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Six essential updates for World Sickle Cell Day World Sickle Cell Day is held every June 19. The observance — established by the United Nations — is designed to increase knowledge and understanding of sickle cell disease, as well as the challenges that patients, their families and their caregivers face. 1. HemOnc Today’s June 10 cover story focused on sickle cell disease, the most common inherited blood disorder in the United States. Hematologists and researchers offered insights into new approaches to treatment and management of sickle cell disease-related pain, research aimed at curing this debilitating illness, and the need for initiatives to improve access to care in the United States and globally. Read more. 2. In the June 10 edition of Point/Counter, two sickle cell disease specialists debate whether new therapies will lead to a change or reduction in use of hydroxyurea for sickle cell disease-related pain management. Read more. 3 . Voxelotor (GBT440, Global Blood Therapeutics) increased hemoglobin levels and reduced markers of hemolysis compared with placebo among patients with sickle cell disease, according to results of a randomized phase 3 study. Read more. 4. Refugees arriving in Europe from countries with high rates of sickle cell disease should be immediately screened for the disease to help prevent acute crises and potentially fatal complications, according to results of a retrospective study published in Blood. Read more. 5. Immersive virtual reality appeared effective as a complementary therapy to manage vaso-occlusive pain among patients with sickle cell disease. Read more. 6. ASH launched a clinical trials network designed to accelerate development of novel therapies for patients with sickle cell disease. The network will match clinical trial sponsors with research sites, facilitate patient recruitment and provide consulting services. A core component will be a centralized data repository. Read more.   Cure Sickle Cell Initiative Research Opportunity Announcement  The NHLBI is soliciting applications for the following research opportunity: “Analytical and/or Clinical Validation of Candidate Biomarkers for Curative Therapies in Sickle Cell Disease.” The proposed projects will develop and validate assays for biomarkers of clinical endpoints, to be used in clinical trials of genetic-based curative treatments for sickle cell disease. Applications are due July 31, 2019. For more information on OTA-19-007 please visit: https://curesickle.org/researchers#pane-121. Questions regarding the ROA should be address to Dr. Traci Mondoro mondorot@nhlbi.nih.gov  or Dr. Lis Welniak welniakla@nhlbi.nih.gov. Genetic Therapies  Also known as Gene Transfer, Genome Editing, Gene Addition Patient information from NHLBI at https://www.nhlbi.nih.gov/health-topics/genetic-therapies

 Rapid Result Test On Track to Transform Sickle Cell Disease Screening for Millions

Soon after birth, a baby in the United States is tested for sickle cell disease, the often-devastating genetic blood disorder affecting more than 100,000 Americans and 20 million of people worldwide. If positive, that newborn typically begins a course of treatment that can greatly prolong life and help stave off complications of the disease. But in sub-Saharan Africa, where the majority of sickle cell disease cases can be found—and where resources are scant—newborn screening programs are virtually non-existent, and as a result, so is treatment that could save lives.

Now, research shows that with a new rapid result test kit, a diagnosis of sickle cell disease may no longer be a death sentence for children in the most affected parts of the world.

Photo of HemoTypeSC product box. Credit: Silver Lakes Research Corporation.

HemoTypeSC, a dipstick-type test, is relatively inexpensive, accurate, and can provide timely diagnosis of sickle cell disease, according to the study external link published in the American Journal of Hematology. The test has the potential to be a game-changer for people with the disease who live in distressed areas around the world.

“Children with sickle cell disease have down to a 10 percent chance of reaching their fifth birthday if they are not diagnosed and get treatment early in life,” said Erik Serrao, Ph.D., a study author who also is the HemoTypeSC project manager at Silver Lake Research Corporation, the Los Angeles-based diagnostic company that developed the test. “That is why it’s extremely important to screen for the disease at birth or within the first year of life.”

Current gold-standard clinical methods for diagnosing sickle cell disease require laboratory equipment, a continuous electrical supply, a dedicated operating staff, about 1 mL of whole blood from each patient, and the ability to transport blood samples from where they were collected to possibly distant testing facilities. While it is often impossible to meet these standards in many parts of sub-Saharan Africa, the diagnostic tests patients do have access to still present problems: They are costly, and often it takes weeks or months before results come back to the families.

Silver Lake Research developed HemoTypeSC to address these challenges. With a Phase 2 Small Business Innovation Research grant from the National Heart, Lung and Blood Institute (NHLBI) in 2017, Serrao and his colleagues took HemoTypeSC into the real world for evaluation after years of product development.

HemoTypeSC uses simple technology—test strips—similar to a pregnancy test. The strips contain specific proteins that, in a few simple steps and after a short waiting period, can detect normal and abnormal hemoglobin proteins in whole blood.

