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Abstract Background Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is one of the most efficient therapeutic options available to cure many hematological malignancies. However, severe complications derived from this procedure, including graft-versus-host disease (GVHD) and infections, can limit its success and negatively impact survival. Previous studies have shown that alterations in the microbiome are associated with the development of allo-HSCT-derived complications. However, most studies relied on single techniques that can only analyze a unique aspect of the microbiome, which hinders our ability to understand how microbiome alterations drive allo-HSCT-associated diseases. Results Here, we have applied multiple “omic” techniques (16S rRNA and shotgun sequencing, targeted and un-targeted metabolomics) in combination with machine learning approaches to define the most significant microbiome changes following allo-HSCT at multiple modalities (bacterial taxa, encoded functions, and derived metabolites). In addition, multivariate approaches were applied to study interactions among the various microbiome modalities (the interactome). Our results show that the microbiome of transplanted patients exhibits substantial changes in all studied modalities. These include depletion of beneficial microbes, mainly from the Clostridiales order, loss of their bacterial encoded functions required for the synthesis of key metabolites, and a reduction in metabolic end products such as short chain fatty acids (SCFAs). These changes were followed by an expansion of bacteria that frequently cause infections after allo-HSCT, including several Staphylococcus species, which benefit from the reduction of bacteriostatic SCFAs. Additionally, we found specific alterations in all microbiome modalities that distinguished those patients who subsequently developed GVHD, including depletion of anti-inflammatory commensals, protective reactive oxygen detoxifying enzymes, and immunoregulatory metabolites such as acetate or malonate. Moreover, extensive shifts in the homeostatic relationship between bacteria and their metabolic products (e.g., Faecalibacterium and butyrate) were detected mainly in patients who later developed GVHD. Conclusions We have identified specific microbiome changes at different modalities (microbial taxa, their encoded genes, and synthetized metabolites) and at the interface between them (the interactome) that precede the development of complications associated with allo-HSCT. These identified microbial features provide novel targets for the design of microbiome-based strategies to prevent diseases associated with stem cell transplantation. Video Abstract

Introduction: Intradialytic hypertension (IDH) is a poorly understood phenomenon with no consensus on its definition, etiology, or related factors, and there is limited evidence on its consequences. Objective: To determine the prevalence of IDH according to different definitions in hemodialysis (HD) units, with different clinical practices and assessment of possible events after 18 months have passed. Materials and methods: A cross-sectional observational study was conducted in 2 HD units, including all prevalent patients from March 2021 to September 2022. We established 3 definitions of IDH: • Def 1: Mean arterial pressure (MAP) difference pre- and pos-HD >15 mmHg • Def 2: Systolic blood pressure (SBP) difference pre- and pos-HD >10 mmHg • Def 3: SBP difference >0 and ultrafiltration rate (UFR) >5 ml/kg/hIDH was considered present if the criterion was met in more than 50% of the 6 consecutive sessions (2 weeks) of follow-up. Personal history, medications, dialysis characteristics, and pre- and post-HD biochemical data were collected. Residual renal function (RRF) was considered as urine output >250 ml/24 h. At 18 months, the possible events of the group were analyzed. Results: We included 169 patients (68% men) with a mean age of 67.9 (14.2) years and a median HD duration of 34.5 (IQR 17.5–67.5) months. Of these, 94 come from one unit and 75 from the other. The prevalence of IDH was 8.3% according to Def 1, 27.2% according to Def 2, and 29.6% according to Def 3. Def 2 showed an association with a history of previous hypertension, use of renin-angiotensin system inhibitors (RASIs), and furosemide, as well as with patients with RRF. Def 3 showed an association only with coronary artery disease. There was an association with different prescriptions of dialysis fluids. Catecholaminergic hormones and aldosterone did not increase in patients with hypertension during the HD session. They did not present a higher incidence of cardiovascular events or mortality at 18 months. Conclusions: IDH has different prevalence rates depending on the definition used and the studied center. The future poses an important challenge: to determine which definition correlates with higher morbidity and mortality and the role of differences found in different HD units. Resumen: Introducción: La hipertensión arterial intradiálisis (HTAID) es un fenómeno poco conocido del que no existe consenso en su definición, ni datos sobre su etiología o factores relacionados, y hay poca evidencia sobre sus repercusiones. Objetivo: Definir la prevalencia según diferentes definiciones en dos unidades de hemodiálisis (HD), de dos hospitales diferentes, con distinta práctica clínica y valoración de posibles eventos después de haber pasado 18 meses. Material y métodos: Estudio observacional transversal realizado en 2 unidades de HD donde se incluyeron todos los pacientes prevalentes desde marzo 2021 hasta septiembre 2022. Establecimos 3 definiciones de HTAID: • Def 1: Diferencia de presión arterial media (PAM) pre- y pos-HD > 15 mmHg • Def 2: Diferencia de presión arterial sistólica (PAS) pre- y pos-HD > 10 mmHg • Def 3: Diferencia de PAS > 0 y UFR > 5 ml/kg/hConsideramos había HTAID si se cumplía el criterio en más del 50% de las 6 sesiones consecutivas (2 semanas) de seguimiento. Se recogieron antecedentes personales, medicamentos, características de diálisis y datos bioquímicos pre y post HD. Se consideró función renal residual (FRR) una diuresis >250 ml/24 h. Se analizó a los 18 meses los posibles eventos del grupo. Resultados: Incluimos 169 pacientes (68% hombres), con una edad media de 67,9 (14,2) años y una mediana de tiempo en HD de 34,5 (AIC 17,5–67,5) meses. De ellos 94 provienen de una unidad y 75 de la otra. La prevalencia de HTAID fue según Def1 (8,3%), Def 2 (27,2%) y Def3 (29,6%). Se evidencia una asociación en la Def2 con antecedente de HTA previa, uso de inhibidores del sistema renina angiotensina (ISRA) y furosemida y en los pacientes con FRR, en la Def3 solo asociación a coronariopatía. Existe asociación con las diferentes prescripciones de los líquidos de diálisis. No aumentaron las hormonas catecolaminérgicas y aldosterona en los pacientes con HTAID durante la sesión de HD. No presentaron mayor incidencia de eventos cardiovasculares o mortalidad a los 18 meses. Conclusiones: La HTAID tiene una prevalencia distinta tanto según la definición utilizada como la unidad estudiada. El futuro plantea un importante reto: conocer cuál de las definiciones determina una mayor implicación clínica y el papel que tienen las diferencias encontradas en las distintas unidades de HD.

