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ASH to Develop Clinical Guidelines to Improve Care for People with Sickle Cell Disease
the American Society of Hematology (ASH) is working on several projects to conquer sickle cell disease (SCD) worldwide. Among them, the Society has launched an effort to develop clinical practice guidelines on the management of SCD. An expansion of ASH’s commitment to identify and confront unmet needs in SCD patient care, these guidelines will be created with input from physicians and patients to address the unique needs of this underserved patient population.
An inherited, lifelong chronic disorder affecting nearly 100,000 Americans, SCD is characterized by rigid, sickle-shaped red blood cells that stick to blood vessels, blocking blood flow. With only one FDA-approved treatment and no widely available cure, life is extremely challenging for people with SCD. Pain — both chronic and acute — is common and results in tremendous suffering and difficulty continuing daily activities like work or school. Brain injury, organ damage, stroke, and death are all devastating complications associated with SCD.
“These guidelines will help specialists provide optimal care for patients throughout their lives,” said Chair of the ASH Sickle Cell Disease Guideline Coordination Panel Robert Liem, MD, Director of the Comprehensive Sickle Cell Program at the Ann & Robert H. Lurie Children’s Hospital of Chicago. “We are eager to work with other hematologists, pediatricians, emergency room physicians, and people with SCD to improve patients’ overall quality of life.”
The guidelines will be based on a systematic review of available evidence and developed according to standards recommended by the National Academy of Medicine (formerly the Institute of Medicine). ASH has contracted with the Mayo Clinic Evidence-Based Practice Research Center to conduct the systematic evidence reviews and to support the guideline development process. Publication of the guidelines is expected in 2019.
These state-of-the-art guidelines will be produced and maintained by five panels of hematologists, other clinicians, people living with SCD, and experts in evidence-based guideline production. The panels will address the care and management of acute and chronic complications of SCD, including pain caused by the disease, stroke prevention and treatment, and prevention and treatment of cardiopulmonary and kidney diseases. One panel has been called to address the use of blood transfusions to improve red blood cell count and mitigate complications of SCD, while another has been convened to improve the understanding of stem cell transplantation, currently the only cure for SCD.
The ASH SCD guidelines will expand on guidelines published by the National Institutes of Health’s National Heart, Lung, and Blood Institute (NHLBI). The NHLBI’s EvidenceBased Management of Sickle Cell Disease: Expert Panel Report, 2014 provides useful guidance and information for primary care, emergency, and other clinicians who may be unfamiliar with this rare disease. The ASH guidelines will provide clinical recommendations for hematologists and other specialists. The ASH guidelines will also take into account new evidence available since the publication of the NHLBI guidelines and will be continually updated to present the latest in optimal care strategies.
These guidelines are part of a broader ASH commitment to conquer SCD worldwide. Last fall, ASH launched a call to action on SCD by publishing a report card that identified the areas of care most in need of improvement and announced the formation of a new Sickle Cell Disease Coalition. The Society also issued the State of Sickle Cell Disease: 2016 Report, at http://scdcoalition.org/report.html which was endorsed by 24 other organizations.
The Society is in the midst of developing a consortium of sub-Saharan African countries to address newborn screening and early intervention. The consortium would introduce standard-of-care practices for screening and early intervention therapies at participating institutions, with the goal of decreasing childhood mortality rates for SCD.
Additionally, ASH continues to work with partners to support legislation that will improve access to SCD care, treatments, and cures. This month, the Society co-hosted a briefing on Capitol Hill to educate policymakers on advancements in SCD research, and has advocated for federal funding to expand surveillance of this population that will help us better understand health outcomes and health care system utilization patterns of people living with SCD.
ASH continues to increase its educational resources through the development of webinars and in-person training opportunities and will also host a broad array of sessions about SCD at the 59th ASH Annual Meeting in Atlanta.
