Scientists uncover new way to grow rare life-saving blood stem cells
Enhanced numbers of stem cells for transplantation possible
A protein called Musashi-2 regulates the function and development of important blood stem cells. This knowledge provides new strategies that can be used to control the growth of these cells — cells that can be used as therapeutics for a range of life-threatening diseases but are, in general, in very short supply.
New revolutionary genome-editing technique could repair disease-causing mutations
Researchers recently unveiled in Nature a significant improvement — a new CRISPR system that can switch single letters of the genome cleanly and efficiently, in a way that they say could reliably repair many disease-causing mutations.
New Sickle Cell Disease Education for Patients and Parents at Coordination of Health Care for Complex Kids (CHECK) at UIC
The Sickle Transplant Alliance for Research (STAR)
STAR is a non-profit organization created by a group of pediatric hematology and stem cell transplant doctors. http://curesicklenow.org/
Our Mission Statement: STAR seeks to enhance the lives of children suffering from sickle cell disease through blood and marrow transplantation. We conduct research to create better transplant approaches-ones that safely achieve cure for the greatest number.
Why is STAR needed? Established sickle cell disease organizations provide important support services for families caring for children with this devastating disease. Unfortunately, no large organization exists with a focus only on research to cure sickle cell disease. This research is best advanced through clinical studies involving many different institutions. STAR provides both critical funding as well as an organized collaborative network for this important research. For more see https://www.facebook.com/Sickle-Transplant-Alliance-for-Research-STAR-235266573473965/ and http://curesicklenow.org/
Careers in Sickle Cell Disease Research and Treatment
Videos about John’s Hopkins Sickle Cell Center https://www.genome.gov/genomiccareers/video_view.cfm?id=267
Article on Genetic Treatments for Sickle Cell Disease
In Scientific American http://www.scientificamerican.com/article/genetic-treatments-for-sickle-cell/
Sickle Cell in the Medical Literature
1. Pediatr Blood Cancer. 2016 Apr 22. doi: 10.1002/pbc.26022. [Epub ahead of print]
Hall EM1, Leonard J2, Smith JL3, Guilliams KP4, Binkley M5, Fallon RJ6, Hulbert ML1.
Children with sickle cell disease (SCD) and moyamoya may benefit from indirect cerebral revascularization surgery in addition to chronic blood transfusion therapy for infarct prevention. We sought to compare overt and silent infarct recurrence rates in children with SCD undergoing revascularization.
This was a retrospective cohort study of all children with SCD and moyamoya treated at two children’s hospitals. Clinical events and imaging studies were reviewed.
Twenty-seven children with SCD and confirmed moyamoya receiving chronic transfusion therapy were identified, of whom 12 underwent indirect cerebral revascularization. Two subjects had postoperative transient ischemic attacks and another had a subarachnoid blood collection, none of which caused permanent consequences. Two subjects had surgical wound infections. Among these 12 children, the rate of overt and silent infarct recurrence decreased from 13.4 infarcts/100 patient-years before revascularization to 0 infarcts/100 patient-years after revascularization (P = 0.0057); the postrevascularization infarct recurrence rate was also significantly lower than the overall infarct recurrence of 8.87 infarcts/100 patient-years in 15 children without cerebral revascularization (P = 0.025).
The rate of overt and silent infarct recurrence was significantly lower following indirect cerebral revascularization. A prospective study of cerebral revascularization in children with SCD is needed.
2. Am J Hematol. 2016 Apr 22. doi: 10.1002/ajh.24397. [Epub ahead of print]
Sins JW1,2, Biemond BJ2, van den Bersselaar SM1,2, Heijboer H1, Rijneveld AW3, Cnossen MH4, Kerkhoffs JH5, van Meurs AH6, von Ronnen FB1,2, Zalpuri S7, de Rijke YB8, van der Schoot CE9, de Haas M9, van der Bom JG7, Fijnvandraat K1,10.
