CAR density influences antitumoral efficacy of BCMA CAR T cells and correlates with clinical outcome

Identification of new markers associated with long-term efficacy in patients treated with CAR T cells is a current medical need, particularly in diseases such as multiple myeloma. In this study, we address the impact of CAR density on the functionality of BCMA CAR T cells. Functional and transcriptional studies demonstrate that CAR T cells with high expression of the CAR construct show an increased tonic signaling with up-regulation of exhaustion markers and increased in vitro cytotoxicity but a decrease in in vivo BM infiltration. Characterization of gene regulatory networks using scRNA-seq identified regulons associated to activation and exhaustion up-regulated in CARHigh T cells, providing mechanistic insights behind differential functionality of these cells. Last, we demonstrate that patients treated with CAR T cell products enriched in CARHigh T cells show a significantly worse clinical response in several hematological malignancies. In summary, our work demonstrates that CAR density plays an important role in CAR T activity with notable impact on clinical response

Implementation and evaluation of a training programme to promote the development of professional competences in nursing: A pilot study

Background: Clinical narratives may be used as a means to improve the acquisition of clinical competences. Even though there are studies that recognize the potential value of clinical narratives to promote nursing professional development, there is no evidence that shows their value as a tool to improve nurses' competences to provide person-centred nursing care. Purpose: To evaluate the preliminary efficacy of narratives for the development of three nursing professional competences -respect, intentional presence and knowing the person- for providing person-centred care. Method: Using a pre-post quasi-experimental design, a pilot study with a total of 34 nurses enrolled in a training course of nursing specialization was conducted between September 2016 and June 2017. All the nurses received a multi-component intervention based on the Critical Reflective Inquiry model. The strategies of this programme consisted of writing three narratives, attending two masterclasses, participating in a discussion group, and participating in a face-to-face interview. The NarratUN Evaluation tool was used to assess the outcomes. Changes among nurses were analysed using the Wilcoxon signed Rank test. Results: The difference in the means between the pre- and post-intervention scores were statistically significant for respect [0.59 (95% CI 0.23-0.95; p = 0.001)], intentional presence [0.75 (95% CI 0.32-1.17; p < 0.0001)] and knowing the person [0.62 (95% CI 0.25-0.99; p = 0.001)]. The difference in the mean score for use of the narrative and reflection also increased significantly [0.65 (95% CI 0.32-0.98, p < 0.001)]. Conclusions: The use of narratives combined with other reflective strategies (masterclass sessions and discussion groups) proved to be effective for the development of professional competences of nurses

Determinación de enfermedad mínima residual molecular en sangre periférica mediante NGS como nueva herramienta en el seguimiento posttrasplante alogénico de progenitores hematopoyéticos

La determinación de la EMR en médula ósea y del quimerismo hematopoyético (QH) en sangre periférica (SP), son herramientas imprescindibles para detectar recaídas en el seguimiento post-alo-TPH. La combinación de tecnologías más sensibles, que identifiquen cambios en el QH, y más específicos que detecten recaídas en sangre periférica, pueden complementar los estudios de EMR realizados en médula ósea (MO) y permitir tomar decisiones clínicas más precoces y específicas. El objetivo de este estudio fue valorar la aplicabilidad clínica de determinar la EMR molecular mediante Next Generation Sequencing (NGS) en SP en aquellos momentos en los que se observa un cambio del QH

A new prognostic model identifies patients aged 80 years and older with diffuse large B-cell lymphoma who may benefit from curative treatment: A multicenter, retrospective analysis by the Spanish GELTAMO group.

The means of optimally managing very elderly patients with diffuse large B-cell lymphoma (DLBCL) has not been established. We retrospectively analyzed 252 patients aged 80-100 years, diagnosed with DLBCL or grade 3B follicular lymphoma, treated in 19 hospitals from the GELTAMO group. Primary objective was to analyze the influence of the type of treatment and comorbidity scales on progression-free survival (PFS) and overall survival (OS). One hundred sixty-three patients (63%) were treated with chemotherapy that included anthracyclines and/or rituximab, whereas 15% received no chemotherapeutic treatment. With a median follow-up of 44 months, median PFS and OS were 9.5 and 12.5 months, respectively. In an analysis restricted to the 205 patients treated with any kind of chemotherapy, comorbidity scales did not influence the choice of treatment type significantly. Independent factors associated with better PFS and OS were: age  85 years, R-IPI 3-5 or CIRS > 5). In conclusion, treatment with R-CHOP-like is associated with good survival in a significant proportion of patients. We have developed a simple prognostic model that may aid the selection patients who could benefit from a curative treatment, although it needs to be validated in larger series

Assessment of minimal residual disease by next generation sequencing in peripheral blood as a complementary tool for personalized transplant monitoring in myeloid neoplasms

