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FDA approves novel treatment to target abnormality in sickle cell disease – November 25, 2019

Today, the U.S. Food and Drug Administration granted accelerated approval to Oxbryta (voxelotor) for the treatment of sickle cell disease (SCD) in adults and pediatric patients 12 years of age and older.

“Today’s approval provides additional hope to the 100,000 people in the U.S., and the more than 20 million globally, who live with this debilitating blood disorder,” said Acting FDA Commissioner Adm. Brett P. Giroir, M.D. “Our scientific investments have brought us to a point where we have many more tools available in the battle against sickle cell disease, which presents daily challenges for those living with it. We remain committed to raising the profile of this disease as a public health priority and to approving new therapies that are proven to be safe and effective. Together with improved provider education, patient empowerment, and improved care delivery systems, these newly approved drugs have the potential to immediately impact people living with SCD.”

Sickle cell disease is a lifelong, inherited blood disorder in which red blood cells are abnormally shaped (in a crescent, or “sickle” shape), which restricts the flow in blood vessels and limits oxygen delivery to the body’s tissues, leading to severe pain and organ damage. It is also characterized by severe and chronic inflammation that worsens vaso-occlusive crises during which patients experience episodes of extreme pain and organ damage. Nonclinical studies have demonstrated that Oxbryta inhibits red blood cell sickling, improves red blood cell deformability (ability of a red blood cell to change shape) and improves the blood’s ability to flow.

“Oxbryta is an inhibitor of deoxygenated sickle hemoglobin polymerization, which is the central abnormality in sickle cell disease,” said Richard Pazdur, M.D., director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research. “With Oxbryta, sickle cells are less likely to bind together and form the sickle shape, which can cause low hemoglobin levels due to red blood cell destruction. This therapy provides a new treatment option for patients with this serious and life-threatening condition.”

Oxbryta’s approval was based on the results of a clinical trial with 274 patients with sickle cell disease. In the study, 90 patients received 1500 mg of Oxbryta, 92 patients received 900 mg of Oxbryta and 92 patients received a placebo. Effectiveness was based on an increase in hemoglobin response rate in patients who received 1500 mg of Oxbryta, which was 51.1% for these patients compared to 6.5% in the placebo group. Common side effects for patients taking Oxbryta were headache, diarrhea, abdominal pain, nausea, fatigue, rash and pyrexia (fever).

Oxbryta was granted Accelerated Approval, which enables the FDA to approve drugs for serious conditions to fill an unmet medical need based on a result that is reasonably likely to predict a clinical benefit to patients. Further clinical trials are required to verify and describe Oxbryta’s clinical benefit.

The FDA granted this application Fast Track designation. Oxbryta also received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases. The FDA granted the approval of Oxbryta to Global Blood Therapeutics.

Time Has Finally Come for Sickle Cell Advancements

SCD Training and Mentoring Program (STAMP)
Many adults living with sickle cell disease (SCD) have challenges accessing care due to a national shortage of SCD-trained hematologists. To help address this gap, the Health Resources and Services Administration is collaborating with the U.S. Health and Human Services’ Office of Minority Health to deliver a new telehealth series for primary care providers called STAMP, the SCD Training and Mentoring Program. This series, taught by hematologists using a case study-based, tele-mentoring approach, will cover the basics of SCD care, such as pain management, hydroxyurea, and preventive services. Participating primary care providers will also be eligible to request on-demand consultative services from hematologists to further support patient care. The next trainings are scheduled for January 2020.  Learn more here
CDC’s Sickle Cell Data Collection Program Announcement Sickle Cell Disease: Give Blood, Save a Life Podcast 

This new Centers for Disease Control and Prevention (CDC) podcasthighlights the importance of blood donations from African Americans to help people with sickle cell disease who might need one or more blood transfusions. 

Novartis Announcements Importance of Raising Disease Awareness in SCD

Novartis has partnered with Dr. Alex Kumar, a global health physician and photographer, who has documented the challenging and inspiring stories of people with SCD from around the world. Visit  to hear the stories and gain information on how SCD and pain crises affect body, mind and overall life of patients with SCD.

Global SCD Quality of Life Survey (SWAY)
During the 61st American Society of Hematology (ASH) Annual Meeting & Exposition, a coalition of organizations and individuals will share compelling data from the Sickle Cell World Assessment Survey (SWAY), the largest ever-conducted international sickle cell survey. SWAY, which was sponsored by Sickle Cell Disease Coalition member Novartis, assessed the impact of sickle cell disease on the daily life of those living with the disease and uncovered critical insights into the real-world impact of the disease. Over 2000 individuals with SCD and 350 doctors from 16 countries contributed to the survey.

The following abstracts, which detail the results of the survey will be presented during the ASH Annual Meeting: 

New Global Sickle Cell Disease Alliance Formed 

The Global Alliance of Sickle Cell Disease Organizations (GASCDO), a non-profit organization registered in Canada, which is an independent network of sickle cell disease (SCD) advocacy groups working together to advance patient care and help eradicate SCD, was recently formed. In March of 2019, 16 patient advocacy group representatives from five continents and 12 countries came together for the first time, for a face-to-face meeting in London, supported by Novartis, to discuss: 

  • Stigma in sickle cell disease (SCD) and patients experience across the world
  • High need around education and level of awareness about SCD 
  • Access to optimal care and treatment
  • Collaboration on issues where there is a shared need

Sickle Cell Disease: Progress in Treatment Options and Policies Briefing 

On November 19, several members of the Sickle Cell Disease Coalition hosted a briefing on Capitol Hill to educate members of Congress and their staff on how policymakers can help support sickle cell disease (SCD) screening, treatment development, and access. The program featured Jennelle Stephenson, SCD gene therapy recipient, Matthew Porteus, MD, PhD, Stanford University, and Remy Brim, PhD, BGR Group. The briefing was co-hosted by the American Society of Gene & Cell Therapy, American Society of Hematology, American Society for Transplantation and Cellular Therapy, Sickle Cell Disease Association of America, and the Pediatric Hospital Sickle Cell Disease Collaborative. The event was also hosted in conjunction with Representatives Michael Burgess (R-TX) Danny Davis (D-IL) and Barbara Lee (D-CA). The program concluded with an overview of how policy makers could help, by supporting: 

•           National Institutes of Health research funding

•           House Resolution 606, recognizing the importance of sickle cell trait awareness and the development of new treatments

•           Novel payment models for approved gene therapies

•           Dedicated funding for the Centers for Disease Control and Prevention Sickle Cell Data Collection program. 

APHA Meeting
Congratulations to the American Public Health Association on a successful 2019 Annual Meeting and Expofocused on Creating the Healthiest Nation: For science. For action. For health.  The conference convened over 13,000 public health professionals. The program included several sessions and abstracts that highlighted sickle cell disease (SCD), including the session entitled Pushing the Envelope of Public Health: A dialogue with Assistant Secretary for Health ADM Brett P. Giroir.  ADM Giroir shared his vision and approaches on addressing the burden of SCD and other critical public health initiatives, and how a modernized U.S. Public Health Service will contribute to “changing the map.” Dr. Kimberly Smith-Whitley, from the Children’s Hospital of Philadelphia served on the panel and highlighted priorities from the SCD expert perspective.

