Chemotherapy or allogeneic transplantation in high-risk Philadelphia chromosome-negative adult lymphoblastic leukemia.

The need for allogeneic hematopoietic stem cell transplantation (allo-HSCT) in adults with Philadelphia chromosome-negative (Ph-) acute lymphoblastic leukemia (ALL) with high-risk (HR) features and adequate measurable residual disease (MRD) clearance remains unclear. The aim of the ALL-HR-11 trial was to evaluate the outcomes of HR Ph- adult ALL patients following chemotherapy or allo-HSCT administered based on end-induction and consolidation MRD levels. Patients aged 15 to 60 years with HR-ALL in complete response (CR) and MRD levels (centrally assessed by 8-color flow cytometry) <0.1% after induction and <0.01% after early consolidation were assigned to receive delayed consolidation and maintenance therapy up to 2 years in CR. The remaining patients were allocated to allo-HSCT. CR was attained in 315/348 patients (91%), with MRD <0.1% after induction in 220/289 patients (76%). By intention-to-treat, 218 patients were assigned to chemotherapy and 106 to allo-HSCT. The 5-year (±95% confidence interval) cumulative incidence of relapse (CIR), overall survival (OS), and event-free survival probabilities for the whole series were 43% ± 7%, 49% ± 7%, and 40% ± 6%, respectively, with CIR and OS rates of 45% ± 8% and 59% ± 9% for patients assigned to chemotherapy and of 40% ± 12% and 38% ± 11% for those assigned to allo-HSCT, respectively. Our results show that avoiding allo-HSCT does not hamper the outcomes of HR Ph- adult ALL patients up to 60 years with adequate MRD response after induction and consolidation. Better postremission alternative therapies are especially needed for patients with poor MRD clearance. This trial was registered at www.clinicaltrials.gov as # NCT01540812.

Outcomes and prognostic factors of adults with refractory or relapsed T-cell acute lymphoblastic leukemia included in measurable residual disease-oriented trials.

Despite high complete remission (CR) rates with frontline therapy, relapses are frequent in adults with T-cell acute lymphoblastic leukemia (T-ALL) with limited salvage options. We analyzed the outcomes and prognostic factors for CR to salvage therapy and overall survival (OS) of patients with R/R T-ALL included in two prospective measurable residual disease-oriented trials. Seventy-five patients (70 relapsed, 5 refractory) were identified. Relapses occurred in bone marrow, isolated or combined in 50 patients, and in the central nervous system (CNS; isolated or combined) in 20. Second CR was attained in 30/75 patients (40%). Treatment with FLAG-Ida and isolated CNS relapse were independently associated with a higher CR rate after first salvage therapy. The median OS was 6.2 (95% confidence interval [CI], 3.9-8.6) months, with a 4-year OS probability of 18% (95% CI, 9%-27%). No differences in survival were observed according to the treatment with hematopoietic stem cell transplantation in patients in CR after first salvage therapy. Multivariable analysis showed a ≥12-month interval between first CR and relapse, CR after first salvage therapy and isolated CNS relapse as favorable prognostic factors for OS with hazard ratios (HR) (95% CI) of 1.931 (1.109-3.362), 2.958 (1.640-5.334), and 2.976 (1.157-7.655), respectively. This study confirms the poor outcomes of adults with R/R T-ALL among whom FLAG-Ida was the best of the rescue therapies evaluated. Late relapse, CR after first rescue therapy and isolated CNS relapse showed prognostic impact on survival. More effective rescue therapies are needed in adults with R/R T-ALL.

Finding Effective Adjustment Levels for Upper Limb Exergames: Focus Group Study With Children With Physical Disabilities.

