Single agent subcutaneous blinatumomab for advanced acute lymphoblastic leukemia.

Blinatumomab is a BiTE® (bispecific T-cell engager) molecule that redirects CD3+ T-cells to engage and lyse CD19+ target cells. Here we demonstrate that subcutaneous (SC) blinatumomab can provide high efficacy and greater convenience of administration. In the expansion phase of a multi-institutional phase 1b trial (ClinicalTrials.gov, NCT04521231), heavily pretreated adults with relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL) received SC blinatumomab at two doses: (1) 250 µg once daily (QD) for week 1 and 500 µg three times weekly (TIW) thereafter (250 µg/500 µg) or (2) 500 µg QD for week 1 and 1000 µg TIW thereafter (500 µg/1000 µg). The primary endpoint was complete remission/complete remission with partial hematologic recovery (CR/CRh) within two cycles. At the data cutoff of September 15, 2023, 29 patients were treated: 14 at the 250 µg/500 µg dose and 13 at 500 µg/1000 µg dose. Data from two ineligible patients were excluded. At the end of two cycles, 12 of 14 patients (85.7%) from the 250 µg/500 µg dose achieved CR/CRh of which nine patients (75.0%) were negative for measurable residual disease (MRD; <10-4 leukemic blasts). At the 500 µg/1000 µg dose, 12 of 13 patients (92.3%) achieved CR/CRh; all 12 patients (100.0%) were MRD-negative. No treatment-related grade 4 cytokine release syndrome (CRS) or neurologic events (NEs) were reported. SC injections were well tolerated and all treatment-related grade 3 CRS and NEs responded to standard-of-care management, interruption, or discontinuation. Treatment with SC blinatumomab resulted in high efficacy, with high MRD-negativity rates and acceptable safety profile in heavily pretreated adults with R/R B-ALL.

Percepción de riesgo de contagio de la COVID-19 en estudiantes de una universidad estatal de Chile / COVID-19 risk perception among students at a state university in Chile

RESUMEN Objetivo: Evaluar el nivel de percepción de riesgo de contagio de la COVID-19 frente al retorno a las clases presenciales y analizar esta percepción con variables sociodemográficas y de salud asociadas a esta enfermedad. Materiales y métodos: Estudio transversal y prospectivo. Se adaptó el cuestionario para evaluar la percepción de riesgo de contagio de la COVID-19 (PCR-CV19) en 532 universitarios. Además, se realizó un análisis de asociación de las cuatro dimensiones del PCR-CV19 (vulnerabilidad cognitiva, vulnerabilidad emocional, conductas de riesgo-protección y gravedad) y el índice de percepción con variables sociodemográficas y de salud. Se utilizaron técnicas estadísticas: análisis de varianza (ANOVA) de una vía (OneWay ANOVA), previa verificación de la prueba de normalidad Shapiro-Wilk y la prueba de Levene para la homogeneidad y la prueba post-hoc de Tukey o Ganes-Howell. Estos análisis se realizaron en el programa estadístico JAMOVI, versión 1.2.2. Resultados: Se evidenció un nivel moderado de percepción de riesgo de contagio, en donde las dimensiones de las conductas de riesgo-protección y gravedad se identificaron como las más relevantes; asimismo, se encontró asociación entre las dimensiones del PCR-CV19 y el índice de percepción con las variables edad, género, consumo de alcohol e indicadores de salud física y mental (ansiedad y depresión) y las experiencias vividas con la enfermedad de la COVID-19. Los aspectos de vulnerabilidad cognitiva y emocional fueron las dimensiones más sensibles en la evaluación de la percepción. Conclusiones: Seguimos enfrentando condiciones de riesgo que surgen de manera constante, lo que hace necesario mantener un esquema de vigilancia de la percepción de riesgo que experimenta la población. En los universitarios, los aspectos de vulnerabilidad cognitiva y emocional fueron las dimensiones más sensibles en la evaluación de la percepción del riesgo y las experiencias vividas con la COVID-19 (enfermedad o muerte). El hecho de que los universitarios no se sientan vulnerables y/o no perciban la gravedad asociada al contagio puede afectar sus conductas de autocuidado. Estos resultados tienen implicaciones claves para la salud pública, por lo que se requiere un abordaje intersectorial, con el objetivo de contar con información relevante para enfrentar futuras pandemias.