“There are many unique challenges that people with SCD face,” said ASH President-Elect Alexis Thompson, MD, MPH. “From enabling patients to find local health care providers with the knowledge and expertise to provide proper care, to supporting efforts to bring newborn screening and early intervention to infants and children with sickle cell disease in sub-Saharan Africa, there is enormous opportunity to transform the way we care for people suffering from SCD. ASH is ready to tackle this effort on all fronts.”
War on Opioids Hurts Sickle Cell Disease Patients
Sickle Cell Disease Sufferers Trapped In Fight Against Opioid Scourge
For the thousands of individuals who suffer from the effects of sickle cell anemia, pain is a common part of their lives.
The inherited disease causes red blood cells of mostly people of African descent to deform into a sickle shape. This inhibits the red blood cells from carrying oxygen throughout the body, which can cause severe pain and organic damage.
So, many of those suffering from sickle cell anemia are prescribed a variety of powerful pain killer derivatives.
Their desire to receive relief may be viewed through the biased lens of racism and criminalization as a result of the opioid epidemic, and deter them from receiving care for their pain.
Many of these painkillers are equal in strength to oxycontin and oxycodone, which many people with sickle cell anemia have been taking since they were children.
They are also the same drugs which are at the center of the nation’s current opioid addiction epidemic. Thus, federal and state governments are seeking to pressure doctors to limit their prescriptions of such drugs to patients to curb the deadly trend.
According to Judy Anderson, the executive director of the Sickle Cell Anemia Association of Hampton Roads, a growing number of people who are suffering from sickle cell anemia may be severely impacted by the government’s effort to curb opioid addiction.
CDC – Sickle Cell Fact sheets to download and print at https://www.cdc.gov/ncbddd/sicklecell/materials/factsheets.html
Articles in the Medical Literature
Int J Adolesc Med Health. 2017 Aug 5. pii: /j/ijamh.ahead-of-print/ijamh-2017-0004/ijamh-2017-0004.xml. doi: 10.1515/ijamh-2017-0004. [Epub ahead of print]
The effects of music therapy on transition outcomes in adolescents and young adults with sickle cell disease.
Rodgers-Melnick SN1, Pell TJG1, Lane D1, Jenerette C1, Fu P1, Margevicius S1, Little JA1.
Background The Build, Educate, Advance, Transition, in Sickle cell disease (BEATS) music therapy program was developed to address health challenges faced by adolescents/young adults (AYA) with sickle cell disease (SCD) during the transition to adult medical care. Objective The purpose of this study was to investigate the effects of BEATS on self-efficacy, trust, knowledge about SCD, and adherence in adolescents/young adults (AYA) with SCD. Subjects Thirty AYA with SCD, 18-23 years old, recruited from an adult SCD clinic agreed to participate in four BEATS sessions over 1 year. Methods Self-efficacy, trust and SCD knowledge were measured prospectively at baseline and months 3, 6, 9, and 12. Adherence to clinic appointments and healthcare utilization were measured retrospectively from medical records. A repeated measures linear mixed-effect model with compound symmetry covariance structure was used to fit the data. Results BEATS participants demonstrated a significant improvement in SCD knowledge (p = 0.0002) compared to baseline, an increase in acute care clinic, but not emergency department, utilization (p = 0.0056), and a non-significant improvement in clinic attendance (p = 0.1933). Participants’ subjective evaluations revealed a positive response to BEATS. There were no significant changes in self-efficacy, trust, hospital admissions, or blood transfusion adherence. Conclusion Culturally tailored, developmentally appropriate music therapy transition interventions can concretely improve SCD knowledge and may improve transition for AYA with SCD.
Am J Hematol. 2017 Aug 4. doi: 10.1002/ajh.24879. [Epub ahead of print]
SIRT1 Activates the Expression of Fetal Hemoglobin Genes.
Dai Y1, Chen T1, Ijaz H1, Cho EH1, Steinberg MH1.
