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In: American Journal of Hematology, Wiley, Vol. 92, No. 9 ( 2017-09)

Abstract: Nephropathy is a common and progressive complication of sickle cell anemia (SCA). In SCA mice, we found that hyperangiotensinemia in the absence of hypertension underlies nephropathy, and its downregulation by losartan, an angiotensin‐II‐receptor‐1 blocker, reduced albuminuria and progression of nephropathy. Therefore, we performed a phase‐2 trial of oral losartan, given for 6 months, to explore whether it reduced albuminuria in children and adults with SCA. Participants were allocated to groups defined by class of baseline urinary albumin‐to‐creatinine ratio (UACR): no albuminuria (NoA), microalbuminuria (MicroA), and macroalbuminuria (MacroA). The primary endpoint was a ≥25% reduction UACR from baseline. There were 32 evaluable participants (mean age 24 years; NoA = 14, MicroA = 12, MacroA = 6). The primary endpoint was met in 83% of the MacroA group ( P   〈  0.0001) and 58% of the MicroA group ( P   〈  0.0001). Median fold‐change in UACR was −0.74 for MacroA and −0.46 for MicroA. In MacroA and MicroA, UACR classification improved in 50% but worsened in 11%. Urine osmolality and estimated glomerular filtration rate (eGFR) did not change significantly. Losartan was discontinued in three participants [leg cramps, N  = 1; decline in eGFR 〉 25% (142➝104 mL/minute/1.73 m 2 ), N  = 1; rise in serum creatinine 〉 50% (0.2➝0.3 mg/dL), N  = 1]. Albuminuria was associated with diastolic dysfunction and impaired functional capacity, although cardiopulmonary status was unchanged after 6 months of losartan therapy. In summary, losartan decreased urinary albumin excretion in most participants with albuminuria. Those with macroalbuminuria had the greatest benefit. This study forms the basis for a phase‐3, randomized, placebo‐controlled trial of losartan for the nephropathy of SCA.

Type of Medium: Online Resource

ISSN: 0361-8609 , 1096-8652

URL: Issue

URL: Article

DOI: 10.1002/ajh.v92.9

DOI: 10.1002/ajh.24810

Language: English

Publisher: Wiley

Publication Date: 2017

detail.hit.zdb_id: 1492749-4

In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 4284-4284

Abstract: Background: Sickle cell anemia (SCA) is a genetically inherited disorder that can lead to severe sequelae in any organ system. The most clinically devastating complications, e.g. stroke, are managed with chronic red blood cell (RBC) transfusions as curing the underlying SCA is often not an option. Chronic RBC exchange (RBCx), is an effective alternative to simple transfusions and often performed every 4-5 weeks. Isovolemic Hemodilution-Red Blood Cell Exchange (IHD-RBCx) is a modified RBCx method used at UT Southwestern Medical Center (UTSW) and increases the time interval between transfusions, i.e. inter-procedure interval (IPI), up to 9 weeks while maintaining the desired hemoglobin S targets at safe levels. This minimizes the overall lifetime procedures and blood exposures. The standard operating procedure for IHD-RBCx is published (Matevosyan et al, 2012). However, we observed IPI variability between patients in this chronic IHD-RBCx program. We sought to analyze hematologic characteristics in a cohort of adult SCA patients that may be associated with this noted variability. Methods: This IRB approved cross-sectional study evaluated medical and blood bank records of adult patients with SCA, i.e. hemoglobin SS or Sβ0 thalassemia genotypes, undergoing chronic IHD-RBCx at UTSW adult hospital sites between January 1, 2012 and December 31, 2013. Excluded participants were those with autoimmune disease, non-compliance with IHD-RBCx leading to delays 〉 7 days, or use of hydroxyurea or steroids within four months of the study period. Patients with 〈 5 exchanges were excluded as several procedures are needed to determine baseline IPIs. The primary indication for IHD-RBCx was secondary stroke prevention. Three subjects had alternative indications (i.e. recurrent severe acute chest syndrome that failed hydroxyurea therapy, intractable pain and severe anemia ineligible for iron chelation due to end-stage renal disease). Median values during the 2 year study were determined for the IPI, laboratory, and RBC properties for use in subsequent analyses. Correlation and multiple regression analyses were performed to determine variables predictive of IPI. Results: Twenty-four SCA patients in this chronic IHD-RBCx transfusion program met inclusion criteria of which 14 (58.3%) were female with age range 18-41 years. Three subjects had incomplete data. The median number of packed RBC (pRBC) units per IHD-RBCx was 8 (range: 6-11 units). The median volume per unit of pRBCs was 304.5 mL (range: 298.8-326.5 mL) with average age of the pRBCs 5.8 days ± 0.7 days. The median IPI was 55.8 days (range: 36.0-65.5 days). The strongest correlation with IPI was the change from the mid to post-procedure hemoglobin and hematocrit values, r=0.56, p=0.005 and r=0.57, p=0.003, respectively. Participants with documented direct antiglobulin test positivity (n=7), compared to those who remained negative (n=16), had 4.9 days increased IPI. This difference was not statistically significant, p=0.19. ABO differences in blood type also did not show statistical significant differences. However, A+ subjects had a 58 day interval compared to 51, 52, 53 days for B+, O+, O- respectively (Figure). In multiple regression models, log blood urea nitrogen (BUN) and post-procedure white blood cell count (WBC) were found to be independent predictors of IPI, beta=-11.3, p=0.04 and -2.1, p=0.03 respectively, with adjusted R2=0.31. Conclusions: Chronic IHD-RBCx effectively treats severe SCA complications. Discontinuing transfusions lead to repeat stroke events or the recurrence of disease manifestations making chronic transfusion programs an indefinite therapy. Outside of the expected correlation between the IPI and hemoglobin/hematocrit, WBC and BUN were found to have negative associations with IPIs. The decrease in WBCs is likely due to the direct clearing effect by the operating system. The association between BUN and IPI may imply relationship with renal function. Interestingly, association with creatinine was not statistically significant. The study is limited by the small sample size. Future studies of similar cohorts should prospectively evaluate target mechanisms which may lead to interventions that can minimize lifetime blood exposures given the growing demands for continued RBCx in severe SCA. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V124.21.4284.4284

