Faculty Opinions recommendation of Longitudinal effect of disease-modifying therapy on tricuspid regurgitant velocity in children with sickle cell anemia.

Abstract Chronic transfusion therapy (CTT) prevents stroke in selected patients with sickle cell anemia (SCA). We have shown that CTT mitigates signatures of cerebral metabolic stress, reflected by elevated oxygen extraction fraction (OEF), which likely drives stroke risk reduction. The region of highest OEF falls within the border zone, where cerebral blood flow (CBF) nadirs; OEF in this region was reduced after CTT. The neuroprotective efficacy of hydroxyurea (HU) remains unclear. To test our hypothesis that patients receiving HU therapy have lower cerebral metabolic stress compared with patients not receiving disease-modifying therapy, we prospectively obtained brain magnetic resonance imaging scans with voxel-wise measurements of CBF and OEF in 84 participants with SCA who were grouped by therapy: no disease-modifying therapy, HU, or CTT. There was no difference in whole-brain CBF among the 3 cohorts (P = .148). However, whole-brain OEF was significantly different (P < .001): participants without disease-modifying therapy had the highest OEF (median 42.9% [interquartile range (IQR) 39.1%-49.1%]), followed by HU treatment (median 40.7% [IQR 34.9%-43.6%]), whereas CTT treatment had the lowest values (median 35.3% [IQR 32.2%-38.9%]). Moreover, the percentage of white matter at highest risk for ischemia, defined by OEF greater than 40% and 42.5%, was lower in the HU cohort compared with the untreated cohort (P = .025 and P = .034 respectively), but higher compared with the CTT cohort (P = .018 and P = .029 respectively). We conclude that HU may offer neuroprotection by mitigating cerebral metabolic stress in patients with SCA, but not to the same degree as CTT.

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Radiological Findings By Magnetic Resonance (MRI) and Arteriography (MRA) Brain Imaging Compared to Neurological, Stroke and TCD Assessment in Children with Sickle Cell Anemia in Uganda

Blood ◽

10.1182/blood-2019-130707 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 2304-2304

Author(s):

Amelia Boehme ◽

Richard Idro ◽

Deogratias Munube ◽

Paul Bangirana ◽

Ezekiel Mupere ◽

...

Keyword(s):

Magnetic Resonance ◽

Mr Imaging ◽

Sickle Cell ◽

Sickle Cell Anemia ◽

Clinical Evidence ◽

Sub Saharan Africa ◽

Disease Modifying Therapy ◽

Disease Modifying ◽

Large Infarct ◽

Small Infarct

Background: Children with sickle cell anemia (SCA) are highly susceptible to stroke and other manifestations of pediatric cerebral vasculopathy. Detailed evaluations of children with SCA in sub-Saharan Africa are limited, especially magnetic resonance imaging and angiography (MRI/MRA). In a sample of Ugandan children receiving care at the Mulago Hospital sickle cell clinic in Kampala and were not on disease-modifying therapy, we examined the range of MR imaging findings, and how those findings correlated with standardized demographic, clinical, neurological and neurocognitive assessments. Methods: From within a larger sample of 265 participants with HbSS ages 1-12 years not taking disease-modifying therapy and enrolled in the BRAIN SAFE study, a sub-sample of 81 underwent non-contrast MRI/MRA on a 1.5 Telsa scanner. Participants also underwent 3 standardized assessments: neurocognitive testing by experienced testers using the Mullen Scales of Early Learning (for ages 1-4 years) or Kaufman Assessment Battery for Children, 2nd edition (for ages 5-12) (abnormal z-score of -2 or lower), stroke examination (PedsNIHSS) and transcranial Doppler ultrasound (TCD) using criteria for pediatric SCA. Participants undergoing MRI/MRA intentionally included 29 without any abnormal findings. MRI scans included T1- and T2- weighted images, T2 FLAIR and MRA three-dimensional time-of-flight technique. MR scans were interpreted by clinical and research methods, the latter per SWiTCH protocol (Helton, Blood 2014). Adjudication of differing reads was performed by a blinded third neuroradiologist. Results: A total of 81 children with SCA were examined by MRI/MRA. Mean age was 6.48 ± 2.75 years; 50.6% were male. Mean hemoglobin was 7.26±0.90 g/dl; 75% had hemoglobin <8.0. In all, 16.7% were malnourished using standard international measures established by age and sex. Infarcts and/or arterial stenoses on MRI/MRA were detected in 42 (52%), including 13 (25%) with no other abnormalities detected. There were 35 children (43.2%) who had medium or large infarcts seen; an additional 16 (19.8%) had 1-2 small infarcts. Four had moya moya. Of the 29 children categorized as normal on each of the 3 other tests, 14 (48.3%) had one or more medium or large infarct(s) on MRI, and 3 (10.3%) had 1-2 small infarcts (Figure 1). The proportion of children with malnutrition was higher among those with an abnormal MRI compared to those with a normal MRI, whereas no children with a small infarct was malnourished (29.4% vs. 10.7% vs. 0% p=0.019). A higher proportion of participants with stroke by exam had medium or large infarct(s) compared to participants with normal or small infarct (28.6% vs. 10% vs. 6.3%; p=0.061). Stroke on exam was associated with medium or large infarct(s) compared to normal or small infarct (unadjusted OR 4.2; 95% CI 1.19-14.8), and remained after adjusting for age and hemoglobin (OR 3.90 95%CI 1.10-13.9). The proportion of abnormal psychological testing was higher in the small infarct group than in the group with larger infarct(s) or the normal group (37.5% vs. 28.6% vs. 17.2%; p=0.307). Conclusion: High prevalence of pediatric cerebral vasculopathy was found on MR scanning. Despite clinical evidence suggesting abnormal neuropsychological testing or a prior stroke, not all of the children who had clinical evidence of neurological disorders had MRI evidence of a stroke. Additionally, a number with no evidence of stroke had infarct(s) on MRI, so-called "silent stroke." The strongest predictors of an abnormal MRI reading included having a detectable stroke or an abnormal TCD. MR imaging is a critical aspect of evaluating cerebral vasculopathy in this patient population, and will be an important measure when prospectively assessing impact in a treatment trial. Disclosures No relevant conflicts of interest to declare.