High fetal hemoglobin (HbF, α2 γ2 ) levels ameliorate the clinical manifestations of sickle cell disease and β thalassemia. The mechanisms that repress HbF expression and silence γ-globin genes in adults are incompletely characterized and only a single HbF inducer, hydroxyurea, is approved for treatment, and only in patients with sickle cell disease. We identified SIRT1, a protein deacetylase, as a new inducer of γ-globin. SIRT1 knockdown decreased, while SIRT1 ectopic expression upregulated γ-globin gene (HBG) expression in primary human erythroid cells and in K562 cells. The small molecule SIRT1 activators SRT2104 and SRT1720 enhanced HBG expression in cord blood human erythroblasts and reactivated silenced HBG in adult human erythroblasts. Furthermore, SIRT1 binds in the β-globin gene cluster locus control region (LCR) and HBG promoters, promotes the looping of the LCR to HBG promoter, and increases the binding of RNA polymerase II and H4K16Ac in the HBG promoter. SIRT1 suppressed the expression of the HBG suppressors BCL11A, KLF1, HDAC1 and HDAC2. Lastly, SIRT1 did not change the proliferation of human erythroid progenitor cells or the expression of differentiation marker CD235a. These data suggest that SIRT1 activates HBG expression through facilitating LCR looping to the HBG promoter, inhibiting the expression of transcriptional suppressors of HBG, and indirectly increasing histone acetylation in HBG promoter. SIRT1 is a potential therapeutic target for γ-globin gene induction, and small molecule SIRT1 activators might serve as a lead compound for the development of new HbF inducers. This article is protected by copyright. All rights reserved.
© 2017 Wiley Periodicals, Inc.
Br J Haematol. 2017 Aug 2. doi: 10.1111/bjh.14850. [Epub ahead of print]
How I manage sickle cell patients with high transcranial doppler results.
Brewin J1, Kaya B2, Chakravorty S3.
Stroke is one of the most severe complications to affect children with sickle cell anaemia (SCA). Transcranial doppler (TCD) is an accurate and non-invasive method to determine stroke risk. Randomised controlled trials have demonstrated the efficacy of chronic transfusion therapy in stroke prevention based on risk stratification determined by TCD velocities. This has led to the regular use of TCD monitoring for children with SCA in order to determine stroke risk. Significant resource allocation is necessary to facilitate training, quality assurance and failsafe arrangements for non-attenders. In a subgroup of patients, chronic transfusions for primary stroke prevention can be replaced by hydroxycarbamide therapy, provided careful monitoring is undertaken; including repeat TCD studies at frequent intervals. The authors propose an evidence-based algorithm for the management of abnormal TCD velocities and discuss the role of this test in other clinical contexts, such as in Haemoglobin SC disease.
© 2017 John Wiley & Sons Ltd.
J Pain Res. 2017 Jul 14;10:1635-1644. doi: 10.2147/JPR.S131859. eCollection 2017.
The effect of hypnosis on pain and peripheral blood flow in sickle-cell disease: a pilot study.
Bhatt RR1, Martin SR1, Evans S2, Lung K1, Coates TD3,4, Zeltzer LK1, Tsao JC1.
Vaso-occlusive pain crises (VOCs) are the “hallmark” of sickle-cell disease (SCD) and can lead to sympathetic nervous system dysfunction. Increased sympathetic nervous system activation during VOCs and/or pain can result in vasoconstriction, which may increase the risk for subsequent VOCs and pain. Hypnosis is a neuromodulatory intervention that may attenuate vascular and pain responsiveness. Due to the lack of laboratory-controlled pain studies in patients with SCD and healthy controls, the specific effects of hypnosis on acute pain-associated vascular responses are unknown. The current study assessed the effects of hypnosis on peripheral blood flow, pain threshold, tolerance, and intensity in adults with and without SCD.
SUBJECTS AND METHODS:
Fourteen patients with SCD and 14 healthy controls were included. Participants underwent three laboratory pain tasks before and during a 30-minute hypnosis session. Peripheral blood flow, pain threshold, tolerance, and intensity before and during hypnosis were examined.
A single 30-minute hypnosis session decreased pain intensity by a moderate amount in patients with SCD. Pain threshold and tolerance increased following hypnosis in the control group, but not in patients with SCD. Patients with SCD exhibited lower baseline peripheral blood flow and a greater increase in blood flow following hypnosis than controls.