Language: English

Publisher: American Society of Hematology

Publication Date: 2014

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 559-559

Abstract: Background: The natural history of sickle cell disease (SCD) includes premature death. Advancements in care, such as penicillin prophylaxis, have made death during childhood uncommon. Prior survival estimates for adults with SCD have been limited by survival bias (subjects enrolled as adults) or the limitations of administrative data. No prior study has estimated survival for adults with SCD from a newborn cohort. Herein, we report an continued observation of subjects in the Dallas Newborn Cohort (DNC)1. Methods: The DNC is an inception cohort of patients with SCD defined by: (1) diagnosis by Texas newborn screening after October 31, 1983; (2) evaluation in the pediatric sickle cell program at UT Southwestern (UTSW) / Children’s Medical Center Dallas (CMCD); and (3) confirmation of SS, SC, Sβ0 or Sβ+ genotype. Patients followed at CMCD are transitioned to adult care before the 19th birthday. To identify transitioned patients or those lost to follow-up (LTFU), we reviewed the medical records at Parkland Memorial Hospital (PMH) and UTSW University Hospital (UH), the public and private hospitals affiliated with CMCD and the most common care-sites for transitioned patients. In addition, for patients no longer actively followed at CMCD, we queried the National Death Index (NDI). The NDI is a centralized database of death records obtained from all state vital statistic bureaus in the US and is maintained by the National Center for Health Statistics. As of our query in April 2014, deaths occurring from 1/1/79 - 12/31/11 were available in the NDI. Probabilistic matching is performed by the NDI to identify subjects using identifiers such as name, social security number, birthdate, gender, state of birth, and race. Patients who were LTFU or transitioned to adult care were censored at 12/31/11 or the date of their last clinical encounter, whichever occurred latest. Patients actively followed at CMCD, PMH, or UH were censored at 12/31/13. In addition to descriptive statistics, we constructed survival curves using the Kaplan-Meier method to evaluate overall survival and survival by genotype. Also, Cox Proportional Hazard modeling was used to assess genotype, baseline hemoglobin, baseline reticulocyte count (%), and baseline oxygen saturation as potential predictors of early mortality. To test the sensitivity of the NDI to identify deceased individuals, we submitted 36 known deaths from the cohort. Results: The DNC is now comprised of 1214 patients with 16,636 years of follow-up. The cohort is 49.2% female with a mean age, and duration of follow-up, of 13.2 years (Range 0.1 – 30.0 years). SCD genotypes included 60.5% HbSS, 30.6% HbSC, 6.8% HbSβ+, and 2.1% HbSβ0. Of the 1214 patients in the cohort, 511 were active in the pediatric program, 195 were in the pediatric age range but had moved or were LTFU, 238 were adults with 1 or more visits at PMH or UH, 234 were adults with no subsequent identifiable clinical encounters, and 36 were deceased. Of 36 known deaths submitted to the NDI, 34 were identified by their databases (94.4% sensitivity). Of the 606 patients who were LTFU or aged out of the pediatric program, only 10 were reported to have died by the NDI. One of them was confirmed to be erroneous because the patient had clinical encounters after the NDI-reported date of death. In addition to these 9 deaths in the NDI, 8 additional patients were known to have died as of 12/31/13, bringing the total number of deaths to 53 (4.3%). Of these, 21 (39.6%) have been identified since the last cohort update in 2007. Overall survival in the DNC to age 25 years was 91.4% (95% CI: 88.4%, 93.7%) for all members (Figure), 87.7% (95% CI: 83.3%, 91%) for those with HbSS or HbSβ0, and 98.6% (95% CI: 96.7%, 99.4%) for those with HbSC or HbSβ+. In univariate analysis, early mortality was associated with SS or Sβ0 genotypes (compared to HbSC or HbSβ+), lower baseline hemoglobin, and low baseline SpO2 but not gender or reticulocytes. In multivariate analysis, early mortality was associated with only lower baseline hemoglobin (Hazard Ratio 0.76 [95% CI 0.59, 0.98], P=0.037). Conclusions: These are the first modern estimates of survival into adulthood with an unbiased newborn cohort of SCD patients. Early mortality is associated with low baseline hemoglobin. Survival to age 20 remains excellent at 95% but the mortality rate appears to accelerate in early adulthood. Reference: 1. Quinn et al. Blood. 115(17):3447-52, 2010. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V124.21.559.559

Language: English

Publisher: American Society of Hematology

Publication Date: 2014

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 140, No. Supplement 1 ( 2022-11-15), p. 8276-8277

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2022-169334

Language: English

Publisher: American Society of Hematology

Publication Date: 2022

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 136, No. Supplement 1 ( 2020-11-5), p. 3-5