In sickle cell disease, abnormal hemoglobin proteins cannot deliver oxygen to the body’s tissues due to defective hemoglobin S and C genes. The end result are sickled shape red blood cells and a cascade of complications such as sudden, severe pain known as pain crises.

The test can also detect the sickle cell trait, which shows up in someone who inherits one hemoglobin S or C and one normal hemoglobin A gene. While the sickle cell trait typically does not result in symptoms or complications from the disease, it is important for couples who are planning to have children to speak with a health professional who can explain the risk of having a child with sickle cell disease. The test does not require sophisticated laboratory equipment, electricity, refrigeration, or highly trained personnel.

To evaluate its effectiveness in people living in low-, medium-, and high-resourced environments, the team tested HemoTypeSC in study centers in Techiman, Ghana; in Martinique, part of the Caribbean Islands; and in Cincinnati, OH. Using a single drop of blood from each of the 587 participants—newborns, children, and adults across the three centers—the HemoTypeSC test correctly identified those with and without sickle cell disease and sickle cell trait in almost all of the cases.

One family in Ghana, for example, learned that their premature baby had sickle-hemoglobin C disease and would have been sent home, undiagnosed, shortly after birth had it not been for the test. Such findings, Serrao said, suggest that HemoTypeSC could set the standard for sickle cell disease testing of newborns, as well as for children at immunization age, across Africa.

Obiageli Nnodu, professor of hematology and blood transfusion and director of the Center of Excellence for Sickle Cell Disease Research and Training at the University of Abuja, has recently published findings on the effectiveness of HemoTypeSC external link and other similar sickle cell disease rapid tests in Nigeria. While the results add to a growing body of evidence, the test may be prone to human error when reading, interpreting and validating test results.

Nnodu is also the Nigeria principal investigator of the Sickle Pan-African Consortium, or SPARCO. The NHLBI-funded consortium currently works to address the burden of sickle cell disease in five African countries, with the development of a database being one of several objectives. Working with existing programs, SPARCO will contribute to the research infrastructure needed to reduce the burden of sickle cell disease across the continent.

“Although newborn screening for sickle cell disease is not a primary SPARCO activity, babies and infants with a sickle cell disease who were diagnosed through our newborn screening program could eventually be enrolled in the registry upon parental consent,” said Nnodu. “These babies could also be part of SPARCO’s implementation studies that focus on preventing infection and administering hydroxyurea, a medicine that can reduce sickle cell disease complications.”

Serrao acknowledged that one limitation of HemoTypeSC is its inability to detect hemoglobin D, E, and O, which are common in some parts of the Middle East and Southeast Asia. While this is also a limitation of other sickle cell screening devices, Serrao said users of HemoTypeSC in regions with a high prevalence of these hemoglobin variants should keep this limitation in mind.

Meanwhile, Serrao said he and his colleagues are focused on bringing HemoTypeSC to as many people as possible, including those living in Europe and its territories, where the test is already approved. The test was recently approved by the Kenya Pharmacy & Poisons Board and the National Agency for Food & Drug Administration & Control in Nigeria, with registration by the Ghanaian Food and Drugs Authority expected to imminently follow. In-depth field validations have been conducted thus far in Uganda and Nigeria, with further evaluation underway in other African countries and India. And in the United States, where Serrao said the test could be helpful at blood banks that need to screen new and archived blood samples, HemoTypeSC is awaiting approval.

“HemoTypeSC can help both children and adults afflicted with sickle cell disease,” Serrao said. “Once these young people are identified with the disease, they can be put on medication and become healthy, happy, and extremely productive members of society.”

Building on Our Legacy of Excellence in Sickle Cell Disease Research

Since its founding in 1948, the National Heart, Lung, and Blood Institute (NHLBI) has advanced the understanding of sickle cell disease and improved clinical care. The NHLBI is committed to building on our legacy of research excellence to find new treatments, cures, and personalized care for the approximately 100,000 Americans, and more than 20 million people worldwide, who have sickle cell disease.

Learn more about NHLBI’s legacy of research a PDF for download ay NHLBI Sickle Cell Legacy

Hope & Destiny 5th Edition (2019): New Book release
Hope & Destiny 5th edition provides clear-cut and in-depth information for the more than 100,000 Americans living with sickle cell disease. Written especially for parents and caregivers, this newly revised edition includes the latest information on:
* Using Endari or L-glutamine as a preventative for younger children;
* Using gene therapy and Hydroxyurea therapy;
* Curative bone marrow transplant and advances in sibling transplants;
* New apps, videos, and social media for communication and care, and more!