Red blood cell (RBC) alloimmunization is a major complication of transfusion therapy in sickle cell disease (SCD). Identification of high-risk patients is hampered by lack of studies that take the cumulative transfusion exposure into account. In this retrospective cohort study among previously non-transfused SCD patients in the Netherlands, we aimed to elucidate the association between the cumulative transfusion exposure, first alloimmunization and independent risk factors. A total of 245 patients received 11 952 RBC units. Alloimmunization occurred in 43 patients (18%), half of them formed their first alloantibody before the 8th unit. In patients with exposure to non-extended matched transfusions (ABO and RhD) the cumulative alloimmunization risk increased up to 35% after 60 transfused units. This was significantly higher compared to a general transfused population (HR 6.6, CI 4.2-10.6). Receiving the first transfusion after the age of 5 was an independent risk factor for alloimmunization (HR 2.3, CI 1.0-5.1). Incidental, episodic transfusions in comparison to chronic scheme transfusions (HR 2.3, CI 0.9-6.0), and exposure to non-extended matched units in comparison to extended matching (HR 2.0, CI 0.9-4.6) seemed to confer a higher alloimmunization risk. The majority of first alloantibodies are formed after minor transfusion exposure, substantiating suggestions of a responder phenotype in SCD and stressing the need for risk factor identification. In this study, older age at first transfusion, episodic transfusions and non-extended matched transfusions appeared to be risk factors for alloimmunization. This article is protected by copyright. All rights reserved.
3. Pediatr Blood Cancer. 2016 Apr 21. doi: 10.1002/pbc.26017. [Epub ahead of print]
Stanley HM1, Friedman DF1,2,3, Webb J1, Kwiatkowski JL1,3.
Transfusions prevent a number of complications of sickle cell disease (SCD), but cause inevitable iron loading. With magnetic resonance imaging (MRI), liver iron can be monitored noninvasively. Erythrocytapheresis can limit iron loading and oral chelation provides a more tolerable alternative to subcutaneous administration. The impact of these factors on control of iron burden in SCD has not been well studied.
Iron monitoring practices, chelation use, and transfusion methods were assessed in our cohort of pediatric patients with SCD receiving chronic transfusion. The impact of these factors on iron burden was assessed.
Among 84 subjects, the proportion that underwent appropriate liver iron concentration (LIC) assessment rose from 21% before to 81% after implementation of R2-MRI in 2006. Among subjects with at least two R2-MRI examinations, median LIC improved (13.2-7.9 mg/g dw, P = 0.027) from initial to final study. Most (67.9%) subjects initially received simple transfusions and subsequently transitioned to erythrocytapheresis. After switching, LIC improved from 13.1 to 4.3 mg/g dw (P < 0.001) after a median of 2.7 years and ferritin improved (2,471-392 ng/ml, P < 0.001) after a median of 4.2 years. Final serum ferritin and LIC correlated negatively with the proportion of transfusions administered by erythrocytapheresis and chelation adherence.
Routine liver R2-MRI should be performed in individuals with SCD who receive chronic red cell transfusions. Adherence with chelation should be assessed regularly and erythrocytapheresis utilized when feasible to minimize iron loading or reduce iron stores accumulated during periods of simple transfusion.
4. J Pain Res. 2016 Mar 30;9:167-75. doi: 10.2147/JPR.S55571. eCollection 2016.
Bakshi N1, Morris CR2.
Sickle cell disease (SCD) is the most common hemoglobinopathy in the US, affecting approximately 100,000 individuals in the US and millions worldwide. Pain is the hallmark of SCD, and a subset of patients experience pain virtually all of the time. Of interest, the arginine metabolome is associated with several pain mechanisms highlighted in this review. Since SCD is an arginine deficiency syndrome, the contribution of the arginine metabolome to acute and chronic pain in SCD is a topic in need of further attention. Normal arginine metabolism is impaired in SCD through various mechanisms that contribute to endothelial dysfunction, vaso-occlusion, pulmonary complications, risk of leg ulcers, and early mortality. Arginine is a semiessential amino acid that serves as a substrate for protein synthesis and is the precursor to nitric oxide (NO), polyamines, proline, glutamate, creatine, and agmatine. Since arginine is involved in multiple metabolic processes, a deficiency of this amino acid has the potential to disrupt many cellular and organ functions. NO is a potent vasodilator that is depleted in SCD and may contribute to vaso-occlusive pain. As the obligate substrate for NO production, arginine also plays a mechanistic role in SCD-related pain, although its contribution to pain pathways likely extends beyond NO. Low global arginine bioavailability is associated with pain severity in both adults and children with SCD as well as other non-SCD pain syndromes. Preliminary clinical studies of arginine therapy in SCD demonstrate efficacy in treating acute vaso-occlusive pain, as well as leg ulcers and pulmonary hypertension. Restoration of arginine bioavailability through exogenous supplementation of arginine is, therefore, a promising therapeutic target. Phase II clinical trials of arginine therapy for sickle-related pain are underway and a Phase III randomized controlled trial is anticipated in the near future.