Abstract: Background: Sickle cell disease (SCD) is associated with many clinical complications, with vaso-occlusive crises (VOCs) being a hallmark of the disease. SCD-related complications are largely driven by vaso-occlusion and hemolytic anemia, and can lead to end-organ damage and early death. Analyses of SWAY, a cross-sectional survey, highlighted a substantial global impact of SCD on patients' quality of life (QoL) (James et al. ASH 2019; Osunkwo et al. ASH 2019). However, understanding how the burden of disease differs for pts of different ages could help improve management of SCD over a pt's lifespan. Aim: To assess, using data from SWAY, whether symptoms (excluding VOCs, as previously analyzed by Osunkwo et al. EHA 2020), treatment goals and the perceived impact of SCD were different for pts of different ages. Methods: Between April and October 2019, 2145 SCD pts aged ≥6 years participated in SWAY. The survey was completed by proxy (parent/caregiver/guardian) for pts aged 6-11 years and could be optionally self-completed by pts aged ≥12 years. Opinions were captured using a 1-7 Likert scale for some questions (5-7 indicated high satisfaction/impact/agreement). SWAY was not designed to assess treatment outcomes; all analyses are descriptive. Age groups were not matched and pts were not followed over time. Results: To understand how the most dominant symptoms of SCD differ for pts of different ages, the top 5 most commonly reported symptoms, stratified by age, were analyzed (Figure 1). Fatigue and bone aches were consistently reported, and the proportion of pts reporting them trended towards increasing with age. Furthermore, when asked which symptoms they most wanted to be resolved, fatigue was ranked in the top 3 by 40.7% of pts. Anxiety was a dominant symptom for pts aged 19-25, 36-45 and 46-50 years, whereas low mood was a dominant symptom for pts aged 19-50 and ≥60 years. Poor appetite was a dominant symptom for pts aged 6-16 years. Breathing issues were a dominant symptom for pts aged 6-18, 46-50 and ≥60 years, whereas vision issues were a dominant symptom for pts aged 51-59 years only. Insomnia was dominant for pts aged 46-50. The treatment goals that pts ranked as the most important were similar across age groups. Pts consistently included improving QoL, preventing worsening of SCD, reducing the number of VOCs and improving overall symptoms in their top 3, although the proportions of pts reporting these varied across age groups (Figure 2). Unsurprisingly, 23.0% of pts aged 12-16 years ranked increasing the ability to attend school in their top 3 goals. For pts aged 46-50 and 51-59 years, 27.5% and 20.7%, respectively, ranked reducing fatigue in their top 3 treatment goals. The highest proportions of pts reporting a high impact of SCD on their emotional wellbeing were aged 46-50 years (74.5%) and ≥60 years (73.9%), compared with 59.6% of all pts. Similarly, the highest proportions of pts reporting a high impact of SCD on daily activities were aged 46-50 years (51.0%) and ≥60 years (60.9%), compared with 38.1% of all pts. Limitations: These findings are based on pt and proxy reports, with potential parental bias being introduced for pediatric patients. There were variations in sample sizes, which was most noticeable for patients aged ≥46 years. Discussion: Fatigue and bone aches were consistently reported as dominant symptoms for all ages. Other dominant symptoms that were not consistent across age groups were anxiety, low mood, poor appetite, breathing issues and vision issues. In addition to the 36-45 years and 46-50 years groups, anxiety was a dominant symptom for pts aged 19-25 years. Along with other changes that could occur at this age, a recent transition from pediatric to adult care may contribute to anxiety being a dominant symptom; however, any direct relationship between anxiety and transitioning between care systems requires further investigation. The consistent reporting of low mood among adults, but not pediatrics, may reflect the increasing burden of disease that occurs with age. This is supported by higher proportions of pts aged ≥46 years versus & lt;45 years reporting a high impact on emotional wellbeing and daily life. Improving QoL was consistently ranked the most important treatment goal for pts. This emphasizes, from the pt's perspective, the need for further improvements in the management of SCD. Disclosures Colombatti: Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Addmedica: Membership on an entity's Board of Directors or advisory committees. James:Sickle Cell Society: Current Employment; Novartis: Honoraria. Andemariam:Hemanext: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; CHNCT: Consultancy; CRISPR/Vertex: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Cyclerion: Consultancy, Membership on an entity's Board of Directors or advisory committees; Accordant: Membership on an entity's Board of Directors or advisory committees; Guidepoint: Honoraria; Global Blood Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; NovoNordisk: Consultancy, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Terumo BCT: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sanofi Genzyme: Consultancy, Membership on an entity's Board of Directors or advisory committees; Imara: Research Funding; Vertex: Honoraria; Emmaus: Membership on an entity's Board of Directors or advisory committees; bluebird bio: Consultancy, Membership on an entity's Board of Directors or advisory committees. Inusa:Vertex: Research Funding; Bluebird bio: Research Funding; AstraZeneca: Honoraria, Other: Steering committee participation, Research Funding, Speakers Bureau; Global Blood Therapeutics: Honoraria, Other: Steering committee participation, Research Funding, Speakers Bureau; Novartis: Honoraria, Other: Steering committee participation, Research Funding, Speakers Bureau. El Rassi:Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Cyclerion: Research Funding; Pfizer: Research Funding; Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees; Bluebird bio: Membership on an entity's Board of Directors or advisory committees. Francis-Gibson:Sickle Cell Disease Association of America: Current Employment. Nero:Bluebird bio: Consultancy; Novartis: Consultancy. Minniti:Global Blood Therapeutics: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Roche: Consultancy, Research Funding; TauTona: Consultancy, Research Funding; Bluebird bio: Consultancy, Research Funding; Emmaus: Consultancy, Research Funding; CLS Bering: Consultancy. Trimnell:Novartis: Consultancy; Cyclerion: Consultancy; Global Blood Therapeutics: Consultancy. Abboud:Amgen: Other: Travel support; Novo Nordisk: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Crispr Therapeutics: Membership on an entity's Board of Directors or advisory committees; Global Blood Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Eli Lilly: Research Funding; Modus Pharmaceuticals: Research Funding. Arlet:Novartis: Consultancy, Honoraria. de Montalembert:Addmedica: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bluebird bio: Honoraria, Membership on an entity's Board of Directors or advisory committees; Vertex: Honoraria, Membership on an entity's Board of Directors or advisory committees. Jain:Thalassemia and Sickle Cell Society: Other: Chief Medical Research Officer and Secretary. Jastaniah:Novartis: Consultancy, Honoraria. Nur:Novartis: Consultancy. Ramscar:Novartis Pharma AG: Current Employment. Bailey:Novartis: Other: Employee of Adelphi Real World, which has received consultancy fees from Novartis; Adelphi Real World: Current Employment. Rajkovic-Hooley:Adelphi Real World: Current Employment; Novartis: Other: Employee of Adelphi Real World, which has received consultancy fees from Novartis. Osunkwo:Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Terumo: Consultancy; Global Blood Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Acceleron: Membership on an entity's Board of Directors or advisory committees; FORMA Therapeutics: Membership on an entity's Board of Directors or advisory committees; Health Resources and Services Administration (HRSA): Research Funding; Patient Centered Outcomes Research Institute (PCORI): Research Funding; Data and Safety Monitoring Board (DSMB) membership for Micella Biopharma: Membership on an entity's Board of Directors or advisory committees.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2020-136073