BACKGROUND: We developed the Blexer system consisting of a database and a web interface for therapists that can host different types of adaptive and personally configurable virtual reality exergames based on Kinect (Microsoft Corp) motion capture to provide entertaining exercises for children with motor disabilities. It allows for parameter adjustment and the monitoring of results remotely, thereby providing a useful tool to complement traditional physical therapy sessions with home exercises. OBJECTIVE: The aim of this study was to observe the motor benefits achieved through the use of a video exergame and the importance and implications of correctly setting the game's difficulty parameters. METHODS: This was an observational case study of 6 children with different physical disabilities receiving physical therapy at school combined with the use of a fully configurable exergame under research that forms a part of the Blexer environment. The game integrates 4 repeatedly appearing upper limb exercises with individually adjustable difficulties (intermittent arm rising, arm forward and backward movement, rising and holding of one arm, and trunk control in all directions). The outcomes were 3 assessments of 2 efficacy measures: Box and Block Test and Jebsen Taylor Hand Function Test. RESULTS: A total of 5 children with cerebral palsy (mean 8.4, SD 2.7 years; Gross Motor Function Classification II-2/5, 40%; III-2/5, 40%; and IV-1/5, 20%) and 1 child with obstetric brachial plexus palsy (aged 8 years; Mallet Classification III) received between 8 and 11 sessions of training (10-20 minutes per session), depending on age, motivation, and fatigue. Significant associations were observed between game parameter settings and improvements in motor function, on the one hand, and between the type of improvement and disability severity, on the other: with adjusted game parameters goal and time in the range of 70% to 100%, only less affected children improved in the Box and Block Test (+11 blocks vs -1 block), and more affected children improved more in the Jebsen Taylor Hand Function Test (+90 seconds vs +27 seconds). CONCLUSIONS: When defining the difficulty parameters for an exergame, we suggest a classification in levels ranging from very easy to very hard. For practical use, we suggest setting the difficulty for the player to an easy or medium level rather than high-commitment goals, as this leads to a longer playtime with more fun and, therefore, seems to improve the results of the game and, consequently, mobility.

Efficacy and safety of native versus pegylated Escherichia coli asparaginase for treatment of adults with high-risk, Philadelphia chromosome-negative acute lymphoblastic leukemia.

Native or pegylated (PEG) asparaginase (ASP) are commonly used in treatment of acute lymphoblastic leukemia (ALL), but have been scarcely compared in the same trial in adult patients. Native vs. PEG-ASP administered according to availability in each center were prospectively evaluated in adults with high-risk ALL. Ninety-one patients received native ASP and 35 PEG-ASP in induction. No significant differences were observed in complete remission, minimal residual disease levels after induction and after consolidation, disease-free survival, and overall survival. No significant differences in grades 3-4 toxicity were observed in the induction period, although a trend for higher hepatic toxicity was observed in patients receiving PEG-ASP. In this trial the type of ASP did not influence patient response and outcome.

Feasibility and results of subtype-oriented protocols in older adults and fit elderly patients with acute lymphoblastic leukemia: Results of three prospective parallel trials from the PETHEMA group.

BACKGROUND AND OBJECTIVE: The prognosis of acute lymphoblastic leukemia (ALL) is poor in older adults and elderly patients, and subtype-oriented prospective trials are scarce in these patients. We present the results of three prospective parallel subtype-oriented protocols in fit patients older than 55 years. PATIENTS AND METHODS: In 2008, three prospective phase II trials in patients older than 55 years were activated: ALLOLD07 for Philadephia (Ph) chromosome-negative ALL, ALLOPH07 for Ph-positive ALL, and BURKIMAB08 for mature B-ALL. Early death (ED), complete remission (CR), disease-free survival (DFS), overall survival (OS) and toxicity were analyzed. RESULTS: 56, 53 and 21 patients from the ALLOLD07, ALLOPH07 and BURKIMAB08 trials, respectively, were evaluable. CR was 74%, 87% and 70%, with an ED rate of 13%, 11% and 15%, respectively. The medians of DFS were 8 and 38 months for ALLOLD07 and ALLOPH07 protocols, not being achieved in the BURKIMAB08 trial (p=0.001), and the median OS was 12, 37 and 25 months, respectively (p=0.030). Neutropenia, thrombocytopenia and infections were less frequent in the ALLOPH07 trial vs. ALLOLD07 and BURKIMAB trials, and renal toxicity and mucositis were more frequent in the BURKIMAB08 trial vs. the ALLOLD07 and ALLOPH07 trials. ECOG score and WBC count had prognostic significance for OS in ALLOPH07 and BURKIMAB08 trials, whereas no prognostic factors were identified in ALLOLD07 protocol. CONCLUSION: Subtype-oriented treatment had an impact in the outcome of older adults with ALL. The poorest outcome was observed in Ph-negative non-Mature B-cell ALL patients, for whom improvements in therapy are clearly needed.