About the Hope & Destiny Sickle Cell Disease Book Series:
Sickle Cell Disease is the most common blood disorder in the U.S. Since first published, more than 75,000 books from the trusted HOPE and DESTINY sickle cell disease (SCD) series have been used by patients, caregivers, family members, students, and healthcare professionals around the globe. Now, newly revised editions are about to be released! HOPE and DESTINY: The Adult Patient and Parent’s Guide to Sickle Cell Trait, and HOPE and DESTINY Jr.: The Adolescent’s Guide to Sickle Cell Disease, provide the most comprehensive education about sickle cell disease available today, including the latest and most accurate information about treatment regimens, medications, and medical insights to help patients and loved one’s cope with the physical, emotional, and psychological distress caused by SCD. HOPE and DESTINY is the nation’s best-selling book series on SCD because it keeps pace with changes in modern medicine while also providing comprehensive information in an easy-to-read and concise format. https://hiltonpub.com/bookstore/product/hope-destiny-5th-ed-2019/

Articles in the medical literature

1. Clin Geriatr Med. 2019 Aug;35(3):349-367. doi: 10.1016/j.cger.2019.03.006. Epub 2019 May 9. A Growing Population of Older Adults with Sickle Cell Disease. Shet AS1, Thein SL2. Abstract In countries with organized access to health care, survival of patients with sickle cell disease (SCD) has greatly improved, shifting the burden of care from a pediatrician to an internal medicine physician. As a consequence, cumulative disease complications related to chronic vasculopathy are becoming more apparent, adding to organ dysfunction from physiologic aging. The time has come for us to reevaluate the approach to managing the older adult with SCD by putting a greater emphasis on geriatric conditions while proactively considering curative options once previously offered only to younger patients, with comprehensive annual assessments and joint clinics with relevant specialists. Copyright © 2019 Elsevier Inc. All rights reserved.
PMID: 31230736
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2. Biol Blood Marrow Transplant. 2019 Jun 20. pii: S1083-8791(19)30377-5. doi: 10.1016/j.bbmt.2019.06.013. [Epub ahead of print] Identification and characterization of hematopoietic stem cell transplant candidates in a sickle cell disease cohort. Flor-Park MV1, Kelly S2, Preiss L3, Custer B4, Carneiro-Proietti ABF5, Araujo AS6, Loureiro P7, Maximo C8, Rodrigues DOW9, Mota RA10, Sabino EC11, Rocha V12; NHLBI Recipient Epidemiology and Donor Evaluation Study-III (REDS-III) – International Component Brazil. Abstract Sickle cell disease (SCD) is associated with significant morbidity and allogeneic hematopoietic stem cell transplantation (HSCT) remains the primary curative treatment. Recently, the Brazilian Ministry of Health released a regulation to require the publically funded healthcare system pay for HSCT for SCD patients with defined indications. We used an existing 2794-member SCD cohort established during the period 2013-2015 to characterize candidates for HSCT and estimate number of possible donors. Of 2064 patients with SC anemia (SCA), 152 of 974 children (16%) and 279 of 1090 adults (26%) had at least 1 HSCT indication. The most common indication for transplant was stroke (n=239) followed by avascular necrosis (n=96), priapism (n=82), cerebrovascular disease (n=55), >2 vasocclusive episodes (n=38), alloantibodies and chronic transfusion therapy (n=18) and >2 acute chest syndrome episodes (n=11). Increasing age, number of transfusions, abnormal transcranial Doppler, retinopathy, dactilytis and use of hydroxyurea were more frequent in the 152 children with an indication for HSCT compared to 822 without (p<0.001). Of 152 children and 279 adults meeting the eligibility definition, 77 (50%) and 204 (73%), respectively, had at least 1 non-SCD full sibling who could potentially serve as a donor. In conclusion, in a large cohort of SCA patients, 16% of children and 26% of adults have at least 1 indication for HSCT; these indications are associated with the severity of the disease. This study provides clinical data necessary for estimating the costs and infrastructure that would be required to implement HSCT in a public healthcare system. Copyright © 2019. Published by Elsevier Inc.
PMID: 31229639
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3. Pediatrics. 2019 Jun 21. pii: e20183285. doi: 10.1542/peds.2018-3285. [Epub ahead of print] Hydroxyurea Use for Sickle Cell Disease Among Medicaid-Enrolled Children. Brousseau DC1, Richardson T2, Hall M2, Ellison AM3, Shah SS4, Raphael JL5, Bundy DG6, Arnold S7. Abstract BACKGROUND: Recent publications should have resulted in increased hydroxyurea usage in children with sickle cell disease (SCD). We hypothesized that hydroxyurea use in children with SCD increased over time and was associated with decreased acute care visits. METHODS: This was a secondary analysis of the Truven Health Analytics-IBM Watson Health MarketScan Medicaid database from 2009 to 2015. The multistate, population-based cohort included children 1 to 19 years old with an International Classification of Diseases, Ninth or 10th Revision diagnosis of SCD between 2009 and 2015. Changes in hydroxyurea were measured across study years. The primary outcome was the receipt of hydroxyurea, identified through filled prescription claims. Acute care visits (emergency department visits and hospitalizations) were extracted from billing data. RESULTS: A mean of 5138 children each year were included. Hydroxyurea use increased from 14.3% in 2009 to 28.2% in 2015 (P < .001). During the study period, the acute-care-visit rate decreased from 1.20 acute care visits per person-year in 2009 to 1.04 acute care visits per person-year in 2015 (P < .001); however, the drop in acute care visits was exclusively in the youngest and oldest age groups and was not seen when only children enrolled continuously from 2009 to 2015 were analyzed. CONCLUSIONS: There was a significant increase in hydroxyurea use in children with SCD between 2009 and 2015. However, in 2015, only ∼1 in 4 children with SCD received hydroxyurea at least once. Increases in hydroxyurea were not associated with consistently decreased acute care visits in this population-based study of children insured by Medicaid. Copyright © 2019 by the American Academy of Pediatrics.
