Persistent or New Cytopenias Predict Relapse Better than Routine Bone Marrow Aspirate Evaluations After Hematopoietic Cell Transplantation for Acute Leukemia or Myelodysplastic Syndrome in Children and Young Adult Patients.

The clinical value of serial routine bone marrow aspirates (rBMAs) in the first year after allogeneic hematopoietic cell transplantation (alloHCT) to detect or predict relapse of acute leukemia (AL) and myelodysplastic syndrome (MDS) in pediatric and young adult patients is unclear. The purpose of this analysis was to determine if assessment of minimal residual disease (MRD) by multiparameter flow cytometry (MFC, MFC-MRD) or donor chimerism (DC) in rBMAs or serial complete blood counts (CBCs) done in the year after alloHCT predicted relapse of AL or MDS in pediatric and young adult patients. We completed a retrospective analysis of patients with AL or MDS who had rBMAs performed after alloHCT between January 2012 and June 2018.

Impact of rabbit anti-thymocyte globulin (ATG) exposure on outcomes after ex vivo T-cell-depleted hematopoietic cell transplantation in pediatric and young adult patients.

Background Aims: Traditional weight-based dosing of rabbit anti-thymocyte globulin (rATG) used in allogeneic hematopoietic cell transplantation (HCT) to prevent graft-versus-host disease (GVHD) and graft rejection leads to variable exposures. High exposures induce delayed CD4+immune reconstitution (CD4+IR) and greater mortality. We sought to determine the impact of rATG exposure in children and young adults receiving various types of EX-VIVO T-cell-depleted (EX-VIVO-TCD) HCT.

Retrospective Evaluation of Cystatin C as a Measure of Renal Function in Pediatric Hematopoietic Stem Cell Transplant Patients Receiving Foscarnet for Cytomegalovirus Reactivation.

Background: Cytomegalovirus (CMV) infection following allogeneic hematopoietic cell transplantation has considerable morbidity and mortality, and foscarnet is a treatment option that requires renal dose adjustment. Serum creatinine (SCr)-based estimated glomerular filtration rate (eGFR) equations are used to estimate renal function for patients receiving foscarnet, but cystatin C (cysC) has been shown as a possible alternative. Data examining cysC-based eGFR in this population is sparse.

Predictors of outcomes in hematopoietic cell transplantation for Fanconi anemia.

Allogeneic hematopoietic cell transplantation (HCT) remains the only cure for the hematologic manifestations of Fanconi anemia (FA). We performed retrospective predictor analyses for HCT outcomes in FA for pediatric and young adult patients transplanted between 2007 and 2020 across three large referral institutions. Eighty-nine patients, 70 with bone marrow failure +/- cytogenetic abnormalities, 19 with MDS/AML, were included.

T-cell depleted allogeneic hematopoietic stem cell transplant for the treatment of Fanconi anemia and MDS/AML.

The only curative approach for myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) arising in patients with Fanconi anemia (FA) is allogeneic hematopoietic stem cell transplantation (HCT); however, HCT approaches are inconsistent and limited data on outcomes exist. We retrospectively evaluated outcomes of thirty patients with FA and MDS/AML who underwent first allogeneic HCT with a T-cell depleted (TCD) graft at our institution. Patients were transplanted on successive protocols with stepwise changes in cytoreduction and GVHD prophylaxis.

CRISPR-Cas9 Editing of the and Promoters to Treat Sickle Cell Disease.

Background: Sickle cell disease is caused by a defect in the β-globin subunit of adult hemoglobin. Sickle hemoglobin polymerizes under hypoxic conditions, producing deformed red cells that hemolyze and cause vaso-occlusion that results in progressive organ damage and early death. Elevated fetal hemoglobin levels in red cells protect against complications of sickle cell disease.

Sex-related differences in benefits of anticoagulation therapy in elderly patients with atrial fibrillation: a subanalysis of the EMERG-AF study.

