Nonmyeloablative HLA-Identical Sibling Donor Transplantation for Children and Young Adults with Sickle Cell Disease: Interim Results of the SUN Multicenter Phase II Trial

Abstract Background: HLA-identical sibling hematopoietic stem cell transplant (HSCT) using myeloablative chemotherapy conditioning is a proven cure for sickle cell disease (SCD), but is associated with serious short and long-term toxicities. Additionally graft versus host disease (GVHD) can complicate care post-HSCT and contribute to mortality. Given these concerns many pediatric hematologists and families are reluctant to pursue HSCT for SCD. Nonmyeloablative HSCT resulting in stable mixed chimerism has been demonstrated to abrogate the SCD phenotype in adults. Data on outcomes of this approach to decrease toxicities and achieve cure in children remains scarce. Objective: To evaluate event-free survival (EFS), toxicity, health-related quality of life (HRQL), and transfusion burden among pediatric patients with SCD using a chemotherapy-free nonmyeloablative regimen. Methods/design: Children and young adults with SCD were prospectively enrolled in the Sickle transplant Using a Nonmyeloablative approach (SUN) multicenter clinical trial (NCT03587272). Six Sickle Cell Transplant Advocacy and Research Alliance (STAR) sites in the United States and Canada enrolled patients. The conditioning regimen consisted of alemtuzumab IV (0.03mg/kg on Day -7, 0.1mg/kg on Day -6, 0.3mg/kg on Days -5 to -3), low-dose total body irradiation with gonadal shielding (300 cGY on day -2), peripheral blood stem cells from an HLA-identical sibling, and sirolimus for at least one year. Baseline HRQL was compared with scores at day +30 and day +100 post-HSCT using the PedsQL and PROMIS measures. EFS was defined by any of the following events: death, graft failure (myeloid donor chimerism <10%), or GVHD. Results: All 30 of the patients planned for the primary endpoint of EFS have been enrolled. As of 7/20/2021, 24 patients are greater than 100 days post-HSCT with a median follow-up of 365 days (range 189-1105). The median age of this group at time of transplant was 13.5 years (range 2-22). All patients had neutrophil recovery (ANC >500/ul x 3 days) at a median of 21.5 days (range 0-29). Eleven patients (46%) did not require any platelet transfusions. Median transplant hospitalization was 16.5 days (range 14-43). Seven patients (29%) were again hospitalized (median 4 days, range 1-26). Three patients had secondary graft rejection at Day +71, +91, and +92 with no major complications and autologous recovery resulting in an EFS of 87.5% (Figure 1). Three additional patients have stable low donor chimerism (myeloid chimerism 11%, 38%, and 47%). The remaining 18 patients (75%) are disease-free and have robust donor engraftment (72-100% myeloid chimerism). Nine of these patients are >1 year post-HSCT and off sirolimus. Overall survival is 100% with no acute or chronic GVHD. Figure 2 shows total PedsQL scores during the peri-transplant time period. The median change in day +30 scores compared to baseline was 0 (IQR -7, +10), p=0.66. The median change in day +100 scores compared to baseline was +5 (IQR 0, +10), p=0.02. Conclusions: Outcomes of pediatric nonmyeloablative HLA-identical sibling HSCT for SCD appear similar to the larger adult experience with a GVHD-free, rejection-free survival of >80%. Importantly, patients have no worsening of their quality of life in the first month post-HSCT and already an improvement at day +100, suggesting that the short-term toxicities experienced by patients transplanted with this regimen are minimal. The majority of patients achieve disease resolution with no GVHD, but graft failure incidence appears higher than with myeloablative HSCT. Given the low intensity of this approach, a reasonable strategy may be to reserve myeloablation for a second transplant in the minority of patients who experience graft failure. Figure 1 Figure 1. Disclosures Rangarajan: Medexus (Treosulfan): Consultancy, Honoraria. Guilcher: BlueBirdBio: Research Funding; Project Sickle Cure Study: Other: Principal Investigator, Research Funding. OffLabel Disclosure: alemtuzumab and sirolimus were used off-label as part of the studied transplant regimen

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Sickle Cell Disease Measures in the Phenx Toolkit

Blood ◽

10.1182/blood.v126.23.281.281 ◽

2015 ◽

Vol 126 (23) ◽

pp. 281-281

Author(s):

Kathryn L. Hassell ◽

James R. Eckman ◽

Elizabeth S Klings ◽

Robert J. Adams ◽

Julie A. Panepinto ◽

...