PMID: 31227564
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4. Acad Emerg Med. 2019 Jun 22. doi: 10.1111/acem.13822. [Epub ahead of print] Resolution of Acute Priapism in Two Children with Sickle Cell Disease who Received Nitrous Oxide. Greenwald MH1,2, Gutman CK1,2, Morris CR1,2. Abstract BACKGROUND: Nitrous oxide (N2O) is an inhalational medication with few side effects that has anxiolytic, amnestic, potent venodilatory and mild-to-moderate analgesic properties commonly used in the emergency department (ED) setting. Priapism is a serious complication of sickle cell disease (SCD) with few treatment options and an adverse impact on quality of life. Although a 50:50 nitrous oxide/oxygen mix is commonly used in France to enhance analgesia in patients with SCD and vaso-occlusive pain events (VOE) there are no reports of its use to treat priapism. We describe the effects of N2O for the treatment of acute priapism associated with SCD in a pediatric ED. METHODS: This is a description of two patients with Hb-SS who presented to the ED with acute priapism that failed oral therapy. On each occasion N2O gas was utilized to help facilitate IV catheter placement. RESULTS: In each presentation the patients experienced complete resolution of the priapism within 5-15 min of receiving N2O (max 60%). The patients had no recurrence requiring intervention during the subsequent week. CONCLUSIONS: Priapism is a challenging complication of SCD associated with long-term morbidity and a paucity of treatment options. Given the risks and inconsistent results of current recommended therapy N2O may represent a potentially superior treatment option for priapism presenting to the ED that warrants further investigation. Although anecdotal N2O inhalation is an option to consider during a time when a treating ED physician may have few alternatives. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
PMID: 31228879
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5. Lancet Haematol. 2019 Jun 18. pii: S2352-3026(19)30111-5. doi: 10.1016/S2352-3026(19)30111-5. [Epub ahead of print] Sickle cell disease: a new era. Simpson S1. Author information:
Free Article
PMID: 31227475
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6. JMIR Mhealth Uhealth. 2019 Jun 20;7(6):e13501. doi: 10.2196/13501. An Electronic Teaching Module for Improving Knowledge of Self-Management of Vaso-Occlusive Pain Crises in Patients With Sickle Cell Disease: Pilot Questionnaire Study. Tam T1, Baer MR2, Hsu LL3, Law JY2. Abstract BACKGROUND: For patients with sickle cell disease (SCD), effective management of vaso-occlusive crises (VOCs) is integral to provision of care, as nearly all affected individuals will suffer from VOCs in their lifetime. A recent systematic review of technological interventions to improve self-management in the care of SCD concluded that electronic health has the potential to improve the care of individuals with SCD. OBJECTIVE: The aim of this study was to assess the value of an electronic teaching module (ETM) provided by Emmi Solutions for educating adult SCD patients on VOC self-management and treatment options for SCD. METHODS: A pretest assessed adults with SCD for baseline knowledge with regard to self-management of VOCs. Participants then watched the 35-min ETM and completed a posttest and survey on the ETM. RESULTS: A total of 20 adults enrolled. Their knowledge scores improved (pretest median 66.5% and posttest median 85%; P<.001). In total, 18 participants (18/20, 90%) agreed that they “learned a lot” or “learned something” from the ETM. The most common topic about which they reported learning was hydroxyurea. A total of 12 participants (12/20, 60%) agreed with the statement that they “would recommend the module to a friend or family member with sickle cell disease.” CONCLUSIONS: The ETM is associated with an increase in knowledge in patients with SCD. Limitations of the study include small sample size, no assessment of knowledge before premodule questionnaire completion, and no longitudinal follow-up. Identifying patients with SCD who demonstrate affinity for self-education via an ETM may further enhance utility of this tool to educate and empower patients. ©Tammie Tam, Maria R Baer, Lewis L Hsu, Jennie Y Law. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 20.06.2019. Free Article
PMID: 31223120