Given that peripheral vasoconstriction plays a role in the development of VOC, current findings provide support for further laboratory and clinical investigations of the effects of cognitive-behavioral neuromodulatory interventions on pain responses and peripheral vascular flow in patients with SCD. Current results suggest that hypnosis may increase peripheral vasodilation during both the anticipation and experience of pain in patients with SCD. These findings indicate a need for further examination of the effects of hypnosis on pain and vascular responses utilizing a randomized controlled trial design. Further evidence may help determine unique effects of hypnosis and potential benefits of integrating cognitive-behavioral neuromodulatory interventions into SCD treatment.
PMCID: PMC5529094 Free PMC Article
Hematology. 2017 Aug 2:1-9. doi: 10.1080/10245332.2017.1359898. [Epub ahead of print]
Stigma and illness uncertainty: adding to the burden of sickle cell disease.
Blake A1, Asnani V2, Leger RR3, Harris J1, Odesina V4, Knight-Madden J1, Wagner L5, Asnani MR1.
Persons with sickle cell disease (SCD) experience multiple medical and physical complications; the disease also has numerous effects on their social and emotional well-being. We hypothesized that adults with SCD in Jamaica experience moderate levels of stigma and illness uncertainty and that these experiences may be associated with socio-demographic factors, such as gender, educational status and economic status.
We surveyed 101 adults with SCD (54.5% female; mean age 31.6 ± 10.4 years; 72.2% homozygous SCD) using the Stigma in Sickle Cell Disease Scale (Adult), Mishel Uncertainty in Illness Scale (Adult) and a Socio-Demographic questionnaire.
The mean stigma score was 33.6 ± 21.6 (range: 2-91) with no significant difference between males and females (32.3 ± 21.3 vs. 34.7 ± 21.9; p-value = 0.58). Illness uncertainty was greater in females than in males, though not statistically significant, (88.7 ± 13.5 vs. 82.6 ± 19.2; p-value: 0.07). Stigma and uncertainty had a significant positive correlation (r: 0.31; p-value: 0.01). In an age and sex controlled model, stigma scores were lower with higher numbers of household items (coef: -2.26; p-value: 0.001) and higher in those living in greater crowding (coef: 7.89; p-value: 0.002). Illness uncertainty was higher in females (coef: 6.94; p-value: 0.02) and lower with tertiary as compared with primary education (coef: -16.68; p-value: 0.03).
The study highlights socioeconomic factors to be significant to the stigma and illness uncertainty experiences in SCD. Efforts by healthcare workers to reduce patient illness uncertainty may have additional impact, reducing their stigma.
Cochrane Database Syst Rev. 2017 Jul 31;7:CD010985. doi: 10.1002/14651858.CD010985.pub3.
Interventions for treating intrahepatic cholestasis in people with sickle cell disease.
Martí-Carvajal AJ1, Martí-Amarista CE.
Sickle cell disease is the most common hemoglobinopathy occurring worldwide and sickle cell intrahepatic cholestasis is a complication long recognized in this population. Cholestatic liver diseases are characterized by impaired formation or excretion (or both) of bile from the liver. There is a need to assess the clinical benefits and harms of the interventions used to treat intrahepatic cholestasis in people with sickle cell disease. This is an update of a previously published Cochrane Review.
To assess the benefits and harms of the interventions for treating intrahepatic cholestasis in people with sickle cell disease.
We searched the Cystic Fibrosis and Genetic Disorders Group’s Haemoglobinopathies Trials Register, which comprises references identified from comprehensive electronic database searches and handsearching of relevant journals and abstract books of conference proceedings. We also searched the LILACS database (1982 to 23 May 2017), the WHO International Clinical Trials Registry Platform Search Portal (23 May 2017) and ClinicalTrials.gov.Date of last search of the Cochrane Cystic Fibrosis and Genetic Disorders Group’s Haemoglobinopathies Trials Register: 12 April 2017.