Language: English

Publisher: American Society of Hematology

Publication Date: 2020

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 128, No. 22 ( 2016-12-02), p. 265-265

Abstract: Background: Sickle nephropathy (SN) is a common and progressive manifestation of sickle cell anemia (SCA). Albuminuria indicates glomerular injury and portends renal failure. In a murine model of SCA, we found that increased TGF-Beta signaling underlies SN, and its downregulation by losartan, an angiotensin receptor blocker, reduced albuminuria and SN progression. The effect of losartan in humans with SCA has not been studied. We performed a phase-2, open-label study to inform the design of a phase-3 randomized trial to estimate the effect of losartan on SN. We also explored the effect of losartan on the cardiac phenotype of SCA. Methods: Oral losartan was administered for 6 months to individuals with SCA (HbSS or SBeta0-thalassemia) 〉 6 years of age. Main exclusion criteria: chronic transfusions, GFR 〈 60 mL/min/1.73m2, hyperkalemia, and contraindications to losartan. Enrollment was in 3 groups defined by urinary albumin-to-creatinine ratio (UACR): no albuminuria (NoA: 〈 30mg/g); microalbuminuria (MicroA: 30-300); and macroalbuminuria (MacroA: 〉 300). The primary endpoint was a 〉 25% reduction UACR from baseline. Sample size was calculated to detect the primary endpoint in 〉 30% of the MicroA group with 〉 80% power. Secondary endpoints: urine osmolality, GFR, UACR classification and toxicity, and cardiac phenotyping by echocardiography and assessment of 6-minute walk distance (6MWD). Results: There were 36 participants (mean age 24.1y; 53% female) in 3 groups (NoA=15; MicroA=13; MacroA=8). Four were not evaluable based on pre-specified criteria (marked non-compliance and/or early termination). The primary endpoint ( 〉 25% reduction in UACR) was met in 83% (5/6) of the MacroA group, 58% (7/12) of the MicroA group, and 7% (1/14) of the NoA group (FigureA). The median fold-change in UACR was -0.74, -0.46, and 0.08 for the MacroA, MicroA, and NoA groups, respectively (FigureB). Among MacroA and MicroA participants, 67% (12/18) met the primary endpoint (FigureC). In MacroA and MicroA participants, UACR classification improved (MacroAˆMicroA or MicroAˆNoA) in 50% but worsened in 11%. Mean UACR was 202 mg/g (S.E.M. 59, median 50) before and 137 (S.E.M. 47, median 16) after losartan (P=0.29). Urine osmolality and GFR did not change significantly (393 vs 370 mosm/kg H20, P=0.11; 147 vs 139 mL/min/1.73m2, P=0.43). Losartan was discontinued for leg cramps (N=1); GFR decline 〉 25% (N=1); and serum creatinine rise 〉 50% (N=1). Interestingly, compared to those with NoA, participants with albuminuria (MicroA and MacroA, mean UACR 373±87 mg/g) had worse diastolic function indicated by lower early-to-late ratio of mitral inflow velocities, E/A (1.81±0.1 vs 2.3±0.1, P=0.018), and septal annular velocities ratio, e'/a' (1.5±0.2 vs 2.4±0.2, P 〈 0.001), and significantly larger left atrial volumes (57.2±3.1 vs 38.9±3.7 ml, P 〈 0.001). Systolic function was normal and similar in both groups (shortening fraction 36.9±2% vs 36.7±1.5%, P=0.94). There was no difference in tricuspid regurgitant jet velocity, left ventricular (LV) mass, or LV diameter. Participants with albuminuria had significantly shorter 6MWD (1182±78 vs 1472±86 ft, P=0.018), which correlated significantly with the diastolic measures E/A and septal e'/a' (P=0.013 and P=0.015, respectively). There was no change in echocardiographic parameters after losartan therapy. Conclusions: Losartan appeared to decrease SCA-related albuminuria in most participants. Those with baseline macroalbuminuria appeared to have the greatest benefit, nearly all of whom showed a response. Albuminuria, a marker of sickle nephropathy, is also associated with evidence of restrictive cardiac physiology, suggesting common underlying mechanisms. However, the short 6-month treatment with losartan had no obvious effects on the cardiac phenotype of SCA. A phase-3, randomized, placebo-controlled trial is being designed to determine the efficacy of losartan in SCA. [This work was supported by NIH R34 HL 108752 (PI: Malik, P)]. Figure Figure. Disclosures Quinn: Silver Lake Research Corporation: Consultancy; Eli Lilly: Research Funding; Amgen: Research Funding. Raj:Novartis: Speakers Bureau.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V128.22.265.265

Language: English

Publisher: American Society of Hematology

Publication Date: 2016

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 120, No. 21 ( 2012-11-16), p. 4753-4753