Patients with myeloid neoplasms who relapsed after allogenic hematopoietic stem cell transplant (HSCT) have poor prognosis. Monitoring of chimerism and specific molecular markers as a surrogate measure of relapse is not always helpful; therefore, improved systems to detect early relapse are needed. We hypothesized that the use of next generation sequencing (NGS) could be a suitable approach for personalized follow-up post-HSCT. To validate our hypothesis, we analyzed by NGS, a retrospective set of peripheral blood (PB) DNA samples previously evaluated by high-sensitive quantitative PCR analysis using insertion/deletion polymorphisms (indel-qPCR) chimerism engraftment. Post-HCST allelic burdens assessed by NGS and chimerism status showed a similar time-course pattern. At time of clinical relapse in 8/12 patients, we detected positive NGS-based minimal residual disease (NGS-MRD). Importantly, in 6/8 patients, we were able to detect NGS-MRD at time points collected prior to clinical relapse. We also confirmed the disappearance of post-HCST allelic burden in non-relapsed patients, indicating true clinical specificity. This study highlights the clinical utility of NGS-based post-HCST monitoring in myeloid neoplasia as a complementary specific analysis to high-sensitive engraftment testing. Overall, NGS-MRD testing in PB is widely applicable for the evaluation of patients following HSCT and highly valuable to personalized early treatment intervention when mixed chimerism is detected

Assessment of minimal residual disease by next generation sequencing in peripheral blood as a complementary tool for personalized transplant monitoring in myeloid neoplasms

Patients with myeloid neoplasms who relapsed after allogenic hematopoietic stem cell transplant (HSCT) have poor prognosis. Monitoring of chimerism and specific molecular markers as a surrogate measure of relapse is not always helpful; therefore, improved systems to detect early relapse are needed. We hypothesized that the use of next generation sequencing (NGS) could be a suitable approach for personalized follow-up post-HSCT. To validate our hypothesis, we analyzed by NGS, a retrospective set of peripheral blood (PB) DNA samples previously evaluated by high-sensitive quantitative PCR analysis using insertion/deletion polymorphisms (indel-qPCR) chimerism engraftment. Post-HCST allelic burdens assessed by NGS and chimerism status showed a similar time-course pattern. At time of clinical relapse in 8/12 patients, we detected positive NGS-based minimal residual disease (NGS-MRD). Importantly, in 6/8 patients, we were able to detect NGS-MRD at time points collected prior to clinical relapse. We also confirmed the disappearance of post-HCST allelic burden in non-relapsed patients, indicating true clinical specificity. This study highlights the clinical utility of NGS-based post-HCST monitoring in myeloid neoplasia as a complementary specific analysis to high-sensitive engraftment testing. Overall, NGS-MRD testing in PB is widely applicable for the evaluation of patients following HSCT and highly valuable to personalized early treatment intervention when mixed chimerism is detected

A new prognostic model identifies patients aged 80 years and older with diffuse large B-cell lymphoma who may benefit from curative treatment: A multicenter, retrospective analysis by the Spanish GELTAMO group

The means of optimally managing very elderly patients with diffuse large B-cell lymphoma (DLBCL) has not been established. We retrospectively analyzed 252 patients aged 80-100 years, diagnosed with DLBCL or grade 3B follicular lymphoma, treated in 19 hospitals from the GELTAMO group. Primary objective was to analyze the influence of the type of treatment and comorbidity scales on progression-free survival (PFS) and overall survival (OS). One hundred sixty-three patients (63%) were treated with chemotherapy that included anthracyclines and/or rituximab, whereas 15% received no chemotherapeutic treatment. With a median follow-up of 44 months, median PFS and OS were 9.5 and 12.5 months, respectively. In an analysis restricted to the 205 patients treated with any kind of chemotherapy, comorbidity scales did not influence the choice of treatment type significantly. Independent factors associated with better PFS and OS were: age  85 years, R-IPI 3-5 or CIRS > 5). In conclusion, treatment with R-CHOP-like is associated with good survival in a significant proportion of patients. We have developed a simple prognostic model that may aid the selection patients who could benefit from a curative treatment, although it needs to be validated in larger series

Ruxolitinib in refractory acute and chronic graft-versus-host disease: a multicenter survey study.

Graft-versus-host disease is the main cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation. First-line treatment is based on the use of high doses of corticosteroids. Unfortunately, second-line treatment for both acute and chronic graft-versus-host disease, remains a challenge. Ruxolitinib has been shown as an effective and safe treatment option for these patients. Seventy-nine patients received ruxolitinib and were evaluated in this retrospective and multicenter study. Twenty-three patients received ruxolitinib for refractory acute graft-versus-host disease after a median of 3 (range 1-5) previous lines of therapy. Overall response rate was 69.5% (16/23) which was obtained after a median of 2 weeks of treatment, and 21.7% (5/23) reached complete remission. Fifty-six patients were evaluated for refractory chronic graft-versus-host disease. The median number of previous lines of therapy was 3 (range 1-10). Overall response rate was 57.1% (32/56) with 3.5% (2/56) obtaining complete remission after a median of 4 weeks. Tapering of corticosteroids was possible in both acute (17/23, 73%) and chronic graft-versus-host disease (32/56, 57.1%) groups. Overall survival was 47% (CI: 23-67%) at 6 months for patients with aGVHD (62 vs 28% in responders vs non-responders) and 81% (CI: 63-89%) at 1 year for patients with cGVHD (83 vs 76% in responders vs non-responders). Ruxolitinib in the real life setting is an effective and safe treatment option for GVHD, with an ORR of 69.5% and 57.1% for refractory acute and chronic graft-versus-host disease, respectively, in heavily pretreated patients