We searched for published or unpublished randomised controlled trials.
DATA COLLECTION AND ANALYSIS:
Each author intended to independently extract data and assess the risk of bias of the trials by standard Cochrane methodologies; however, no trials were included in the review.
There were no randomised controlled trials identified.
This updated Cochrane Review did not identify any randomised controlled trials assessing interventions for treating intrahepatic cholestasis in people with sickle cell disease. Randomised controlled trials are needed to establish the optimum treatment for this condition.
Cochrane Database Syst Rev. 2017 Jul 31;7:CD005406. doi: 10.1002/14651858.CD005406.pub5.
Fluid replacement therapy for acute episodes of pain in people with sickle cell disease.
Treating vaso-occlusive painful crises in people with sickle cell disease is complex and requires multiple interventions. Extra fluids are routinely given as adjunct treatment, regardless of the individual’s state of hydration with the aim of slowing or stopping the sickling process and thereby alleviating pain. This is an update of a previously published Cochrane Review.
To determine the optimal route, quantity and type of fluid replacement for people with sickle cell disease with acute painful crises.
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises of references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.We also conducted searches of Embase (November 2007), LILACS, www.ClinicalTrials.gov (05 January 2010), and the WHO ICTRP (30 June 2017).Date of most recent search of the Group’s Haemoglobinopathies Trials Register: 16 February 2017.
Randomised and quasi-randomised controlled trials that compared the administration of supplemental fluids adjunctive to analgesics by any route in people with any type of sickle cell disease during an acute painful episode, under medical supervision (inpatient, day care or community).
DATA COLLECTION AND ANALYSIS:
No relevant trials have yet been identified.
Sixteen trials were identified by the searches, all of which were not eligible for inclusion in the review.
Treating vaso-occlusive crises is complex and requires multiple interventions. Extra fluids, generally oral or intravenous, are routinely administered during acute painful episodes to people with sickle cell disease regardless of the individual’s state of hydration. Reports of their use during these acute painful episodes do not state the efficacy of any single route, type or quantity of fluid compared to another. However, there are no randomised controlled trials that have assessed the safety and efficacy of different routes, types or quantities of fluid. This systematic review identifies the need for a multicentre randomised controlled trial assessing the efficacy and possible adverse effects of different routes, types and quantities of fluid administered to people with sickle cell disease during acute painful episodes.
Clin Trials. 2017 Jul 1:1740774517723307. doi: 10.1177/1740774517723307. [Epub ahead of print]
Successful utilization of an electronic pain diary in a multinational phase 3 interventional study of pediatric sickle cell anemia.
Heath LE1, Heeney MM2, Hoppe CC3, Adjei S4,5, Agbenyega T4,5, Badr M6, Masera N7, Zhou C1, Brown PB1, Jakubowski JA1, Dampier C8.
Patients with sickle cell anemia can experience recurrent pain episodes, which affect quality of life. The reported prevalence of pain is higher in studies using patient diaries than in healthcare facility utilization data. Determining Effects of Platelet Inhibition on Vaso-Occlusive Events was a multinational study that assessed the efficacy and safety of prasugrel in reducing the rate of vaso-occlusive events in children with sickle cell anemia (NCT01794000) and included an electronic patient-reported outcome diary to record pain occurrence. We aimed to capture diary completion rates and compliance in children who used the electronic patient-reported outcome diary during the Determining Effects of Platelet Inhibition on Vaso-Occlusive Events study and examine factors contributing to diary completion rates and compliance.
Daily electronic patient-reported outcome diary data were collected for up to 9 months in Determining Effects of Platelet Inhibition on Vaso-Occlusive Events participants aged 4 to <18 years in Africa, the Americas, Europe, and the Middle East. The questionnaires were available in 11 languages/dialects for collecting subjective (pain intensity, activity interference) and objective (study drug use, analgesic use, school attendance) data. Pain intensity was measured using the Faces Pain Scale-Revised. Data were entered by participants or caregivers and transferred wirelessly each day to a central database. Diary completion rates were the number of daily diary entries divided by the total number of expected daily diary entries. Percentages of participants who were compliant with the diary (≥80% diary completion) were calculated.