ABSTRACT Objective: To evaluate the level of COVID-19 risk perception (PCR-CV19) by returning to in-person classes and to analyze this perception with sociodemographic and health variables associated with such disease. Materials and methods: A cross-sectional and prospective study. The questionnaire was adapted to assess the PCR-CV19 among 532 university students. Moreover, an association analysis of the four dimensions of the PCR-CV19 (cognitive vulnerability, emotional vulnerability, risky-protective behaviors and severity) and the perception index was performed with sociodemographic and health variables. The following statistical methods were used: one-way analysis of variance (ANOVA), Shapiro-Wilk test for normality, Levene's test for homogeneity of variances and Tukey's honest significant difference or Games-Howell post hoc tests. These analyses were performed using the Jamovi statistical software, version 1.2.2. Results: A moderate level of PCR-CV19 was found, where the most relevant dimensions were risky-protective behaviors and severity. In addition, there was an association between the dimensions PCR-CV19 and perception index with the variables age, gender, alcohol consumption, physical and mental health indicators (anxiety and depression), and experiences with COVID-19. Cognitive vulnerability and emotional vulnerability were the most sensitive dimensions in the evaluation of the PCR-CV19. Conclusions: We continue to face constant risk conditions, thus making it necessary to maintain a surveillance scheme of the PCR-CV19 experienced by the population. In university students, cognitive vulnerability and emotional vulnerability were the most sensitive dimensions in the evaluation of PCR-CV19 and experiences with COVID-19 (illness or death). The fact that university students do not feel vulnerable and/or do not perceive the severity associated with COVID-19 transmission may affect their self-care behaviors. These results have key implications for public health; therefore, an intersectoral approach is required to have relevant information in order to face future pandemics.

Incidence, risk factors, and outcomes of second neoplasms in patients with acute promyelocytic leukemia: the PETHEMA-PALG experience.

The most important challenges in acute promyelocytic leukemia (APL) is preventing early death and reducing long-term events, such as second neoplasms (s-NPLs). We performed a retrospective analysis of 2670 unselected APL patients, treated with PETHEMA "chemotherapy based" and "chemotherapy free" protocols. Only de novo APL patients who achieved complete remission (CR) and completed the three consolidation cycles were enrolled into the analysis. Out of 2670 APL patients, there were 118 (4.4%) who developed s-NPLs with the median latency period (between first CR and diagnosis of s-NPL) of 48.0 months (range 2.8-231.1): 43.3 (range: 2.8-113.9) for s-MDS/AML and 61.7 (range: 7.1-231.1) for solid tumour. The 5-year CI of all s-NPLs was of 4.43% and 10 years of 7.92%. Among s-NPLs, there were 58 cases of s-MDS/AML, 3 cases of other hematological neoplasms, 57 solid tumours and 1 non-identified neoplasm. The most frequent solid tumour was colorectal, lung and breast cancer. Overall, the 2-year OS from diagnosis of s-NPLs was 40.6%, with a median OS of 11.1 months. Multivariate analysis identified age of 35 years (hazard ratio = 0.2584; p < 0.0001) as an independent prognostic factor for s-NPLs. There were no significant differences in CI of s-NPLs at 5 years between chemotherapy-based vs chemotherapy-free regimens (hazard ratio = 1.09; p = 0.932). Larger series with longer follow-up are required to confirm the potential impact of ATO+ATRA regimens to reduce the incidence of s-NPLs after front-line therapy for APL.

Calidad de vida y factores de influencia en universitarios chilenos para el retorno a clases presenciales por la pandemia de Covid-19 / Quality of Life and Influence Factors in Chilean University Students for the Return to Face-to-Face Classes Due to the Covid-19 Pandemic / Qualidade de vida e fatores de influência em estudantes universitários chilenos no retorno às aulas presenciais devido à pandemia de Covid-19

Las afectaciones en la salud mental han sido una temática de interés presente en el contexto de pandemia por Covid-19. Por lo tanto, este trabajo tuvo como objetivo evaluar la calidad de vida percibida y otras variables asociadas en estudiantes universitarios frente al retorno a clases presenciales. Se definió el índice de calidad de vida (icv) a través del instrumento MQLI-Sp, se analizó junto a otras variables de contexto y salud en un estudio transversal, de alcance descriptivo y relacional, con una muestra de 532 estudiantes. Entre los resultados se destacan asociaciones significativas entre el icv con las variables: género, cambio de vivienda por el retorno a la presencialidad, el hecho de convivir con personas con alto riesgo en salud por Covid-19 y la percepción de la vacuna como una medida eficaz. Además, se estableció que quienes se vacunaron, permanecieron en su lugar de vivienda, no vivían con personas de alto riesgo, no tenían a alguien cercano con diagnóstico Covid, no consumían tabaco, practicaban deporte, no eran obesos y no presentaban un diagnóstico de ansiedad, estrés o depresión reportaron un icv significativamente mayor. En conclusión, hacer actividad física y no manifestar síntomas de depresión pueden considerarse como varia-bles que favorecieron la calidad de vida ante el retorno a las clases presenciales.