Abstract: Abstract 4753 Introduction For many patients with sickle cell anemia (SCA), jaundice, yellow discoloration of the skin and mucous membranes, may be the most visible manifestation of their disease. The degree to which jaundice impacts the daily lives of patients with SCA has not been previously described. This study aims to assess the effect of jaundice on the health-related quality of life (HRQOL) of adults living with SCA. Methods This study was a cross-sectional survey of patients with SCA. A convenience sample of patients age 〉 17 years with SCA were approached during routine clinic visits to Parkland Memorial Hospital or UT Southwestern University Hospitals. Consenting patients completed a 15 question survey instrument. The survey was divided into three subscales (personal, relational, and behavioral) where individual items were presented in a 5-point Likert scale. This instrument was reviewed by non-study hematologists, nurses and patients for face validity. No other assessment of reliability or validity was performed. Additional data collected included serum total bilirubin (TB), hemoglobin, reticulocyte count (%) and patient self-report of current treatment for SCA (hydroxyurea [HU], chronic blood transfusions, or other). We tested for associations between survey subscales and TB, reticulocyte count, or hemoglobin using Spearman correlation coefficients. We compared the Spearman correlations of the survey subscales and TB between treatment and non-treatment groups using the Fisher's z transformation. Gender and age adjustments were made using linear regression. TB was transformed by natural log for regression analysis. Results We surveyed 100 subjects (58% female) with SCA. The median age was 25 years (range: 18–63), and the median TB was 2.5 mg/dL (range: 0.4–13.8). Nearly half of patients reported receiving treatment with 28% on HU and 14% on chronic transfusions. The majority of patients reported a history of jaundice, with 79% listing responses of ‘sometimes’, ‘often’, or ‘always’. Summary results for the remainder of the survey are listed in the table. TB was positively correlated with the 3 subscales (personal, r=0.32, p=0.002; relational, r=0.38, p=0.0002; behavioral, r=0.31, p=0.003). We compared these correlations between ‘treatment’ and ‘no treatment’ groups and observed strong correlations in the ‘no treatment’ group (personal, r=0.55, p 〈 0.0001; relational, r=0.63, p 〈 0.0001; behavioral, r=0.52, p=0.0002). TB was not correlated with the subscales in the ‘treatment’ group. After adjusting for age, gender, and disease-modifying therapy, the three subscales were associated with TB (personal, β = 0.066, 95% Confidence Interval (CI) [0.027, 0.104], p=0.001; relational, β = 0.061, 95% CI [0.031, 0.092] , p=0.0001; behavioral, β = 0.104, 95% CI [0.045, 0.164], p=0.0009). Conclusion Jaundice negatively impacts the lives of many adults with SCA. The personal and relational subscales suggest more impact on the self-image of respondents, but only a few reported behavioral changes. The impact of jaundice appears to be mitigated by disease-modifying therapy for SCA (HU or chronic transfusions); however, this study was not created to determine the effectiveness of these reported treatments. Despite the fact this instrument was not validated, our study results suggest jaundice should be well-represented in HRQOL assessment tools in adults with SCA. Moreover, prospective studies are needed to clarify potential benefits of disease-modifying therapies, particularly HU, on the burden of jaundice in SCA. Disclosures: Buchanan: HemaQuest Pharmacuetical, Inc.: Research Funding.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V120.21.4753.4753

Language: English

Publisher: American Society of Hematology

Publication Date: 2012

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 138, No. Supplement 1 ( 2021-11-05), p. 3100-3100

