Overall survival of patients with CLL treated with ibrutinib in the first line compared to second-line ibrutinib after chemotherapy/chemoimmunotherapy.

Objective: To evaluate the overall survival (OS) of patients with chronic lymphocytic leukemia (CLL) receiving either ibrutinib monotherapy as a first-line (1L) treatment or chemotherapy/chemoimmunotherapy-based (CT/CIT) regimens in 1L followed by ibrutinib in the second line (1L CT/CIT-2L ibrutinib) after disease progression by emulating a randomized trial comparing both treatment sequences.

Methods: Patient-level data from the RESONATE-2 trial (NCT01722487) and real-world PHEDRA databases were analyzed. Three scenarios were considered using the following data sources: (1) RESONATE-2, (2) combined RESONATE-2/PHEDRA, (3) combined RESONATE-2/PHEDRA for 1L ibrutinib and PHEDRA for 1L CT/CIT-2L ibrutinib.

Engaging Caregivers and Providers of Children With Sickle Cell Anemia in Shared Decision Making for Hydroxyurea: Protocol for a Multicenter Randomized Controlled Trial.

Background: Sickle cell anemia (SCA) is a genetic blood disorder that puts children at a risk of serious medical complications, early morbidity and mortality, and high health care utilization. Until recently, hydroxyurea was the only disease-modifying treatment for this life-threatening disease and has remained the only option for children younger than 5 years. Evidence-based guidelines recommend using a shared decision-making (SDM) approach for offering hydroxyurea to children with SCA (HbSS or HbS/β0 thalassemia) aged as early as 9 months.

Sacrificing one visual hemifield during pediatric epilepsy surgery: Effects on visual search.

Objectives: To investigate early and late effects of planned surgically acquired homonymous hemianopias on visual search in children and adolescents.

Methods: This prospective study included five patients (5y 5 m-18y 0 m; 2 girls) with pharmaco-refractory epilepsies in whom one visual hemifield was sacrificed as part of the surgical strategy, and, as controls, seven patients (5y 11 m-18y 0 m; 6 girls) undergoing epilepsy surgeries not affecting the visual fields. Visual search was studied using the "Table Test", which is an everyday life-like visual search test.

Sickle cell disease: current treatment and emerging therapies.

Sickle cell disease (SCD) is among the most common genetic diseases in the United States, affecting approximately 100,000 people. In the United States, SCD is characterized by a shortened life expectancy of only about 50 years in severe subtypes, significant quality-of-life impairments, and increased healthcare utilization and spending. SCD is characterized by chronic hemolytic anemia, vaso-occlusion, and progressive vascular injury affecting multiple organ systems.

Osteonecrosis in sickle cell disease: an update on risk factors, diagnosis, and management.

Osteonecrosis, a form of ischemic bone injury that leads to degenerative joint disease, affects ∼30% of people with sickle cell disease. Although osteonecrosis most commonly affects the femoral head (often bilaterally, with asymmetric clinical and radiographic progression), many people with sickle cell disease also present with multifocal joint involvement. We present the case of a young woman with bilateral osteonecrosis of the femoral head at varying stages of progression; we also highlight other important comorbid complications (eg, chronic pain requiring long-term opioids, debility, and social isolation) and postoperative outcomes.

Uncovering homonymous visual field defects in candidates for pediatric epilepsy surgery.

Objectives: Perimetry in children can be challenging due to low cooperation and short attention span. Especially during the pre-surgical work-up of children with pharmaco-refractory epilepsies, however, diagnosing homonymous visual field defects (HVFDs) can be crucial for planning surgical strategies. Here, we evaluated "campimetry" for visual field testing in children.

Safety and efficacy of deferiprone for pantothenate kinase-associated neurodegeneration: a randomised, double-blind, controlled trial and an open-label extension study.

Background: Pantothenate kinase-associated neurodegeneration (PKAN) is a rare genetic disorder characterised by progressive generalised dystonia and brain iron accumulation. We assessed whether the iron chelator deferiprone can reduce brain iron and slow disease progression.

Methods: We did an 18-month, randomised, double-blind, placebo-controlled trial (TIRCON2012V1), followed by a pre-planned 18-month, open-label extension study, in patients with PKAN in four hospitals in Germany, Italy, England, and the USA.

Sickle Cell Disease: Monitoring, Current Treatment, and Therapeutics Under Development.