Resumen: Introducción: La hipertensión arterial intradiálisis (HTAID) es un fenómeno poco conocido del que no existe consenso en su definición, ni datos sobre su etiología o factores relacionados, y hay poca evidencia sobre sus repercusiones. Objetivo: Definir la prevalencia según diferentes definiciones en 2 unidades de hemodiálisis (HD), de 2 hospitales diferentes, con distinta práctica clínica y valoración de posibles eventos después de haber pasado 18 meses. Material y métodos: Estudio observacional transversal realizado en 2 unidades de HD donde se incluyeron todos los pacientes prevalentes desde marzo de 2021 hasta septiembre de 2022. Establecimos 3 definiciones de HTAID: - Def 1: Diferencia de presión arterial media (PAM) pre- y pos-HD > 15 mmHg. - Def 2: Diferencia de presión arterial sistólica (PAS) pre- y pos-HD > 10 mmHg. - Def 3: Diferencia de PAS > 0 y UFR > 5 ml/kg/h.Consideramos que había HTAID si se cumplía el criterio en más del 50% de las 6 sesiones consecutivas (2 semanas) de seguimiento. Se recogieron antecedentes personales, medicamentos, características de diálisis y datos bioquímicos pre- y pos-HD. Se consideró función renal residual (FRR) una diuresis > 250 ml/24 h. Se analizó a los 18 meses los posibles eventos del grupo. Resultados: Incluimos 169 pacientes (68% varones), con una edad media de 67,9 (14,2) años y una mediana de tiempo en HD de 34,5 (AIC 17,5-67,5) meses. De ellos, 94 provienen de una unidad y 75 de la otra. La prevalencia de HTAID fue según Def 1 (8,3%), Def 2 (27,2%) y Def 3 (29,6%). Se evidencia una asociación en la Def 2 con antecedente de HTA previa, uso de inhibidores del sistema renina angiotensina (ISRA) y furosemida y en los pacientes con FRR, en la Def 3 solo asociación a coronariopatía. Existe asociación con las diferentes prescripciones de los líquidos de diálisis. No aumentaron las hormonas catecolaminérgicas y aldosterona en los pacientes con HTAID durante la sesión de HD. No presentaron mayor incidencia de eventos cardiovasculares o mortalidad a los 18 meses. Conclusiones: La HTAID tiene una prevalencia distinta tanto según la definición utilizada como la unidad estudiada. El futuro plantea un importante reto: conocer cuál de las definiciones determina una mayor implicación clínica y el papel que tienen las diferencias encontradas en las distintas unidades de HD. Abstract: Introduction: Intradialytic hypertension (IDH) is a poorly understood phenomenon with no consensus on its definition, etiology, or related factors, and there is limited evidence on its consequences. Objective: To determine the prevalence of IDH according to different definitions in hemodialysis (HD) units, with different clinical practices and assessment of possible events after 18 months have passed. Materials and methods: A cross-sectional observational study was conducted in two HD units, including all prevalent patients from March 2021 to September 2022. We established three definitions of IDH: Def 1: Mean arterial pressure (MAP) difference pre- and pos-HD > 15 mmHg. Def 2: Systolic blood pressure (SBP) difference pre- and pos-HD > 10 mmHg. Def 3: SBP difference >0 and ultrafiltration rate (UFR) > 5 ml/kg/h.IDH was considered present if the criterion was met in more than 50% of the six consecutive sessions (2 weeks) of follow-up. Personal history, medications, dialysis characteristics, and pre- and post-HD biochemical data were collected. Residual renal function (RRF) was considered as urine output >250 ml/24 h. At 18 months, the possible events of the group were analyzed. Results: We included 169 patients (68% men) with a mean age of 67.9 (14.2) years and a median HD duration of 34.5 (IQR: 17.5-67.5) months. Of these, 94 come from one unit and 75 from the other. The prevalence of IDH was 8.3% according to Def 1, 27.2% according to Def 2, and 29.6% according to Def 3. Def 2 showed an association with a history of previous hypertension, use of renin-angiotensin system inhibitors (RASIs), and furosemide, as well as with patients with RRF. Def 3 showed an association only with coronary artery disease. There was an association with different prescriptions of dialysis fluids. Catecholaminergic hormones and aldosterone did not increase in patients with hypertension during the HD session. They did not present a higher incidence of cardiovascular events or mortality at 18 months. Conclusions: IDH has different prevalence rates depending on the definition used and the studied center. The future poses an important challenge: to determine which definition correlates with higher morbidity and mortality and the role of differences found in different HD units.

Abstract We compared outcomes of adult patients with secondary acute myeloid leukemia (sAML) versus de novo AML after non-T-depleted haploidentical stem cell transplant (HaploSCT) with post-transplant cyclophosphamide (PTCy). Seventeen hundred and eleven AML patients (sAML-231, de novo-1480) in first complete remission transplanted from 2010 to 2021, were included. Patients with de novo AML were younger, median age 55.8 versus 60.8 years, p

Multidrug-resistant Enterobacteriaceae (MRE) represent a major threat for patients’ health. Here, the authors describe how cooperation between gut commensal bacteria (Lactobacillus spp. And Clostridiales) restrict MRE colonization in mice and patients

Objectives To estimate the readiness of Spanish National Health Service (NHS) hospitals to provide chimeric antigen receptor T cell (CAR-T), and to identify and quantify the different resources needed to provide CAR-T considering three scenarios defined by 10, 25 and 50 patients per centre per year.Design Targeted literature review and quantitative study using a questionnaire and telephone interviews. An algorithm was created to determine hospitals’ readiness based on their capacity and capability. All the requirements for quantification were assessed and validated by the steering committee, formed by members of the Spanish Group of Haematopoietic Transplantation and Cell Therapy. A weighting system (from 0 to 1) was established for capability quantification. For resources quantification, a scoring system was established, with 0 points representing the minimum and 3 points the maximum of additional resources that a hospital indicated necessary.Setting 40 Spanish hospital centres that perform allogeneic haematopoietic stem cell transplantation were invited to complete the questionnaire for capacity quantification, 28 of which provided valid responses. Nine hospitals participated in the interviews for resource quantification, eight of which had previously been designated by the Ministry of Health (MoH) to provide CAR-T.Outcome measure Current capacity of NHS Spanish sites to administer CAR-T under different theoretical scenarios with varying numbers of procedures, and the potential healthcare resources that would be needed to realise the theoretical capacity requirements.Results Four hospitals were optimally ready, 17 were somewhat ready and 7 were not ready. The actual extrapolated capacity of the currently designated MoH CAR-T sites would allow treatment of approximately 250 patients per year. Regarding healthcare resource needs, the numbers of haematologists, nurses and beds were the most important limiting factors, and those requiring further growth as patient numbers increased.Conclusions Increasing the number of CAR-T-qualified centres and/or increasing resources in the current designated sites are two potential strategies that should be considered to treat CAR-T-eligible patients in Spain.

Availability of haploidentical donors has broadened utilization of allogeneic hematopoietic cell transplantation (allo-HCT). Peripheral blood stem cells (PBSC) are being used with increased frequency in haploidentical allo-HCT. We evaluated extent of HLA disparity (2–3/8 versus 4/8 HLA antigen mismatches) on post-allograft outcomes when using T-cell replete PBSC from haploidentical donors for acute myeloid leukemia in first complete remission. Primary objectives entailed assessing cumulative incidence of grade 2–4 acute graft-versus-host disease (GVHD) and chronic GVHD (any grade). A total of 645 patients received a haploidentical allo-HCT from a donor with either 2–3 of 8 HLA antigen mismatches (n = 180) or with 4 of 8 HLA antigen mismatches (n = 465). Presence of 2–3 of 8 versus 4 of 8 HLA mismatches did not affect the incidence of acute GVHD (grade 2–4) and chronic GVHD (any grade). Overall survival (OS), leukemia-free survival (LFS) relapse incidence (RI), nonrelapse mortality and the composite endpoint of GVHD-free relapse-free survival were also similar among the groups. Pertaining to HLA-B leader matching effect, our analysis did not discern any difference in aforementioned post-allograft outcomes for this variable. However, in univariate analysis, absence of an antigen mismatch in HLA-DPB1 showed a trend for better OS. Notwithstanding inherent limitations associated with registry data, our results did not show an advantage of selecting a haploidentical donor with 2–3 of 8 HLA antigen mismatches over one with 4 of 8 HLA antigen mismatches when using PBSC as the cell source. Adverse cytogenetics remains a major adverse determinant of inferior OS and LFS and a higher RI. Using reduced-intensity conditioning yielded worse OS and LFS.