Abstract: Background: Sickle cell disease (SCD) is an inherited systemic disorder in which sickle hemoglobin (HbS) polymerization triggers red blood cell sickling, chronic hemolytic anemia, and recurrent episodes of vaso-occlusion. SCD-related complications lead to acute and chronic life-threatening events, cumulative organ damage, disability, and early mortality. Voxelotor (Oxbryta ®) tablets are approved in the United States for treatment of SCD in adults and adolescents aged ≥12 years, based on the efficacy and safety data from the randomized, placebo-controlled, multicenter HOPE trial. Voxelotor is an oral, once-daily HbS-polymerization inhibitor that has been shown to increase hemoglobin (Hb) levels and reduce markers of hemolysis. The Retrospective Study to Evaluate Outcomes in Patients with Sickle Cell Disease Treated with Oxbryta (RETRO) is designed to collect, aggregate, and characterize real-world, retrospective laboratory and clinical data on adults and adolescents with SCD treated with voxelotor as part of their usual care at multiple clinical centers in the United States. Methods: RETRO is a multicenter, post-marketing, retrospective study of approximately 300 patients (aged ≥12 years) with SCD from 10 US study sites. Independent SCD expertise is provided by a steering committee to inform the design and conduct of the voxelotor registry. Clinical and laboratory data have been collected and aggregated 12 months before initiation of voxelotor treatment and compared with post-treatment data outcomes. Patients with documented SCD (all genotypes) who received voxelotor treatment for ≥2 consecutive weeks were included in this analysis. Only data available from patients' medical records (and other secondary data sources) 1 year before and up to 1 year after the first voxelotor dose were documented in de-identified case report forms via an electronic data capture system. Results: Forty-nine patients whose data were entered at 5 sites at the time of data cutoff (June 25, 2021) were included (mean age [SD]: 34.3 [12.91] years; 57.1% female; 85.7% HbSS and 6.1% HbSβ 0 genotype). Mean (SD) duration of voxelotor treatment was 48.1 (23.0) weeks. The initial prescribed voxelotor dose strengths (n, %) were 500 mg (4, 8.2%), 1000 mg (7, 14.3%), and 1500 mg (38, 77.6%). Rationale for prescription (n, %) included reduction of anemia (36, 73.5%), reduction in frequency of vaso-occlusive crises (23, 46.9%), reduction in pain (34, 69.4%), reduction in the need for blood transfusion (8, 16.3%) and other (5, 10.2%); more than 1 reason may have been selected. In 35 patients with recorded baseline and post-treatment Hb values, the peak observed post-treatment Hb (mean [SD]) was 9.4 (2.44) g/dL, an increase of 1.6 (1.5) g/dL from baseline (7.8 [2.02] g/dL). Fifty percent (11/22) of patients had a clinical response (Hb increase of & gt;1.0 g/dL from baseline) within 12 months of voxelotor treatment. Per-patient peak changes in Hb during the study period showed that 62.9% of patients experienced a response at some time up to 12 months during treatment (Figure). Change in hemolytic markers was also evaluated. In patients with recorded baseline and post-treatment reticulocyte percentage (N=19) and indirect bilirubin (N=24), the mean (SD) absolute post-treatment value was 7.4% (4.65%) for reticulocyte percentage, a decrease of 4.9% (6.63%) compared with baseline (12.4% [8.32%]), and 1.9 (1.66) mg/dL for indirect bilirubin, a decrease of 17.7 (81.83) mg/dL compared with baseline (19.6 [81.82] mg/dL). The most common non-SCD-related treatment-emergent adverse events (AEs) were diarrhea, headache, and rash (Table); 19 (38.8%) patients reported ≥1 AE, and most non-SCD-related AEs were mild in severity. Conclusions: RETRO is the first multicenter, retrospective study to examine the real-world effectiveness of voxelotor and describe the observed changes in laboratory and clinical outcomes after ≥2 weeks of therapy. This study shows that voxelotor treatment was associated with increased Hb levels and decreased hemolytic markers. The safety data are consistent with those from the HOPE trial. Further evaluation is needed, with additional data from all 10 sites, and will be presented later. Funding: This study was supported by Global Blood Therapeutics. Figure 1 Figure 1. Disclosures Achebe: Fulcrum Therapeutics: Consultancy; Pharmacosmos: Membership on an entity's Board of Directors or advisory committees; Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees. Clay: GBT: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria. Nero: Global Blood Therapeutics: Consultancy; Editas Medicine: Consultancy; bluebird bio: Consultancy; Novartis: Consultancy. Osunkwo: Terumo: Consultancy; Global Blood Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Acceleron: Consultancy; Forma Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Health and Services Administration: Research Funding; Patient Centered Outcomes Research Instituted: Research Funding; Micella Biopharma: Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Chiesi: Consultancy; Cyclerion: Consultancy; Emmaus: Consultancy. Idowu: Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Ironwood: Research Funding; Forma Therapeutics, Inc.: Research Funding; Pfizer: Research Funding. Shah: Novartis: Research Funding, Speakers Bureau; Alexion: Speakers Bureau; Emmaus: Consultancy; GBT: Consultancy, Research Funding, Speakers Bureau; Guidepoint Global: Consultancy; CSL Behring: Consultancy; GLG: Consultancy; Bluebird Bio: Consultancy. Curtis: GBT: Consultancy. Minniti: Bluebird Bio: Other: Endpoint adjudicator ; F. Hoffmann-La Roche Ltd: Consultancy; Chiesi: Consultancy; Novo Nordisk: Consultancy; Forma: Consultancy; Novartis: Consultancy; GBT: Consultancy; CSL Behring: Other: Endpoint adjudicator .

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2021-153459

Language: English

Publisher: American Society of Hematology

Publication Date: 2021

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 138, No. Supplement 1 ( 2021-11-05), p. 3026-3026