The effects on mental health have been a topic of interest present in the context of the Covid-19 pandemic. Therefore, this work aimed to evaluate the perceived quality of life and other associated variables in university students when faced with the return to face-to-face classes. The quality of life index (icv) was defined through the MQLI-Sp instrument, it was analyzed together with other context and health variables in a cross-sectional study, descriptive and relational in scope, with a sample of 532 students. Among the results, significant associations stand out between the icv with the variables: gender, change of home due to the return to face-to-face attendance, the fact of living with people at high health risk due to Covid-19 and the perception of the vaccine as a measure effective. In addition, it was established that those who were vaccinated, remained in their place of residence, did not live with high-risk people, did not have someone close to them with a Covid diagnosis, did not consume tobacco, practiced sports, were not obese and did not present anxiety, stress and/or depression reported a significantly higher icv. In conclusion, doing physical activity and not presenting symptoms of depression can be considered as variables that favored the quality of life before returning to face-to-face classes.

Os problemas de saúde mental têm sido um tema de interesse atual no contexto da pandemia da Covid-19. Portanto, este trabalho teve como objetivo avaliar a qualidade de vida percebida e outras variáveis associadas, em estudantes universitários, no retorno às aulas presenciais. O índice de qualidade de vida (iqv) foi definido através do instrumento MQLI-sp, foi analisado conjuntamente com outras variáveis de contexto e de saúde num estudo transversal, de âmbito descritivo e relacional, com uma amostra de 532 estudantes. Entre os resultados destacamse associações significativas entre o iqv e as variáveis: sexo, mudança de residência devido ao retorno à presencialidade, o fato de conviver com pessoas de alto risco à saúde devido à Covid-19 e a percepção da vacina como medida efi-caz. Além disso, ficou estabelecido que aqueles que foram vacinados permaneceram no local de residência, não conviveram com pessoas de alto risco, não tinham alguém próximo com diagnóstico de Covid, não consumiam tabaco, praticavam esportes, não eram obesos e sem diagnóstico de ansiedade, estresse e/ou depressão, foram os indivíduos que relataram iqvsignificativamente maior. Em conclusão, fazer atividade física e não apresentar sintomas de depressão podem ser consideradas variáveis que favoreceram a qualidade de vida no retorno às aulas presenciais.

Results of the compassionate program of inotuzumab ozogamicin for adult patients with relapsed or refractory acute lymphoblastic leukemia in Spain.

INTRODUCTION: The prognosis of relapsed B cell precursor acute lymphoblastic leukemia (B-ALL) is poor and few patients can be successfully rescued with conventional therapies. Inotuzumab ozogamicin (IO), an antibody against the CD22 antigen linked to calicheamicin, has been approved as a rescue treatment in relapsed/refractory (R/R) B-ALL. PATIENTS AND METHODS: This was an observational, retrospective, multicenter study of adult patients included in the Spanish program of compassionate use of IO in centers from the PETHEMA group (Programa Español de Tratamientos en Hematología). RESULTS: Thirty-four patients with a median age of 43 years (range, 19-73) were included. Twenty patients (59%) were refractory to the last treatment, IO treatment was given as ≥3rd salvage treatment in 25 patients (73%) and 20 patients (59%) received allogeneic hematopoietic stem cell transplantation before IO treatment. After a median of 2 cycles of IO, 64% of patients achieved complete response (CR)/complete response with incomplete recovery. The median response duration, progression-free survival and overall survival (OS) were 4.7 (95%CI, 2.4-7.0 months), 3.5 (95%CI, 1.0-5.0 months) and 4 months (95%CI, 1.9-6.1 months) respectively, with better OS for patients with relapsed B-ALL versus refractory disease (10.4 vs. 2.5 months, respectively) (p = .01). There was a trend for better OS for patients with first CR duration >12 months (7.2 months [95%CI, 3.2-11.2] vs. 3 months [95% CI, 1.8-4.2] respectively) (p = .054). There was no sinusoidal obstruction syndrome (SOS) event during IO treatment, but three patients (9%) developed grade 3-4 SOS during alloHSCT after IO treatment. CONCLUSIONS: Our study showed slightly inferior outcomes of the pivotal trial probably due to poorer risk factors and late onset of IO therapy of recruited patients. Our results support early use of IO in relapsed/refractory ALL patients.