The results of haploidentical stem cell transplantation (haploHCT) for patients with acute lymphoblastic leukemia (ALL) transplanted in active disease remain largely unknown. We retrospectively analyzed adult patients with R/R ALL who underwent haploHCT or matched sibling donor (MSD-HCT) as a first transplantation between 2012 and 2020. The analysis comprised 274 patients, 94 had a haploHCT, and 180 had an MSD-HCT. The median follow-up was 32 months. The median age was 33 (range 18–76) and 37 (18–76) years in the haplo- and MSD-HCT groups, respectively. Post-transplant cyclophosphamide (PTCy) was used in 88% of haploHCT and in 4% of the MSD-HCT group. Graft-versus-host disease grade III–IV was higher in haploHCT than in the MSD-HCT group (18% versus 9%; P = 0.042). The 2-year chronic (c) graft-versus-host disease rates were 17% versus 33% (hazard ratio [HR] = 0.56; P = 0.14), respectively. By multivariate analysis, relapse incidence, and leukemia-free survival were not significatively different between the transplant groups, while nonrelapse mortality (NRM) was significantly higher (25% versus 18% at 2 years; HR = 2.03; P = 0.042) and overall survival (OS) lower (22% versus 38% at 2 years; HR = 1.72; P = 0.009) in the haploHCT group compared with the MSD-HCT group. We conclude that the 2-year OS of R/R ALL patients undergoing MSD transplants is significantly better than in haploHCT with a higher NRM in the latter.

Real-world evidence comparing the efficacy of chimeric antigen receptor (CAR) T-cell therapy against that of the previous standard of care (SOC) for refractory large B-cell lymphoma (LBCL) is scarce. We retrospectively collected data from patients with LBCL according to SCHOLAR-1 criteria treated with commercial CAR T-cell therapy in Spain (204 patients included and 192 treated, 101 with axicabtagene ciloleucel [axi-cel], and 91 with tisagenlecleucel [tisa-cel]) and compared the results with a historical refractory population of patients (n = 81) obtained from the GELTAMO-IPI study. We observed superior efficacy for CAR-T therapy (for both axi-cel and tisa-cel) over pSOC, with longer progression-free survival (PFS) (median of 5.6 vs. 4–6 months, p ≤ 0.001) and overall survival (OS) (median of 15 vs. 8 months, p < 0.001), independently of other prognostic factors (HR: 0.59 (95% CI: 0.44–0.80); p < 0.001] for PFS, and 0.45 [(95% CI: 0.31–0.64)] for OS). Within the CAR-T cohort, axi-cel showed longer PFS (median of 7.3 versus 2.8 months, respectively, p = 0.027) and OS (58% versus 42% at 12 months, respectively, p = 0.048) than tisa-cel. These differences were maintained in the multivariable analysis. On the other hand, axi-cel was independently associated with a higher risk of severe cytokine release syndrome and neurotoxicity. Our results suggest that the efficacy of CAR-T cell therapy is superior to pSOC in the real-world setting. Furthermore, axi-cel could be superior in efficacy to tisa-cel, although more toxic, in this group of refractory patients according to SCHOLAR-1 criteria.

Axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) are CD19-targeted chimeric antigen receptor (CAR) T cells approved for relapsed/refractory (R/R) large B-cell lymphoma (LBCL). We performed a retrospective study to evaluate safety and efficacy of axi-cel and tisa-cel outside the setting of a clinical trial. Data from consecutive patients with R/R LBCL who underwent apheresis for axi-cel or tisa-cel were retrospectively collected from 12 Spanish centers. A total of 307 patients underwent apheresis for axi-cel (n=152) and tisa-cel (n=155) from November 2018 to August 2021, of which 261 (85%) received a CAR T infusion (88% and 82%, respectively). Median time from apheresis to infusion was 41 days for axi-cel and 52 days for tisa-cel (P=0.006). None of the baseline characteristics were significantly different between both cohorts. Both cytokine release syndrome and neurologic events (NE) were more frequent in the axi-cel group (88% vs. 73%, P=0.003, and 42% vs. 16%, P

BackgroundThe impact of glucagon-like peptide-1 receptor agonists on patients with heart failure has not been fully described. Our main objective was to evaluate the safety and clinical and glycemic efficacy of once-weekly semaglutide in obese patients with type 2 diabetes and heart failure.MethodsIn this observational, retrospective, real-world study, we enrolled outpatients with type 2 diabetes, obesity, and heart failure who started semaglutide and were followed-up on at 3, 6, and 12 months.ResultsA total of 136 patients were included. From baseline to 12 months, there was a significant improvement on the Kansas City Cardiomyopathy Questionnaire total symptom score (59.0 ± 24.1 vs 79.9 ± 28.4 points, p

Abstract Sirolimus has emerged as an alternative to calcineurin inhibitors‐based (CNI) graft‐versus‐host disease (GVHD) prophylaxis. This retrospective study compares the outcome of 133 consecutive adult patients with haematological malignancies undergoing haploidentical stem cell transplantation with posttransplant cyclophosphamide (PTCy) and mycophenolate mofetil (MMF), combined with cyclosporine A (PTCy–CsA–MMF, n = 67) or sirolimus (PTCy–Sir–MMF, n = 66) as GVHD prophylaxis strategy. The median follow‐up was 48 (range 22–83) and 13 (range 3–33) months, respectively. PTCy–CsA–MMF was associated in multivariate analyses with a higher risk of acute kidney injury (HR 2.1, 95% CI, 1.21–3.57, p = .008) and thrombotic microangiopathy (HR 12.5, 95% CI, 1.66–93.5, p = .014), whereas PTCy–Sir–MMF was associated with a higher risk of hepatic sinusoidal obstruction syndrome (SOS) (HR 10.8, 95% CI, 1.52–77, p = .018), especially late‐onset forms, which totally resolved and none of the patients needed discontinuation of sirolimus. Two SOS‐related deaths were detected, both in the PTCy–CsA–MMF subgroup. Both GVHD prophylaxis strategies were otherwise comparable in terms of engraftment, GVHD incidence and survival.

Abstract Background Allogeneic hematopoietic cell transplantation (allo-HCT) using a mismatched unrelated donor (MMUD) and cord blood transplantation (CBT) are valid alternatives for patients without a fully human leukocyte antigen (HLA)-matched donor. Here, we compared the allo-HCT outcomes of CBT versus single-allele-mismatched MMUD allo-HCT with post-transplant cyclophosphamide (PTCy) in acute myeloid leukemia. Methods Patients who underwent a first CBT without PTCy (N = 902) or allo-HCT from a (HLA 9/10) MMUD with PTCy (N = 280) were included in the study. A multivariate regression analysis was performed for the whole population. A matched-pair analysis was carried out by propensity score-based 1:1 matching of patients (177 pairs) with known cytogenetic risk. Results The incidence of grade II–IV and grade III–IV acute graft-versus-host disease (GVHD) at 6 months was 36% versus 32% (p = 0.07) and 15% versus 11% (p = 0.16) for CBT and MMUD cohorts, respectively. CBT was associated with a higher incidence of graft failure (11% vs. 4%, p