Screening and early detection of organ injury, as well as expanded use of red cell transfusion and hydroxyurea in children have changed best practices for clinical care in sickle cell disease. The current standard of care for children with sickle cell disease is discussed through a review of screening recommendations, disease monitoring, and approach to treatment. Novel pharmacologic agents under investigation in clinical trials are also reviewed.

Double-blind, randomized, multicenter phase 2 study of SC411 in children with sickle cell disease (SCOT trial).

Blood cell membranes in sickle cell disease (SCD) have low docosahexaenoic acid (DHA). DHA treatment reduces sickle cell crisis (SCC) rate and ameliorates the inflammation, oxidative stress, and hypercoagulable state of SCD. SC411 is a novel DHA ethyl ester formulation with a proprietary delivery platform (Advanced Lipid Technology) that enhances DHA bioavailability.

A Phase 3 Trial of l-Glutamine in Sickle Cell Disease.

Background: Oxidative stress contributes to the complex pathophysiology of sickle cell disease. Oral therapy with pharmaceutical-grade l-glutamine (USAN, glutamine) has been shown to increase the proportion of the reduced form of nicotinamide adenine dinucleotides in sickle cell erythrocytes, which probably reduces oxidative stress and could result in fewer episodes of sickle cell-related pain.

Methods: In a multicenter, randomized, placebo-controlled, double-blind, phase 3 trial, we tested the efficacy of pharmaceutical-grade l-glutamine (0.

Encephaloduroarteriosynangiosis (EDAS) in young patients with cerebrovascular complications of sickle cell disease: Single-institution experience.

Moyamoya syndrome occurs in sickle cell disease (SCD) as a secondary complication of large-artery stenosis. Moyamoya increases the risk of stroke, but its optimal management in SCD is not established.  Encephaloduroarteriosynangiosis (EDAS) is a neurosurgical revascularization procedure for moyamoya whose use has been reported in SCD patients.

Emergency department utilization by Californians with sickle cell disease, 2005-2014.

Background: Clinical care for children and adults living with sickle cell disease (SCD) is often provided in the emergency department (ED). Population-based surveillance data can be used to describe the ED utilization patterns of this patient population.

Procedure: A cohort of pediatric and adult California patients with SCD was identified from multiple data sources, and 10 years (2005-2014) of their treat-and-release ED utilization data were analyzed.

Increased prevalence of potential right-to-left shunting in children with sickle cell anaemia and stroke.

'Paradoxical' embolization via intracardiac or intrapulmonary right-to-left shunts (RLS) is an established cause of stroke. Hypercoagulable states and increased right heart pressure, which both occur in sickle cell anaemia (SCA), predispose to paradoxical embolization. We hypothesized that children with SCA and overt stroke (SCA + stroke) have an increased prevalence of potential RLS.

Erythrocytapheresis for chronic transfusion therapy in sickle cell disease: survey of current practices and review of the literature.

Background: Chronic red blood cell (RBC) transfusion therapy (CTT) is an integral component of the management of severe sickle cell disease (SCD) and can prevent complications, such as stroke. RBC units can be administered via simple transfusion or exchange transfusion, and erythrocytapheresis (automated RBC exchange transfusion [aRBX]), is increasingly used for CTT. Comparisons of simple and aRBX transfusions are limited, and the current scope of aRBX use is not known.

Mechanisms of plasma non-transferrin bound iron generation: insights from comparing transfused diamond blackfan anaemia with sickle cell and thalassaemia patients.

In transfusional iron overload, extra-hepatic iron distribution differs, depending on the underlying condition. Relative mechanisms of plasma non-transferrin bound iron (NTBI) generation may account for these differences. Markers of iron metabolism (plasma NTBI, labile iron, hepcidin, transferrin, monocyte SLC40A1 [ferroportin]), erythropoiesis (growth differentiation factor 15, soluble transferrin receptor) and tissue hypoxia (erythropoietin) were compared in patients with Thalassaemia Major (TM), Sickle Cell Disease and Diamond-Blackfan Anaemia (DBA), with matched transfusion histories.

Population based surveillance in sickle cell disease: methods, findings and implications from the California registry and surveillance system in hemoglobinopathies project (RuSH).

Background: There are no population-based surveillance systems to determine prevalence, impact or outcomes in sickle cell disease (SCD). Estimates of the SCD population in California range broadly from 4,500 to 7,000, and little is known about their health status, health care utilization or health outcomes. A surveillance strategy was implemented using diverse data sources to develop a multi-dimensional, state-based surveillance system for SCD that includes adults and children and describes utilization, treatment and outcomes.