Keyword(s):

Quality Of Life ◽

Sickle Cell Disease ◽

Data Collection ◽

Sickle Cell ◽

Research Funding ◽

Core Collection ◽

Cell Disease ◽

Data Comparability ◽

The Web

Abstract Background: Common measures and common data elements (CDEs) for sickle cell disease (SCD) are needed to help improve data quality and data comparability necessary for meta-analyses, guidelines development, and implementation science. In recent years, the National Heart, Lung, and Blood Institute (NHLBI) has undertaken several activities to develop CDEs and measures for SCD. These include developing 1) the Sickle Cell Quality of Life Measurement Information System (ASCQ-Me); 2) clinical practice recommendations for the management of SCD; and 3) a lexicon and consensus definitions for the most frequently occurring complications of SCD. In 2014, the NHLBI funded an Administrative Supplement to the PhenX Toolkit to identify common measures to further promote data comparability across SCD research. The Web-based PhenX Toolkit (consensus measures for Phen otypes and eX posures, https://www.phenxtoolkit.org/) provides a catalog of 449 standard measures and associated interoperability resources to help investigators improve quality of data collection and identify opportunities for collaborative research. The development and maintenance of PhenX Toolkit content is driven by the scientific research community. A Steering Committee, comprised of 11 scientists with a wide range of expertise, provides overarching guidance for the project and Working Groups (WG) of subject matter experts select measures for inclusion the PhenX Toolkit. Methods: An 11 member Sickle Cell Disease Research and Scientific Panel (SRSP) was assembled to provide guidance to the project, establish a Core Collection of SCD-related measures, and to define the scope of two Specialty Collections: 1) Cardiovascular, Pulmonary, and Renal Complications and 2) Neuroglogy, Quality of Life, and Health Services. For each Specialty Collection, a Working Group (WG) of seven SCD experts was convened to select high priority measures for inclusion in the Toolkit. Each WG selected representative measures available in the published literature or already in the Toolkit using a consensus process which included input from the scientific community. For each measure, the Toolkit provides a description of the measure, the rationale for its inclusion, detailed protocol(s), and supporting documentation. The Toolkit also provides data collection worksheets and data dictionaries to help integrate PhenX measures into their study design. To support investigators who want to collect data via the Web, PhenX protocols are available as REDCap Instrument Zip files. Results: The Sickle Cell Disease Core and Specialty Collections were released into the Toolkit in August of 2015. The Core Collection, which includes 25 measures covering demographics, socioeconomic status, anthropometrics, pulse oximetry, hemoglobin characterization, history of transfusion, and SCD-related pain episodes, is recommended for use by all NHLBI-funded investigators performing human subjects SCD research. The Specialty Collections are recommended for use within more specialized research areas. The Cardiovascular, Pulmonary, and Renal Specialty Collection includes 11 measures that address heart disease, lung function, and biomarkers for hemolysis, anemia, and iron overload. The Neurology, Quality of Life, and Health Services Specialty Collection includes 8 measures that address developmental delays, stroke risk factors and outcomes, quality of life, and quality of care. A list of other potentially relevant measures from the Toolkit was also developed and annotated for SCD. These measures, including the process, criteria, and rationale for their selection, will be presented. We now have consensus phenotypes of complications in SCD that are available for use in future clinical and epidemiologic studies and for use in harmonizing data across previous studies Implications: For researchers, adoption and use of PhenX standard measures will promote collaborations with clinicians and patients, facilitate cross-study analysis domestically and internationally, accelerate translational research, and lead to greater understanding of phenotypes and epigenetics in SCD. For clinicians, using PhenX measures will help improve patient care and quality of life. Consistent use of these standard measures will establish a common currency to help better understand the etiology, progression, and treatment of SCD. Funding provided by U01 HG004597 and U41 HG007050. Disclosures Klings: Pfizer: Consultancy; Actelion Pharmaceuticals: Research Funding. Panepinto:HRSA, NIH: Research Funding; NKT Therapeutics, Inc: Consultancy.