Abstract: Background: SCD is an inherited blood disorder that for many patients (pts) has a high clinical burden, results in poor quality of life (QoL), and reduces life expectancy. Gaining a deeper understanding of pt and HCP experiences of SCD is important to improve pt management. Aims: SWAY was a cross-sectional survey that assessed pt and HCP experiences of SCD. Here we focus on the experiences of HCPs from various regions on SCD symptoms and complications, impact of SCD on QoL, treatment goals and treatment satisfaction. Methods: SWAY was developed by international SCD expert physicians, pt advocates and Novartis. HCPs completed the survey between Apr and Oct 2019. Eligible HCPs had qualified in their primary specialty by 2014 and were managing ≥10 SCD pts at the time of survey (≥5 pts per HCP in Canada; ≥2 pts in the Netherlands). Responses to questions on how much SCD impacts pt QoL, and on HCP treatment satisfaction, were ranked on a Likert scale (1-7, where 1=not at all/strongly dissatisfied, 7=a great deal/strongly satisfied; 5-7 indicated high impact/satisfaction). The data reflect only the experiences of the surveyed HCPs in each region (recruited by Adelphi Real World fieldwork). A limitation is that Asia and South America (SA) were represented by single countries (India and Brazil, respectively). Results: SWAY was completed by 365 HCPs from 6 regions (Table). In all regions HCPs recognized the prevalence of acute and chronic pain, however acute pain was reported less frequently by HCPs in Africa than in other regions (Table). Acute chest syndrome and joint issues were among the top 5 most frequently mentioned complications by HCPs in all regions. Globally, HCPs recognized the high impact of SCD symptoms and complications on pt QoL and the high negative impact of SCD on pt emotional wellbeing (Likert score 5-7 reported by 79-100% and 71-97%, respectively). Fewer HCPs in the Middle East (ME) reported a high impact of SCD on physical and sexual activity, compared with HCPs in other regions. Around 40% of HCPs in the ME and Asia thought SCD has a high impact on daily activities, compared with 79-90% of HCPs in other regions. In Asia, fewer HCPs reported that SCD has a high impact on pts' education and ability to maintain a job compared with HCPs in other regions (Figure). Hydroxyurea (HU) was among the top 3 most common therapies ever initiated and was the therapy most likely to be initiated in any age group by HCPs in almost all regions. In Africa, the most common therapy ever initiated and the therapy most likely to be initiated in any age group was opioids (Table). Fewer HCPs in North America (NA; 32%) and SA (27%) were highly satisfied with current SCD treatments, compared with HCPs in other regions (46-72%). The main reason for dissatisfaction was limited treatment options in all regions except Asia, where HCPs said they were unable to reach their treatment goals with current therapies. Improving pts' QoL was among the top 3 treatment goals for 51-84% of HCPs across all regions. For HCPs in NA and the ME, the most important goal when treating vaso-occlusive crises was to improve QoL; in SA, Europe and Asia it was to avoid organ damage; and in Africa it was to eliminate pain completely. Discussion: The top 5 most frequent SCD symptoms and complications that HCPs reported were similar across all regions. There were regional differences in HCP experiences of how SCD impacts aspects of pts' daily life, with fewer HCPs in the ME reporting a high impact on physical and sexual activity, and fewer HCPs in Asia and the ME reporting a high impact on daily activities compared with other regions. This may be due to cultural variations, with pts in these regions being less comfortable discussing these topics with HCPs. There was a difference in the reported impact of SCD on school and work between HCPs in Asia and other regions, which could be due to varying expectations regarding school/work productivity. HU was one of the top 3 most common treatments ever initiated by HCPs for pts of any age, except in Africa, which may be due to an educational knowledge gap about HU, high cost, or poor access in this region. HCPs in almost all regions, except Asia, were dissatisfied with current SCD treatments because of limited therapeutic options, indicating a global unmet need for additional treatment choices. Improving QoL was the most important treatment goal for HCPs in all regions, demonstrating the high negative impact that SCD has on pt QoL and the ongoing need for methods to address this. Figure 1 Figure 1. Disclosures Osunkwo: Novartis Pharmaceuticals: Consultancy, Honoraria, Speakers Bureau; FORMA Therapeutics: Consultancy; Global Blood Therapeutics: Consultancy, Speakers Bureau; Chiesi: Consultancy; Acceleron: Consultancy; Cyclerion: Consultancy; Emmaus: Consultancy. Minniti: Roche: Consultancy, Honoraria; NovoNordisk: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; GBT: Consultancy, Research Funding. Nur: Roche: Speakers Bureau; Celgene: Speakers Bureau; Novartis: Research Funding, Speakers Bureau. Nero: Global Blood Therapeutics: Consultancy; Editas Medicine: Consultancy; bluebird bio: Consultancy; Novartis: Consultancy. Colombatti: Global Blood Therapeutics: Research Funding; Addmedica: Consultancy; Forma Therapeutics: Consultancy; Novartis: Consultancy; NovoNordisk: Consultancy; BlueBirdBio: Consultancy; Global Blood Therapeutics: Consultancy; BlueBirdBio: Research Funding. de Montalembert: Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Addmedica: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; bluebird bio: Membership on an entity's Board of Directors or advisory committees; Vertex: Membership on an entity's Board of Directors or advisory committees. Abboud: Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Research Support and Advisory Board, Research Funding; AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Other: Reserach support and advisory board , Research Funding; GBT: Other: Research Support, Research Funding; Vertex Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: DSMB. Arlet: Addmedica: Research Funding; Pfizer: Honoraria; Novartis company: Consultancy, Honoraria, Research Funding. Jastaniah: Novartis: Consultancy, Honoraria, Research Funding. Pita: GLOBAL ALLIANCE OF SCD: Membership on an entity's Board of Directors or advisory committees; LUA VERMELHA SCD ASSOCIATION: Membership on an entity's Board of Directors or advisory committees. Francis-Gibson: Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees; Sickle Cell Disease Association of America: Current Employment; ASH: Membership on an entity's Board of Directors or advisory committees; Alliance for Regenerative Medicine Foundation for Cell and Gene Medicine: Membership on an entity's Board of Directors or advisory committees; Global Alliance of SCD Organizations: Membership on an entity's Board of Directors or advisory committees. Trimnell: Novartis: Consultancy; Cyclerion: Consultancy; Global Blood Therapeutics: Consultancy. DeBonnett: Novartis Pharmaceuticals Corporation: Current Employment. Bailey: Novartis Pharmaceuticals: Other: I am an employee of Adelphi Real World, which received payment from Novartis Pharmaceuticals for this research. Rajkovic-Hooley: Novartis Pharmaceuticals: Other: I am an employee of Adelphi Real World, which received payment from Novartis Pharmaceuticals for this research. James: GBT: Honoraria; Novartis: Honoraria.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2021-145409

Language: English

Publisher: American Society of Hematology

Publication Date: 2021

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 136, No. Supplement 1 ( 2020-11-5), p. 8-10