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7. J Pediatr Hematol Oncol. 2019 Jun 18. doi: 10.1097/MPH.0000000000001533. [Epub ahead of print] Longitudinal Trend in Emergency Department Reliance for Pain Among Sickle Cell Disease Patients in Wisconsin. Singh A1, Yan K, Brandow AM, Panepinto JA. Abstract Patients with sickle cell disease frequently visit the emergency department for pain. The metric of emergency department reliance (EDR) describes emergency department utilization in relation to all ambulatory visits and serves as a quality of care indicator. This study uses Wisconsin Medicaid data from 2011 to 2015 to examine trend of EDR for pain over the period of 5 years. We stratified our cohort (N=750) by patient ages into 4 groups: (1) children; (2) transition group; (3) young adults; and (4) adults. Using a linear mixed model, we estimated longitudinal trends adjusting for age group and hydroxyurea possession calculated as medication possession ratio. Results show that EDR for pain has distinct temporal patterns for each group. EDR for pediatrics continually remained less than the established threshold of 0.33. The EDR for transition group significantly increased over time; however, the EDR for young adults has significantly decreased since 2011. There were no significant differences in EDR over time for adults older than 30 years. Overall, increase in medication possession ratio was associated with lower EDR. The low EDR for pain among children and the improvements among adults indicate the success of efforts for sickle cell disease patients. However, further interventions are needed for the transition age group.
PMID: 31219908
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8. JMIR Mhealth Uhealth. 2019 Jun 18;7(6):e8130. doi: 10.2196/mhealth.8130. A Medication Adherence App for Children With Sickle Cell Disease: Qualitative Study. Curtis K1,2, Lebedev A3, Aguirre E4,5, Lobitz S6. Abstract BACKGROUND: Young people with sickle cell disease (SCD) often demonstrate low medication adherence and low motivation for effectively self-managing their condition. The growing sophistication of mobile phones and their popularity among young people render them a promising platform for increasing medication adherence. However, so far, few apps targeting SCD have been developed from research with the target population and underpinned with theory and evidence. OBJECTIVE: The aim of this study was to develop a theory-and-evidence-based medication adherence app to support children and adolescents with SCD. METHODS: The Behavior Change Wheel (BCW), a theoretically based intervention development framework, along with a review of the literature, 10 interviews with children and adolescents with SCD aged between 12 and 18 years, and consultation with experts informed app development. Thematic analysis of interviews provided relevant theoretical and evidence-based components to underpin the design and development of the app. RESULTS: Findings suggested that some patients had lapses in memory for taking their medication (capability); variation in beliefs toward the effectiveness of medication and confidence in self-managing their condition (motivation); a limited time to take medication; and barriers and enablers within the changing context of social support during the transition into adulthood (opportunity). Steps were taken to select the appropriate behavioral change components (involving behavior change techniques [BCTs] such as information on antecedents, prompts/cues; self-monitoring of the behavior; and social support) and translate them into app features designed to overcome these barriers to medication adherence. CONCLUSIONS: Patients with SCD have complex barriers to medication adherence necessitating the need for comprehensive models of behavior change to analyze the problem. Children and adolescents require an app that goes beyond simple medication reminders and takes into account the patient’s beliefs, emotions, and environmental barriers to medication adherence. ©Kristina Curtis, Anastasiya Lebedev, Elisa Aguirre, Stephan Lobitz. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 18.06.2019. Free Article
PMID: 31215518
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9. Br J Haematol. 2019 Jun 18. doi: 10.1111/bjh.16063. [Epub ahead of print] Hydroxycarbamide treatment in children with Sickle Cell Anaemia is associated with more intact white matter integrity: a quantitative MRI study. Kapustin D1,2, Leung J1, Odame I2, Williams S3, Shroff M4, Kassner A1. Abstract Sickle cell anaemia (SCA) is a devastating genetic blood disorder leading to chronic anaemia, impaired cerebrovascular dilatory capacity and cerebral infarctions. Our aim was to assess the relationship between microstructural properties of the white matter (WM) and both cerebrovascular reactivity (CVR) and cerebral blood flow, as well as the effects of hydroxycarbamide on these relationships. Our results demonstrate that mean CVR was increased in hydroxycarbamide-treated patients compared to untreated patients. Moreover, untreated SCA patients had increased skew and kurtosis of mean diffusivity histograms in the WM compared to hydroxycarbamide-treated patients and healthy age-matched controls, indicating disruption of WM integrity. Regression analysis of CVR and WM mean diffusivity (MD) revealed a significant linear relationship between CVR and MD histogram skew and kurtosis in healthy controls, but not in either of the two SCA groups. These findings suggest that patients treated with hydroxycarbamide possess white matter MD histogram parameters which more closely resemble those of healthy controls. © 2019 British Society for Haematology and John Wiley & Sons Ltd.
PMID: 31215028