Articles in the medical literature

1. BMC Health Serv Res. 2019 Nov 21;19(1):876. doi: 10.1186/s12913-019-4726-5.Not being heard: barriers to high quality unplanned hospital care during young people’s transition to adult services – evidence from ‘this sickle cell life’ research.Renedo A1Miles S1Chakravorty S2Leigh A3Telfer P4Warner JO5Marston C6.AbstractBACKGROUND: Young people’s experiences of healthcare as they move into adult services can have a major impact on their health, and the transition period for young people with sickle cell disease (SCD) needs improvement. In this study, we explore how young people with SCD experience healthcare during this period of transition.METHODS: We conducted a co-produced longitudinal qualitative study, including 80 interviews in 2016-2017 with young people with SCD aged 13-21 (mean age 16.6) across two cities in England. We recruited 48 participants (30 female, 18 male): 27 interviews were one-off, and 53 were repeated 2-3 times over approximately 18 months. We used an inductive analytical approach, combining elements of Grounded Theory and thematic analysis.RESULTS: Participants reported significant problems with the care they received in A&E during painful episodes, and in hospital wards as inpatients during unplanned healthcare. They experienced delays in being given pain relief and their basic care needs were not always met. Participants said that non-specialist healthcare staff did not seem to know enough about SCD and when they tried to work with staff to improve care, staff often seemed not prepared to listen to them or act on what they said. Participants said they felt out of place in adult wards and uncomfortable with the differences in adult compared with paediatric wards. Because of their experiences, they tried to avoid being admitted to hospital, attempting to manage their painful episodes at home and accessing unplanned hospital care only as a last resort. By contrast, they did not report having problems within SCD specialist services during planned, routine care.CONCLUSIONS: Our study underscores the need for improvements to make services youth-friendly and youth-responsive, including training staff in SCD-specific care, compassionate care and communication skills that will help them elicit and act on young people’s voices to ensure they are involved in shaping their own healthcare. If young people are prevented from using transition skills (self-management, self-advocacy), or treated by staff who they worry do not have enough medical competency in their condition, they may well lose their trust in services, potentially compromising their own health.Free Article 
PMID: 31752858 
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2. J Med Internet Res. 2019 Nov 20;21(11):e13579. doi: 10.2196/13579.Mobile and Web-Based Apps That Support Self-Management and Transition in Young People With Chronic Illness: Systematic Review.Virella Pérez YI1,2Medlow S1,2Ho J3Steinbeck K1,2.AbstractBACKGROUND: More adolescents with chronic physical illness are living into adulthood, and they require the development of proficient self-management skills to maintain optimal physical health as they transition into adult care services. It is often during this vulnerable transition period that deterioration in illness control is seen as a result of inadequate self-management skills and understanding of their chronic illness. Mobile technology has been proposed as an innovative opportunity to assist in improving the management of chronic conditions as young people transition to adult care services. Over the past 5 years, there has been a significant increase in research into the use of health-related apps.OBJECTIVE: This study aimed to evaluate the utility and effectiveness of mobile and Web-based health apps that support self-management and transition in young people with chronic physical health illnesses.METHODS: We conducted a comprehensive review of the literature in 5 bibliographic databases, using key search terms, considering only articles published from 2013, as we were extending the data from 2 previous systematic reviews. Abstracts were screened for possible inclusion by 2 reviewers. Data extraction and quality assessment tools were used for the evaluation of included studies.RESULTS: A total of 1737 records were identified from the combined electronic searches, and 854 records were removed as duplicates. A total of 68 full articles were further assessed for eligibility, and 6 articles met our review criteria: 3 pilot studies, 2 randomized controlled trials, and 1 prospective cohort study. Publication years ranged from 2015 to 2018. The apps reported were targeted at type 1 diabetes mellitus, epilepsy, asthma, beta thalassemia major, and sickle cell disease, with a combined sample size of 336. A total of 4 studies included in this review reported being effective in increasing knowledge of the targeted condition and increasing therapy adherence, including increased medication adherence. A total of 2 manuscripts only mentioned the word transition. Participant’s satisfaction was reported for all studies. Heterogeneity of the studies prevented meta-analysis.CONCLUSIONS: There remain limited data on the effectiveness and use of mobile and Web-based apps, which might facilitate the transition of adolescents with chronic illnesses from pediatric to adult health care services. This systematic review provides an updated overview of available apps for adolescents with chronic illnesses. This systematic review has been unable to provide evidence for effectiveness of this approach, but it does provide insights into future study design, with reference to the development, evaluation, and efficacy of apps tailored for adolescents with chronic illnesses, including the involvement of adolescents in such designs.TRIAL REGISTRATION: PROSPERO CRD42018104611;©Yisselle Ilene Virella Pérez, Sharon Medlow, Jane Ho, Katharine Steinbeck. Originally published in the Journal of Medical Internet Research (, 20.11.2019.Free Article 
PMID: 31746773 
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3. J Pediatr Hematol Oncol. 2019 Nov 14. doi: 10.1097/MPH.0000000000001669. [Epub ahead of print]Social Determinants of Health and Emergency Department Use Among Children With Sickle Cell Disease.Cortright L1Buckman CTumin DHolder DLeonard S.AbstractSickle cell disease (SCD) is associated with disproportionate emergency department (ED) use. This study described the social determinants of health associated with ED visits and hospital admission from the ED among children with SCD using a nationally representative dataset. We analyzed data from 126 children aged 0 to 17 years with SCD included in the 2011 to 2017 rounds of the National Health Interview Survey (mean age, 8 y; 50% female individuals; 74% African American). Study variables were summarized using weighted means and proportions and compared according to ED use and admission by Wald tests. Fifty-two identified children had visited the ED within the last 12 months and 21 were admitted to the hospital after their most recent ED visit. Children living in a single-mother household were more likely to visit the ED (P=0.040), as were younger children (mean age, 6 vs. 9 y; P=0.034), with no evaluated social determinants of health significantly impacting hospital admission from the ED. The lack of association between ED use and either poverty or insurance type may be related to the overall high level of social disadvantage among children with SCD. Our findings demonstrate the need to better characterize specific social factors impacting acute care use among children with SCD.
PMID: 31743315 