A total of 311 participants received a diary; 268 provided diary data through Month 9. Diary completion rates and compliance were high throughout the collection period and across all groups and regions, despite no games being included on the device. For subjective data, the overall completion rate was 94.4%, and 92.6% of participants were compliant. For objective data, the overall completion rate was 93.3%, and 89.7% of participants were compliant. Completion rates and compliance differed significantly by age and region and were higher for 4 to <12 year olds and very much higher for participants from Africa and the Middle East. Caregivers almost always entered data for participants <6 years and rarely entered data for participants ≥12 years. Comparing participant-entered and caregiver-entered data, pain intensity score data were more consistent for 4 to <12 year olds than older children, but pain intensity scores for older children were higher when entered by caregivers.
With appropriate design, participant training, and sufficient monitoring, an electronic patient-reported outcome diary can capture daily sickle cell-related pain data in large multinational studies. Providing a mechanism for caregiver reporting is particularly valuable for participants <6 years and may also facilitate compliance in older children who experience high levels of pain.
J Pediatr Hematol Oncol. 2017 Jul 21. doi: 10.1097/MPH.0000000000000919. [Epub ahead of print]
New Ways to Detect Pediatric Sickle Cell Retinopathy: A Comprehensive Review.
Pahl DA1, Green NS, Bhatia M, Chen RWS.
Sickle retinopathy reflects disease-related vascular injury of the eye, which can potentially result in visual loss from vitreous hemorrhage or retinal detachment. Here we review sickle retinopathy among children with sickle cell disease, describe the epidemiology, pediatric risk factors, pathophysiology, ocular findings, and treatment. Newer, more sensitive ophthalmological imaging modalities are available for retinal imaging, including ultra-widefield fluorescein angiography, spectral-domain optical coherence tomography, and optical coherence tomography angiography. Optical coherence tomography angiography provides a noninvasive view of retinal vascular layers that could previously not be imaged and can be quantified for comparative or prospective analyses. Ultra-widefield fluorescein angiography provides a more comprehensive view of the peripheral retina than traditional imaging techniques. Screening for retinopathy by standard fundoscopic imaging modalities detects a prevalence of approximately 10%. In contrast, these more sensitive methods allow for more sensitive examination that includes the retina perimeter where sickle retinopathy is often first detectable. Use of these new imaging modalities may detect a higher prevalence of early sickle pathology among children than has previously been reported. Earlier detection may help in better understanding the pathogenesis of sickle retinopathy and guide future screening and treatment paradigms.
Am J Hematol. 2017 Jul 24. doi: 10.1002/ajh.24872. [Epub ahead of print]
Fetal Hemoglobin in Sickle Cell Anemia: The Arab-Indian Haplotype and New Therapeutic Agents.
Habara AH1, Shaikho EM1, Steinberg MH1.
Fetal hemoglobin (HbF) has well-known tempering effects on the symptoms of sickle cell disease and its levels vary among patients with different haplotypes of the sickle hemoglobin gene. Compared with sickle cell anemia haplotypes found in patients of African descent, HbF levels in Saudi and Indian patients with the Arab-Indian (AI) haplotype exceed that in any other haplotype by nearly two-fold. Genetic association studies have identified some loci associated with high HbF in the AI haplotype but these observations require functional confirmation. Saudi patients with the Benin haplotype have HbF levels almost twice as high as African patients with this haplotype but this difference is unexplained. Hydroxyurea is still the only FDA approved drug for HbF induction in sickle cell disease. While most patients treated with hydroxyurea have an increase in HbF and some clinical improvement, 10 to 20% of adults show little response to this agent. We review the genetic basis of HbF regulation focusing on sickle cell anemia in Saudi Arabia and discuss new drugs that can induce increased levels of HbF. This article is protected by copyright. All rights reserved.
© 2017 Wiley Periodicals, Inc.