Abstract Background There is no information on the impact of donor type in allogeneic hematopoietic stem cell transplantation (HCT) using homogeneous graft-versus-host (GVHD) prophylaxis with post-transplant cyclophosphamide (PTCy) in acute lymphoblastic leukemia (ALL). Methods We retrospectively analyzed outcomes of adult patients with ALL in CR1 that had received HCT with PTCy as GVHD prophylaxis from HLA-matched sibling (MSD) (n = 78), matched unrelated (MUD) (n = 94) and haploidentical family (Haplo) (n = 297) donors registered in the EBMT database between 2010 and 2018. The median follow-up period of the entire cohort was 2.2 years. Results Median age of patients was 38 years (range 18–76). Compared to MSD and MUD, Haplo patients received peripheral blood less frequently. For Haplo, MUD, and MSD, the cumulative incidence of 100-day acute GVHD grade II–IV and III–IV, and 2-year chronic and extensive chronic GVHD were 32%, 41%, and 34% (p = 0.4); 13%, 15%, and 15% (p = 0.8); 35%, 50%, and 42% (p = 0.01); and 11%, 17%, and 21% (p = 0.2), respectively. At 2 years, the cumulative incidence of relapse and non-relapse mortality was 20%, 20%, and 28% (p = 0.8); and 21%, 18%, and 21% (p = 0.8) for Haplo, MUD, and MSD, respectively. The leukemia-free survival, overall survival and GVHD-free, relapse-free survival for Haplo, MUD, and MSD was 59%, 62%, and 51% (p = 0.8); 66%, 69%, and 62% (p = 0.8); and 46%, 44%, and 35% (p = 0.9), respectively. On multivariable analysis, transplant outcomes did not differ significantly between donor types. TBI-based conditioning was associated with better LFS. Conclusions Donor type did not significantly affect transplant outcome in patient with ALL receiving SCT with PTCy.

The application of alternative dielectric oils as esters in power transformers is hindered by the lack of knowledge regarding their properties and respecting which are the best techniques to ensure their proper performance. In this sense one of the fields needing an impulse is the impregnation processes of transformers cellulosic materials with these alternative oils, currently impregnated in most of the cases with mineral oils. This paper studies the impregnation behavior of eight usual dielectric solids, with two esters and a traditional mineral oil. Empirical equations of the impregnation evolution with time have been obtained, from these the rigid cellulosic materials present in the transformers and the viscosity of the dielectric oils have been identified as the key materials and properties to consider during impregnation. An adaptation of the current impregnation processes to the alternative oils have been proposed by increasing their temperature from ambient temperature up to 61-74°C, depending on the viscosity of the oil used.

Abstract Background Graft-versus-host disease (GVHD) remains a major contributor to mortality and morbidity after allogeneic stem-cell transplantation (allo-HSCT). The updated recommendations suggest that rabbit antithymocyte globulin or anti-T-lymphocyte globulin (ATG) should be used for GVHD prophylaxis in patients undergoing matched-unrelated donor (MUD) allo-HSCT. More recently, using post-transplant cyclophosphamide (PTCY) in the haploidentical setting has resulted in low incidences of both acute (aGVHD) and chronic GVHD (cGVHD). Therefore, the aim of our study was to compare GVHD prophylaxis using either PTCY or ATG in patients with acute myeloid leukemia (AML) who underwent allo-HSCT in first remission (CR1) from a 10/10 HLA-MUD. Methods Overall, 174 and 1452 patients from the EBMT registry receiving PTCY and ATG were included. Cumulative incidence of aGVHD and cGVHD, leukemia-free survival, overall survival, non-relapse mortality, cumulative incidence of relapse, and refined GVHD-free, relapse-free survival were compared between the 2 groups. Propensity score matching was also performed in order to confirm the results of the main analysis Results No statistical difference between the PTCY and ATG groups was observed for the incidence of grade II–IV aGVHD. The same held true for the incidence of cGVHD and for extensive cGVHD. In univariate and multivariate analyses, no statistical differences were observed for all other transplant outcomes. These results were also confirmed using matched-pair analysis. Conclusion These results highlight that, in the10/10 HLA-MUD setting, the use of PTCY for GVHD prophylaxis may provide similar outcomes to those obtained with ATG in patients with AML in CR1.

Abstract Background The use of post-transplant cyclophosphamide (PTCy) is highly effective in preventing graft-versus-host disease (GVHD) in the haploidentical (Haplo) transplant setting and is being increasingly used in matched sibling (MSD) and matched unrelated (MUD) transplants. There is no information on the impact of donor types using homogeneous prophylaxis with PTCy. Methods We retrospectively compared outcomes of adult patients with acute myeloid leukemia (AML) in first complete remission (CR1) who received a first allogeneic stem cell transplantation (SCT) with PTCy as GVHD prophylaxis from MSD (n = 215), MUD (n = 235), and Haplo (n = 789) donors registered in the EBMT database between 2010 and 2017. Results The median follow-up was 2 years. Haplo-SCT carried a significantly increased risk of acute grade II–IV GVHD (HR 1.6; 95% CI 1.1–2.4) and NRM (HR 2.6; 95% CI 1.5–4.5) but a lower risk of relapse (HR 0.7; 95% CI 0.5–0.9) that translated to no differences in LFS (HR 1.1; 95% CI 0.8–1.4) or GVHD/relapse-free survival (HR 1; 95% CI 0.8–1.3). Interestingly, the use of peripheral blood was associated with an increased risk of acute (HR 1.9; 95% CI 1.4–2.6) and chronic GVHD (HR 1.7; 95% CI 1.2–2.4) but a lower risk of relapse (HR 0.7; 95% CI 0.5–0.9). Conclusions The use of PTCy in patients with AML in CR1 receiving SCT from MSD, MUD, and Haplo is safe and effective. Haplo-SCT had increased risk of acute GVHD and NRM and lower relapse incidence but no significant difference in survival.

BackgroundValproic acid (VPA) has shown beneficial effects in vitro against SARS-CoV-2 infection, but no study has analyzed its efficacy in the clinical setting.MethodsThis multicenter, retrospective study included 165 adult patients receiving VPA at the time of admission to hospital, and 330 controls matched for sex, age and date of admission. A number of clinical, outcome and laboratory parameters were recorded to evaluate differences between the two groups. Four major clinical endpoints were considered: development of lung infiltrates, in-hospital respiratory worsening, ICU admissions and death.ResultsVPA-treated patients had higher lymphocyte (PConclusionsVPA-treated patients seem to develop less serious COVID-19 than control patients, according to diverse clinical endpoints and laboratory markers.

Background and aimsObesity is linked to elevated levels of inflammatory serum markers such as C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNFa). Adiponectin and resistin are adipokines related to obesity. It has been described that adipose tissue presents a high production and secretion of these diverse pro-inflammatory molecules, which may have local effects on the physiology of fat cells as well as systemic effects on other organs. Our aim was to evaluate the impact that lifestyle modifications, by following a Mediterranean Diet (MedDiet) program and physical activity (PA) training, would have on inflammatory biomarkers and adipokine profile in a Metabolically Healthy Obese (MHO) elderly population from Malaga (Andalusia, Spain).Subjetcs and methodsSubjects aged ≥65 years (65 to 87 years old) with obesity (BMI ≥30 kg/m2) were included in this study if they met ≤1 of the following criteria: systolic blood pressure ≥130 mmHg and/or diastolic blood pressure ≥ 85 mmHg; triglycerides ≥150 mg/dL; HDL-C Results166 MHO elderly subjects, 40 (24.1%) male and 126 (75.9%) female (p < 0.0001), aged 71.7±5.2 years old (65 to 87 years old) were included in the study. After 12 months of intervention, only the waist circumference was significantly reduced in all the population (-2.5 cm, pConclusionHealthy aging is a multifactorial biological process in which lifestyle is essential. The presence of obesity in elderly metabolically healthy population is not a problem necessarily. Elderly MHO population who eat a MedDiet and practice regularly PA are capable to modulate their production of inflammatory cytokines (CRP, IL-6, TNFa) and adipokines profile (adiponectin, resistin), preventing other metabolic disorders.