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4. Cochrane Database Syst Rev. 2019 Nov 14;2019(11). doi: 10.1002/14651858.CD012187.pub2.Pharmacological interventions for painful sickle cell vaso-occlusive crises in adults.Cooper TE1Hambleton IR2Ballas SK3Johnston BA4Wiffen PJ5.AbstractBACKGROUND: Sickle cell disease (SCD) is a group of inherited disorders of haemoglobin (Hb) structure in a person who has inherited two mutant globin genes (one from each parent), at least one of which is always the sickle mutation. It is estimated that between 5% and 7% of the world’s population are carriers of the mutant Hb gene, and SCD is the most commonly inherited blood disorder. SCD is characterized by distorted sickle-shaped red blood cells. Manifestations of the disease are attributed to either haemolysis (premature red cell destruction) or vaso-occlusion (obstruction of blood flow, the most common manifestation). Shortened lifespans are attributable to serious comorbidities associated with the disease, including renal failure, acute cholecystitis, pulmonary hypertension, aplastic crisis, pulmonary embolus, stroke, acute chest syndrome, and sepsis. Vaso-occlusion can lead to an acute, painful crisis (sickle cell crisis, vaso-occlusive crisis (VOC) or vaso-occlusive episode). Pain is most often reported in the joints, extremities, back or chest, but it can occur anywhere and can last for several days or weeks. The bone and muscle pain experienced during a sickle cell crisis is both acute and recurrent. Key pharmacological treatments for VOC include opioid analgesics, non-opioid analgesics, and combinations of drugs. Non-pharmacological approaches, such as relaxation, hypnosis, heat, ice and acupuncture, have been used in conjunction to rehydrating the patient and reduce the sickling process.OBJECTIVES: To assess the analgesic efficacy and adverse events of pharmacological interventions to treat acute painful sickle cell vaso-occlusive crises in adults, in any setting.SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Register of Studies Online, MEDLINE via Ovid, Embase via Ovid and LILACS, from inception to September 2019. We also searched the reference lists of retrieved studies and reviews, and searched online clinical trial registries.SELECTION CRITERIA: Randomized, controlled, double-blind trials of pharmacological interventions, of any dose and by any route, compared to placebo or any active comparator, for the treatment (not prevention) of painful sickle cell VOC in adults.DATA COLLECTION AND ANALYSIS: Three review authors independently assessed studies for eligibility. We planned to use dichotomous data to calculate risk ratio (RR) and number needed to treat for one additional event, using standard methods. Our primary outcomes were participant-reported pain relief of 50%, or 30%, or greater; Patient Global Impression of Change (PGIC) very much improved, or much or very much improved. Our secondary outcomes included adverse events, serious adverse events, and withdrawals due to adverse events. We assessed GRADE and created three ‘Summary of findings’ tables.MAIN RESULTS: We included nine studies with data for 638 VOC events and 594 participants aged 17 to 42 years with SCD presenting to a hospital emergency department in a painful VOC. Three studies investigated a non-steroidal anti-inflammatory drug (NSAID) compared to placebo. One study compared an opioid with a placebo, two studies compared an opioid with an active comparator, two studies compared an anticoagulant with a placebo, and one study compared a combination of three drugs with a combination of four drugs. Risk of bias across the nine studies varied. Studies were primarily at an unclear risk of selection, performance, and detection bias. Studies were primarily at a high risk of bias for size with fewer than 50 participants per treatment arm; two studies had 50 to 199 participants per treatment arm (unclear risk). Non-steroidal anti-inflammatory drugs (NSAID) compared with placebo No data were reported regarding participant-reported pain relief of 50% or 30% or greater. The efficacy was uncertain regarding PGIC very much improved, and PGIC much or very much improved (no difference; 1 study, 21 participants; very low-quality evidence). Very low-quality, uncertain results suggested similar rates of adverse events across both the NSAIDs group (16/45 adverse events, 1/56 serious adverse events, and 1/56 withdrawal due to adverse events) and the placebo group (19/45 adverse events, 2/56 serious adverse events, and 1/56 withdrawal due to adverse events). Opioids compared with placebo No data were reported regarding participant-reported pain relief of 50% or 30%, PGIC, or adverse events (any adverse event, serious adverse events, and withdrawals due to adverse events). Opioids compared with active comparator No data were reported regarding participant-reported pain relief of 50% or 30% or greater. The results were uncertain regarding PGIC very much improved (33% of the opioids group versus 19% of the placebo group). No data were reported regarding PGIC much or very much improved. Very low-quality, uncertain results suggested similar rates of adverse events across both the opioids group (9/66 adverse events, and 0/66 serious adverse events) and the placebo group (7/64 adverse events, 0/66 serious adverse events). No data were reported regarding withdrawal due to adverse events. Quality of the evidence We downgraded the quality of the evidence by three levels to very low-quality because there are too few data to have confidence in results (e.g. too few participants per treatment arm). Where no data were reported for an outcome, we had no evidence to support or refute (quality of the evidence is unknown).AUTHORS’ CONCLUSIONS: This review identified only nine studies, with insufficient data for all pharmacological interventions for analysis. The available evidence is very uncertain regarding the efficacy or harm from pharmacological interventions used to treat pain related to sickle cell VOC in adults. This area could benefit most from more high quality, certain evidence, as well as the establishment of suitable registries which record interventions and outcomes for this group of people.Copyright © 2019 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
PMID: 31742673 
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5. Blood. 2019 Nov 19. pii: blood.2019001055. doi: 10.1182/blood.2019001055. [Epub ahead of print]Beneficial effects of endurance exercise training on skeletal muscle microvasculature in sickle cell disease patients.Merlet AN1Messonnier LA2Coudy-Gandilhon C3Bechet D3Gellen B4Rupp T5Galacteros F6Bartolucci P7Féasson L8.AbstractSickle cell disease (SCD) is a genetic hemoglobinopathy leading to two major clinical manifestations: severe chronic hemolytic anemia and iterative vaso-occlusive crises. SCD is also accompanied by profound muscle microvascular remodeling. The beneficial effects of endurance training on microvasculature are widely known. The aim of this study was to evaluate the effects of an endurance training program on microvasculature of skeletal muscle in SCD patients. A biopsy of the vastus lateralis muscle and submaximal incremental exercise were performed before and after the training period. Of the forty randomized SCD patients, complete data sets from 32 were obtained. The training group (n=15) followed a personalized moderate-intensity endurance training program, while the non-training (n=17) group maintained a normal lifestyle. Training consisted of three 40-minute cycle ergometer exercise sessions per week for 8 weeks. Histological analysis highlighted microvascular benefits in the training SCD patients compared to non-training patients, including increases in capillary density (CD) (P = .003), number of capillaries around a fiber (CAF) (P = .015) and functional exchange surface (LC/PF) (P < .0001). Conversely, no significant between-group difference was found in the morphology of capillaries. Indexes of physical ability also improved in the training patients. The moderate-intensity endurance exercise training program improved the muscle capillary network and partly reversed the microvascular defects commonly observed in skeletal muscle of SCD patients. This trial was registered at as #NCT02571088.Copyright © 2019 American Society of Hematology.
PMID: 31742587 
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6. CRISPR J. 2019 Nov 19. doi: 10.1089/crispr.2019.0034. [Epub ahead of print]Perspectives of Sickle Cell Disease Stakeholders on Heritable Genome Editing.Hollister BM1Gatter MC1Abdallah KE1Armsby AJ2,3Buscetta AJ1Byeon YJJ1Cooper KE1Desine S1Persaud A1,4Ormond KE2,5Bonham VL1.AbstractAdvances in CRISPR technology and the announcement of the first gene-edited babies have sparked a global dialogue about the future of heritable genome editing (HGE). There has been an international call for public input to inform a substantive debate about benefits and risks of HGE. This study investigates the views of the sickle cell disease (SCD) community. We utilized a mixed-methods approach to examine SCD stakeholders’ views in the United States. We found SCD stakeholders hold a nuanced view of HGE. Assuming the technology is shown to be safe and effective, they are just as supportive of HGE as genetics professionals, but more supportive than the general public. However, they are also concerned about the potential implications of HGE, despite this support. As discourse surrounding HGE advances, it is crucial to engage disease communities and other key stakeholders whose lives could be altered by these interventions.
PMID: 31742431 
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7. Front Pediatr. 2019 Oct 31;7:443. doi: 10.3389/fped.2019.00443. eCollection 2019.Autologous Stem-Cell-Based Gene Therapy for Inherited Disorders: State of the Art and Perspectives.Staal FJT1Aiuti A2,3Cavazzana M4.