Objectives: To analyze the long-term benefits and safety of oral anticoagulation therapy prescribed in emergency departments for elderly patients with atrial fibrillation, and to detect any sex-related differences present.

Material And Methods: Post-hoc analysis of data compiled by the EMERG-AF group (Spanish acronym for Emergency Department Stroke Prophylaxis and Guidelines Implementation in Atrial Fibrillation). Consecutive patients aged 75 years or older with atrial fibrillation who were treated in 62 EDs were included.

Association between busulfan exposure and survival in patients undergoing a CD34+ selected stem cell transplantation.

Busulfan is an alkylating drug routinely used in conditioning regimens for allogeneic hematopoietic cell transplantation (allo-HCT). A myeloablative conditioning regimen, including busulfan, is commonly used in patients undergoing T-cell depletion (TCD) and allo-HCT, but data on optimal busulfan pharmacokinetic (PK) exposure in this setting are limited. Between 2012 and 2019, busulfan PK was performed to target an area under the curve exposure between 55 and 66 mg × h/L over 3 days using a noncompartmental analysis model.

Long-term prognosis and emergency management for patients with an implantable cardioverter defibrillator: the EMERGE-ICD study.

Objectives: Patients with implantable cardioverter defibrillators (ICDs) are at risk of serious complications that are often treated in hospital emergency departments (EDs). The EMERG-ICD study (Emergency Department Management and Long-term Prognosis for Patients with ICDs) analysed management and long-term prognosis of ED patients with an ICD after an acute clinical event.

Material And Methods: Observational multicenter cohort study including consecutive adult patients with ICDs who came to 27 hospital EDs in Spain for treatment and were followed for 10 years.

Durable Engraftment and Excellent Overall Survival After CD34-Selected Peripheral Blood Stem Cell Boost in Pediatric Patients With Poor Graft Function Following Allogeneic Stem Cell Transplantation.

Poor graft function (PGF) is a life-threatening complication after allogeneic stem cell transplantation (alloSCT). Historically, outcomes of patients with PGF have been very poor, and there are no standardized approaches to treatment. Furthermore, few outcomes after CD34-selected stem cell boost (CD34+SCB) for PGF in pediatric alloSCT recipients have been reported.

Emergency department prescription of sinus rhythm maintenance therapy for patients treated for atrial fibrillation: a secondary analysis of the HERMES-AF study.

Objectives: The maintenance of sinus rhythm by means of antiarrhythmic drugs and/or upstream therapy to counter cardiac remodeling is fundamental to the management of atrial fibrillation (AF). This study aimed to analyze this approach and its appropriateness in the setting of hospital emergency departments.

Material And Methods: Secondary analysis of data from the multicenter observational cross-sectional HERMES-AF study carried out in 124 hospitals representative of the Spanish national health service in 2011.

Pulmonary microbiome and gene expression signatures differentiate lung function in pediatric hematopoietic cell transplant candidates.

Impaired baseline lung function is associated with mortality after pediatric allogeneic hematopoietic cell transplantation (HCT), yet limited knowledge of the molecular pathways that characterize pretransplant lung function has hindered the development of lung-targeted interventions. In this study, we quantified the association between bronchoalveolar lavage (BAL) metatranscriptomes and paired pulmonary function tests performed a median of 1 to 2 weeks before allogeneic HCT in 104 children in The Netherlands. Abnormal pulmonary function was recorded in more than half the cohort, consisted most commonly of restriction and impaired diffusion, and was associated with both all-cause and lung injury-related mortality after HCT.

Time to initiation of pre-emptive therapy for cytomegalovirus impacts overall survival in pediatric hematopoietic stem cell transplant recipients.

Background Aims: Cytomegalovirus (CMV) reactivation is a significant complication following allogeneic hematopoietic stem cell transplant (HSCT) and affects upwards of 40% of pediatric HSCT patients. Pre-emptive therapy remains the only effective treatment strategy available for pediatric patients following CMV reactivation. Little is known about how the timing of induction treatment following CMV reactivation impacts outcomes in pediatric patients, especially following ex vivo T-cell-depleted (TCD) HSCT.