Genomics improves risk stratification of adults with T-cell acute lymphoblastic leukemia enrolled in measurable residual disease-oriented trials.

Genetic information has been crucial to understand the pathogenesis of T-cell acute lymphoblastic leukemia (T-ALL) at diagnosis and at relapse, but still nowadays has a limited value in a clinical context. Few genetic markers are associated with the outcome of T-ALL patients, independently of measurable residual disease (MRD) status after therapy. In addition, the prognostic relevance of genetic features may be modulated by the specific treatment used. We analyzed the genetic profile of 145 T-ALL patients by targeted deep sequencing. Genomic information was integrated with the clinicalbiological and survival data of a subset of 116 adult patients enrolled in two consecutive MRD-oriented trials of the Spanish PETHEMA (Programa Español de Tratamientos en Hematología) group. Genetic analysis revealed a mutational profile defined by DNMT3A/ N/KRAS/ MSH2/ U2AF1 gene mutations that identified refractory/resistant patients. Mutations in the DMNT3A gene were also found in the non-leukemic cell fraction of patients with T-ALL, revealing a possible mutational-driven clonal hematopoiesis event to prime T-ALL in elderly. The prognostic impact of this adverse genetic profile was independent of MRD status on day +35 of induction therapy. The combined worse-outcome genetic signature and MRD on day +35 allowed risk stratification of T-ALL into standard or high-risk groups with significantly different 5- year overall survival (OS) of 52% (95% confidence interval: 37-67) and 17% (95% confidence interval: 1-33), respectively. These results confirm the relevance of the tumor genetic profile in predicting patient outcome in adult T-ALL and highlight the need for novel gene-targeted chemotherapeutic schedules to improve the OS of poor-prognosis T-ALL patients.

Percepción de la Vacuna contra la COVID-19 en Población Chilena / Perception of the COVID-19 Vaccine in the Chilean Population / Percepção da Vacina COVID-19 na População Chilena

Introducción: La vacuna ha demostrado ser la forma más efectiva para controlar la pandemia por COVID-19 previniendo complicaciones como sintomatología grave y mortalidad. En la decisión de vacunarse y la percepción de la vacuna han influido los medios de comunicación y factores psicológicos, socioculturales y biológicos. Objetivos: IIdentificar en población chilena la percepción de la vacuna contra la COVID-19, sus factores biopsicosociales y la influencia de variables sociodemográficas y relacionadas con la vacunación. Métodos: Estudio de cohorte transversal, cuyo nivel de profundización es descriptivo-inferencial. Tamaño muestral con un nivel de confianza del 95% y un error de estimación de 5%, en un muestreo aleatorio (proba-bilístico o sin intencionalidad) y estratificado. Se adaptó un cuestionario para obtener un índice de percepción de la vacuna y se aplicó a 695 chilenos. Se efectuaron análisis de asociación y regresión lineal múltiple. Resultados: Se observó que, aunque el 96.3% de los participantes se encuentran vacunados contra la COVID-19, la percepción general de la vacuna es regular, con predominio de la dimensión psicológica. Variables como el nivel socioeconómico, la decisión voluntaria de vacunarse contra la COVID-19, la muerte de alguien cercano por COVID-19 estando vacunado y el conflicto por la decisión de vacunarse, se encuentran significativamente relacionadas y tienen influencia en la percepción de la vacuna. Conclusiones: Para comprender la percepción de una vacuna, debe tomarse en cuenta la perspectiva biopsicosocial, la per-cepción del riesgo en relación con las conductas de salud, la influencia de los medios y otros factores implicados.