AbstractGene therapy using patient’s own stem cells is rapidly becoming an alternative to allogeneic stem cell transplantation, especially when suitably compatible donors cannot be found. The advent of efficient virus-based methods for delivering therapeutic genes has enabled the development of genetic medicines for inherited disorders of the immune system, hemoglobinopathies, and a number of devastating metabolic diseases. Here, we briefly review the state of the art in the field, including gene editing approaches. A growing number of pediatric diseases can be successfully cured by hematopoietic stem-cell-based gene therapy.Copyright © 2019 Staal, Aiuti and Cavazzana.PMCID: PMC6834641 Free PMC Article 
PMID: 31737588 
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8. Blood Rev. 2019 Nov 5:100637. doi: 10.1016/j.blre.2019.100637. [Epub ahead of print]Not all red cells sickle the same: Contributions of the reticulocyte to disease pathology in sickle cell anemia.Carden MA1Fasano RM2Meier ER3.AbstractSickle cell anemia (SCA) is associated with morbidity and early death. While the switch from fetal to sickle hemoglobin during the first months of life results in hemolytic anemia with reticulocytosis, the role of the reticulocyte in the pathophysiology and prognosis of SCA is not well-defined. Reticulocytes have unique cytoskeletal and membrane components that allow them to be distinguished from mature sickle erythrocytes in the circulation. Reticulocytes in patients with SCA are less dense than more mature and ‘sickled’ erythrocytes, and have increased adhesive properties. The circulating reticulocyte number in peripheral blood may assist in predicting disease severity in SCA; characterization of patient-specific reticulocyte properties during infancy and childhood may assist in predicting therapeutic response to therapies. Here, we review the biological and clinical data regarding reticulocytes and their potential impact on SCA pathophysiology and disease severity.Copyright © 2019 Elsevier Ltd. All rights reserved.
PMID: 31735458 
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9. J Clin Med. 2019 Nov 15;8(11). pii: E1997. doi: 10.3390/jcm8111997.Choice of Donor Source and Conditioning Regimen for Hematopoietic Stem Cell Transplantation in Sickle Cell Disease.Limerick E1Fitzhugh C1.AbstractIn the United States, one out of every 500 African American children have sickle cell disease (SCD), and SCD affects approximately 100,000 Americans. Significant advances in the treatment of this monogenetic disorder have failed to substantially extend the life expectancy of adults with SCD over the past two decades. Hematopoietic stem cell transplantation (HSCT) remains the only curative option for patients with SCD. While human leukocyte antigen (HLA) matched sibling HSCT has been successful, its availability is extremely limited. This review summarizes various conditioning regimens that are currently available. We explore recent efforts to expand the availability of allogeneic HSCT, including matched unrelated, umbilical cord blood, and haploidentical stem cell sources. We consider the use of nonmyeloablative conditioning and haploidentical donor sources as emerging strategies to expand transplant availability, particularly for SCD patients with complications and comorbidities who can undergo neither matched related transplant nor myeloablative conditioning. Finally, we show that improved conditioning agents have improved success rates not only in the HLA-matched sibling setting but also alternative donor settings.Free Article 
PMID: 31731790 
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10. JAMA Netw Open. 2019 Nov 1;2(11):e1915374. doi: 10.1001/jamanetworkopen.2019.15374.Estimated Life Expectancy and Income of Patients With Sickle Cell Disease Compared With Those Without Sickle Cell Disease.Lubeck D1Agodoa I2Bhakta N3Danese M1Pappu K2Howard R2Gleeson M1Halperin M1Lanzkron S4.AbstractImportance: Individuals with sickle cell disease (SCD) have reduced life expectancy; however, there are limited data available on lifetime income in patients with SCD.Objective: To estimate life expectancy, quality-adjusted life expectancy, and income differences between a US cohort of patients with SCD and an age-, sex-, and race/ethnicity-matched cohort without SCD.Design, Setting, and Participants: Cohort simulation modeling was used to (1) build a prevalent SCD cohort and a matched non-SCD cohort, (2) identify utility weights for quality-adjusted life expectancy, (3) calculate average expected annual personal income, and (4) model life expectancy, quality-adjusted life expectancy, and lifetime incomes for SCD and matched non-SCD cohorts. Data sources included the Centers for Disease Control and Prevention, National Newborn Screening Information System, and published literature. The target population was individuals with SCD, the time horizon was lifetime, and the perspective was societal. Model data were collected from November 29, 2017, to March 21, 2018, and the analysis was performed from April 28 to December 3, 2018.Main Outcomes and Measures: Life expectancy, quality-adjusted life expectancy, and projected lifetime income.Results: The estimated prevalent population for the SCD cohort was 87 328 (95% uncertainty interval, 79 344-101 398); 998 were male and 952 were female. Projected life expectancy for the SCD cohort was 54 years vs 76 years for the matched non-SCD cohort; quality-adjusted life expectancy was 33 years vs 67 years, respectively. Projected lifetime income was $1 227 000 for an individual with SCD and $1 922 000 for a matched individual without SCD, reflecting a lost income of $695 000 owing to the 22-year difference in life expectancy. One study limitation is that the higher estimates of life expectancy yielded conservative estimates of lost life-years and income. The analysis only considered the value of lost personal income owing to premature mortality and did not consider direct medical costs or other societal costs associated with excess morbidity (eg, lost workdays for disability, time spent in the hospital). The model was most sensitive to changes in income levels and mortality rates.Conclusions and Relevance: In this simulated cohort modeling study, SCD had societal consequences beyond medical costs in terms of reduced life expectancy, quality-adjusted life expectancy, and lifetime earnings. These results underscore the need for disease-modifying therapies to improve the underlying morbidity and mortality associated with SCD.
PMID: 31730182 
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11. Hemoglobin. 2019 Nov 14:1-4. doi: 10.1080/03630269.2019.1689997. [Epub ahead of print]Use of Direct Oral Anticoagulants in Patients with Sickle Cell Disease and Venous Thromboembolism: A Prospective Cohort Study of 12 Patients.Christen JR1Bertolino J1Jean E1Camoin L2Ebbo M1Harlé JR1Schleinitz N1Sarlon G3Bernit E1.AbstractPatients with sickle cell disease have an increased risk of venous thromboembolism (VTE) and with a mortality 2-fold higher. The anticoagulation of VTE in a young population is an important question. Indeed, hemorrhagic complications of anticoagulation may occur more frequently than in the general population. The use of a direct oral anticoagulant (DOAC) is not recommended for VTE in patients with sickle cell disease because those patients were not included in the clinical studies. We aimed to study the safety of using DOACs in a prospective cohort of patients with sickle cell disease and VTE. We prospectively followed the cohort of all sickle cell disease patients undergoing recent DOAC treatment for VTE at a sickle cell disease reference center. Twelve patients received rivaroxaban for VTE (eight women and four men). The median age was 27 years (20-45). The sickle cell disease variants included homozygous Hb SS (HBB: c.20A>T) in eight patients, Hb S-β+-thalassemia (Hb S-β+-thal) in two, Hb S-β0-thal in one and Hb S-Hb C (HBB: c.19G>A) in one. The cumulative duration of follow-up was 3134 days under rivaroxaban treatment. There were two thrombotic events, including a patient with a double positivity of antiphospholipid antibodies. No major bleeding was observed, and 6/12 patients presented minor bleeding (epistaxis: n = 4; anal fissure bleeding: n = 1; menorrhagia n = 4). Of these, 3/6 required their treatment to be switched to apixaban, which stopped the bleeding. Direct oral anticoagulants may be an alternative treatment for VTE in patients with sickle cell disease, except for an associated antiphospholipid syndrome.