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Comprehensive Handbook of Childhood Cancer and Sickle Cell Disease

10.1093/oso/9780195169850.001.0001 ◽

2006 ◽

Keyword(s):

Quality Of Life ◽

Sickle Cell Disease ◽

Childhood Cancer ◽

Children And Adolescents ◽

Peer Relationships ◽

Sickle Cell ◽

Cell Disease ◽

Life Issues ◽

Art Research

Over recent decades, tremendous advances in the prevention, medical treatment, and quality of life issues in children and adolescents surviving cancer have spawned a host of research on pediatric psychosocial oncology. This important volume fulfills the clear need for an up-to-date, comprehensive handbook for practitioners that delineates the most recent research in the field--the first of its kind in over a decade. Over 60 renowned authors have been assembled to provide a thorough presentation of the state-of-the art research and literature, with topics including: -Neuropsychological effects of chemotherapy and radiation therapy -Bone marrow transplantation -Important issues about quality of life during and following treatment -Collaborative research among child-focused psychologists -Standards of psychological care for children and adolescents -Stress and coping in the pediatric cancer experience -The role of family and peer relationships The Comprehensive Handbook of Childhood Cancer and Sickle Cell Disease represents both multidisciplinary and international efforts, an alliance between physicians and parents, and a combination of research and service. With a wealth of information of great interest to patients and their families, this volume will also be a welcome resource to the psychologists, psychiatrists, pediatricians, oncologists, nurses, and social workers who confront these issues as they help children and their families through the treatment, recovery, and grieving processes.

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Health-related quality of life and neuropathic pain in sickle cell disease in Jamaica

Disability and Health Journal ◽

10.1016/j.dhjo.2021.101107 ◽

2021 ◽

pp. 101107

Author(s):

Rachel Bartlett ◽

Zachary Ramsay ◽

Amza Ali ◽

Justin Grant ◽

Angela Rankine-Mullings ◽

...

Keyword(s):

Quality Of Life ◽

Neuropathic Pain ◽

Sickle Cell Disease ◽

Sickle Cell ◽

Health Related Quality ◽

Cell Disease ◽

Related Quality ◽

Health Related

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Chronic brain damage in sickle cell disease and its relation with quality of life

Medicina Clínica (English Edition) ◽

10.1016/j.medcle.2016.12.041 ◽

2016 ◽

Vol 147 (12) ◽

pp. 531-536

Author(s):

Elena Cela ◽

Ana G. Vélez ◽

Alejandra Aguado ◽

Gabriela Medín ◽

José M. Bellón ◽

...

Keyword(s):

Quality Of Life ◽

Sickle Cell Disease ◽

Brain Damage ◽

Sickle Cell ◽

Cell Disease

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Hip Dysfunction and Quality of Life in Patients With Sickle Cell Disease

Clinical Pediatrics ◽

10.1177/0009922815586051 ◽

2015 ◽

Vol 54 (14) ◽

pp. 1354-1358 ◽

Cited By ~ 7

Author(s):

Cristiane Dias Malheiros ◽

Luanne Lisle ◽

Marilda Castelar ◽

Katia Nunes Sá ◽

Marcos Almeida Matos

Keyword(s):

Quality Of Life ◽

Sickle Cell Disease ◽

Sickle Cell ◽

Cell Disease

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Anxiety, depressive disorders, and quality of life in adults with sickle cell disease

Middle East Current Psychiatry ◽

10.1097/01.xme.0000426319.48898.03 ◽

2013 ◽

Vol 20 (2) ◽

pp. 80-86 ◽

Cited By ~ 1

Author(s):

H. El-Shinnawy ◽

T. Goueli ◽

M. Nasreldin ◽

A. Meshref

Keyword(s):

Quality Of Life ◽

Sickle Cell Disease ◽

Sickle Cell ◽

Depressive Disorders ◽

Cell Disease

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Parent-reported sleep problems in children and adolescents with sickle cell disease: relationship to health-related quality of life

Archives of Medical Science ◽

10.5114/aoms/124154 ◽

2021 ◽

Author(s):

Serkan Gunes ◽

Rahime Aldemir ◽

Adem Gunes ◽

Ozalp Ekinci

Keyword(s):