Introduction: The vaccine has proven to be the most effective way to control the COVID-19 pandemic, preventing complications such as severe symptoms and mortality. The decision to get vaccinated and the perception of the vaccine have been influenced by the media and psy-chological, sociocultural and biological factors. Objectives: Identify in the Chilean popula-tion the perception of the COVID-19 vaccine, its biopsychosocial factors and the influence of sociodemographic and vaccination-related variables. Methods: Cross-sectional cohort study, whose level of depth is descriptive-inferential. Sample size with a confidence level of 95% and an estimation error of 5%, in a random (probabilistic or unintentional) and stratified sam-pling. A questionnaire was adapted to obtain an index of perception of the vaccine and was applied to 695 Chileans. Association and multiple linear regression analyzes were carried out.Results: It was observed that, although 96.3% of the participants are vaccinated against COV-ID-19, the general perception of the vaccine is regular, with the psychological dimension pre-dominating. Variables such as socioeconomic level, the voluntary decision to get vaccinated against COVID-19, the death of someone close to COVID-19 while vaccinated, and the con-flict over the decision to get vaccinated are significantly related and have an influence on the perception of the vaccine. Conclusions: To understand the perception of a vaccine, the biopsy-chosocial perspective, the perception of risk in relation to health behaviors, the influence of the media and other factors involved must be taken into account

Introdução: A vacina provou ser a forma mais eficaz de controlar a pandemia de COVID-19, prevenindo complicações como sintomas graves e mortalidade. A decisão de se vacinar e a per-cepção da vacina têm sido influenciadas pela mídia e por fatores psicológicos, socioculturais e biológicos. Objetivos: Identificar na população chilena a percepção da vacina contra a COV-ID-19, seus fatores biopsicossociais e a influência de variáveis sociodemográficas e relacionadas à vacinação. Métodos: Estudo de coorte transversal, cujo nível de profundidade é descritivo-in-ferencial. Tamanho da amostra com nível de confiança de 95% e erro de estimativa de 5%, em amostragem aleatória (probabilística ou não intencional) e estratificada. Um questionário foi adaptado para obter um índice de percepção da vacina e foi aplicado a 695 chilenos. Foram real-izadas análises de associação e de regressão linear múltipla. Resultados: Observou-se que, emb-ora 96,3% dos participantes estejam vacinados contra a COVID-19, a percepção geral da vacina é regular, predominando a dimensão psicológica. Variáveis como o nível socioeconômico, a decisão voluntária de se vacinar contra a COVID-19, a morte de alguém próximo da COVID-19 durante a vacinação e o conflito na decisão de se vacinar estão significativamente relacionados e influenciam a percepção do vacina. Conclusões: Para compreender a percepção de uma vacina, a perspectiva biopsicossocial, a percepção do risco em relação aos comportamentos de saúde, a in-fluência dos meios de comunicação social e outros factores envolvidos devem ser tidos em conta

Ponatinib, chemotherapy, and transplant in adults with Philadelphia chromosome-positive acute lymphoblastic leukemia.

Promising results have been shown with the combination of ponatinib and chemotherapy in adults with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). The PONALFIL (Ponatinib With Chemotherapy for Young Adults Ph Positive Acute Lymphoblastic Leukemia) trial combined ponatinib (30 mg/d) with standard induction and consolidation chemotherapy followed by allogeneic hematopoietic stem cell transplant (alloHSCT) in newly diagnosed Ph+ ALL patients aged 18 to 60 years. Ponatinib was only given pre-emptively after alloHSCT. Primary end points were hematologic and molecular response before alloHSCT and event-free survival (EFS), including molecular relapse as event. Thirty patients (median age, 49 years; range, 19-59 years) entered the trial. All exhibited hematologic response, and alloHSCT was performed in 26 patients (20 in complete molecular response and 6 in major molecular response). Only 1 patient died (of graft-versus-host disease), and 5 patients exhibited molecular relapse after alloHSCT. No tyrosine kinase inhibitor was given after HSCT in 18 of 26 patients. Twenty-nine patients are alive (median follow-up, 2.1 years; range, 0.2-4.0 years), with 3-year EFS and overall survival (OS) of 70% (95% confidence interval, 51-89) and 96% (95% confidence interval, 89-100), respectively. Comparison of the PONALFIL and the ALLPh08 (Chemotherapy and Imatinib in Young Adults With Acute Lymphoblastic Leukemia Ph [BCR-ABL] Positive; same schedule, using imatinib as the tyrosine kinase inhibitor) trials by propensity score showed significant improvement in OS for patients in PONALFIL (3-year OS, 96% vs 53%; P = .002). The most frequent grade 3 to 4 adverse events were hematologic (42%), infectious (17%), and hepatic (22%), with only one vascular occlusive event. The combination of chemotherapy with ponatinib followed by alloHSCT is well tolerated, with encouraging EFS in adults with newly diagnosed Ph+ ALL. Cross-trial comparison suggests improvement vs imatinib (clinicaltrials.gov identifier #NCT02776605).