PMID: 31724442 
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12. J Clin Med. 2019 Oct 26;8(11). pii: E1796. doi: 10.3390/jcm8111796.Is There Any Improvement of the Coagulation Imbalance in Sickle Cell Disease after Hematopoietic Stem Cell Transplantation?Rozen L1Noubouossie DF1Dedeken L2Lê PQ2Ferster A2Demulder A1.AbstractSeveral components of the clotting system are modified towards hypercoagulability in sickle cell disease (SCD). To date, hematopoietic stem cell transplantation (HSCT) is the only validated curative treatment of SCD. Here, we investigated the changes in the hemostatic potential of SCD children who’ve received a successful HSCT. Seventeen children with severe SCD were enrolled in the study. Thrombin generation (TG) was performed on citrated platelet-poor plasma, obtained before and 3, 6, 9, 12 and 15 months after HSCT. TG was triggered using 1 pM tissue factor and 4 µM phospholipids with or without thrombomodulin (TM). Before the HSCT, SCD children showed a higher endogenous thrombin potential (ETP), higher peak, higher velocity and shorter time-to-peak of TG than the normal controls (NC). ETP did not significantly change following the HSCT. However, the peak, velocity and time-to-peak of TG reversed to normal ranges from 3 months post-HSCT and remained so up to 15 months post-HSCT. The reduction of ETP after the addition of thrombomodulin (RETP) was dramatically reduced in SCD children before HSCT as compared with the NC. A partial reversal of RETP was observed from 3 months through 15 months post-HSCT. No statistical difference was observed for patient age or donor hemoglobinopathy status. In summary, successful HSCT improves the kinetics of TG but not the total thrombin capacity in SCD children.Free Article 
PMID: 31717804 
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13. J Clin Med. 2019 Nov 9;8(11). pii: E1927. doi: 10.3390/jcm8111927.Genetic Modifiers at the Crossroads of Personalised Medicine for Haemoglobinopathies.Stephanou C1Tamana S1Minaidou A1Papasavva P1Kleanthous M1Kountouris P1.AbstractHaemoglobinopathies are common monogenic disorders with diverse clinical manifestations, partly attributed to the influence of modifier genes. Recent years have seen enormous growth in the amount of genetic data, instigating the need for ranking methods to identify candidate genes with strong modifying effects. Here, we present the first evidence-based gene ranking metric (IthaScore) for haemoglobinopathy-specific phenotypes by utilising curated data in the IthaGenes database. IthaScore successfully reflects current knowledge for well-established disease modifiers, while it can be dynamically updated with emerging evidence. Protein-protein interaction (PPI) network analysis and functional enrichment analysis were employed to identify new potential disease modifiers and to evaluate the biological profiles of selected phenotypes. The most relevant gene ontology (GO) and pathway gene annotations for (a) haemoglobin (Hb) F levels/Hb F response to hydroxyurea included urea cycle, arginine metabolism and vascular endothelial growth factor receptor (VEGFR) signalling, (b) response to iron chelators included xenobiotic metabolism and glucuronidation, and (c) stroke included cytokine signalling and inflammatory reactions. Our findings demonstrate the capacity of IthaGenes, together with dynamic gene ranking, to expand knowledge on the genetic and molecular basis of phenotypic variation in haemoglobinopathies and to identify additional candidate genes to potentially inform and improve diagnosis, prognosis and therapeutic management.Free Article 
PMID: 31717530 
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14. PLoS One. 2019 Nov 11;14(11):e0224886. doi: 10.1371/journal.pone.0224886. eCollection 2019.Vasopressin SNP pain factors and stress in sickle cell disease.Powell-Roach KL1,2Yao Y3,4Jhun EH5,6He Y6,7Suarez ML4Ezenwa MO3Molokie RE6,8,9Wang ZJ6,7Wilkie DJ2,3,4.AbstractPURPOSE: Frequencies of single nucleotide polymorphisms (SNPs) from pain related candidate genes are available for individuals with sickle cell disease (SCD). One of those genes, the arginine vasopressin receptor 1A gene (AVPR1A) and one of its SNPs, rs10877969, has been associated with pain and disability in other pain populations. In patients with SCD, clinical factors such as pain and stress have been associated with increased health care utilization, but it is not known if the presence of the AVPR1A SNP plays a role in this observation. The study purpose was to explore the relationships between rs10877969 and self-reported pain, stress, and acute care utilization events among individuals with SCD.METHODS: In a cross-sectional investigation of outpatients with SCD, participants completed PAINReportIt®, a computerized pain measure, to describe their pain experience and contributed blood or saliva samples for genetic analysis. We extracted emergency department and acute care utilization from medical records.RESULTS: The SNP genotype frequencies (%) for this sample were CC 30 (28%), CT 44 (41%), TT 33 (31%). Acute care utilization and stress as an aggravator of pain were significantly associated with the rs10877969 genotype (p = .02 and p = .002, respectively). The CT genotype had the highest mean utilization and CC genotype was associated with not citing stress as a pain aggravator. Chronic pain was not associated with rs10877969 (p = .41).CONCLUSION: This study shows that rs10877969 is related to indicators of stress and acute pain. Further research is recommended with other measures of stress and acute pain.PMCID: PMC6844466 Free PMC Article 
PMID: 31710639 
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Conflict of interest statementThe authors have declared that no competing interests exist.
15. Mediterr J Hematol Infect Dis. 2019 Nov 1;11(1):e2019067. doi: 10.4084/MJHID.2019.067. eCollection 2019.Curing Hemoglobinopathies: Challenges and Advances of Conventional and New Gene Therapy Approaches.Motta I1,2Ghiaccio V3Cosentino A2Breda L3.AbstractInherited hemoglobin disorders, including beta-thalassemia (BT) and sickle-cell disease (SCD), are the most common monogenic diseases worldwide, with a global carrier frequency of over 5%.1 With migration, they are becoming more common worldwide, making their management and care an increasing concern for health care systems. BT is characterized by an imbalance in the α/β-globin chain ratio, ineffective erythropoiesis, chronic hemolytic anemia, and compensatory hemopoietic expansion.1 Globally, there are over 25,000 births each year with transfusion-dependent thalassemia (TDT). The currently available treatment for TDT is lifelong transfusions and iron chelation therapy or allogenic bone marrow transplantation as a curative option. SCD affects 300 million people worldwide2 and severely impacts the quality of life of patients who experience unpredictable, recurrent acute and chronic severe pain, stroke, infections, pulmonary disease, kidney disease, retinopathy, and other complications. While survival has been dramatically extended, quality of life is markedly reduced by disease- and treatment-associated morbidity. The development of safe, tissue-specific and efficient vectors, and efficient gene-editing technologies have led to the development of several gene therapy trials for BT and SCD. However, the complexity of the approach presents its hurdles. Fundamental factors at play include the requirement for myeloablation on a patient with benign disease, the age of the patient, and the consequent bone marrow microenvironment. A successful path from proof-ofconcept studies to commercialization must render gene therapy a sustainable and accessible approach for a large number of patients. Furthermore, the cost of these therapies is a considerable challenge for the health care system. While new promising therapeutic options are emerging,3,4 and many others are on the pipeline,5 gene therapy can potentially cure patients. We herein provide an overview of the most recent, likely potentially curative therapies for hemoglobinopathies and a summary of the challenges that these approaches entail.PMCID: PMC6827604 Free PMC Article 