Development of the management for parenteral nutrition traceability in a standard hospital.

OBJECTIVE: to develop the traceability control and the hazard analysis in the processes of parenteral nutrients (PN). METHOD: a standardized graphical notation was generated, describing in detail each of the stages in the overall process. The presence of hazards was analysed by sequencing decisions. The existence of Control Points (CP) or Critical Control Points (CCP) was estimated by Criticality Index (CI) for each hazard taking into account the probability of occurrence and the severity of the damage. The threshold for the IC was set in 6. RESULTS: a specific flow chart for the management and traceability of PN was obtained, defining each of the stages in CPs (validation and transcription of the prescription and administration) or CCPs (preparation, storage and infusion pump -flow and filter-). Stages regarding the delivery, the recovery and the recycle of the packing material of PNs are not considered CPs and, therefore, they were not included in the dashboard. CONCLUSIONS: PN must be dealt with in the frame of a standardized management system in order to improve patient safety, clinical relevance, maximize resource efficiency and minimize procedural issues. The proposed system provides a global management model whose steps are fully defined, allowing monitoring and verification of PN. It would be convenient to make use of a software application to support the monitoring of the traceability management and to store the historical records in order to evaluate the system.

Objetivo: desarrollar el control de la trazabilidad y el análisis de riesgos en el proceso de mezcla de nutrientes parenterales (NP). Método: se diseñó la notación gráfica normalizada, caracterizando cada una de las etapas dentro del proceso global. Se analizó la presencia de riesgos mediante la secuenciación de decisiones. La existencia de Puntos de Control (PC) o de Puntos Críticos de Control (PCC) se calculó mediante el Índice de Criticidad (IC) para cada uno de los riesgos, teniendo en cuenta la probabilidad del suceso y la gravedad de los daños. El punto de corte del IC se estableció en 6. Resultados: se obtuvo el diagrama de flujo específico para la gestión y trazabilidad de la NP, caracterizándose cada una de las etapas en PC (validación y transcripción de la prescripción y administración) o PCC (preparación, conservación y bomba de infusión -flujo y filtro-). Las etapas de entrega de la NP y de recuperación y reciclado del material de envasado no se consideraron PC y, en consecuencia, no fueron incluidos en el cuadro de gestión. Conclusiones: la NP debe integrarse en un sistema normalizado de gestión con el fin de mejorar la seguridad del paciente y la pertinencia clínica, maximizar la eficiencia de los recursos y minimizar los incidentes procesales. El sistema propuesto permite establecer una gestión global cuyas etapas quedan totalmente caracterizadas, permitiendo su control y verificación. Sería deseable disponer de una aplicación informática que facilitara el seguimiento de la gestión de la trazabilidad y tener un histórico de los registros que permita evaluar el sistema.

Alexithymia--state or trait?

Alexithymia refers to a specific disturbance in emotional processing that is manifested by difficulties in identifying and verbalizing feelings and a tendency to focus on and amplify the somatic sensations that accompany emotional arousal. Alexithymia is conceptualized both as an affect-deficit disorder and a continuous personality variable. The main purpose of the present study was to investigate the stability levels of alexithymia with regard to changes in emotional distress levels caused by university exams. We tested 20 university students at four different times, before and after the exams. Alexithymic features and self-reported emotional distress (trait anxiety and physical symptoms) were measured. Whereas emotional distress measures changed significantly during the diverse phases, the level of alexithymia remained unchanged. We therefore conclude that alexithymia represents a constant trait.