Cerebral Hemodynamic Responses to Disease-Modifying and Curative Sickle Cell Disease Therapies.

Background And Objectives: Sickle cell disease (SCD) is a hemoglobinopathy resulting in hemoglobin-S production, hemolytic anemia, and elevated stroke risk. Treatments include oral hydroxyurea, blood transfusions, and hematopoietic stem cell transplantation (HSCT). Our objective was to evaluate the neurologic relevance of these therapies by characterizing how treatment-induced changes in hemoglobin (Hb) affect brain health biomarkers.

Multidisciplinary Management of Morbidities Associated with Chronic Graft-Versus-Host Disease.

Chronic graft-versus-host disease (cGVHD) represents a common long-term complication after allogeneic hematopoietic stem cell transplantation (HSCT). It imposes a significant morbidity burden and is the leading cause of non-relapse mortality among long-term HSCT survivors. cGVHD can manifest in nearly any organ, severely affecting the quality of life of a transplant survivor.

Evaluating Antibiotic De-escalation for Autologous Stem Cell Transplant Patients With Febrile Neutropenia in a Real-World Clinical Setting.

Febrile neutropenia (FN) is a complication in approximately 90% of autologous stem cell transplant (SCT) patients. Guidelines support early broad-spectrum antibiotics (BSA) to prevent morbidity and mortality. However, in patients who are clinically stable and deemed to have a fever of unknown origin, the optimal duration of BSA is unknown.

Efficacy and safety of outpatient fludarabine, cyclophosphamide, and rituximab based allogeneic hematopoietic cell transplantation in adults with severe aplastic anemia.

The age effect in severe aplastic anemia (SAA) following allogeneic hematopoietic cell transplantation (HCT) favors the use of reduced intensity conditioning (RIC) regimens in older adults. We implemented a non-myeloablative regimen consisting of fludarabine, cyclophosphamide, and rituximab (FCR) to improve HCT outcomes in SAA. Patients who underwent first HCT for SAA utilizing an FCR regimen between January 2016 and May 2022 were included.

Incidence and Risk Factors for New and Recurrent Infarcts in Adults With Sickle Cell Disease.

Background: Most adults with sickle cell disease will experience a silent cerebral infarction (SCI) or overt stroke. Identifying patient subgroups with increased stroke incidence is important for future clinical trials focused on stroke prevention. Our 3-center prospective cohort study tested the primary hypothesis that adults with sickle cell disease and SCIs have a greater incidence of new stroke or SCI compared with those without SCI.

Distribution of Silent Cerebral Infarcts in Adults With Sickle Cell Disease.

Background And Objectives: Previously we demonstrated that 90% of infarcts in children with sickle cell anemia occur in the border zone regions of cerebral blood flow (CBF). We tested the hypothesis that adults with sickle cell disease (SCD) have silent cerebral infarcts (SCIs) in the border zone regions, with a secondary hypothesis that older age and traditional stroke risk factors would be associated with infarct occurrence in regions outside the border zones.

Methods: Adults with SCD 18-50 years of age were enrolled in a cross-sectional study at 2 centers and completed a 3T brain MRI.

Bone Marrow Harvest: A White Paper of Best Practices by the NMDP Marrow Alliance.

Data on recent bone marrow harvest (BMH) collections from the NMDP has shown that bone marrow (BM) quality has decreased based on total nucleated cell count in the product. To ensure that quality BM products are available to all recipients, the NMDP Marrow Alliance was formed in April 2021 to increase the capability of BM collection centers to safely deliver high-quality products consistently and to identify and disseminate guidelines for performing BMH. This white paper describes the best practices for BMH as defined by the NMDP Marrow Alliance.

An international learning collaborative phase 2 trial for haploidentical bone marrow transplant in sickle cell disease.

In the setting of a learning collaborative, we conducted an international multicenter phase 2 clinical trial testing the hypothesis that nonmyeloablative-related haploidentical bone marrow transplant (BMT) with thiotepa and posttransplant cyclophosphamide (PTCy) will result in 2-year event-free survival (no graft failure or death) of at least 80%. A total of 70 participants were evaluable based on the conditioning protocol. Graft failure occurred in 8 of 70 (11.

Transcranial doppler velocity in iron-deficient Nigerian children with sickle cell anemia.

Oral iron supplementation in iron deficient children with sickle cell anemia and normal transcranial Doppler ultrasound (TCD) velocities does not reduce arterial flow in the middle cerebral artery.

The range of haploidentical transplant protocols in sickle cell disease: all haplos are not created equally.

The ideal curative therapy for sickle cell disease (SCD) must be applicable across all ages and include individuals with strokes and preexisting heart, lung, and kidney disease. Myeloablative, matched sibling donor hematopoietic stem cell transplant (HCT) for children with SCD has shown excellent outcomes over the past 3 decades but has been restricted due to the limited availability of a human leukocyte antigen-matched sibling donor (10%-15%) and increased treatment-related death in adults with myeloablative conditioning. To overcome these 2 significant barriers to curative therapy in SCD, related haploidentical HCT has become an active area of research.