PMID: 31700592 
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16. Blood Adv. 2019 Nov 12;3(21):3297-3306. doi: 10.1182/bloodadvances.2019000838.Association between clinical outcomes and metformin use in adults with sickle cell disease and diabetes mellitus.Badawy SM1,2Payne AB3.AbstractMetformin was recently found to increase fetal hemoglobin, which is protective in sickle cell disease (SCD). We tested the hypothesis that, among adults with SCD and diabetes mellitus (DM), metformin use is associated with fewer adverse SCD clinical outcomes and lower health care utilization. This is a retrospective cohort study using the MarketScan Medicaid claims database for 2006 to 2016, comparing metformin users and nonusers. Patients on hydroxyurea, insulin, or iron chelation were excluded. Main outcomes included annual rates of all-cause inpatient encounters, all-cause emergency department (ED) encounters, inpatient and ED encounters with SCD codes, vaso-occlusive episodes (VOEs), strokes, acute chest syndrome (ACS), avascular necrosis (AVN), and gallstones. Of 457 adults (median age [interquartile range], 43 years [33-52 years]; 72% female), 142 (31%) were treated with metformin. Adjusted for age, sex, and Charlson Comorbidity Index, metformin users had significantly lower rate ratios of all-cause inpatient encounters (0.68; 95% confidence interval [CI], 0.52-0.88; P < .01), inpatient encounters with SCD codes (0.45; 95% CI, 0.30-0.66; P < .01), ED encounters with SCD codes (0.34; 95% CI, 0.21-0.54; P < .01), VOE (0.22; 95% CI, 0.12-0.41; P < .01), ACS (0.17; 95% CI, 0.05-0.60; P = .01), and AVN (0.30; 95% CI, 0.11-0.87; P = .03). A subgroup analysis of 54 enrollees preinitiation and postinitiation of metformin did not indicate significant changes in rates of clinical events. Metformin was associated with significantly fewer inpatient and ED SCD encounters in adults with SCD and DM; however, confounding of underlying SCD severity cannot be excluded.PMCID: PMC6855104 Free PMC Article 
PMID: 31698459 
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17. Blood. 2019 Oct 28. pii: blood.2019000821. doi: 10.1182/blood.2019000821. [Epub ahead of print]How I treat sickle cell disease with hematopoietic cell transplantation.Stenger EO1Shenoy S2Krishnamurti L3.AbstractSickle cell disease (SCD) leads to significant morbidity and early mortality, and hematopoietic cell transplantation (HCT) is the only widely available cure, with impacts seen on SCD-related organ dysfunction. Outcomes are excellent following matched related donor (MRD) HCT, leading to significantly expanded application of this treatment over the past decade. The majority of SCD patients lack a MRD, but outcomes following alternative donor HCT continue to improve on clinical trials. Within this framework, we aim to provide our perspective on how to apply research findings to clinical practice, for an individual patient. We also emphasize that the preparation of SCD recipients for HCT and supporting them through HCT has special nuances that require awareness and close attention. Through the use of clinical vignettes, we provide our perpsective on the complex decision-making process in HCT for SCD as well as recommendations for the evaluation and support of these patients through HCT.Copyright © 2019 American Society of Hematology.
PMID: 31697818 
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18. Blood Adv. 2019 Nov 12;3(21):3379-3392. doi: 10.1182/bloodadvances.2019000820.Genome editing of HBG1 and HBG2 to induce fetal hemoglobin.Métais JY1Doerfler PA1Mayuranathan T1Bauer DE2,3,4,5,6Fowler SC1Hsieh MM7Katta V1Keriwala S1Lazzarotto CR1Luk K8Neel MD9Perry SS10Peters ST11Porter SN11Ryu BY1Sharma A12Shea D2Tisdale JF7Uchida N7Wolfe SA8Woodard KJ1Wu Y2Yao Y1Zeng J2Pruett-Miller S11Tsai SQ1Weiss MJ1.AbstractInduction of fetal hemoglobin (HbF) via clustered regularly interspaced short palindromic repeats/Cas9-mediated disruption of DNA regulatory elements that repress γ-globin gene (HBG1 and HBG2) expression is a promising therapeutic strategy for sickle cell disease (SCD) and β-thalassemia, although the optimal technical approaches and limiting toxicities are not yet fully defined. We disrupted an HBG1/HBG2 gene promoter motif that is bound by the transcriptional repressor BCL11A. Electroporation of Cas9 single guide RNA ribonucleoprotein complex into normal and SCD donor CD34+ hematopoietic stem and progenitor cells resulted in high frequencies of on-target mutations and the induction of HbF to potentially therapeutic levels in erythroid progeny generated in vitro and in vivo after transplantation of hematopoietic stem and progenitor cells into nonobese diabetic/severe combined immunodeficiency/Il2rγ-/-/KitW41/W41 immunodeficient mice. On-target editing did not impair CD34+ cell regeneration or differentiation into erythroid, T, B, or myeloid cell lineages at 16 to 17 weeks after xenotransplantation. No off-target mutations were detected by targeted sequencing of candidate sites identified by circularization for in vitro reporting of cleavage effects by sequencing (CIRCLE-seq), an in vitro genome-scale method for detecting Cas9 activity. Engineered Cas9 containing 3 nuclear localization sequences edited human hematopoietic stem and progenitor cells more efficiently and consistently than conventional Cas9 with 2 nuclear localization sequences. Our studies provide novel and essential preclinical evidence supporting the safety, feasibility, and efficacy of a mechanism-based approach to induce HbF for treating hemoglobinopathies.PMCID: PMC6855127 Free PMC Article 
PMID: 31698466 
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19. Treatment for Acute Pain: An Evidence Map [Internet].EditorsBrasure M1Nelson VA1Scheiner S1Forte ML1Butler M1Nagarkar S1Saha J1Wilt TJ1. Rockville (MD): Agency for Healthcare Research and Quality (US); 2019 Oct. Report No.: 19(20)-EHC022-EF.
AHRQ Comparative Effectiveness Technical Briefs.Author information: 
1. Minnesota Evidence-based Practice CenterExcerptINTRODUCTION: Acute pain is a common ailment in the U.S. often treated with opioids. This technical brief maps the current evidence on pain treatments for select acute pain conditions (postdischarge postoperative pain, musculoskeletal pain, acute migraine, dental pain, renal colic, and acute pain associated with sickle cell disease).METHODS: We conducted Key Informant discussions to develop the context around the acute pain conditions, settings, and current clinical practice. We then conducted a systematic literature search to identify recent systematic reviews of sufficient quality that evaluated pain treatments for select acute pain conditions. We screened results and extracted relevant data into evidence tables. We subsequently searched for original research published after systematic review search dates.RESULTS: Key Informant discussions identified important issues regarding common acute pain conditions and treatments. Certain acute pain conditions have not received sufficient attention in rigorous comprehensive systematic review; for most types of acute pain, pain etiology is critical to selecting appropriate treatment; the value of acute pain assessments in guiding treatment decisions is unclear; and regional and health system level policies play a large role in treatment decisions. Our search for systematic reviews for pain treatments for priority acute pain conditions identified 1226 potentially relevant references, of which 527 underwent full text review. After supplemental searching and full text review, 110 systematic reviews met basic eligibility criteria. Most acute pain conditions had systematic reviews that met eligibility criteria, but few reviews were sufficiently rigorous and comprehensive. Few eligible reviews focused on specific settings except emergency departments for several acute pain conditions. Eligible reviews rarely addressed specific subpopulations such as racial and ethnic groups, rural residents, pregnant women, individuals with comorbidities, or those with a history of substance use disorder, overdose, or mental illness. Comparisons addressed by many systematic reviews often included opioids.DISCUSSION: Our discussions with Key Informants and review of the literature show that additional original research and up-do-date comprehensive systematic reviews would help inform treatment decisions for a wide variety of acute pain conditions.Free Books & Documents 