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10. N Engl J Med. 2019 Jun 14. doi: 10.1056/NEJMoa1903212. [Epub ahead of print] A Phase 3 Randomized Trial of Voxelotor in Sickle Cell Disease. Vichinsky E1, Hoppe CC1, Ataga KI1, Ware RE1, Nduba V1, El-Beshlawy A1, Hassab H1, Achebe MM1, Alkindi S1, Brown RC1, Diuguid DL1, Telfer P1, Tsitsikas DA1, Elghandour A1, Gordeuk VR1, Kanter J1, Abboud MR1, Lehrer-Graiwer J1, Tonda M1, Intondi A1, Tong B1, Howard J1; HOPE Trial Investigators. Abstract BACKGROUND: Deoxygenated sickle hemoglobin (HbS) polymerization drives the pathophysiology of sickle cell disease. Therefore, direct inhibition of HbS polymerization has potential to favorably modify disease outcomes. Voxelotor is an HbS polymerization inhibitor. METHODS: In a multicenter, phase 3, double-blind, randomized, placebo-controlled trial, we compared the efficacy and safety of two dose levels of voxelotor (1500 mg and 900 mg, administered orally once daily) with placebo in persons with sickle cell disease. The primary end point was the percentage of participants who had a hemoglobin response, which was defined as an increase of more than 1.0 g per deciliter from baseline at week 24 in the intention-to-treat analysis. RESULTS: A total of 274 participants were randomly assigned in a 1:1:1 ratio to receive a once-daily oral dose of 1500 mg of voxelotor, 900 mg of voxelotor, or placebo. Most participants had sickle cell anemia (homozygous hemoglobin S or hemoglobin Sβ0-thalassemia), and approximately two thirds were receiving hydroxyurea at baseline. In the intention-to-treat analysis, a significantly higher percentage of participants had a hemoglobin response in the 1500-mg voxelotor group (51%; 95% confidence interval [CI], 41 to 61) than in the placebo group (7%; 95% CI, 1 to 12). Anemia worsened between baseline and week 24 in fewer participants in each voxelotor dose group than in those receiving placebo. At week 24, the 1500-mg voxelotor group had significantly greater reductions from baseline in the indirect bilirubin level and percentage of reticulocytes than the placebo group. The percentage of participants with an adverse event that occurred or worsened during the treatment period was similar across the trial groups. Adverse events of at least grade 3 occurred in 26% of the participants in the 1500-mg voxelotor group, 23% in the 900-mg voxelotor group, and 26% in the placebo group. Most adverse events were not related to the trial drug or placebo, as determined by the investigators. CONCLUSIONS: In this phase 3 randomized, placebo-controlled trial involving participants with sickle cell disease, voxelotor significantly increased hemoglobin levels and reduced markers of hemolysis. These findings are consistent with inhibition of HbS polymerization and indicate a disease-modifying potential. (Funded by Global Blood Therapeutics; HOPE ClinicalTrials.gov number, NCT03036813.). Copyright © 2019 Massachusetts Medical Society.
PMID: 31199090
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11. Clin Adv Hematol Oncol. 2019 Apr;17(4):234-243. Antiplatelet agents for preventing vaso-occlusive events in people with sickle cell disease: a systematic review. Martí-Carvajal A1, Abd El Aziz MA2, Martí-Amarista C3, Solà I4. Abstract BACKGROUND: Sickle cell disease (SCD) is the most common hemoglobinopathy, occurring worldwide, and vaso-occlusive events (VOEs) are its paramount, hallmark clinical manifestation. Evidence exists that platelets play an important role in generating VOEs. OBJECTIVE: To assess the clinical benefits and harms of antiplatelet agents for preventing VOEs in patients with SCD. METHODS: We conducted searches of the Cochrane Central Register of Controlled Trials (CENTRAL; up to 2018, issue 3 of 12), PubMed/MEDLINE (up to April 20, 2018), and the Excerpta Medica database (EMBASE; from 1980 to week 16 of 2018). We also searched the Latin American and Caribbean Health Sciences Literature (LILACS) database, the US Food and Drug Administration (FDA) website, the European Medicines Agency (EMA) website, the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP), and www.ClinicalTrials.gov. We checked the bibliographies of included studies and any relevant systematic reviews. Our systematic review included randomized clinical trials (RCTs) conducted in people who had SCD without VOEs at trial entry. Eligible trials compared a single or combination treatment regimen (with each treatment classified as a conventional or nonconventional antiplatelet agent) with conventional care, placebo, or another regimen. No restrictions were placed on the route of administration, dose, frequency, or duration of treatment. We selected RCTs, assessed the risk for bias, and extracted data in a duplicate and independent fashion. We estimated risk ratios for dichotomous outcomes and mean differences for continuous outcomes. We also subjected our analyses to a random-effects model, and Trial Sequential Analysis (TSA) was used. We used the grading of recommendations, assessment, development, and evaluation (GRADE) approach to assess the overall quality of data for each individual outcome. RESULTS: We identified 5 RCTs (N=747) that met our criteria. Of these, 4 trials were multicenter and multinational. The trials included patients of all ages and assessed prasugrel, ticagrelor, crizanlizumab, and aspirin vs either placebo or no intervention. The most frequent route of administration was oral. The trials were small and carried a high risk for bias, given that pharmaceutical companies sponsored 4 of them. None of the trials reported information on quality of life. No meta-analysis was performed owing to heterogeneity in the ages of the participants and in the interventions. No single trial showed evidence of certainty regarding all-cause mortality. One trial showed uncertainty in comparing prasugrel vs placebo for preventing VOEs in patients younger than 18 years (relative risk [RR], 0.92; 95% CI, 0.80 to 1.06; low quality of evidence). TSA for this outcome suggested that a new trial should be conducted. One trial found a difference in the size effect of uncomplicated VOEs, favoring high-dose crizanlizumab vs placebo (mean difference, -1.50; 95% CI, -2.61 to -0.39; very low quality of evidence). No difference in VOEs was found in studies that compared either ticagrelor in children or prasugrel in adults vs placebo. The overall incidence of harms in any intervention did not differ from that in the control. CONCLUSIONS: The current evidence does not support or reject the use of any antiplatelet agent for preventing VOEs in people with SCD. This conclusion was based on small RCTs that carried a high risk for bias. No conclusive evidence exists regarding relevant clinical outcomes because the evidence is limited and of very low quality.