(1) Background: Acute COVID-19 infections produce alterations in the skeletal muscle, leading to acute sarcopenia, but the medium- and long-term consequences are still unknown. The aim of this study was to evaluate: (1) body composition; (2) muscle strength and the prevalence of sarcopenia; and (3) the relationship between muscle strength with symptomatic and functional evolution in older patients affected by/recovered from COVID-19; (2) Methods: A prospective, longitudinal study of patients aged ≥65 years who had suffered from COVID-19 infection between 1 March and 31 May 2020, as confirmed by PCR or subsequent seroconversion. Persistent symptoms, as well as anthropometric, clinical, and analytical characteristics, were analyzed at 3 and 12 months after infection. The degree of sarcopenia was determined by dynamometry and with SARC-F; (3) Results: 106 participants, aged 76.8 ± 7 years, were included. At 3 months postinfection, a high percentage of sarcopenic patients was found, especially among women and in those with hospitalization. At 12 months postinfection, this percentage had decreased, coinciding with a functional and symptomatic recovery, and the normalization of inflammatory parameters, especially interleukin-6 (4.7 ± 11.6 pg/mL vs. 1.5 ± 2.4 pg/mL, p < 0.05). The improvement in muscle strength was accompanied by significant weight gain (71.9 ± 12.1 kg vs. 74.7 ± 12.7 kg, p < 0.001), but not by an increase in lean mass (49.6 ± 10 vs. 49.9 ± 10, p 0.29); (4) Conclusions: Older COVID-19 survivors presented a functional, clinical, and muscular recovery 12 months postinfection. Even so, it is necessary to carry out comprehensive follow-ups and assessments that include aspects of nutrition and physical activity.

The prevalence of type 2 diabetes mellitus (T2DM) is rising in the general population. This increase leads to higher cardiovascular risk, with cardiovascular diseases being the main cause of death in diabetic patients. New therapeutic weapons for diabetes mellitus are now available. Sodium-glucose cotransporter type 2 (SGLT2) inhibitors are novel drugs that are widely used due to their strong benefit in preventing hospitalization for decompensated heart failure and renal protection, limiting the deterioration of the glomerular filtration rate, independently of the presence of diabetes mellitus. These drugs have also shown benefit in the prevention of atherosclerotic cardiovascular events and cardiovascular mortality in diabetic patients with established cardiovascular disease. On the other hand, patients with T2DM usually present a high burden of associated comorbidities. Some of these entities are arterial hypertension, dyslipidemia, hyperuricemia, obesity, non-alcoholic fatty liver disease (NAFLD), polycystic ovary syndrome (PCOS), vascular aging, respiratory diseases, or osteoporosis and fractures. Healthcare professionals should treat these patients from an integral point of view, and not manage each pathology separately. Therefore, as potential mechanisms of SGLT2 inhibitors in metabolic diseases have not been fully reviewed, we conducted this review to know the current evidence of the use and effect of SGLT2 inhibitors on these metabolic diseases.

Peripheral arterial disease (PAD) is a highly prevalent atherosclerotic condition. In patients with PAD, the presence of intermittent claudication leads to a deterioration in quality of life. In addition, even in asymptomatic cases, patients with PAD are at high risk of cardiac or cerebrovascular events. Treatment of PAD is based on lifestyle modifications; regular exercise; smoking cessation; and control of cardiovascular risk factors, including hypercholesterolemia. A growing number of studies have shown that statins reduce cardiovascular risk and improve symptoms associated with PAD. Current guidelines recommend the use of statins in all patients with PAD in order to decrease cardiovascular events and mortality. However, the prescribing of statins in patients with PAD is lower than in those with coronary heart disease. This review provides relevant information from the literature that supports the use of statins in patients with PAD and shows their potential benefit in decreasing lower limb complications as well as cardiovascular morbidity and mortality.

Atherosclerotic cardiovascular diseases (ASCVD) are the leading cause of death worldwide. High levels of total cholesterol—and of low-density lipoprotein cholesterol in particular—are one of the main risk factors associated with ASCVD. Statins are first-line treatment for hypercholesterolemia and have been proven to reduce major vascular events in adults with and without underlying ASCVD. Findings in the literature show that statins reduce coronary and cerebrovascular morbidity and mortality in middle-aged people, but their benefits in older adults are not as well-established, especially in primary prevention. Furthermore, many particularities must be considered regarding their use in old subjects, such as age-related changes in pharmacokinetics and pharmacodynamics, comorbidities, polypharmacy, and frailty, which decrease the safety and efficacy of statins in this population. Myopathy and a possible higher risk of falling along with cognitive decline are classic concerns for physicians when considering statin use in the very old. Additionally, some studies suggest that the relative risk for coronary events and cardiovascular mortality associated with high levels of cholesterol decreases after age 70, making the role of statins unclear. On the other hand, ASCVD are one of the most important causes of disability in old subjects, so cardiovascular prevention is of particular interest in this population in order to preserve functional status. This review aims to gather the current available evidence on the efficacy and safety of statin use in very old patients in both primary and secondary prevention.

The poor prognosis of refractory or relapsed (R/R) classical Hodgkin’s lymphoma (cHL) after autologous stem cell transplantation has improved greatly due to the introduction of brentuximab vedotin and PD-1 inhibitors. However, the duration of response achieved with these novel agents is too short. The information about the management of patients after anti-PD-1 therapy failure is very limited in cHL, although chemotherapy alone or combined with PD-1 inhibitors has shown encouraging results. We report three cases of heavily pretreated cHL, refractory to nivolumab monotherapy, successfully rescued with the addition of chemotherapy to nivolumab, as a bridge to allogeneic stem cell transplantation (allo-SCT). All three patients presented poor clinical features such as three to four previous lines including brentuximab vedotin and autologous stem cell transplantation, refractoriness to the last line of therapy previous to nivolumab, and rapid disease progression. Notwithstanding these characteristics and nivolumab failure, they achieved a complete response after the addition of chemotherapy, were consolidated with allo-SCT, and still remain in complete response. There are few studies concerning the combination of PD-1 inhibitors and chemotherapy after nivolumab failure, including one retrospective study and one phase II trial with nivolumab plus bendamustine. Therefore, only few patients are consolidated with allo-SCT. However, there are several ongoing trials investigating new combinations of chemotherapy and PD-1 inhibitors in R/R cHL, as well as in first line. All these data suggest that anti-PD-1 therapy may reprogram the immune system, activating and inhibiting effector and immunosuppressive cells, respectively, leading to overtake of chemorefractoriness. Allo-SCT can increase the immune-related events of patients treated with anti-PD-1 previously, consistent on acute graft- versus -host disease, sinusoidal obstruction syndrome, and noninfectious febrile syndrome. In conclusion, the combination of PD-1 inhibitor and chemotherapy may be a feasible therapy after anti-PD-1 treatment failure as a bridge to allo-SCT.