Prognostic heterogeneity of adult B-cell precursor acute lymphoblastic leukaemia patients with t(1;19)(q23;p13)/TCF3-PBX1 treated with measurable residual disease-oriented protocols.

The prognosis of t(1;19)(q23;p13)/transcription factor 3-pre-B-cell leukaemia homeobox 1 (TCF3-PBX1) in adolescent and adult patients with acute lymphoblastic leukaemia (ALL) treated with measurable residual disease (MRD)-oriented trials remains controversial. In the present study, we analysed the outcome of adolescent and adult patients with t(1;19)(q23;p13) enrolled in paediatric-inspired trials. The patients with TCF3-PBX1 showed similar MRD clearance and did not have different survival compared with other B-cell precursor ALL patients. However, patients with TCF3-PBX1 had a significantly higher cumulative incidence of relapse, especially among patients aged ≥35 years carrying additional cytogenetic alterations. These patients might benefit from additional/intensified therapy (e.g. immunotherapy in first complete remission with or without subsequent haematopoietic stem cell transplantation).

Diseño y validación de un cuestionario para evaluar la percepción de riesgo de contagio de COVID-19 en población colombiana / Design and validation of a questionnaire to assess the perceived risk of contracting COVID-19 in the colombian population

RESUMEN Objetivos. Diseñar y validar un instrumento para evaluar la percepción de riesgo de contagio de COVID-19 en población colombiana. Materiales y métodos. Estudio observacional transversal de tipo psicométrico con una muestra de 2350 personas entre los 16 a 65 años, se propusieron las dimensiones e ítems a partir de la revisión de estudios previos sobre la evaluación de la percepción de riesgo en enfermedad y desastres, integrando los lineamientos expuestos por la Organización Mundial de la Salud respecto a las medidas de autoprotección y protocolos de bioseguridad para evitar el contagio de la COVID-19. El proceso de validación ocurrió en dos momentos, primero con una revisión por jueces expertos que evaluaron claridad, suficiencia y pertinencia de cada ítem con respecto a la variable y su dimensión; en segundo momento un análisis factorial confirmatorio y se estimó la consistencia interna con los índices de alpha de Cronbach (α) y omega de McDonald (ω). Resultados. El instrumento elaborado tuvo adecuadas propiedades psicométricas para evaluar la percepción de riesgo de contagio de COVID-19 (α=0,924), con cuatro dimensiones: vulnerabilidad cognitiva (α=0,873); vulnerabilidad emocional (α=0,882); gravedad (α=0,893) y las conductas de riesgo-protección (α=0,941). Conclusiones. Los hallazgos muestran que el instrumento de percepción de riesgo de contagio de COVID-19 (PCR-CV19) es una herramienta válida y confiable para evaluar la percepción de riesgo contagio, el cual puede ser adaptado en diferentes grupos poblacionales y contextos.

ABSTRACT Objective. To design and validate an instrument to assess the perceived risk of contracting COVID-19 in the Colombian population. Materials and methods. Cross-sectional observational study of psychometric type with a sample of 2350 people between 16 and 65 years of age. The dimensions and items were proposed based the review of previous studies on the evaluation of risk perception of disease and disasters, by integrating the guidelines issued by the World Health Organization regarding self-protection measures and biosecurity protocols to avoid COVID-19 transmission. The validation process was carried out in two stages; the first stage included a review by expert judges who evaluated the clarity, sufficiency, and relevance of each item in relation to the variable and its dimension; in the second stage we carried out a confirmatory factor analysis and estimated internal consistency with the Cronbach's Alpha (α) and McDonald's omega (ω) indexes. Results. The designed instrument had adequate psychometric properties to evaluate the risk perception of contracting COVID-19 (α=0.924), with four dimensions: cognitive vulnerability (α=0.873), emotional vulnerability (α=0.882), severity (α=0.893) and risk-protective behaviors (α=0.941). Conclusions. These findings show that the instrument to evaluate the risk perception of contracting COVID-19 (PCR-CV19) is a valid and reliable tool to assess contagion risk perception and can be adapted to different population groups and contexts.

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.

Frequency, Clinical Characteristics and Outcome of Adults With Acute Lymphoblastic Leukemia and COVID 19 Infection in the First vs. Second Pandemic Wave in Spain.