PMID: 31188815
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12. Br J Haematol. 2019 Jun 5. doi: 10.1111/bjh.16003. [Epub ahead of print] Rapid decline in estimated glomerular filtration rate is common in adults with sickle cell disease and associated with increased mortality. Derebail VK1, Zhou Q2, Ciccone EJ3, Cai J4, Ataga KI5. Abstract We evaluated the prevalence of rapid decline in kidney function, its potential risk factors and influence upon mortality in sickle cell disease (SCD) in a retrospective single-center study. Rapid decline of kidney function was defined as estimated glomerular filtration rate (eGFR) loss of >3·0 ml/min/1·73 m2 per year. A multivariable logistic regression model for rapid eGFR decline was constructed after evaluating individual covariates. We constructed multivariate Cox-regression models for rapid eGFR decline and mortality. Among 331 SCD patients (median age 29 years [interquartile range, IQR: 20, 41]; 187 [56·5%] female) followed for median 4·01 years (IQR: 1·66, 7·19), rapid eGFR decline was noted in 103 (31·1%). History of stroke (odds ratio [OR]: 2·91, 95% confidence interval [CI]: 1·25-6·77) and use of angiotensin converting enzyme inhibitors/angiotensin receptor blockers (OR: 3·17, 95% CI: 1·28-7·84) were associated with rapid eGFR decline. The rate of eGFR change over time was associated with mortality (hazard ratio [HR]: 0·99, 95% CI: 0·984-0·995, P = 0·0002). In Cox-regression, rapid eGFR decline associated with mortality (HR: 2·07, 95% CI: 1·039-4·138, P = 0·04) adjusting for age, sex and history of stroke. Rapid eGFR decline is common in SCD and associated with increased mortality. Long-term studies are needed to determine whether attenuating loss of kidney function may decrease mortality in SCD. © 2019 British Society for Haematology and John Wiley & Sons Ltd.
PMID: 31168785
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13. Pediatr Blood Cancer. 2019 Jun 3:e27816. doi: 10.1002/pbc.27816. [Epub ahead of print] Prospective longitudinal follow-up of children with sickle cell disease treated with hydroxyurea since infancy. Thomas R1, Dulman R1,2, Lewis A1, Notarangelo B1, Yang E1,2,3. Abstract BACKGROUND: Hydroxyurea (HU) increases fetal hemoglobin (HgbF) and ameliorates sickle cell disease (SCD) symptoms. Studies have demonstrated the safety and efficacy of HU in infants and children. Initiation of HU in infancy for children with SCD needs to be implemented in community practice. PROCEDURE: Starting in 2011, the Pediatric Sickle Cell Program of Northern Virginia initiated HU in infants with SCD. A prospective longitudinal database tracked the clinical course and outcomes. RESULTS: Twenty-four children with HgbSS who started HU by age 1 were continuously followed for a total of 95 person-years. Age at the time of analysis ranged from 2 to 7 years. Average hemoglobin at 6-month intervals ranged from 9.5 + 1.9 to 10.7 + 0.8 g/dL, and average HgbF ranged from 27.8 + 5.0% to 34.1 + 6.6%. Twenty-seven hospitalizations occurred (0.28/person-year), all before age 3, including 19 (70%) for fever or infection, five (19%) for splenic sequestration, and one (4%) for pain in an infant prior to starting HU. The treat-and-release emergency department visits totaled 68 (0.72/person-year), including 62 visits (91%) for fever, infection, or viral illness, and two visits (3%) for pain/dactylitis in infants before HU initiation. Splenic sequestration accounted for all five transfusions. No pain episodes requiring medical attention were documented after HU initiation. No complicated acute chest syndrome, no abnormal or conditional transcranial Doppler ultrasound, and no overt strokes occurred. CONCLUSION: Implementation of HU in infancy for patients with SCD in community practice is feasible and is highly effective in preventing disease complications. © 2019 Wiley Periodicals, Inc.
PMID: 31157521
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14. Br J Haematol. 2019 May 31. doi: 10.1111/bjh.16002. [Epub ahead of print] Management of vaso-occlusive episodes in the day hospital decreases admissions in children with sickle cell disease. Karkoska K1, Appiah-Kubi A2, Rocker J3, Stoffels G4, Aygun B2.   Abstract Acute vaso-occlusive episodes (VOE) are the most common reason for presentation to the Emergency Department (ED) and inpatient admission in people living with sickle cell disease (SCD). The goal of this study was to compare the hospital admission rate for VOE from our centre’s day hospital (Pediatric Ambulatory Chemotherapy and Transfusion Unit; PACT) versus the ED, and to determine which factors influence admission rate. The study included a total of 370 visits involving 140 children with SCD with a mean age of 10·9 ± 5·5 years. The timing from triage to the first analgesic was significantly different between the PACT and the ED (median, 32 vs. 70 min, P < 0·0001). The initial choice of opioid dosage adhered to our centre’s guidelines 84% of the time in the PACT v. 45% in the ED for morphine (P = 0·0003) and 100% in the PACT vs. 43% (P = 0·002) for hydromorphone. The admission rate from the ED (57%) was significantly higher than that of the PACT (29%) even when accounting for differences in baseline variables (P = 0·0001). In conclusion, the odds of being admitted were 3·8 times higher if the patient was treated in the ED. Timely administration and appropriate dosing of intravenous opioids may change this outcome in the future. © 2019 British Society for Haematology and John Wiley & Sons Ltd.
PMID: 31148158
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Sickle Cell Conferences and Events