J Pediatr. 2017 Jul 20. pii: S0022-3476(17)30885-5. doi: 10.1016/j.jpeds.2017.06.035. [Epub ahead of print]
Autoimmune Liver Disease in Children with Sickle Cell Disease.
Jitraruch S1, Fitzpatrick E2, Deheragoda M3, Deganello A4, Mieli-Vergani G2, Height S5, Rees D5, Hadzic N2, Samyn M6.
To assess the incidence, clinical features, and outcome of autoimmune liver disease (AILD) in patients with sickle cell disease (SCD).
Single center retrospective review of patients with SCD with AILD referred between 1999 and 2015.
Thirteen of 77 (17%) patients with SCD with hepatic dysfunction were diagnosed with AILD (median age 11, range, 3.4-16 years) with a female preponderance (77%). Acute hepatitis and insidious onset were the commonest presentations. Two patients (15%) presented with acute liver failure. In 2 patients (15%), parvovirus B19-induced transient red cell aplasia preceded the diagnosis of AILD. All patients were positive for antinuclear and/or smooth muscle autoantibodies. Six of 12 patients (50%) had cholangiopathy on cholangiogram suggesting autoimmune sclerosing cholangitis (ASC). Liver biopsy, performed in 11 patients without complications, showed interface hepatitis in 90%. Patients with AILD were treated with standard immunosuppression. After a median follow-up of 3.8 years (range, 0.2-14.3), 10 patients are alive (1 was transplanted 6.4 years after diagnosis); 2 are lost to follow-up; 1 died of subdural hemorrhage before starting treatment for AILD. Five (42%) achieved full and 4 (33%) partial biochemical remission. Ulcerative colitis, present in 4 patients (2 male patients, 3 with ASC) was diagnosed in 2 patients before and in 2 patients after the diagnosis of AILD.
AILD is not uncommon in patients with SCD, affecting mainly female patients and responding satisfactorily to immunosuppressive treatment. Liver biopsy is helpful in confirming the diagnosis and can be safely performed in the absence of acute vaso-occlusive sickling episodes. Ulcerative colitis is common in the presence of ASC.
Copyright © 2017 Elsevier Inc. All rights reserved.
Cytotherapy. 2017 Jul 18. pii: S1465-3249(17)30601-1. doi: 10.1016/j.jcyt.2017.06.002. [Epub ahead of print]
Preclinical studies for a phase 1 clinical trial of autologous hematopoietic stem cell gene therapy for sickle cell disease.
Urbinati F1, Wherley J1, Geiger S1, Fernandez BC1, Kaufman ML1, Cooper A1, Romero Z1, Marchioni F1, Reeves L2, Read E3, Nowicki B4, Grassman E5, Viswanathan S5, Wang X6, Hollis RP1, Kohn DB7.
Gene therapy by autologous hematopoietic stem cell transplantation (HSCT) represents a new approach to treat sickle cell disease (SCD). Optimization of the manufacture, characterization and testing of the transduced hematopoietic stem cell final cell product (FCP), as well as an in depth in vivo toxicology study, are critical for advancing this approach to clinical trials.
Data are shown to evaluate and establish the feasibility of isolating, transducing with the Lenti/βAS3-FB vector and cryopreserving CD34+ cells from human bone marrow (BM) at clinical scale. In vitro and in vivo characterization of the FCP was performed, showing that all the release criteria were successfully met. In vivo toxicology studies were conducted to evaluate potential toxicity of the Lenti/βAS3-FB LV in the context of a murine BM transplant.
Primary and secondary transplantation did not reveal any toxicity from the lentiviral vector. Additionally, vector integration site analysis of murine and human BM cells did not show any clonal skewing caused by insertion of the Lenti/βAS3-FB vector in cells from primary and secondary transplanted mice.
We present here a complete protocol, thoroughly optimized to manufacture, characterize and establish safety of a FCP for gene therapy of SCD.
Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.