BACKGROUND AND OBJECTIVE: SARS-CoV-2 infection has bimodal distribution in Europe with a first wave in March to June 2020 and a second in September 2020 to February 2021. We compared the frequency, clinical characteristics and outcomes of adults with acute lymphoblastic leukemia (ALL) and infection in the first vs. second pandemic waves in Spain. PATIENTS AND METHODS: In this prospective study the characteristics of ALL and COVID-19 infection, comorbidities, treatment and outcome in the two periods were compared. The study ended when vaccination against SARS-CoV-2 was implemented in Spain. RESULTS: Twenty eight patients were collected in the first wave and 24 in the second. The median age was 46.5 years (range 20-83). Patients from the first wave had a trend to more severe ALL (higher frequency of patients under induction or submitted to transplantation or under immunosuppressive therapy). No significant differences were observed in need for oxygen support, intensive care unit (ICU) requirement, days in ICU and time to COVID-19 infection recovery. Seventeen patients (33%) died, with death attributed to COVID infection in 15 (29%), without significant differences in the 100 day overall survival (OS) probabilities in the two waves (68% ± 17% vs. 56% ± 30%). The only prognostic factor for OS identified by was the presence of comorbidities at COVID-19 infection (HR: 5.358 [95% CI: 1.875- 15.313]). CONCLUSION: The frequency and mortality of COVID-19 infection were high in adults with ALL, without changes over time, providing evidence in favor of vaccination priority for these patients.

Adverse prognostic impact of complex karyotype (≥3 cytogenetic alterations) in adult T-cell acute lymphoblastic leukemia (T-ALL).

The potential prognostic value of conventional karyotyping in adult T-cell acute lymphoblastic leukemia (T-ALL) remains an open question. We hypothesized that a modified cytogenetic classification, based on the number and type of cytogenetic abnormalities, would allow the identification of high-risk adult T-ALL patients. Complex karyotype defined by the presence of ≥3 cytogenetic alterations identified T-ALL patients with poor prognosis in this study. Karyotypes with ≥3 abnormalities accounted for 16 % (22/139) of all evaluable karyotypes, corresponding to the largest poor prognosis cytogenetic subgroup of T-ALL identified so far. Patients carrying karyotypes with ≥3 cytogenetic alterations showed a significantly inferior response to therapy, and a poor outcome in terms of event-free survival (EFS), overall survival (OS) and cumulative incidence of relapse (CIR), independently of other baseline characteristics and the end-induction minimal residual disease (MRD) level. Additional molecular analyses of patients carrying ≥3 cytogenetic alterations showed a unique molecular profile that could contribute to understand the underlying molecular mechanisms of resistance and to evaluate novel targeted therapies (e.g. IL7R directed) with potential impact on outcome of adult T-ALL patients.

Long-Term Impact of an Educational Antimicrobial Stewardship Program on Management of Patients with Hematological Diseases.

Antimicrobial stewardship programs (ASPs) in hematological patients are especially relevant. However, information about ASPs in this population is scarce. For 11 years, we quarterly assessed antimicrobial consumption and incidence and death rates of multidrug-resistant (MDR) bloodstream infections (BSI) in the hematology Department. Healthcare activity indicators were also monitored yearly. We performed an interrupted time-series analysis. Antimicrobials showed a sustained reduction with a relative effect of -62.3% (95% CI -84.5 to -40.1) nine years after the inception of the ASP, being especially relevant for antifungals (relative effect -80.4%, -90.9 to -69.9), quinolones (relative effect -85.0%, -102.0 to -68.1), and carbapenems (relative effect -68.8%, -126.0 to -10.6). Incidence density of MDR BSI remained low and stable (mean 1.10 vs. 0.82 episodes per 1000 occupied bed days for the pre-intervention and the ASP period, respectively) with a quarterly percentage of change of -0.3% (95% CI -2.0 to 1.4). Early and late mortality of MDR BSI presented a steady trend (quarterly percentage of change -0.7%, 95% CI -1.7 to 0.3 and -0.6%, 95% CI -1.5 to 0.3, respectively). Volume and complexity of healthcare activity increased over the years. The ASP effectively achieved long-term reductions in antimicrobial consumption and improvements in the prescription profile, without increasing the mortality of MDR BSI.

Design and validation of a questionnaire to assess the perceived risk of contracting COVID-19 in the colombian population. / Diseño y validación de un cuestionario para evaluar la percepción de riesgo de contagio de COVID-19 en población colombiana.