Cerebral hemodynamic changes after haploidentical hematopoietic stem cell transplant in adults with sickle cell disease.

Preliminary evidence from a series of 4 adults with sickle cell disease (SCD) suggests that hematopoietic stem cell transplant (HSCT) improves cerebral hemodynamics. HSCT largely normalizes cerebral hemodynamics in children with SCD. We tested the hypothesis in adults with SCD that cerebral blood flow (CBF), oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen (CMRO2) measured using magnetic resonance imaging, normalized to healthy values, comparing measurements from ∼1 month before to 12 to 24 months after HSCT (n = 11; age, 33.

A feasibility randomized controlled trial of an mHealth app vs booklets for patient-facing guidelines in adults with SCD.

Despite the increased number of evidence-based guidelines for sickle cell disease (SCD), dissemination of evidence-based guidelines in lay language for individuals or families with SCD has not been evaluated. We conducted a feasibility randomized controlled trial to determine the acceptability of a mobile health (mHealth) app with patient-facing guidelines to improve the knowledge of individuals with SCD about SCD-specific knowledge and reduce hospitalizations. Primary outcome measures include recruitment, retention, and adherence rates.

Silent infarction in sickle cell disease is associated with brain volume loss in excess of infarct volume.

Introduction: Sickle cell disease (SCD) increases cerebral infarct risk, but reported effects on brain volume have varied. More detailed information using larger cohorts and contemporary methods could motivate the use of longitudinal brain volume assessment in SCD as an automated marker of disease stability or future progression. The purpose of this study was to rigorously evaluate whether children and young adults with SCD have reduced gray matter volume (GMV) and white matter volume (WMV) compared to healthy controls using high-resolution MRI.

TP53 Mutations Are Associated with Increased Infections and Reduced Hematopoietic Cell Transplantation Rates in Myelodysplastic Syndrome and Acute Myeloid Leukemia.

Although allogeneic hematopoietic cell transplantation (HCT) is the sole potentially curative therapy for patients with poor-risk myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), only a minority of these patients undergo HCT. Patients with TP53-mutated (TP53) MDS/AML are at particularly high risk, yet fewer TP53 patients undergo HCT compared with poor-risk TP53-wild type (TP53) patients. We hypothesized that TP53 MDS/AML patients have unique risk factors affecting the rate of HCT and thus investigated phenotypic changes that may prevent patients with TP53 MDS/AML from receiving HCT.

NCCN Guidelines® Insights: Hematopoietic Cell Transplantation, Version 3.2022.

The NCCN Guidelines for Hematopoietic Cell Transplantation (HCT) provide an evidence- and consensus-based approach for the use of autologous and allogeneic HCT in the management of malignant diseases in adult patients. HCT is a potentially curative treatment option for patients with certain types of malignancies; however, recurrent malignancy and transplant-related complications often limit the long-term survival of HCT recipients. The purpose of these guidelines is to provide guidance regarding aspects of HCT, including pretransplant recipient evaluation, hematopoietic cell mobilization, and treatment of graft-versus-host disease-a major complication of allogeneic HCT-to enable the patient and clinician to assess management options in the context of an individual patient's condition.

Relapsed or refractory large B-cell lymphoma after chimeric antigen receptor T-cell therapy: Current challenges and therapeutic options.

Chimeric antigen receptor (CAR) T-cell (CAR-T) therapy can provide durable remission in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) after failure of chemoimmunotherapy. However, patients who are refractory or relapsing after CAR-T therapy have poor outcomes. Multiple mechanisms of CAR-T therapy failure have been proposed but management of these patients remains a challenge.

Creating an automated contemporaneous cohort in sickle cell anemia to predict survival after disease-modifying therapy.

The Food and Drug Administration requires contemporaneous controls to compare clinical outcomes for participants receiving experimental gene therapy or gene editing clinical trials. However, developing a contemporaneous cohort of rare diseases requires multiple person-hours. In a single referral center for sickle cell disease, we tested the hypothesis that we could create an automated contemporaneous cohort of children and adults with sickle cell anemia (SCA) to predict mortality.

Hydroxyurea for secondary stroke prevention in children with sickle cell anemia in Nigeria: a randomized controlled trial.

We tested the hypothesis that fixed oral moderate-dose hydroxyurea (20 mg/kg per day) for initial treatment of secondary stroke prevention results in an 80% relative risk reduction of stroke or death when compared with fixed oral low-dose hydroxyurea (10 mg/kg per day) in a phase 3 double-blind, parallel-group, randomized controlled trial in children with sickle cell anemia (SCA) living in Nigeria. A total of 101 participants were randomly allocated to low-dose (n = 49) and moderate-dose (n = 52) hydroxyurea treatment groups. The median participant follow-up was 1.