Abstract Background The emergence of carbapenemase-producing (CP) Citrobacter freundii poses a significant threat to public health, especially in high-risk populations. In this study, whole genome sequencing was used to characterize the carbapenem resistance mechanism of three C. freundii clinical isolates recovered from fecal samples of patients with acute leukemia (AL) from Spain. Materials and methods Twelve fecal samples, collected between 2013 and 2015 from 9 patients with AL, were screened for the presence of CP strains by selecting them on MacConkey agar supplemented with ertapenem (0.5 mg/L). Bacteria were identified by MALDI-TOF mass spectrometry and were phenotypically characterized. Whole genome sequencing of C. freundii isolates was performed using the MinION and MiSeq Illumina sequencers. Bioinformatic analysis was performed in order to identify the molecular support of carbapenem resistance and to study the genetic environment of carbapenem resistance encoding genes. Results Three carbapenem-resistant C. freundii strains (imipenem MIC≥32 mg/L) corresponding to three different AL patients were isolated. Positive modified Carba NP test results suggested carbapenemase production. The genomes of each C. freundii tested were assembled into a single chromosomal contig and plasmids contig. In all the strains, the carbapenem resistance was due to the coproduction of OXA-48 and VIM-1 enzymes encoded by genes located on chromosome and on an IncHI2 plasmid, respectively. According to the MLST and the SNPs analysis, all strains belonged to the same clone ST169. Conclusion We report in our study, the intestinal carrying of C. freundii clone ST169 coproducing OXA-48 and VIM-1 identified in leukemic patients.

The indication of hematopoietic stem cell transplantation (HSCT) in acute promyelocytic leukemia (APL) has evolved historically from a widespread use in front-line therapy during the pre-ATRA era to a virtual rejection of this indication for patients treated with modern treatments. HSCT in first complete remission could only be considered for an extremely small fraction of patients with persistent MRD at the end of consolidation or for those who relapse. In the pre-ATO era, relapsed patients were usually treated with readministration of ATRA and chemotherapy as salvage therapy, generally containing high-dose cytarabine and an anthracycline, followed by further post-remission chemotherapy and/or HSCT. ATO-based regimens are presently regarded as the first option for relapsed APL. The selection of the most appropriate post-remission treatment option for patients in second CR (CR2), as well as the modality of HSCT when indicated, depends on several variables, such as pre-transplant molecular status, duration of first remission, age, and donor availability. Although with a moderate level of evidence, based on recent retrospective studies, autologous HSCT would be at present the preferred option for consolidation for patients in molecular CR2. Allogeneic HSCT could be considered in patients with a very early relapse or those beyond CR2. Nevertheless, the superiority of HSCT as consolidation over other alternatives without transplantation has recently been questioned in some studies, which justify a prospective controlled study to resolve this still controversial issue.

Introducción: Los pacientes sometidos a Trasplante de Células Madre Hematopoyéticas o trasplante de médula padecen varias complicaciones nutricionales. El objetivo del estudio fue realizar una descripción prospectiva en estos pacientes. Material y métodos: Se reclutaron 14 pacientes con una edad media de 48,0±9,8 años. Resultados: El 28,6% padecía sobrepeso, el 14,3% obesidad y el 57,1% tenía un peso normal, con una evoluciónentre -0,3±0,3 kg/m2 (normopeso) hasta -3,1±0,2 kg/m2 (obesidad). Se observó una pérdida de peso variable, de hasta 7,3±0,7% en pacientes con mayor Índice de Masa Corporal (IMC). La composición corporal también empeoró al alta, con una evolución de la circunferencia braquial de -1,7±0,4 cm en trasplantes alogénicos y -2±4,5 cm en trasplantes autólogos. Un 42,9% de hombres y 28,6% de mujeres eran dados de alta con un Índice de Masa Libre de Grasa (IMLG) por debajo de las recomendaciones, incrementándose desde el ingreso en hombres (desde un 14,3%). Se observa una pérdida de fuerza muscular, en trasplantes alogénicos de -5,0±1,5 kg en el caso de hombres, y -3,0±0,5 kg en mujeres; en autólogos, de -5 kg y -4 kg respectivamente. Sobre síntomas, al inicio existía una alta prevalencia de vómitos (71,4%), náuseas (42,9%) o saciedad temprana (57,1%); durante la hospitalización, destaca la saciedad temprana (92,9%), náuseas (71,4%), vómitos (71,4%), disgeusia (57,1%), diarrea (50%) y anorexia (50%). Conclusiones: Los pacientes admitidos para trasplante de médula ósea están aparentemente bien nutridos, y existe un deterioro durante la hospitalización; parece adecuado implementar estrategias dietéticas durante la hospitalización para optimizar la ingesta y prevenir la malnutrición.

The FMS-like tyrosine kinase 3 (FLT3) gene is mutated in 25-30% of patients with acute myeloid leukemia (AML). Because of the poor prognosis associated with FLT3-internal tandem duplication mutated AML, allogeneic hematopoietic stem-cell transplantation (SCT) was commonly performed in first complete remission. Remarkable progress has been made in frontline treatments with the incorporation of FLT3 inhibitors and the development of highly sensitive minimal/measurable residual disease assays. Similarly, recent progress in allogeneic hematopoietic SCT includes improvement of transplant techniques, the use of haploidentical donors in patients lacking an HLA matched donor, and the introduction of FLT3 inhibitors as post-transplant maintenance therapy. Nevertheless, current transplant strategies vary between centers and differ in terms of transplant indications based on the internal tandem duplication allelic ratio and concomitant nucleophos-min-1 mutation, as well as in terms of post-transplant maintenance/consolidation. This review generated by international leukemia or transplant experts, mostly from the European Society for Blood and Marrow Transplantation, attempts to develop a position statement on best approaches for allogeneic hematopoietic SCT for AML with FLT3-internal tandem duplication including indications for and modalities of such transplants and on the potential optimization of post-transplant maintenance with FLT inhibitors.

Abstract Background Thiotepa-busulfan-fludarabine (TBF) is a widely used conditioning regimen in single umbilical cord blood transplantation (SUCBT). More recently, it was introduced in the setting of non-T cell depleted haploidentical stem cell transplantation (NTD-Haplo). Whether TBF based conditioning provides additional benefit in transplantation from a particular alternative donor type remains to be established. Methods This was a retrospective study based on an international European registry. We compared outcomes of de-novo acute myeloid leukemia patients in complete remission receiving NTD-Haplo (n = 186) vs. SUCBT (n = 147) following myeloablative conditioning (MAC) with TBF. Median follow-up was 23 months. Treatment groups resembled in baseline characteristics. Results SUCBT was associated with delayed engraftment and higher graft failure. In multivariate analysis no statistically significant differences were observed between the two groups in terms of acute or chronic graft-versus-host disease (GvHD) (HR = 1.03, p = 0.92 or HR = 1.86, p = 0.21) and relapse incidence (HR = 0.8, p = 0.65). Non-relapse mortality (NRM) was significantly higher in SUCBT as compared to NTD-Haplo (HR = 2.63, p = 0.001); moreover, SUCBT did worse in terms of overall survival (HR = 2.18, p = 0.002), leukemia-free survival (HR = 1.94, p = 0.007), and GvHD relapse-free survival (HR = 2.38, p = 0.0002). Conclusions Our results suggest that TBF-MAC might allow for a potent graft-versus-leukemia, regardless of the alternative donor type. Furthermore, in patients receiving TBF-MAC, survival with NTD-Haplo may be better compared to SUCBT due to decreased NRM.