Antithymocyte globulin exposure in CD34+ T-cell-depleted allogeneic hematopoietic cell transplantation.

Traditional weight-based dosing results in variable rabbit antithymocyte globulin (rATG) clearance that can delay CD4+ T-cell immune reconstitution (CD4+ IR) leading to higher mortality. In a retrospective pharmacokinetic/pharmacodynamic (PK/PD) analysis of patients undergoing their first CD34+ T-cell-depleted (TCD) allogeneic hematopoietic cell transplantation (HCT) after myeloablative conditioning with rATG, we estimated post-HCT rATG exposure as area under the curve (arbitrary unit per day/milliliter [AU × day/mL]) using a validated population PK model. We related rATG exposure to nonrelapse mortality (NRM), CD4+ IR (CD4+ ≥50 cells per µL at 2 consecutive measures within 100 days after HCT), overall survival, relapse, and acute graft-versus-host disease (aGVHD) to define an optimal rATG exposure.

Outcomes in Hematopoietic Stem Cell Transplantation for Congenital Amegakaryocytic Thrombocytopenia.

Congenital amegakaryocytic thrombocytopenia (CAMT) is a rare, inherited bone marrow failure syndrome. Hematopoietic stem cell transplantation (HSCT) is considered a curative treatment option, but existing descriptions of patient and transplant characteristics and outcomes after related and unrelated donor HSCT are sparse. We describe outcomes after HSCT for congenital amegakaryocytic thrombocytopenia (CAMT; n = 86) from 2000 to 2018.

Factors associated with poor prognosis in patients with atrial fibrillation: An emergency department perspective the EMERG-AF study.

Objective: We sought to identify the factors associated with a worse prognosis in Emergency Department (ED) patients with atrial fibrillation (AF), crucial information to guide management decisions.

Methods: This is a secondary analysis of a prospective, multicenter, observational cohort of consecutive AF patients attended in 62 EDs in Spain. Clinical variables were collected on enrollment.

Association between acute heart failure and major cardiovascular events in atrial fibrillation patients presenting at the emergency department: an EMERG-AF ancillary study.

Background: There is little evidence concerning the impact of acute heart failure (AHF) on the prognosis of atrial fibrillation patients attending the emergency department (ED).

Objective: To know the influence of AHF on adverse long-term outcomes in patients presenting with atrial fibrillation in ED.

Design, Setting And Participants: Secondary analysis of a prospective, multicenter, observational cohort of consecutive atrial fibrillation patients, performed in 62 Spanish EDs.

CD4+ T-cell reconstitution predicts survival outcomes after acute graft-versus-host-disease: a dual-center validation.

Acute graft-versus-host-Disease (aGVHD) is a major cause of morbidity and mortality after allogeneic hematopoietic cell transplantation (HCT). We previously showed that early CD4+ T-cell immune reconstitution (IR; CD4+ IR) predicts survival after HCT. Here, we studied the relation between CD4+ IR and survival in patients developing aGVHD.

Early CD4+ T cell reconstitution as predictor of outcomes after allogeneic hematopoietic cell transplantation.

Background: An association between early CD4+ T cell immune reconstitution (CD4+ IR) and survival after T-replete allogeneic hematopoietic cell transplantation (HCT) has been previously reported. Here we report validation of this relationship in a separate cohort that included recipients of ex vivo T-cell-depleted (TCD) HCT. We studied the relationship between CD4+ IR and clinical outcomes.

Emerging trends in COVID-19 treatment: learning from inflammatory conditions associated with cellular therapies.

Coronavirus disease 2019 (SARS-CoV2) is an active global health threat for which treatments are desperately being sought. Even though most people infected experience mild to moderate respiratory symptoms and recover with supportive care, certain vulnerable hosts develop severe clinical deterioration. While several drugs are currently being investigated in clinical trials, there are currently no approved treatments or vaccines for COVID-19 and hence there is an unmet need to explore additional therapeutic options.