scholarly journals Functional and Radiologic Assessment of the Brain after Reduced-Intensity Unrelated Donor Transplantation for Severe Sickle Cell Disease: Blood and Marrow Transplant Clinical Trials Network Study 0601

2019 ◽  
Vol 25 (5) ◽  
pp. e174-e178 ◽  
Author(s):  
Allison A. King ◽  
Robert C. McKinstry ◽  
Juan Wu ◽  
Mary Eapen ◽  
Regina Abel ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Marrow Transplant ◽  
Unrelated Donor ◽  
Cell Disease ◽  
Blood And Marrow Transplant ◽  
Radiologic Assessment ◽  
The Brain ◽  
Reduced Intensity

scholarly journals End points for sickle cell disease clinical trials: patient-reported outcomes, pain, and the brain

2019 ◽  
Vol 3 (23) ◽  
pp. 3982-4001 ◽  
Author(s):  
Ann T. Farrell ◽  
Julie Panepinto ◽  
C. Patrick Carroll ◽  
Deepika S. Darbari ◽  
Ankit A. Desai ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Patient Reported Outcomes ◽  
Cell Disease ◽  
End Points ◽  
Additional Clinical Trial ◽  
Patient Reported ◽  
The Brain

Abstract To address the global burden of sickle cell disease (SCD) and the need for novel therapies, the American Society of Hematology partnered with the US Food and Drug Administration to engage the work of 7 panels of clinicians, investigators, and patients to develop consensus recommendations for clinical trial end points. The panels conducted their work through literature reviews, assessment of available evidence, and expert judgment focusing on end points related to: patient-reported outcomes (PROs), pain (non-PROs), the brain, end-organ considerations, biomarkers, measurement of cure, and low-resource settings. This article presents the findings and recommendations of the PROs, pain, and brain panels, as well as relevant findings and recommendations from the biomarkers panel. The panels identify end points, where there were supporting data, to use in clinical trials of SCD. In addition, the panels discuss where further research is needed to support the development and validation of additional clinical trial end points.

scholarly journals Allogeneic transplantation strategies including haploidentical transplantation in sickle cell disease

Hematology ◽  
2013 ◽  
Vol 2013 (1) ◽  
pp. 370-376 ◽  
Author(s):  
Eliane Gluckman
Keyword(s):  
Stem Cell ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Perceived Risk ◽  
Marrow Transplant ◽  
Cell Disease ◽  
Hematopoietic Stem ◽  
Screening Programs ◽  
Blood And Marrow Transplant ◽  
Antenatal Counseling

Abstract Sickle cell disease (SCD) is the most common inherited hemoglobinopathy. Despite antenatal counseling and neonatal screening programs implemented in higher income countries, SCD is still associated with multiple morbidities and early mortality. To date, the only curative approach to SCD is hematopoietic stem cell transplantation, but this therapy is not yet established worldwide. The registries of the European Blood and Marrow Transplant (EBMT) and the Centre for International Blood and Marrow Transplant Research (CIBMTR) account, respectively, for 611 and 627 patients receiving transplantations for SCD. Most of these patients were transplanted with grafts from an HLA-identical sibling donor. The main obstacles to increasing the number of transplantations are a lack of awareness on the part of physicians and families, the absence of reliable prognostic factors for severity, and the perceived risk that transplantation complications may outweigh the benefits of early transplantation. Results show that more than 90% of patients having undergone an HLA-identical sibling transplantation after myeloablative conditioning are cured, with very limited complications. Major improvement is expected from the use of new reduced-toxicity conditioning regimens and the use of alternative donors, including unrelated cord blood transplantations and related haploidentical bone marrow or peripheral blood stem cell transplantations.

scholarly journals Excellent Overall Survival and Low Incidence of Late Effects in Patients Undergoing Allogeneic Hematopoietic Cell Transplant for Sickle Cell Disease: A Report from the Center for International Blood and Marrow Transplant Research (CIBMTR)

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 697-697 ◽  
Author(s):  
Elizabeth Stenger ◽  
Rachel Phelan ◽  
Bronwen E. Shaw ◽  
Minoo Battiwalla ◽  
Stephanie Bo-Subait ◽  
...  
Keyword(s):  
Risk Factors ◽  
Overall Survival ◽  
Sickle Cell Disease ◽  
Multivariable Analysis ◽  
Marrow Transplant ◽  
Acute Chest Syndrome ◽  
Unrelated Donor ◽  
Cell Disease ◽  
Blood And Marrow Transplant