5. Expert Rev Hematol. 2016 Apr 21. [Epub ahead of print]
Adams-Graves P1, Jordan LB2,3.
Advances in research, medical care, and public health practice have led to individuals with sickle cell disease (SCD) living into adulthood. However, premature mortality persists in youth and young adults with SCD, and adults with SCD are subjected to increased disease burden, organ damage, pain, and disruptions in family and work life. These issues have led to inappropriate utilization of hospital resources, significantly increasing costs related to prolonged inpatient stays, high readmission rates, and increased emergency room visits. Steps are being taken to address these challenges to improve care, including development of evidence-based guidelines targeted to primary care providers, innovative care models, and programs to prepare adolescents for transition to adult care. Here we review previous and current guidelines for treatment of adults with SCD.
6. J Community Genet. 2016 Apr 18. [Epub ahead of print]
Anie KA1,2, Treadwell MJ3, Grant AM4, Dennis-Antwi JA5,6, Asafo MK7, Lamptey ME6,8, Ojodu J9, Yusuf C9, Otaigbe A10, Ohene-Frempong K6,8,11.
Sickle cell disease (SCD) and sickle cell trait (SCT) are highly prevalent in Africa. Despite public health implications, there is limited understanding of community issues for implementing newborn screening and appropriate family counseling. We conducted a 3-day workshop in Kumasi, Ghana, with community leaders as lay program development advisors to assist the development and implementation of a Sickle Cell Counselor Training and Certification Program. We employed qualitative methods to understand cultural, religious, and psychosocial dimensions of SCD and SCT, including the advisors’ attitudes and beliefs in relation to developing a culturally sensitive approach to family education and counseling that is maximally suited to diverse communities in Ghana. We collated advisors’ discussions and observations in order to understand community issues and potential challenges and guide strategies for advocacy in SCD family education and counseling. Results from the workshop revealed that community leaders representing diverse communities in Ghana were engaged constructively in discussions about developing a culturally sensitive counselor training program. Key findings included the importance of improved knowledge about SCD among the public and youth in particular, the value of stakeholders such as elders and religious and traditional leaders, and government expectations of reduced SCD births. We submitted a report to the Ministry of Health in Ghana with recommendations for the next steps in developing a national sickle cell counselor training program. We named the program “Genetic Education and Counseling for Sickle Cell Conditions in Ghana” (GENECIS-Ghana). The first GENECIS-Ghana Training and Certification Program Workshop was conducted from June 8 to 12, 2015.
7. J Clin Med Res. 2016 May;8(5):357-60. doi: 10.14740/jocmr2508w. Epub 2016 Mar 20.
In the 1970s, sickle cell pain was treated with trial and error approach by increasing or decreasing the dose of an opioid or switching from one analgesic to another. This approach was controversial with criticism and doubt about its usefulness. Since then, advances in determining the structure of opioid receptors and the role of the CYP450 enzymes in metabolizing opioids revealed that these anatomic and metabolic findings are not the same in all persons, thus explaining the variability in response to opioids among patients. Thus, the “trial and error approach” has a scientific basis after all.
8. PLoS One. 2016 Apr 14;11(4):e0153257. doi: 10.1371/journal.pone.0153257. eCollection 2016.
Dupervil B1, Grosse S1, Burnett A2, Parker C1.
People with sickle cell disease (SCD) suffer from numerous acute complications that can result in multiple hospitalizations and emergency department (ED) and outpatient care visits. Priapism, a prolonged unwanted erection of the penis not due to sexual stimulation, is a serious complication among males with SCD. Variations in estimates of prevalence make it difficult to accurately assess the burden of this complication of SCD. We analyzed data from the Nationwide Emergency Department Sample (NEDS), a product of the Healthcare Cost and Utilization Project, for the years 2006 through 2010 to measure the numbers of ED visits and to examine patterns of subsequent hospitalizations associated with priapism among male patients with SCD. We find that among ED visits associated with males with SCD, those prompted by priapism are more likely to result in hospitalization than are those associated with pain.
9. Cochrane Database Syst Rev. 2016 Feb 8;2016(2). pii: CD012082.
Estcourt LJ1, Fortin PM2, Hopewell S3, Trivella M4.