Abstract: Background: SWAY was a cross-sectional survey that assessed the global impact and treatment of sickle cell disease (SCD) (James et al. ASH 2019). SCD puts patients at risk of multiple complications driven by vaso-occlusion and hemolytic anemia. Vaso-occlusive crises (VOCs) are the hallmark of SCD and can require healthcare attention. VOC frequency may be reduced by HU (Charache et al. N Engl J Med 1995). Aims: We assessed self-reported symptoms and quality of life (QoL) indicators for patients who reported using HU at the time of SWAY versus patients who did not, and we collected data on all treatments reported by SCD patients, by geographical region. Data were also collected regarding historical patient-reported use of HU prior to SWAY but these are not included here. Methods: SWAY was completed between April and October 2019 by SCD patients from 16 countries across 6 regions. A limitation is that Asia and South America were represented by single countries (India and Brazil, respectively). SWAY was completed by proxy (parent/guardian/caregiver) for patients aged 6-11 years and could be optionally self-completed by patients aged ≥12 years. Opinions were captured using a 1-7 Likert scale for some questions (5-7 indicated high satisfaction/impact/agreement). SWAY did not assess treatment outcomes. Results: Of 2145 patients, 652 (30%) reported receiving HU at the time of SWAY (56% female; 50% aged 6-25 years); 1493 patients reported not receiving HU at the time of SWAY (51% female; 59% aged 6-25 years). The number of patients reporting HU use varied regionally (Table). Patients who reported using HU also reported a lower VOC burden than patients who did not report using HU at the time of SWAY (median: 3 vs 4 VOCs in the 12 months before SWAY, respectively). However, considering other symptoms commonly experienced in the month prior to SWAY, a greater proportion of patients who reported using HU experienced these symptoms than patients who did not report using HU, except for headache and poor appetite, which were experienced by a lower proportion of patients who reported HU use (Figure). Similar proportions of patients reported that SCD had a high impact (Likert scale 5-7) on emotional wellbeing (61% [reported HU use at time of SWAY] vs 59% [did not report HU use at time of SWAY] ) and daily activities (39% vs 40%, respectively). Overall, when including dietary supplements, the most common treatment reported at the time of SWAY in all regions except the Middle East was folic acid. Common treatments varied regionally when excluding supplements (Table). Top treatment goals for patients in all regions were to improve QoL and prevent SCD worsening. Treatment satisfaction (range: 57-92%) was highest in Asia (Table). Over 70% of patients wanted alternatives to their ongoing pain medications in all regions, except Asia (44%). Discussion: The proportion of patients reporting HU use at the time of SWAY was variable, but relatively low; HU was not in the top 3 treatments for Africa, Europe or North America. HU use was lowest in Africa, where no patients reported receiving HU at the time of the survey, which probably reflects high relative cost and poor access. Our regional analysis showed that many patients take supplements, such as folic acid, rather than HU. This may be indicative of limited alternatives to HU and reflects the differing global costs and availability of both medication and monitoring blood tests. Low reported use of HU may also reflect patients' concerns about side effects or reluctance to take daily medication. It should be noted that some patients may be familiar with 'hydroxycarbamide' as a name for HU and might not have recognized the term 'hydroxyurea' on the survey. Data from SWAY were not validated by medical records and depended on patients' recall. Patients reporting HU use at the time of SWAY had a lower VOC burden than patients not reporting HU use. QoL indicators were similar for the 2 groups, but the overall symptom burden was higher for patients who reported HU use compared with those who did not. However, the 2 groups were not matched for pre-treatment disease burden and no information was collected regarding adherence or duration of previous HU use. Overall, although many patients reported treatment satisfaction, many wanted alternative pain management therapies. A wider range of treatment options are needed to reduce SCD symptoms and improve QoL, ultimately helping patients achieve their treatment goals. Disclosures El Rassi: Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Cyclerion: Research Funding; Pfizer: Research Funding; Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees; Bluebird bio: Membership on an entity's Board of Directors or advisory committees. James:Sickle Cell Society: Current Employment; Novartis: Honoraria. Andemariam:Terumo BCT: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sanofi Genzyme: Consultancy, Membership on an entity's Board of Directors or advisory committees; Guidepoint: Honoraria; Accordant: Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; NovoNordisk: Consultancy, Membership on an entity's Board of Directors or advisory committees; Imara: Research Funding; Hemanext: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; CHNCT: Consultancy; Global Blood Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Vertex: Honoraria; bluebird bio: Consultancy, Membership on an entity's Board of Directors or advisory committees; Emmaus: Membership on an entity's Board of Directors or advisory committees; CRISPR/Vertex: Consultancy, Membership on an entity's Board of Directors or advisory committees; Cyclerion: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees. Inusa:Bluebird bio: Research Funding; AstraZeneca: Honoraria, Other: Steering committee participation, Research Funding, Speakers Bureau; Global Blood Therapeutics: Honoraria, Other: Steering committee participation, Research Funding, Speakers Bureau; Vertex: Research Funding; Novartis: Honoraria, Other: Steering committee participation, Research Funding, Speakers Bureau. Francis-Gibson:Sickle Cell Disease Association of America: Current Employment. Nero:Novartis: Consultancy; Bluebird bio: Consultancy. Minniti:Global Blood Therapeutics: Consultancy, Research Funding; Emmaus: Consultancy, Research Funding; Roche: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; TauTona: Consultancy, Research Funding; Bluebird bio: Consultancy, Research Funding; CLS Bering: Consultancy. Trimnell:Novartis: Consultancy; Cyclerion: Consultancy; Global Blood Therapeutics: Consultancy. Abboud:Eli Lilly: Research Funding; Modus Pharmaceuticals: Research Funding; Crispr Therapeutics: Membership on an entity's Board of Directors or advisory committees; Amgen: Other: Travel support; Novartis: Consultancy, Honoraria, Research Funding; Novo Nordisk: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Global Blood Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Research Funding. Arlet:Novartis: Consultancy, Honoraria. Colombatti:Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Addmedica: Membership on an entity's Board of Directors or advisory committees. de Montalembert:Addmedica: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bluebird bio: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Vertex: Honoraria, Membership on an entity's Board of Directors or advisory committees. Jain:Thalassemia and Sickle Cell Society: Other: Chief Medical Research Officer and Secretary. Jastaniah:Novartis: Consultancy, Honoraria. Nur:Novartis: Consultancy. Ramscar:Novartis Pharma AG: Current Employment. Bailey:Novartis: Other: Employee of Adelphi Real World, which has received consultancy fees from Novartis; Adelphi Real World: Current Employment. Rajkovic-Hooley:Adelphi Real World: Current Employment; Novartis: Other: Employee of Adelphi Real World, which has received consultancy fees from Novartis. Osunkwo:Global Blood Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Acceleron: Membership on an entity's Board of Directors or advisory committees; Data and Safety Monitoring Board (DSMB) membership for Micella Biopharma: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; FORMA Therapeutics: Membership on an entity's Board of Directors or advisory committees; Health Resources and Services Administration (HRSA): Research Funding; Patient Centered Outcomes Research Institute (PCORI): Research Funding; Terumo: Consultancy; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2020-137103

Language: English

Publisher: American Society of Hematology

Publication Date: 2020

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7