Introduction: Allogeneic hematopoietic cell transplantation (HCT) is curative therapy for sickle cell disease (SCD). Good outcomes have spurred an increase in the use of HCT for SCD, including an increasing number of trials using alternative donors. As survival improves, assessment of long-term outcomes and potential late effects (LEs) in this patient population is critical. We evaluated the data reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) to study incidence and risk factors for LEs following HCT for SCD. Methods: Patients reported to the CIBMTR with a diagnosis of SCD who had undergone their first HCT between 1996 and June 2015 were included in this analysis. Patients with graft failure were excluded. We performed a descriptive analysis of patient, disease, donor, and transplant-related factors. The cumulative incidence (CI) of LEs was estimated at 1, 3, and 7 years post-HCT. The number of pre- versus post-HCT SCD-specific disease complications was computed. Overall survival (OS) probabilities were calculated using the Kaplan-Meier method. Multivariable Cox regression analysis was used to evaluate risk factors related to OS and LEs. Results: The study population consisted of 355 patients. The median age at HCT was 10 years (range <1-52) and median follow-up was 50 months (range 9-248). The most common indications for HCT were recurrent pain (30%), stroke (29%), and acute chest syndrome (13%). Majority of patients received myeloablative HCT (66%), had a matched sibling donor (59%), and had bone marrow as the graft source (70%). OS at 2, 5, and 7 years was 91%, 89%, and 89%, respectively. Most common causes of death were organ failure (36%), graft-versus-host disease (GVHD; 18%), and infection (13%). Chronic GVHD developed in 30% of patients. Four patients developed a new malignancy post-HCT: AML (N=1; 11 months), MDS/MPN (N=1; 119 months), and lymphoma/lymphoproliferative disease (N=2; 1 and 6 months). The CI of LEs is shown in Figure 1, with highest incidences seen of diabetes, gonadal dysfunction, and avascular necrosis (10%, 6.7%, and and 4.1% at 7 years, respectively, with majority of diabetes occurring in year 1). In multivariable analysis, undergoing HCT when >15 years of age was associated with significantly inferior OS (mortality HR 7.26, 95% CI 3.57-14.77). Multivariable analysis for LEs demonstrated an increased risk of diabetes (HR 7.29, 95% CI 2.94-18.08) and pulmonary abnormalities (HR 5.90, 95% CI 1.14-30.42) with unrelated donor, while older age at HCT was associated with avascular necrosis (HR 14.19, 95% CI 1.86-108.47), diabetes (HR 3.45, 95% CI 1.69-7.05), and congestive heart failure (HR 8.02, 95% CI 1.13-56.94). SCD-related symptoms overall decreased from pre- to post-HCT (Table 1), most notably acute chest syndrome, vaso-occlusive pain crises, and stroke. Conclusions: Patients with SCD who have undergone HCT for SCD in recent years have excellent OS, confirmed in this CIBMTR multicenter dataset, with diminished SCD-related symptom burden post-HCT. However, they remain at-risk for a myriad of LEs, with risk factors including older age at HCT and unrelated donor, necessitating systemic organ-based follow up post-HCT. Continued follow-up of this patient population is critical to provide appropriate counseling for medical providers, patients, and families considering HCT as a treatment option for SCD. Disclosures Shaw: Therakos: Other: Speaker Engagement.

scholarly journals A trial of unrelated donor marrow transplantation for children with severe sickle cell disease

Blood ◽  
2016 ◽  
Vol 128 (21) ◽  
pp. 2561-2567 ◽  
Author(s):  
Shalini Shenoy ◽  
Mary Eapen ◽  
Julie A. Panepinto ◽  
Brent R. Logan ◽  
Juan Wu ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Marrow Transplantation ◽  
Unrelated Donor ◽  
Cell Disease ◽  
Reduced Intensity Conditioning ◽  
Key Points ◽  
High Incidence ◽  
Reduced Intensity

Key Points Children with sickle cell disease engrafted unrelated donor marrow after reduced intensity conditioning. A high incidence of GVHD and associated mortality compromised safety of the trial.

Quantitative MRI of the brain in children with sickle cell disease reveals abnormalities unseen by conventional MRI

1998 ◽  
Vol 8 (3) ◽  
pp. 535-543 ◽  
Author(s):  
R. Grant Steen ◽  
Wilburn E. Reddick ◽  
Raymond K. Mulhern ◽  
James W. Langston ◽  
Robert J. Ogg ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Quantitative Mri ◽  
Cell Disease ◽  
Conventional Mri ◽  
The Brain
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