This is the protocol for a review and there is no abstract. The objectives are as follows: To summarize the evidence in Cochrane reviews of the effectiveness and safety of red cell transfusions versus no transfusion, or restrictive (to increase the total haemoglobin) versus liberal (to decrease the haemoglobin S level below a specified percentage) transfusion, for treatment or prevention of complications experienced by people with SCD.
10. JAMA Pediatr. 2016 Apr 11. doi: 10.1001/jamapediatrics.2015.4859. [Epub ahead of print]
Reeves SL1, Madden B1, Freed GL1, Dombkowski KJ1.
With transcranial Doppler (TCD) screening, we can identify children and adolescents with sickle cell anemia who are at the highest risk of stroke. An accurate claims-based method for identifying children and adolescents with sickle cell anemia was recently developed and validated that establishes the necessary groundwork to enable large population-based assessments of health services utilization among children and adolescents with sickle cell anemia using administrative claims data.
To assess the feasibility of using administrative claims data to identify and describe the receipt of TCD screening among children and adolescents with sickle cell anemia and to characterize opportunities for intervention.
Design, Setting, and Participants:
Retrospective cross-sectional study using Medicaid claims data from 2005 to 2010. Medicaid claims data were obtained from the following states: Florida, Illinois, Louisiana, Michigan, South Carolina, and Texas. Children and adolescents 2 to 16 years of age with sickle cell anemia were identified by the presence of 3 or more Medicaid claims with a diagnosis of sickle cell anemia within a calendar year (2005-2010). A total of 4775 children and adolescents contributed 10 787 person-years throughout the study period. Data were analyzed in 2015. A subset of children and adolescents enrolled for 2 or more consecutive years was identified to examine potential predictors of TCD screening, which included age, sex, previous receipt of TCD screening, state of residence, and health services utilization (well-child visits, outpatient visits, emergency department visits, and inpatient visits).
Main Outcomes and Measures:
Receipt of TCD screening was assessed by year and state. Using logistic regression with generalized estimating equations, we included associated predictors in a multivariable model to estimate odds of TCD screening.
For a total of 4775 children and adolescents 2 to 16 years of age, TCD screening rates increased over the 6-year study period from 22% to 44% (P < .001); rates varied substantially across states. A subset of 2388 children and adolescents with sickle cell anemia (50%) was enrolled for 2 or more consecutive years. Each year of increasing age was associated with 3% lower odds of TCD screening (odds ratio, 0.97 [95% CI, 0.95-0.98]; P = .002). Previous receipt of TCD screening (odds ratio, 2.44 [95% CI, 2.11-2.81]; P < .001) and well-child visits (odds ratio, 1.10 [95% CI, 1.03-1.18]; P = .007) were associated with higher odds of receiving a TCD screening.
Conclusions and Relevance:
Despite national recommendations, TCD screening rates remain low. Successful strategies to improve TCD screening rates may capitalize on the numerous health care interactions among children and adolescents with sickle cell anemia.
11. Transl Res. 2016 Mar 19. pii: S1931-5244(16)00100-6. doi: 10.1016/j.trsl.2016.03.008. [Epub ahead of print]
Alapan Y1, Kim C1, Adhikari A1, Gray KE1, Gurkan-Cavusoglu E2, Little JA3, Gurkan UA4.
Sickle cell disease (SCD) afflicts millions of people worldwide and is associated with considerable morbidity and mortality. Chronic and acute vaso-occlusion are the clinical hallmarks of SCD and can result in pain crisis, widespread organ damage, and early mortality. Even though the molecular underpinnings of SCD were identified more than 60 years ago, there are no molecular or biophysical markers of disease severity that are feasibly measured in clinic. Abnormal cellular adhesion to vascular endothelium is at the root of vaso-occlusion. However, cellular adhesion is not currently evaluated clinically. Here, we present a clinically applicable microfluidic device (SCD biochip) that allows serial quantitative evaluation of red blood cell (RBC) adhesion to endothelium-associated protein-immobilized microchannels, in a closed and preprocessing-free system. With the SCD biochip, we have analyzed blood samples from more than 100 subjects and have shown associations between the measured RBC adhesion to endothelium-associated proteins (fibronectin and laminin) and individual RBC characteristics, including hemoglobin content, fetal hemoglobin concentration, plasma lactate dehydrogenase level, and reticulocyte count. The SCD biochip is a functional adhesion assay, reflecting quantitative evaluation of RBC adhesion, which could be used at baseline, during crises, relative to various long-term complications, and before and after therapeutic interventions.