PMID: 31693321 
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20. J Pediatr Hematol Oncol. 2019 Nov 1. doi: 10.1097/MPH.0000000000001627. [Epub ahead of print]Cold External Temperatures and Sickle Cell Morbidity in Children: A Retrospective Analysis.Wachnian C1Tompkins N2Corriveau-Bourque C3Belletrutti M3Bruce AAK3.AbstractBACKGROUND: Genetic and environmental factors affect the occurrence of vaso-occlusive crises (VOCs) in patients with sickle cell disease (SCD). Research provides inconsistent evidence on how environmental temperature affects SCD. Edmonton, Alberta, has an increasing SCD population and is the northern-most city in North America with a population of over a million.OBJECTIVE: The objective of this study was to identify whether pediatric patients with SCD experience increased morbidity in cold external temperatures.MATERIALS AND METHODS: This study was a retrospective case series. Emergency visits, phone calls, and admission data for VOC in children were recorded from July 2011 to June 2016. Temperatures were recorded and statistically analyzed using descriptive statistics, to determine the relation to VOC.RESULTS: A total of 118 patients with 257 VOC events were reviewed. When analyzing the mean, minimum, and change in temperatures at presentation, the largest percentage of VOC events occurred at mild to moderate temperatures. Temperature data at 24 and 48 hours before the presentation had similar results. When accounting for the relative frequency of extreme weather days, there are increased VOC events with temperature fluctuations >20°C.CONCLUSIONS: There was no correlation between mean and minimum temperature change. Fluctuation in temperature of >20°C was associated with increased relative VOC frequency, suggesting that large temperature variability should be avoided in SCD, but a prospective study is required to determine causality.
PMID: 31688640 
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22. Cochrane Database Syst Rev. 2019 Oct 25;2019(10). doi: 10.1002/14651858.CD008360.pub5.Regular long-term red blood cell transfusions for managing chronic chest complications in sickle cell disease.Estcourt LJ1Hopewell S2Trivella M3Hambleton IR4Cho G5.AbstractBACKGROUND: Sickle cell disease is a genetic haemoglobin disorder, which can cause severe pain, significant end-organ damage, pulmonary complications, and premature death. Sickle cell disease is one of the most common severe monogenic disorders in the world, due to the inheritance of two abnormal haemoglobin (beta globin) genes. The two most common chronic chest complications due to sickle cell disease are pulmonary hypertension and chronic sickle lung disease. These complications can lead to morbidity (such as reduced exercise tolerance) and increased mortality. This is an update of a Cochrane Review first published in 2011 and updated in 2014 and 2016.OBJECTIVES: We wanted to determine whether trials involving people with sickle cell disease that compare regular long-term blood transfusion regimens with standard care, hydroxycarbamide (hydroxyurea) any other drug treatment show differences in the following: mortality associated with chronic chest complications; severity of established chronic chest complications; development and progression of chronic chest complications; serious adverse events.SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group’s Haemoglobinopathies Trials Register. Date of the last search: 19 September 2019. We also searched for randomised controlled trials in the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library, Issue 10, 14 November 2018), MEDLINE (from 1946), Embase (from 1974), CINAHL (from 1937), the Transfusion Evidence Library (from 1950), and ongoing trial databases to 14 November 2018.SELECTION CRITERIA: We included randomised controlled trials of people of any age with one of four common sickle cell disease genotypes, i.e. Hb SS, Sβº, SC, or Sβ+ that compared regular red blood cell transfusion regimens (either simple or exchange transfusions) to hydroxycarbamide, any other drug treatment, or to standard care that were aimed at reducing the development or progression of chronic chest complications (chronic sickle lung and pulmonary hypertension).DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane.MAIN RESULTS: No studies matching the selection criteria were found.AUTHORS’ CONCLUSIONS: There is a need for randomised controlled trials looking at the role of long-term transfusion therapy in pulmonary hypertension and chronic sickle lung disease. Due to the chronic nature of the conditions, such trials should aim to use a combination of objective and subjective measures to assess participants repeatedly before and after the intervention.Copyright © 2019 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.PMCID: PMC6814284 [Available on 2020-10-25]
PMID: 31684693 
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23. Cochrane Database Syst Rev. 2019 Nov 4;2019(11). doi: 10.1002/14651858.CD003489.pub2.Malaria chemoprophylaxis in sickle cell disease.Oniyangi O1Omari AA2.AbstractBACKGROUND: Malaria is the most common precipitating cause of crises in sickle cell disease in malaria-endemic countries. Health professionals often recommend life-long malaria chemoprophylaxis for people with sickle cell disease living in these areas. It is therefore important we have good evidence of benefit.OBJECTIVES: To assess the effects of routine malaria chemoprophylaxis in people with sickle cell disease.SEARCH METHODS: We searched the Cochrane Infectious Diseases Group Specialized Register (January 2006), Cochrane Cystic Fibrosis and Genetic Disorders Group Specialized Register (July 2006), CENTRAL (The Cochrane Library 2006, Issue 1), MEDLINE (1966 to January 2006), EMBASE (1974 to January 2006), LILACS (1982 to January 2006), and reference lists. We also contacted organizations and pharmaceutical companies.SELECTION CRITERIA: Randomized and quasi-randomized controlled trials comparing chemoprophylaxis with any antimalarial drug given for a minimum of three months compared with a placebo or no intervention.DATA COLLECTION AND ANALYSIS: Two authors independently applied the inclusion criteria, assessed the risk of bias in the trials, and extracted data. Dichotomous data were analysed using risk ratios (RR) and presented with 95% confidence intervals (CI).MAIN RESULTS: Two trials with a total of 223 children with homozygous sickle cell disease met the inclusion criteria. A randomized controlled trial in Nigeria compared two different antimalarial drugs with a placebo, and reported that chemoprophylaxis reduced sickle cell crises (RR 0.17, 95% CI 0.04 to 0.83; 97 children), hospital admissions (RR 0.27, 95% CI 0.12 to 0.63; 97 participants), and blood transfusions (RR 0.16, 95% CI 0.05 to 0.56; 97 participants). A quasi-randomized controlled trial of 126 children in Uganda compared an antimalarial drug plus antibiotics with no antimalarial plus placebo. Chemoprophylaxis reduced the number of episodes of malaria and dactylitis, and increased mean haemoglobin values in this trial.AUTHORS’ CONCLUSIONS: It is beneficial to give routine malaria chemoprophylaxis in sickle cell disease in areas where malaria is endemic. 4 November 2019 Update pending New contributors needed The CIDG Editors are looking for contributors to update and maintain this Cochrane Review. Contact the CIDG Managing Editor for further information.Copyright © 2019 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
PMID: 31681984 
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Sickle Cell Conferences and Events

