Stem-cell transplantation in children and adults with sickle cell disease: an update

Khoury, Ruby; Abboud, Miguel R.

doi:10.1586/ehm.11.23

Cited by 16 publications

(14 citation statements)

References 62 publications

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“…As of 2011, 1000 children are born with sickle cell disease (SCD) annually in the United States, with over 100,000 people living with the disease [1]. SCD is an hereditary hemoglobinopathy that negatively impacts quality of life and shortens life expectancy in affected individuals [2,3].…”

Section: Introductionmentioning

confidence: 99%

Health-Related Quality of Life after Allogeneic Hematopoietic Stem Cell Transplantation for Sickle Cell Disease

Bhatia

Kolva

Cimini

et al. 2015

Biology of Blood and Marrow Transplantation

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Sickle cell disease (SCD) is a hereditary hemoglobinopathy that affects over 100,000 people in the United States. Patients with SCD are known to experience suboptimal health-related quality of life (HRQoL). In addition to the physical manifestations of SCD, psychological and social stress, along with academic difficulties, secondary to the chronicity of the disease and its complications often affect patients with SCD. Although medical therapy of SCD has improved, allogeneic hematopoietic cell transplantation (allo-HCT) remains the only curative therapy. The objective of this study was to measure HRQoL before and after allo-HCT by assessing physical, psychological, and social functioning in patients with SCD who have undergone reduced-toxicity conditioning (busulfan/fludarabine/alemtuzumab) followed by allo-HCT. Patients < 21 years of age undergoing allo-HCT (matched siblings and unrelated donors) for SCD and their primary caregiver were enrolled using either the English or Spanish version of the PedsQoL 4.0. Data were collected at 3 time points: before allo-HCT and on days 180 and 365 after allo-HCT. The change in HRQoL from baseline was assessed with unadjusted and adjusted mixed-effects models in which subjects were treated as random effects, and variance component structure was used. Seventeen patients and 23 primary caregivers were enrolled and reported a mean overall HRQoL of 66.05 (SD, 15.62) and 72.20 (SD, 15.50) at baseline, respectively. In the patient-reported analysis with adjusted mixed-effects models, the estimated improvements in overall HRQoL were 4.45 (SE, 4.98; P = .380) and 16.58 (SE, 5.06; P = .003) at 180 and 365 days, respectively, after allo-HCT. For parent-reported overall HRQoL, the estimated improvements were 1.57 (SE, 4.82; P = .747) and 9.28 (SE, 4.62; P = .053) at 180 and 365 days, respectively, after allo-HCT. Similar results were found across the physical, social, and emotional HRQoL domains with mixed-effects models after adjustment of demographic and medical variables. In addition to the alleviation of clinical manifestations of SCD, these patients demonstrated significant improvement in most aspects of HRQoL by 1 year after allo-HCT. These data represent the trajectory of HRQoL during the initial year of follow-up within this population and should be integrated into the decision-making process when considering allo-HCT in patients with SCD.

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Section: Introductionmentioning

confidence: 99%

Health-Related Quality of Life after Allogeneic Hematopoietic Stem Cell Transplantation for Sickle Cell Disease

Bhatia

Kolva

Cimini

et al. 2015

Biology of Blood and Marrow Transplantation

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“…While the numbers of children receiving transplant have continued to grow and now total in the hundreds, the majority are still performed with myeloablative conditioning (recently reviewed in [31]). The outcomes of these transplants in children are generally good with high levels of disease-free survival.…”

Section: Discussionmentioning

confidence: 99%

Hematopoietic Stem Cell Function in a Murine Model of Sickle Cell Disease

Javazon

Radhi

Gangadharan

et al. 2012

Anemia

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Previous studies have shown that the sickle environment is highly enriched for reactive oxygen species (ROS). We examined the oxidative effects of sickle cell disease on hematopoietic stem cell function in a sickle mouse model. In vitro colony-forming assays showed a significant decrease in progenitor colony formation derived from sickle compared to control bone marrow (BM). Sickle BM possessed a significant decrease in the KSL (c-kit+, Sca-1+, Lineage−) progenitor population, and cell cycle analysis showed that there were fewer KSL cells in the G0 phase of the cell cycle compared to controls. We found a significant increase in both lipid peroxidation and ROS in sickle-derived KSL cells. In vivo analysis demonstrated that normal bone marrow cells engraft with increased frequency into sickle mice compared to control mice. Hematopoietic progenitor cells derived from sickle mice, however, demonstrated significant impairment in engraftment potential. We observed partial restoration of engraftment by n-acetyl cysteine (NAC) treatment of KSL cells prior to transplantation. Increased intracellular ROS and lipid peroxidation combined with improvement in engraftment following NAC treatment suggests that an altered redox environment in sickle mice affects hematopoietic progenitor and stem cell function.

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“…A retrospective review demonstrated that introduction of an evidencebased guideline initiating mandatory incentive spirometry in children with SCD admitted for non-respiratory complaints resulted in a reduced number of transfusions and ACS episodes [33]. Stem cell transplantation in adults and children has been associated with no recurrence of painful crisis in those with stable engraftment [34]. The best results were obtained in young children who have HLA-identical sibling donors and transplanted early in the course of their disease [35].…”

Section: Preventionmentioning

confidence: 99%

Pulmonary Complications and Lung Function Abnormalities in Children with Sickle Cell Disease

Greenough¹

2016

Sickle Cell Disease - Pain and Common Chronic Complications

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The pulmonary complications of sickle cell disease (SCD) have a high morbidity and mortality. Fatal pulmonary complications occur in % of adults those with sickle chronic lung disease (SCLD) and pulmonary hypertension have a signiicantly increased mortality. Treatment of SCLD is only supportive. Recurrent acute chest syndrome (ACS) episodes are the major risk factor for SCLD, and ACS is the leading cause of death. Adults with SCD tend to have restrictive lung function abnormalities, whereas, in children, obstructive abnormalities are more frequent. Lung function abnormalities are common even in young children and may relect their chronic anaemia and increased pulmonary capillary blood volume, which increases airway obstruction and may be responsible for their increased wheezing. Whether more aggressive treatment of anaemia would improve lung function and long-term outcomes merits testing. Children with SCD experience a decline in lung function, which is most rapid in younger children in whom ACS episodes are most common highlighting the importance of identifying efective strategies to prevent and optimally treat ACS.

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Stem-cell transplantation in children and adults with sickle cell disease: an update

Cited by 16 publications

References 62 publications

Health-Related Quality of Life after Allogeneic Hematopoietic Stem Cell Transplantation for Sickle Cell Disease

Health-Related Quality of Life after Allogeneic Hematopoietic Stem Cell Transplantation for Sickle Cell Disease

Hematopoietic Stem Cell Function in a Murine Model of Sickle Cell Disease

Pulmonary Complications and Lung Function Abnormalities in Children with Sickle Cell Disease

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