The Foundation for Sickle Cell Disease Research will be hosting its 13th Annual Symposium June 7-9, 2019 in Fort Lauderdale, FL. Registration is now open.  

The EMBRACE-SCD (Education and Mentoring to BRing Access to CarE for Sickle Cell) Network is hosting the Inaugural Acute Care Mini-Symposium on Friday, July 19, 2019 from 12:00-5:30PM at Atrium Health’s Levine Cancer Institute (Conference Room 3035ABC), located at: 1021 Morehead Medical Drive Charlotte, NC 28204.

This half-day symposium will focus on acute care provider education on NHLBI guidelines and comfort care to patients living with SCD. This event is free. CME/MOC/CEUs will be provided. RSVP at: tiffany.mackey@atriumhealth.org

September 21, 2019 * Sickle Cell Disease… Let’s Talk About It” Health & Wellness Conference * 9am to 2pm * Friendship Missionary Baptist Church 3400 Beatties Ford Road Charlotte, NC

$5 Registration: https://scpocconference2019.eventbrite.com

Thanksgiving Day , November 28, 2019 * University City Turkey Trot 5K * 8am * 3024 Prosperity Church Road Charlotte, NC * Register @ universitycityturkeytrot.com

Sickle Cell Disease Association of America’s 47th National Convention will be held October 9-12, 2019 in Baltimore, MD. https://www.sicklecelldisease.org/2019/01/18/47th-annual-national-convention-call-for-abstracts/

Sickle Cell in Focus 2019 will be held October 10 – 11, 2019 in Kingston, Jamaica at The Jamaica Pegasus Hotel. More details to come.

 5th Annual Sickle Cell Symposium:

Sickle Cell Disease: The Next Generation of Patients and Providers

Saturday November 9th, 2019

at the Charlotte Speedway Club in Concord, NC

The Keynote address will be given by Wayne Frederick, MD, MBA, the 17th President of Howard University. Join us for a day of education focused on the new understanding of sickle cell disease pathophysiology and novel therapeutic approaches to management, culminating with a live Q & A with experts in the field. We ‘re excited and look forward to you attending the event. Info Lawrence.Black@atriumhealth.org