ASH Annual Meeting 

The61st American Society of Hematology (ASH) Annual Meeting & Exposition, is scheduled for December 7-10, 2019, in Orlando, FL. The meeting provides an invaluable educational experience and an opportunity to review thousands of scientific abstracts highlighting updates in the hottest topics in hematology, including sickle cell disease (SCD). The following is a list of SCD specific programming.

Sickle Cell Disease Kiosk 
This year’s SCD Kioskwill focus on care for individuals living with SCD. Visit the Kiosk to learn about ASH’s new SCD Guidelines and watch rapid fire 5-minute presentations on several guideline chapters. Are you an ASH member? Complete your Find a Hematologistprofile so that individuals living with SCD can locate SCD providers in their area.  

Friday Scientific Workshop
Friday, December 6, 2019, 1:00 pm – 6:00 pm, Room W314, Level 3 (Orange County Convention Center) Learn More
Novel Curative Options: Gene-Editing and Gene Therapy for Hemoglobinopathies with a Focus on Sickle Cell Disease

News Worthy SCD Abstracts 

Three exciting sickle cell abstracts have been selected to be covered during ASH’s press briefing. ASH strictly limits attendance at the press briefings to registered media to ensure that the focus remains on communicating study details to media reporting on the meeting. However, the abstracts selected are available for those interested:

812.Chromatin Accessibility Mapping of Primary Erythroid Cell Populations Leads to Identification and Validation of Nuclear Factor I X (NFIX) As a Novel Fetal Hemoglobin (HbF) Repressor (presenter Jeff Shearstone, Syros Pharmaceuticals)

613. Oral Arginine Therapy As a Novel Adjuvant in the Management of Acute Pain in Children with Sickle Cell Anemia in Nigeria: A Randomized Placebo-Controlled Trial (presenter Richard Onalo, FCPaed, University of Abuja, Nigeria)

4667. Fragmentation of Care for Young Adults with Sickle Cell Disease in California(presenter Anjlee Mahajan, MD, UC Davis Cancer Center)

Educational Sessions
Management of Sickle Cell Disease Complications Beyond Acute Chest

This session is offered twice:

Saturday, December 7, 2019: 7:30am-9:00am, Hall E2, Level 2 (Orange County Convention Center)

Monday, December 9, 2019: 2:45pm-4:15pm, Tangerine 1 (WF1), Level 2 (Orange County Convention Center)Learn more

Sickle Cell Disease in Young and Old: A Time for Re-Evaluation

This session is offered twice:

Saturday, December 7, 2019: 2:00pm-3:30pm, W304, Level 3 (Orange County Convention Center)

Sunday, December 8, 2019: 9:30am-11:00am, W304, Level 3 (Orange County Convention Center)Learn more

Point-Counterpoint: Curative Therapies for SCD-Does it Make More Sense to Target the Root Cause Than All the Downstream Events

This is an Education Spotlight Session.

Sunday, December 8, 2019: 4:30pm-6:00pm, W312, Level 3 (Orange County Convention Center)Learn more

Scientific Session
Scientific Committee on Transplantation Biology and Cellular Therapies: Genome Editing for Transplantation and Cellular Therapies

This session is offered twice: 

Saturday, December 7, 2019: 9:30am-11:00am, Hall D, Level 2 (Orange County Convention Center)

Sunday, December 8, 2019: 7:30am-9:00am, Hall D, Level 2 (Orange County Convention Center) Learn more

Special Sessions

Special-Interest Session on Sickle Cell Disease Centers

Saturday, December 7, 2019, 4:00 pm – 6:00 pm, Tangerine 3 (WF3-4), Level 2 (Orange County Convention Center)Learn more

Special Education Session on ASH Clinical Practice Guidelines on Sickle Cell Disease

Sunday, December 8, 2019, 12:00 pm – 1:30 pm, Tangerine 2 (WF2), Level 2 (Orange County Convention Center)Learn more

 Global Sickle Cell Disease Network-Sponsored Meeting 

Improving Outcomes for Sickle Cell Disease in Low-resource Settings: Bridging the Implementation Gaps

Sunday, December 8, 2019: 11:15am-12:30pm, Barrel Spring Room, Convention Space, Hyatt Regency Orlando Hotel

To RSVP for this meeting, email:

Consultative Hematology Course

Monday, December 9, 2019, 7:00 am – 11:30 am, Hyatt Regency Orlando, Regency Ballroom T-U

Molly Weidner Mandernach, MD, MPH will discuss: Sickle Cell Disease: Old and New Truths.Learn more

ASH Research Collaborative Update 

Monday, December 9, 2019, 6:15 pm – 7:45 pm, W315, Level 3 (Orange County Convention Center) Learn more. 

The ASH Research Collaborative (ASH RC) is a non-profit organization that was established by ASH last year to foster collaborative partnerships to accelerate progress in hematology, with the goal of improving the lives of people affected by blood diseases. The foundation of the ASH RC is its Data Hub, a technology platform that facilitates the exchange of information by aggregating in one place, and making available for inquiry, research-grade data on hematologic diseases. The first research initiative of the ASH RC is a Sickle Cell Disease (SCD) Clinical Trials Network (CTN), which launched in 2019 with the goal of optimizing the conduct of clinical trials research in SCD. The Network will leverage the Data Hub to collect key information and identify gaps that will help advance SCD research and treatment.

The ASH Research Collaborative will provide updates on site selection for the SCD Clinical Trials Network and technology and data set developments for the Data Hub.

The Hemoglobinopathy Counselor Training Course will be held in Cincinnati on April 15-16, 2020.  The two-day course, presented by the Cincinnati Comprehensive Sickle Cell Center, will be held at Cincinnati Children’s Hospital Medical Center.  The course registration fee is $250.  The deadline to register is April 1, 2020 and registration space is limited.  For more information, please email:  Registration is available online at



3030 Holiday Drive, Fort Lauderdale, FL 33316