Traffic Light: prognosis-based eligibility for clinical trials of hematopoietic SCT in adults with sickle cell anemia

Rotz, Seth J.; O’Riordan, Mary Ann; Kim, C; Lima, Marcos de; Gladwin, Mark T.; Little, Jane A.

doi:10.1038/bmt.2015.11

Cited by 17 publications

(16 citation statements)

References 36 publications

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“…Using a two-variable positive-predictive value assessment of 2-year mortality risk in this same cohort, it was possible to identify very high-risk patients. Subjects who had a combination of TRV >3 m/sec with WBC> 13,500 or chronic transfusion therapy had a 2-year mortality rate that exceeded 20% 34 . Finally, 43 of 240 subjects from a cohort of adults with SCD died between 2000–2005 with a median survival of 40 years 35 .…”

Section: Eligibility Criteria – Adults With Scdmentioning

confidence: 98%

Indications and Results of HLA-Identical Sibling Hematopoietic Cell Transplantation for Sickle Cell Disease

Walters

Castro

Sullivan

et al. 2016

Biology of Blood and Marrow Transplantation

106

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Although there are a number of published trials of human leukocyte antigen (HLA) – identical sibling hematopoietic cell transplantation (HCT) for sickle cell disease (SCD) that span 2 decades, when and for whom this therapy should be pursued is a subject of debate. Assessments of the risks of transplant-related complications that include infertility and debilitating graft-versus-host disease and long-term quality of life after successful HCT are difficult to perform without prospective trials in transplant and non-transplant cohorts. However, it is possible to assess the risk of mortality and to compare published rates of survival in individuals with sickle cell disease treated and not treated by HCT. In this brief review, projections about mortality risk based upon recent published reports are reviewed and summarized. The published data show overall survival and event-survival rates of 95% and 92%, respectively, in children treated by HLA-identical sibling HCT. The overall survival in the Center for International Blood and Marrow Transplant Research (CIBMTR) (N=412) and European Blood and Marrow Transplant (EBMT) (N=487) registries was 91% and 95%, respectively. These results provide broad support for the therapeutic value of HLA-identical sibling HCT for children with sickle cell disease and serve as the basis for a strong recommendation in favor of the option of HCT when a suitable donor is available. The experience of HLA-identical sibling HCT in adults with SCD is limited but appears similar to results in children, and these preliminary observations warrant further investigation.

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Section: Eligibility Criteria – Adults With Scdmentioning

confidence: 98%

Indications and Results of HLA-Identical Sibling Hematopoietic Cell Transplantation for Sickle Cell Disease

Walters

Castro

Sullivan

et al. 2016

Biology of Blood and Marrow Transplantation

106

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“…78 Tools to predict SCD severity to determine transplant eligibility are limited and predominantly include major SCD complications. 79 In 2014, an international expert panel recommended that HSCT with unrelated or haploidentical grafts in a controlled trial setting be considered for patients with severe complications of SCD, including stroke, recurrent vasoocclusive crisis (>2 episodes per year), recurrent priapism, impaired neuropsychological function, stage I or II sickle cell lung disease, 80 acute chest syndrome, sickle nephropathy, bilateral proliferative retinopathy, osteonecrosis, or transfusionrelated alloimmunization. 81 The panel also recommended that symptomatic patients be offered transplant from available HLA-identical sibling stem cells or HLA-identical sibling cord blood as early as preschool age.…”

Section: Long-term Transfusion Therapymentioning

confidence: 99%

Advances in the Treatment of Sickle Cell Disease

Kapoor

Little

Pecker

2018

Mayo Clinic Proceedings

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Sickle cell disease (SCD) is a monogenic disorder that afflicts approximately 100,000 Americans and millions of people worldwide. It is characterized by hemolytic anemia, vaso-occlusive crises, relentless end-organ injury, and premature death. Currently, red blood cell transfusion and hydroxyurea are the major disease-modifying therapies available for SCD. Hematopoetic stem cell transplant is curative, but barriers to treatment are substantial and include a lack of suitable donors, immunologic transplant rejection, long-term adverse effects, prognostic uncertainty, and poor end-organ function, which is especially problematic for older patients. Gene therapy to correct the b s point mutation is under investigation as another curative modality. Deeper insights into the pathophysiology of SCD have led to the development of novel agents that target cellular adhesion, inflammation, oxidant injury, platelets and/or coagulation, vascular tone, and hemoglobin polymerization. These agents are in preclinical and clinical trials. One such agent, L-glutamine, decreases red blood cell oxidant injury and is recently US Food and Drug Administration approved to prevent acute pain episodes of SCD in patients 5 years of age or older. The purpose of this review is to describe the currently established therapies, barriers to curative therapies, and novel therapeutic agents that can target sickle cell hemoglobin polymerization and/or its downstream sequelae. A PubMed search was conducted for articles published up to May 15, 2018, using the search terms sickle cell disease, novel treatments, hematopoietic stem cell transplantation, and gene therapy. Studies cited include case series, retrospective studies, prospective clinical trials, meta-analyses, online abstracts, and original reviews.

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“…11 Although several reports have demonstrated that HLA-identical sibling transplantation with bone marrow (BM) or umbilical cord blood (CB) establishes normal hematopoiesis and is associated with excellent survival, most studies were conducted at single institutions or in the context of clinical trials. [12][13][14][15][16][17] The current study sought to describe outcomes after HLA-identical sibling transplantation for SCD worldwide.…”

Section: Introductionmentioning

confidence: 99%

Sickle cell disease: an international survey of results of HLA-identical sibling hematopoietic stem cell transplantation

Gluckman

Cappelli

Bernaudin

et al. 2017

Blood

390

359

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Key Points• HLA-identical sibling transplantation for SCD offers excellent long-term survival. • Mortality risk is higher for older patients; event-free survival has improved in patients transplanted after 2006.Despite advances in supportive therapy to prevent complications of sickle cell disease (SCD), access to care is not universal. Hematopoietic cell transplantation is, to date, the only curative therapy for SCD, but its application is limited by availability of a suitable HLA-matched donor and lack of awareness of the benefits of transplant. Included in this study are 1000 recipients of HLA-identical sibling transplants performed between 1986 and 2013 and reported to the European Society for Blood and Marrow Transplantation, Eurocord, and the Center for International Blood and Marrow Transplant Research. The primary endpoint was event-free survival, defined as being alive without graft failure; risk factors were studied using a Cox regression models. The median age at transplantation was 9 years, and the median follow-up was longer than 5 years. Most patients received a myeloablative conditioning regimen (n 5 873; 87%); the remainder received reduced-intensity conditioning regimens (n 5 125; 13%). Bone marrow was the predominant stem cell source (n 5 839; 84%); peripheral blood and cord blood progenitors were used in 73 (7%) and 88 (9%) patients, respectively. The 5-year event-free survival and overall survival were 91.4% (95% confidence interval, 89.6%-93.3%) and 92.9% (95% confidence interval, 91.1%-94.6%), respectively. Eventfree survival was lower with increasing age at transplantation (hazard ratio [HR], 1.09; P < .001) and higher for transplantations performed after

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Traffic Light: prognosis-based eligibility for clinical trials of hematopoietic SCT in adults with sickle cell anemia

Cited by 17 publications

References 36 publications

Indications and Results of HLA-Identical Sibling Hematopoietic Cell Transplantation for Sickle Cell Disease

Indications and Results of HLA-Identical Sibling Hematopoietic Cell Transplantation for Sickle Cell Disease

Advances in the Treatment of Sickle Cell Disease

Sickle cell disease: an international survey of results of HLA-identical sibling hematopoietic stem cell transplantation

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