Sickle Cell Conferences and Events
NHLBI’s Annual Sickle Cell Disease Clinical Research Meetings
Register for the National Heart, Lung, and Blood Institute’s 2017 Annual Sickle Cell Disease (SCD) Clinical Research Meetings, scheduled for August 14-16, 2017, at the Natcher Conference Center on the main campus of the National Institutes of Health in Bethesda, MD. The meeting serves as a yearly forum for investigators and health care providers to discuss new developments in scientific and clinical aspects of SCD in an informal setting. For more information and to register, please click here.
6th Annual Sickle Cell Disease Therapeutics Conference
The 6th Annual Sickle Cell Disease Conference, a forum to discover the latest advancements and future trends for sickle cell disease and drug development is scheduled for September 14, 2017, in New York, NY. Conference attendees will hear from innovative industry leaders, patients, physicians, and clinical-stage companies. To register for the conference, please visit www.SCDconference.com.
11th Annual Sickle Cell Disease and Thalassemia Conference
The 2017 Annual Scientific Conference on Sickle Cell and Thalassemia is a three-day conference aimed at all those with a common interest in sickle cell disease and thalassemia. It will be held in London on October 11-13, 2017. There will also be sessions on genetics and genomic progress, curative therapies and emerging services, as well as abstract and poster presentations. For more information and to register click here.
Join Sickle Cell Partners of the Carolinas for the 4th annual conference, “Sickle Cell Disease… Let’s Talk About It”
Saturday September 9, 2017 | 8 am to 2 pm | Charlotte, NC
Friendship Missionary Baptist Church Conference Center
3400 Beatties Ford Road, Charlotte NC 28216
This day conference will feature a myriad of topics designed to engage patients, families and the at-large community and to build broader awareness about the challenges of sickle cell disease and how patients and families may be able to get beyond those challenges. Keynote Luncheon Speaker: Howard University President, Wayne A.I. Frederick, M.D., MBA.
Friendship Missionary Baptist Church Conference Center Charlotte, North Carolina. Cost is $5 for participants.
For more information, visit our website www.sicklecellpartnersofthecarolinas.org and register for the event at http://scpocconference2017.eventbrite.com
Pediatric Sickle Cell Mini Symposium: The School-Aged Child
Saturday, September 9, 2017 7:45 a.m. to 3:15 p.m. Atlanta,GA
Who Should Attend:The conference will benefit pediatricians, family practice physicians, advanced practice providers (NP’s, PA’s), nurses, fellows, and residents. Other healthcare professionals involved in the care of pediatric patients with sickle cell disease mayfind the information useful and are welcome to attend.
The purpose of this symposium is to update pediatricians and family practitioners
on the most current research and clinical guidelines related to pediatric sickle cell
disease, particularly in the school-aged child, and to discuss key considerations
when caring for these patients.
Location & Accommodations Emory Health Sciences Research Building
1760 Haygood Drive NE Atlanta, Georgia 30322
For more information, contact email@example.com.
SCDAA 45th Annual National Convention on Sickle Cell Disease
With over 447 researchers, physicians, nurses, socials workers, individuals living with SCD & SCT and more we are excited to reunite with you again on October 25-28, 2017
The SCDAA Annual Convention is a four-day conference designed to address the multi-factorial aspects of Sickle Cell Disease. This year the event will be held in Atlanta, Georgia, a city near and dear to the sickle cell community! https://www.sicklecelldisease.org/2017/03/07/45th-annual-national-convention/
The 11th Sickle Cell in Focus Conference
26-27, October 2017
We are pleased to announce that Sickle Cell in Focus (SCiF) will be held for the first time in Kingston, Jamaica on October 26-27, 2017. This year, SCiF will be co-hosted by the National Heart, Lung, and Blood Institute and the University of West Indies, Jamaica. SCiF is a two-day, intensive, educational update on sickle cell disease. This year’s conference will focus on the latest clinical trials, the science and mechanisms for new therapeutic targets, and curative therapies. This two-day intensive educational conferences includes both clinical and scientific lectures, aimed at clinicians, academics, and other healthcare professionals involved in sickle cell disease around the world. Contact Rusinel Amarante | firstname.lastname@example.org