Abstract: We retrospectively compared the clinical outcomes of adults with acute leukemia who received single-unit umbilical cord blood (UCB) transplantation (sUCBT) (n = 135) or stem cell transplant using coinfusion of a UCB graft with CD34+ cells from a third-party donor (Haplo-Cord) (n = 72) at different institutions within the Grupo Español de Trasplante Hematopoyético. In multivariable analysis, patients in the Haplo-Cord group showed more rapid neutrophil (hazard ratio [HR], 2.3; 95% confidence interval [CI], 1.5-3.3; P < .001) and platelet recovery (HR, 1.6; 95% CI, 1.2-2.3; P = .015) and lower incidence of chronic graft-versus-host disease (GVHD) (relative risk, 0.5; 95% CI, 0.3-0.8; P = .01). Nonrelapse mortality, relapse, disease-free survival (DFS), and GVHD/relapse-free survival were similar in the 2 groups. Regarding disease-specific outcomes, DFS in both acute myeloid leukemia (AML) and acute lymphoblastic leukemia patients was not significantly different; however, a significantly higher relapse rate was found in patients with AML treated with Haplo-Cord (HR, 2.3; 95% CI, 1-5.4; P = .04). Our study confirms that Haplo-Cord was an effective strategy to accelerate neutrophil and platelet recovery and shows that, in the context of specific treatment platforms, sUCBT and Haplo-Cord offer similar long-term outcomes.

Abstract Background Acute myeloid leukaemia (AML) with 17p abnormalities (abn(17p)) carries a very poor prognosis due to high refractoriness to conventional chemotherapy, and allogeneic stem cell transplantation (allo-SCT) appears as the only potential curative option. Methods To address outcomes after allo-SCT in patients with abn(17p), we retrospectively analysed de novo or secondary AML undergoing SCT between 2000 and 2013 from the EBMT registry. Results One hundred thirty-nine patients with confirmed abn(17p) have been selected. At the time of transplant, one hundred twenty-five were in first remission (CR1). Median age was 54 years old. Abn(17p) was associated with a monosomal karyotype in 83% of patients, complex karyotype in 91%, monosomy 5 or 5q deletion (-5/5q-) in 55%, monosomy 7 (-7) in 39% and both -5/5q and -7 in 27%. Seventy-three patients (59%) had a reduced-intensity conditioning regimen. The 2-year overall survival (OS) and leukaemia-free survival (LFS) were 28 and 24%, respectively. The 2-year non-relapse mortality (NRM) was 15%, and 2-year relapse incidence (RI) was 61%. The cumulative incidence of grade II to IV acute graft-versus-host disease (GvHD) was 24% and that of chronic GvHD was 21%. In multivariate analysis, the presence of a -5/5q- in addition to abn(17p) was significantly and independently associated with worse OS, LFS and higher RI. Age and donor types did not correlate with outcome. Conditioning intensity was not statistically associated with OS, LFS and NRM when adjusted for patients’ age. Conclusions In contrast to the dismal prognosis reported for AML patients harbouring abn(17p) undergoing conventional chemotherapy, allogeneic SCT provides responses in about 25% of those patients transplanted in CR1.

The microbiome has a strong impact on human health and disease and is, therefore, increasingly studied in a clinical context. Metaproteomics is also attracting considerable attention, and such data can be efficiently generated today owing to improvements in mass spectrometry-based proteomics. As we will discuss in this study, there are still major challenges notably in data analysis that need to be overcome. Here, we analyzed 212 fecal samples from 56 hospitalized acute leukemia patients with multidrug-resistant Enterobactericeae (MRE) gut colonization using metagenomics and metaproteomics. This is one of the largest clinical metaproteomic studies to date, and the first metaproteomic study addressing the gut microbiome in MRE colonized acute leukemia patients. Based on this substantial data set, we discuss major current limitations in clinical metaproteomic data analysis to provide guidance to researchers in the field. Notably, the results show that public metagenome databases are incomplete and that sample-specific metagenomes improve results. Furthermore, biological variation is tremendous which challenges clinical study designs and argues that longitudinal measurements of individual patients are a valuable future addition to the analysis of patient cohorts.

Umbilical cord-blood (UCB) is a well-recognized alternative source of stem cells for unrelated donor hematopoietic stem cell transplantation (HSCT). As compared with other stem cell sources from adult donors, it has the advantages of immediate availability of cells, absence of risk to the donor and reduced risk of graft-versus-host disease despite donor-recipient HLA disparity. However, the use of UCB is limited by the delayed post-transplant hematologic recovery due, at least in part, to the reduced number of hematopoietic cells in the graft and the delayed or incomplete immune reconstitution. As a result, severe infectious complications continue to be a leading cause of morbidity and mortality following UCB transplantation (UCBT). We will address the complex differences in the immune properties of UCB and review the incidence, characteristics, risk factors, and severity of bacterial, fungal and viral infectious complications in patients undergoing UCBT.

La presencia de pacientes con síntomas refractarios e intensas crisis emocionales en la fase final de la vida irrumpen en la actividad diaria de los profesionales sanitarios. Esta eventualidad puede convertirse en una experiencia desconcertante por la escasez de recursos y habilidades adquiridas durante el periodo de formación. La medicina y sus profesionales son inculpados de prolongar el proceso de agonía y no aliviar el sufrimiento y la angustia. La dificultad de atender al paciente moribundo reside en las demandas psicológicas que produce y los conflictos internos que genera. ¿Qué se necesitaríamos nosotros en esa situación?. Es imprescindible disponer de una guía de actuación que oriente nuestro proceso terapéutico defendiendo siempre el mejor interés de la persona. En el presente trabajo se hacen algunas reflexiones sobre la muerte, el énfasis en curar y cuidar, sobre las necesidades y carencias de las personas en la fase final de sus vidas, las directivas anticipadas, los síntomas refractarios y la sedación paliativa y en como saber actuar en situaciones donde las fronteras éticas y legales están poco definidas o en debate permanente.

En el presente artículo se detalla una forma de incluir un psicólogo especialista en Oncología en un Servicio o en un hospital monográfico de cáncer. Se hace una introducción histórica de la Psico-Oncología en Estados Unidos y en España. Se contemplan los puntos de vista del oncólogo médico y el psicólogo ante las múltiples demandas del entorno familiar y del paciente con cáncer. Se describe el método de interacción actual Modelo de Interconsulta (MIC) del psicólogo en Oncología, desarrollando posteriormente el Modelo Fundacional (MFU) establecido en el MSKCC de Nueva York. Por último presentamos la experiencia de integración de un psico-oncólogo en un Servicio de Oncología Médica llevada a cabo en el Hospital Universitario Marqués de Valdecilla (HUMV). La integración del psico-oncólogo en los equipos de Oncología es posible, necesaria y beneficiosa.

Delirium is a functional disorder of the central nervous system, very common among oncological patients, consequence of the presence in the organism of “false neurotransmitters” that could be exogenous or endogenous and give place to alterations inside several aspects (cognitive, perceptive, behavior, attention). The restoration of the symptoms is acute and the course is fluctuating along the day. In an important percentage of the cases the situation is reversible. Nevertheless, in other occasions it is an indicator of a situation premortem of the patient (“terminal agitation”). Most of cases etiology is multifactorial and there can be implied both, the proper tumor and the treatments administered to fight it or to solve the symptoms that this one causes (chemotherapy, opioids, steroids). The managing of this entity implies several questions of psychological area (information to the family), of environmental hygiene (skills of reorientation) and pharmacologist (control the symptoms with neuroleptics, benzodiacepines). Nevertheless, the most important point is to eliminate the ethiologic factor, in case of this one exists.