Quality Of Life ◽

Children And Adolescents ◽

Sickle Cell ◽

Sleep Problems ◽

Well Being ◽

Health Related Quality ◽

Cell Disease ◽

Related Quality ◽

Health Related

IntroductionChildren with sickle cell disease (SCD) can present a variety of clinical symptoms that may affect their sleep and health-related quality of life (HRQOL). This study aims to investigate the relation between sleep problems and HRQOL in children and adolescents with SCD.Material and methodsThe sample included 86 children and adolescents in the SCD patient group and 82 healthy controls, with an age range of 8-16 years. Subjects for the study were recruited from the Sickle Cell and Thalassemia Center of Hatay State Hospital, Hatay, Turkey. The Children’s Sleep Habits Questionnaire (CSHQ) was used to evaluate sleep problems and Kinder Lebensqualitätsfragebogen: Children’s Quality of Life Questionnaire – revised (KINDL-R) was used to examine HRQOL.ResultsTotal score, bedtime resistance, and night waking subscores of CSHQ were significantly higher in children with SCD when compared to healthy children. Total score, physical well-being, emotional well-being, social, and school subscores of KINDL-R were significantly lower in the patient group. Among SCD children, total score, bedtime resistance, sleep onset delay, daytime sleepiness, and parasomnias subscores of CSHQ were negatively correlated with KINDL-R total score. In the regression model, disease severity and CSHQ total score had significant negative associations with KINDL-R total score.ConclusionsSleep problems in SCD children appear to be negatively linked with HRQOL. Disease severity and sleep problems may be predictors of overall HRQOL in children and adolescents with SCD.

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COVID Symptoms and COVID Anxiety in Sickle Cell Disease

Blood ◽

10.1182/blood-2020-143054 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 16-17

Author(s):

Wally R Smith ◽

Benjamin Jaworowski ◽

Shirley Johnson ◽

Thokozeni Lipato ◽

Daniel M Sop

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Research Funding ◽

Telephone Survey ◽

Cell Disease ◽

Weighted Mean ◽

The Us ◽

Associated Symptoms ◽

At Home

Background Even before the US upswing of the current COVID pandemic, the number of sickle cell disease (SCD) patients coming to hospitals and EDs appeared to fall drastically. This happened despite SCD patients having often been heavy utilizers of the ED and hospital for their iconic vaso-occlusive crises (VOC). Though ambulatory SCD clinics quick converted largely to telehealth in order to comply with stay-at-home orders designed to suppress person-to-person transmission, some SCD patients appeared to avoid care, delay care, or refuse doctors' invitations for care. Presumably patients did so out of COVID fears, but this has not been confirmed in the literature. Further, whether these patients had COVID symptoms but stayed at home has not been studied. As part of quality improvement (QI) to conduct COVID surveillance in an adult sickle cell program, we sought to explain and predict SCD health care utilization patterns we were observing, as well as to determine urgent physical and mental health needs of patients who appeared to be avoiding care. Methods Fifteen staff in the Adult Sickle Cell Medical Home at Virginia Commonwealth University, a large urban academic medical center, conducted a telephone survey ("wellness check"was used when we talked to patients) of all known adults with SCD over 19 days in 2020. A staff member confirmed the patient had SCD, asked permission to proceed, then asked about symptoms consistent with COVID-19. At the end of the telephone survey, respondents wer invited to complete an email survey of sickle cell and COVID-19 utilization attitudes (19-33 items, depending on the response pattern, either drawn from the National Health Interview Survey, from the Adult Sickle Cell Quality of Life Measurement quality of care survey, or drafted by the authors), the Sickle Cell Stress Survey-Adult (SCSS-A, a 10-item previously validated survey), and anxiety and depression (PHQ9 of the PRIME-MD). Results Of 622 adults approached by phone call, 353 responded to the following yes/no screening questions regarding the prior 14 days: fever over 100 F 0/353 (0.00%); cough 3/353(0.01%); difficulty breathing 0/353(0.00%); unexplained shortness of breath 2/353(0.01%); sore throat 2/353 (0.01%); unexplained muscle soreness 2/353(0.01%);contact with anyone who tested positive for COVID-19 2/353(0.01%); testing for COVID 19 6/353(0.02%). For QI purposes, we set a threshold of three or more COVID-associated symptoms or the presence of fever as criteria requiring intense telephone or in-person staff monitoring for the following week. Only three patients met criteria. A total of 219/353 had email surveys sent. Of 63 patients (28.8%) who returned email surveys by June 10, 2020, 35.9% had already managed a "pain attack" at home 4 or more times in the prior 12 months, and 45.5% of these said their bad ER experiences were very or somewhat important in that decision. In the prior 14 days, although 30/64 reported a crisis for at least one day, only 4/64 had visited the Emergency Department for pain. On a 0-10 scale, 21/61 patients endorsed "0" for worry that they would be COVID-infected by going for medical care (weighted mean 3.9), but 18/59 endorsed "10" for worry they were more at risk of COVID because of SCD (weighted mean 6.31), and 22/60 endorsed "10" for worry they would fare worse than others if COVID infected (weighted mean 6.97). Many patients forwent "needed" care (16/62) or delayed "needed" care by at least a day (36/61). Eleven patients met criteria for moderately severe to severe depression on the PHQ-9, and 28/63 somewhat or strongly agreed with the statement "death is always on the back of my mind" on the SCSS-A. Conclusions In adolescents and adults with SCD, many were already reticent to come to the ED for pain, but a significant portion reported delays or avoidance of needed care during the early stages of the US COVID pandemic, and few reported using the ED despite over half reporting at least one crisis day in 14. Patients nonetheless reported very few COVID-associated symptoms. Fears of COVID infection/susceptibility may limit visits for needed sickle cell care among adults. Acknowledgements: Mica Ferlis RN, FNP, Caitlin McManus, RN, FNP, Emily Sushko, RN, FNP, Justin West, RN, Kate Osborne, RN, Stefani Vaughan-Sams, Marla Brannon, BS, Nakeiya Williams, BS Disclosures Smith: GlycoMimetics, Inc.: Consultancy; Emmaeus Pharmaceuticals, Inc.: Consultancy; Novartis, Inc.: Consultancy, Other: Investigator, Research Funding; Global Blood Therapeutics, Inc.: Consultancy, Research Funding; Shire, Inc.: Other: Investigator, Research Funding; NHLBI: Research Funding; Patient-Centered Outcomes Research Institute: Other: Investigator, Research Funding; Health Resources and Services Administration: Other: Investigator, Research Funding; Incyte: Other: Investigator; Pfizer: Consultancy; Ironwood: Consultancy; Novo Nordisk: Consultancy; Imara: Research Funding; Shire: Research Funding.

