the advanced state of disease of the participants. Despite the encouraging of these results, it is necessary to confirm them in studies with larger samples and control groups.

Rapid screening of ASXL1, IDH1, IDH2, and c-CBL mutations in de novo acute myeloid leukemia by high-resolution melting.

Recently, many novel molecular abnormalities were found to be distinctly associated with acute myeloid leukemia (AML). However, their clinical relevance and prognostic implications are not well established. We developed a new combination of high-resolution melting assays on a LightCycler 480 and direct sequencing to detect somatic mutations of ASXL1 (exon 12), IDH1 (exon 4), IDH2 (exon 4), and c-CBL (exons 8 and 9) genes to know their incidence and prognostic effect in a cohort of 175 patients with de novo AML: 16 patients (9%) carried ASXL1 mutations, 16 patients had IDH variations (3% with IDH1(R132) and 6% with IDH2(R140)), and none had c-CBL mutations. Patients with ASXL1 mutations did not harbor IDH1, [corrected] or CEBPA mutations, and a combination of ASXL1 and IDH2 mutations was found only in one patient. In addition, we did not find IDH1 and FLT3 or CEBPA mutations concurrently or IDH2 with CEBPA. IDH1 and IDH2 mutations were mutually exclusive. Alternatively, NPM1 mutations were concurrently found with ASXL1, IDH1, or IDH2 with a variable incidence. Mutations were not significantly correlated with any of the clinical and biological features studied. High-resolution melting is a reliable, rapid, and efficient screening technique for mutation detection in AML. The incidence for the studied genes was in the range of those previously reported. We were unable to find an effect on the outcome.