In the present article we expose a model for a first psychological interview with cancer patients. We set our basis on the integration of the psychologist on the Oncology teams. We refer the importance of communication. Communication is the central element of the therapeutic relationship. The meeting ought to be warm and empathic. We detach the presence of both patient and care-givers emotions. Psychologists should be experts managing their own emotions, the patient and his family’s emotions and the sanitary team emotions. The first interview objective is as simple as getting to know the patient and to establish a profitable link. We aim to reach a mutual confidence to allow an assistance relationship. Two key moments that we shall not neglect are greeting and farewell. The information we manage to get includes socio demographic data, illness news and the illness patient narration. In the psycho-oncologist exploration we examine the symptoms area, behaviour, emotions, cognitions, spiritual beliefs and socio familiar support. The most important thing in a first psycho-oncologist interview is listening, connecting with the patient and come to an agreement to reach the objectives

The anorexia-cachexia syndrome is a paraneoplasic, metabolic disorder characterized by the appearance of appetite decrease, loss of weight and muscular mass atrophy, which in spite of a correct caloric and nutritional contribution is not achieved to solve. This entity is frequent among patients with malignant tumors. And its result, the malnutrition, drives to a series of complications in the shape of alterations at immune system and related to the oncological treatments, attributing to these patients a worse prognosis. The fisiopathology is explained by the existence of a deregulation at hypothalamic center that has the control of the appetite consequence of the production of several cytokines. According to the irreversibility of the syndrome, once it is established, the most relevant aspect to manage it will be the preventive measurements and obviously a good psycho-emotional support from the sanitary professionals.

The purpose of our article is to communicate the need of taking into account ethic values in the decision making process. The reason for this need is the lack of communication among the professionals of different medicine fields. We show a 84 year-old patient with many comorbidities, to whom a Neurophysiological Study was performed in order to confirm an irrelevant diagnosis in his overall process. This study did not suppose any therapeutic change and, therefore was useless. Taking into account the happenings and values of the described situation, we show the ethic dilemma the professional has to think about. This reveals the imbalance between both aspects of nowaday’s medicine: the scientific and technique (episteme) and the humanistic (doxa). The right junction between both aspects is needed to reach medicine´s main goal which is to defend the patient’s interest.

Umbilical cord blood transplant recipients are exposed to an increased risk of graft failure, a complication leading to a higher rate of transplant-related mortality. The decision and timing to offer a second transplant after graft failure is challenging. With the aim of addressing this issue, we analyzed engraftment kinetics and outcomes of 1268 patients (73% children) with acute leukemia (64% acute lymphoblastic leukemia, 36% acute myeloid leukemia) in remission who underwent single-unit umbilical cord blood transplantation after a myeloablative conditioning regimen. The median follow-up was 31 months. The overall survival rate at 3 years was 47%; the 100-day cumulative incidence of transplant-related mortality was 16%. Longer time to engraftment was associated with increased transplant-related mortality and shorter overall survival. The cumulative incidence of neutrophil engraftment at day 60 was 86%, while the median time to achieve engraftment was 24 days. Probability density analysis showed that the likelihood of engraftment after umbilical cord blood transplantation increased after day 10, peaked on day 21 and slowly decreased to 21% by day 31. Beyond day 31, the probability of engraftment dropped rapidly, and the residual probability of engrafting after day 42 was 5%. Graft failure was reported in 166 patients, and 66 of them received a second graft (allogeneic, n=45). Rescue actions, such as the search for another graft, should be considered starting after day 21. A diagnosis of graft failure can be established in patients who have not achieved neutrophil recovery by day 42. Moreover, subsequent transplants should not be postponed after day 42.

There are very few disease-specific studies focusing on outcomes of umbilical cord blood transplantation for Philadelphia chromosome-positive acute lymphoblastic leukemia. We report the outcome of 45 patients with Philadelphia chromosome-positive acute lymphoblastic leukemia who underwent myeloablative single unit cord blood transplantation from unrelated donors within the GETH/GITMO cooperative group. Conditioning regimens were based on combinations of thiotepa, busulfan, cyclophospamide or fludarabine, and antithymocyte globulin. At the time of transplantation, 35 patients (78%) were in first complete remission, four (8%) in second complete remission and six (14%) in third or subsequent response. The cumulative incidence of myeloid engraftment was 96% at a median time of 20 days and significantly better for patients receiving higher doses of CD34+ cells. The incidence of acute grade II–IV graft-versus-host disease was 31%, while that of overall chronic graft-versus-host disease was 53%. Treatment-related mortality was 17% at day +100 and 31% at 5 years. The 5-year relapse, event-free survival and overall survival rates were 31%, 36% and 44%, respectively. Although the event-free and overall survival rates in patients without BCR/ABL transcripts detectable at time of transplant were better than those in whom BCR/ABL transcripts were detected (46% versus 24% and 60% versus 30%, respectively) these differences were not statistically significant in the univariate analysis (P=0.07). These results demonstrate that umbilical cord blood transplantation from unrelated donors can be a curative treatment for a substantial number of patients with Philadelphia chromosome-positive acute lymphoblastic leukemia.

Accumulated evidence demonstrates the existence of bone marrow-derived cells origin in the endometria of women undergoing bone marrow transplantation (BMT). In these reports, cells of a bone marrow (BM) origin are able to differentiate into endometrial cells, although their contribution to endometrial regeneration is not yet clear. We have previously demonstrated the functional relevance of side population (SP) cells as the endogenous source of somatic stem cells (SSC) in the human endometrium. The present work aims to understand the presence and contribution of bone marrow-derived cells to the endometrium and the endometrial SP population of women who received BMT from male donors. Five female recipients with spontaneous or induced menstruations were selected and their endometrium was examined for the contribution of XY donor-derived cells using fluorescent in situ hybridization (FISH), telomapping and SP method investigation. We confirm the presence of XY donor-derived cells in the recipient endometrium ranging from 1.7% to 2.62%. We also identify 0.45-0.85% of the donor-derived cells in the epithelial compartment displaying CD9 marker, and 1.0-1.83% of the Vimentin-positive XY donor-derived cells in the stromal compartment. Although the percentage of endometrial SP cells decreased, possibly being due to chemotherapy applied to these patients, they were not formed by XY donor-derived cells, donor BM cells were not associated with the stem cell (SC) niches assessed by telomapping technique, and engraftment percentages were very low with no correlation between time from transplant and engraftment efficiency, suggesting random terminal differentiation. In conclusion, XY donor-derived cells of a BM origin may be considered a limited exogenous source of transdifferentiated endometrial cells rather than a cyclic source of BM donor-derived stem cells.

The risk factors for and incidence of central nervous system involvement at first relapse in adult patients with acute myeloid leukemia have not been established. This single-center study analyzed the prognostic factors for and cumulative incidence of meningeal relapse in 458 adult patients achieving complete remission. Before 1990, patients received old chemotherapy approaches without stem cell transplantation that often included prophylactic intrathecal chemotherapy. Since 1990, modern protocols included stem cell transplantation without intrathecal prophylaxis. Meningeal relapse occurred in 6 patients (overall 5-year cumulative incidence 1.3%). The 5-year cumulative incidence of meningeal relapse in patients treated with old and modern protocols were 3.9% and 0.3%, respectively. Univariate and multivariate analyses showed that the chemotherapy approach was the main prognostic factor for central nervous system relapse (P=0.02). This study shows an extremely low incidence of meningeal relapse in adult patients with acute myeloid leukemia treated with modern protocols including stem cell transplantation without intrathecal prophylaxis.