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Health Related Quality of Life of Children with Sickle Cell Anemia and Their Parents; Quantitative Study in Albaha; Saudi Arabia

Journal of Pharmaceutical Research International ◽

10.9734/jpri/2021/v33i27a31487 ◽

2021 ◽

pp. 9-17

Author(s):

Turki Alzahrani ◽

Raed Alzahrani ◽

Amer Alzahrani ◽

Abdullah Alzahrani ◽

Abdu Adawi ◽

...

Keyword(s):

Quality Of Life ◽

Saudi Arabia ◽

Sickle Cell Disease ◽

Sickle Cell ◽

Healthy Children ◽

Health Related Quality ◽

Cell Disease ◽

Related Quality ◽

Health Related

Aims: To gain a better understanding of the quality of life (QoL) of children and impact of this disease on parents QoL. Study Design: Cross-sectional study. Place and Duration of Study: The study was conducted in King Fahd Hospital, Albaha city, Albaha, Saudi Arabia, between March2020 and February 2021. Methodology: We included 95 responses. Two different tools were used for the purpose of this study. PedsQL™ Sickle Cell Disease Module was used to measure health-related quality of life (HRQoL) in healthy children and adolescents and those with acute and chronic health conditions. Moreover, PedsQL™ Family Information Form was completed by caregivers. Median and interquartile range were used for numerical variables since they were skewed. Bivariate analyses were carried out using non-parametrical tests and Pearson correlation. The prediction of QoL was accomplished through multivariate analysis. Results: A total of (95) responses were analyzed. Female respondents were 52.6%. The age median was 12 (IQR=10-14). Mothers represented the most frequent informant 46.3% in this current study. Significant association was found between QoL and certain independent factors, some of which is parental level of education (P< .001) and marital support (P< .001). Conclusion: Sickle cell disease (SCD) is a major condition accounts for a huge burden on variable levels. This study reported that low QoL among children affected by SCD. Higher education and current marital status of the parents were significantly associated with high QoL in SCD patients. Number of workdays affected due to child health was significantly correlated with low QoL.

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