Sickle Cell Conferences and Events
Conference Name: Integrating Care in Sickle Cell Disease from Pediatrics to Adulthood
Conference Date: Saturday, May 21, 2016
Time: 7:30 am – 4:30pm
Location: St. Jude Children’s Research Hospital
262 Danny Thomas Place
Memphis, TN 38104
Target Audience: This conference is designed for any practitioner providing treatment to people with sickle cell disease: hematologists, internal medicine physicians, nurses, nurse practitioners, physician assistants, residents, fellows, emergency room physicians, psychologists, and social workers. Adults with sickle cell disease and their significant others are also invited to the conference. CME and Nursing credits will be offered.
Sickle Cell Empowerment Day Saturday, May 21, 2016 / 10a–2p
The Wells Barn & Lawn @ The Franklin Park Conservatory & Botanical Gardens
1777 East Broad Street, Columbus, Ohio 43203
FOR PERSONS LIVING WITH SICKLE CELL DISEASE – LET’S GET BACK TO THE BASICS
The Ohio Sickle Call and Health Association will conduct a one-day educational session to raise awareness and educate and empower adults, teenagers and youth. Participants will hear from healthcare professionals as well as individuals living with Sickle Cell Disease. In addition, information regarding the “Get Connected” Patient Powered Registry and Resources will be available for participants.
Bring your entire family or caregivers to this informational event, special accommodations made for children.
Event: Sickle Cell in Focus (SCiF) 2016, National Institutes of Health, Bethesda, Maryland, USA
Date: Thursday 2nd – Friday 3rd June 2016
Venue: Natcher Conference Centre, National Institutes of Health, Bethesda, MD 20894 USA
The 10th Sickle Cell in Focus conference returns to the USA in June 2016. Sickle Cell in Focus is an internationally renowned educational update for sickle cell disease. It attracts a wide audience of clinicians, academics and other healthcare professionals involved in the disease from around the world.
To book: Free registration will be opening soob. If you would like to be kept up-to-date, please join the STSTN mailing list by sending an email to: firstname.lastname@example.org
The California Rare Disease Surveillance Program
The California Rare Disease Surveillance Program invites you to attend a webinar to hear representatives from four companies talk about their sickle cell disease (SCD) treatments under development, clinical trials, and the FDA approval process on Tuesday, June 14, 2016, from 10-11:30 am PST. The featured speakers are from Emmaus Life Sciences, Global Blood Therapeutics, Mast Therapeutics, and Pfizer Inc.
The agenda will include a brief update on California’s SCD Long-term Data Collection program (the host of the webinar) and an announcement about the fall webinar on creating a statewide SCD plan for South Carolina.
June 18, 2016 Sickle & Flow – Atlanta GA
Sickle & Flow is a partnership with members of the Atlanta community, including local hip hop producers, DJs, patient advocates, health care workers, and scientists. We’re hosting a sickle cell awareness event as part of World Blood Day, on Saturday June 18, 2016. We want to engage the ATL community to promote patient advocacy and biomedical research. As a part of the evening, we will host a Be the Match event, collecting cheek swabs from potential donors, to partner with us in our efforts to more effectively treat and cure sickle cell disease.
6th International African Symposium on Sickle Cell Disease
July 11th – 15th, 2016 Labadi Beach Hotel Accra, Ghana
The Symposium website: www.chop.edu/sicklecellghana to register online (in English only) or download the Registration Form in French or Portuguese. Please use the French or Portuguese templates to complete the online registration or fax to 215-590-4342.
Sickle Cell Partners of the Carolinas presents, Sickle Cell Disease, “Let’s talk about it” day conference
Saturday September 10, 2016 9 am to 2 pm
Friendship Missionary Baptist Church Conference Center
3400 Beatties Ford Road, Charlotte NC 28216
Calling All Abstracts!
Submit your abstracts for the 44th SCDAA annual convention Baltimore, MD on September 27-October 1st, 2016
Interested in highlighting your work as a community based member organization, physician, nurse, social worker, or other team working on behalf of people with sickle cell disease and their families? Submit an abstract on the work that you or your team has completed or is in the process of completing for an opportunity to share at the 44th Annual Sickle Cell Convention. This year’s convention will be held in the great city of Baltimore, MD on September 27-October 1st, 2016 at the Hyatt Regency hotel. For more information on abstracts or to submit your application clicking HERE. http://www.sicklecelldisease.org/index.cfm?page=convention-abstract-submission
SCDAA 44th Annual Convention Sept 27 – Oct 1 Baltimore MD