OBJECTIVE.: To design and validate an instrument to assess the perceived risk of contracting COVID-19 in the Colombian population. MATERIALS AND METHODS.: Cross-sectional observational study of psychometric type with a sample of 2350 people between 16 and 65 years of age. The dimensions and items were proposed based the review of previous studies on the evaluation of risk perception of disease and disasters, by integrating the guidelines issued by the World Health Organization regarding self-protection measures and biosecurity protocols to avoid COVID-19 transmission. The validation process was carried out in two stages; the first stage included a review by expert judges who evaluated the clarity, sufficiency, and relevance of each item in relation to the variable and its dimension; in the second stage we carried out a confirmatory factor analysis and estimated internal consistency with the Cronbach's Alpha (α) and McDonald's omega (ω) indexes. RESULTS.: The designed instrument had adequate psychometric properties to evaluate the risk perception of contracting COVID-19 (α=0.924), with four dimensions: cognitive vulnerability (α=0.873), emotional vulnerability (α=0.882), severity (α=0.893) and risk-protective behaviors (α=0.941). CONCLUSIONS.: These findings show that the instrument to evaluate the risk perception of contracting COVID-19 (PCR-CV19) is a valid and reliable tool to assess contagion risk perception and can be adapted to different population groups and contexts.

OBJETIVOS.: Diseñar y validar un instrumento para evaluar la percepción de riesgo de contagio de COVID-19 en población colombiana. MATERIALES Y MÉTODOS.: Estudio observacional transversal de tipo psicométrico con una muestra de 2350 personas entre los 16 a 65 años, se propusieron las dimensiones e ítems a partir de la revisión de estudios previos sobre la evaluación de la percepción de riesgo en enfermedad y desastres, integrando los lineamientos expuestos por la Organización Mundial de la Salud respecto a las medidas de autoprotección y protocolos de bioseguridad para evitar el contagio de la COVID-19. El proceso de validación ocurrió en dos momentos, primero con una revisión por jueces expertos que evaluaron claridad, suficiencia y pertinencia de cada ítem con respecto a la variable y su dimensión; en segundo momento un análisis factorial confirmatorio y se estimó la consistencia interna con los índices de alpha de Cronbach (α) y omega de McDonald (ω). RESULTADOS.: El instrumento elaborado tuvo adecuadas propiedades psicométricas para evaluar la percepción de riesgo de contagio de COVID-19 (α=0,924), con cuatro dimensiones: vulnerabilidad cognitiva (α=0,873); vulnerabilidad emocional (α=0,882); gravedad (α=0,893) y las conductas de riesgo-protección (α=0,941). CONCLUSIONES.: Los hallazgos muestran que el instrumento de percepción de riesgo de contagio de COVID-19 (PCR-CV19) es una herramienta válida y confiable para evaluar la percepción de riesgo contagio, el cual puede ser adaptado en diferentes grupos poblacionales y contextos.

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.

Treatment of Frail Older Adults and Elderly Patients With Philadelphia Chromosome-negative Acute Lymphoblastic Leukemia: Results of a Prospective Trial With Minimal Chemotherapy.

BACKGROUND: The treatment of acute lymphoblastic leukemia (ALL) in older adults and elderly patients is a challenge, and modern protocols include targeted therapy and immunotherapy in combination with attenuated or minimal chemotherapy. However, frail patients are excluded from these trials, and reports on the outcome of this subgroup of patients are scarce. Our objective was to analyze the outcome of unfit older adults and elderly patients with Philadelphia chromosome-negative ALL included in a prospective trial (ALL-07FRAIL). PATIENTS AND METHODS: Older adults and elderly patients with Charlson Comorbidity Index (CCI) ≥ 4 were included. Induction therapy consisted of vincristine and dexamethasone, and maintenance therapy with mercaptopurine and methotrexate for 2 years. RESULTS: Seventy-two patients with a median age of 67 years (range, 57-89 years) and a median CCI of 5 (range, 4-12) were included. The rates of early withdrawal, early death, resistance, and complete response (CR) were 5%, 10%, 31%, and 54%, respectively. Six patients with CR abandoned the study, 5 died in CR, and 23 relapsed (cumulative relapse incidence 75%). The medians of disease-free and overall survival (OS) were 6.9 months (95% confidence interval [CI], 0.3-13.5 months) and 7.6 months (95% CI, 6.3-8.9 months), respectively. The most frequent toxic events were hematologic (neutropenia 77% and thrombocytopenia 54%, of grade III-IV in all cases). Eastern Cooperative Oncology Group score but not the CCI had significant impact on OS. CONCLUSION: Complete remission with very attenuated chemotherapy can be attained in one-half of older or elderly infirm patients with ALL. These results suggest that some of these patients could benefit from the concomitant or subsequent use of immunotherapy and/or targeted therapy.