Neuroimaging abnormalities in adults with sickle cell anemia: associations with cognition.

Objective: This study was conducted to determine the relationship of frontal lobe cortical thickness and basal ganglia volumes to measures of cognition in adults with sickle cell anemia (SCA).

Methods: Participants included 120 adults with SCA with no history of neurologic dysfunction and 33 healthy controls (HCs). Participants were enrolled at 12 medical center sites, and raters were blinded to diagnostic group.

Transfusion complications in thalassemia patients: a report from the Centers for Disease Control and Prevention (CME).

Background: Transfusions are the primary therapy for thalassemia but have significant cumulative risks. In 2004, the Centers for Disease Control and Prevention (CDC) established a national blood safety monitoring program for thalassemia. This report summarizes the population and their previous nonimmune and immune transfusion complications.

A randomized, placebo-controlled trial of arginine therapy for the treatment of children with sickle cell disease hospitalized with vaso-occlusive pain episodes.

Painful episodes of vaso-occlusion are the leading cause of hospitalizations and emergency department visits in sickle cell disease, and are associated with increased mortality. Low nitric oxide bioavailability contributes to vasculopathy in sickle cell disease. Since arginine is the obligate substrate for nitric oxide production, and an acute deficiency is associated with pain, we hypothesized that arginine may be a beneficial treatment for pain related to sickle cell disease.

Combined chelation therapy with deferasirox and deferoxamine in thalassemia.

Iron overload is the primary cause of mortality and morbidity in thalassemia major despite advances in chelation therapy. We performed a pilot clinical trial to evaluate the safety and efficacy of combined therapy with deferasirox (DFX, 20-30 mg/kg daily) and deferoxamine (DFO, 35-50mg/kg on 3-7 days/week) in 22 patients with persistent iron overload or organ damage. In the 18 subjects completing 12 months of therapy, median liver iron concentration decreased by 31% from 17.

A phase 1/2 trial of HQK-1001, an oral fetal globin inducer, in sickle cell disease.

Therapeutics which reduce the pathology in sickle cell syndromes are needed, particularly noncytotoxic therapeutics. Fetal hemoglobin (HbF, α(2) γ(2) ) is established as a major regulator of disease severity; increased HbF levels correlate with milder clinical courses and improved survival. Accordingly, sodium dimethylbutyrate (HQK-1001), an orally-bioavailable, promoter-targeted fetal globin gene-inducing agent, was evaluated in a randomized, blinded, dose-ranging Phase I/II trial in 24 adult patients with HbSS or S/β thalassemia, to determine safety and tolerability of three escalating dose levels.

Lip cancer: retrospective analysis of 181 cases.

Background: In Germany little data on the epidemiology and histology of lip cancers are available, as lip cancers are commonly pooled together with head and neck tumors.

Patients And Methods: Retrospective analysis of 181 patients with malignant tumors of the lips with respect to gender, location, histology, risk factors and comorbidity.

Results: There were 90 women and 91 men with a mean age of 71 years.

Red blood cell transfusion in pediatric patients with severe chronic anemia: how slow is necessary?

Historic practice recommends slow transfusion for children with chronic anemia and hemoglobin less than 5.0 g/dl due to the theoretical risk of transfusion-associated circulatory overload (TACO). In our pediatric intensive care unit (PICU), we have been utilizing a more liberal transfusion practice in patients without underlying cardiopulmonary disease, and a faster transfusion rate appears safe in this population.

Improved engraftment with minimal graft-versus-host disease after major histocompatibility complex-mismatched cord blood transplantation with photochemically treated donor lymphocytes.

There is a significant risk of severe graft-versus-host disease (GVHD) and graft failure after unrelated umbilical cord blood transplantation (CBT) if donor-recipient pairs are mismatched at major histocompatibility complex (MHC) loci. To mitigate these risks after MHC-mismatched CBT, we infused psoralen-treated, photochemically inactivated, mature donor T-lymphocytes with MHC (H2-haplotype) mismatched murine donor fetal near-term peripheral blood (FNPB) cells after sublethal irradiation. We analyzed the rates of donor engraftment, GVHD and long-term survival in H2 haplotype disparate (C57BL/6 [H-2(b)/Thy1.