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Prognostic Significance of Early Vaso-Occlusive Complications in Children Who Have Sickle Cell Anemia.

Blood ◽

10.1182/blood.v106.11.3176.3176 ◽

2005 ◽

Vol 106 (11) ◽

pp. 3176-3176

Author(s):

Charles T. Quinn ◽

Elizabeth P. Shull ◽

Naveed Ahmad ◽

Zora R. Rogers ◽

George R. Buchanan

Keyword(s):

Sickle Cell ◽

Sickle Cell Anemia ◽

Strong Predictor ◽

Prognostic Significance ◽

Adverse Outcomes ◽

Acute Chest Syndrome ◽

Disease Modifying Therapy ◽

Pain Crisis ◽

Disease Modifying

Abstract Sickle cell anemia (SS) is a phenotypically variable disease whose course is difficult to predict. The Cooperative Study of Sickle Cell Disease (CSSCD) found that dactylitis in the 1st year of life predicted adverse outcomes in later childhood. We aimed to determine whether early vaso-occlusive complications, including dactylitis, were prognostic in the Dallas Newborn Cohort. We studied all cohort members with SS or sickle-β0-thalassemia who were <1 yr of age at their first clinic visit, ≥5 yrs of age at last follow-up, and who had complete records. We defined 3 potential “early” (occurring in the first 3 yrs of life) predictors: any hospitalization for (1) pain crisis (non-dactylitis), (2) dactylitis, or (3) acute chest syndrome (ACS). We studied the associations of these predictors with the following “late” (occurring on or after the 3rd birthday) outcomes: death of any cause; overt stroke; use of hydroxyurea (HU), chronic transfusion (CT), or stem cell transplantation (SCT); and mean number of hospitalizations for late pain crisis and ACS. Late pain and ACS episodes were enumerated for each patient between the 3rd birthday and the last clinical encounter or the start date of a disease-modifying therapy (HU, CT, or SCT), whichever was first. Mean number of pain and ACS events was analyzed for the late follow-up period in total and in 2-yr intervals. Outcomes up to age 20 were included. Two-sided Fisher exact and t-tests were used appropriately. There were 264 subjects (256 SS; 54.9% male). Mean age at first visit was 4.1±2.3 mos (±S.D.) and mean follow-up was 12.1±4.3 yrs. The following early hospitalizations occurred: 53 subjects (20.1%) had pain crisis; 16 (6.1%) had dactylitis, and 85 (32.9%) had ACS. There were 5 deaths and 30 overt strokes. Sixty-six subjects were treated with HU (37), CT (40), and/or SCT (1). We found that subjects who had early pain, dactylitis, or ACS (compared with those who did not) were not more likely to die (1.7 vs. 2.1%; P>0.99) or have a stroke (12.2 vs. 10.3%; P=0.69). However, the use of a disease-modifying therapy was more common among subjects who had early pain (37.7 vs. 19.9%; P=0.01) and ACS (37.6 vs. 16.2%; P<0.001), but not dactylitis (18.8 vs. 23.6%; P>0.99). This prediction held only for HU use when the treatments (HU, CT, or SCT) were analyzed separately. Subjects who experienced early pain or ACS had on average a 2.2-fold (P=0.02) or 2.1-fold (P=0.01), respectively, higher number of late pain crises between ages 3 and 11, but not beyond (all P>0.05). Dactylitis did not predict a higher number of late painful events at any age (all P>0.05). Likewise, neither early pain nor dactylitis was associated with a higher number of hospitalizations for late ACS (all P>0.05). However, subjects who had early ACS had a 1.7 to 3.6-fold higher mean number of ACS events throughout all late age groups (all P<0.05). In summary, early hospitalization for pain, dactylitis, or ACS did not predict death or stroke. Early pain and ACS were associated with use of HU in later childhood, but not CT or SCT. Early pain and ACS predicted an increased number of hospitalizations for pain until age 11, but not beyond. Early ACS was a strong predictor of recurrent ACS throughout childhood. Notably, we found that hospitalization for dactylitis had no particular prognostic significance, unlike the CSSCD. In conclusion, the prognostic significance of early vaso-occlusive complications is limited.

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Impact of Jaundice On Adults with Sickle Cell Anemia

Blood ◽

10.1182/blood.v120.21.4753.4753 ◽

2012 ◽

Vol 120 (21) ◽

pp. 4753-4753

Author(s):

Alecia C. Nero ◽

Timothy L. McCavit ◽

Leah M. Adix ◽

Bonnie L. Davis ◽

Beena S. Mathew ◽

...

Keyword(s):

Treatment Group ◽

Sickle Cell ◽

Sickle Cell Anemia ◽

Reticulocyte Count ◽

Assessment Tools ◽

Treatment Groups ◽

Disease Modifying Therapy ◽

Study Results ◽

Disease Modifying ◽

The Impact

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.

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Longitudinal effect of disease-modifying therapy on tricuspid regurgitant velocity in children with sickle cell anemia

Blood Advances ◽

10.1182/bloodadvances.2020003197 ◽

2021 ◽

Vol 5 (1) ◽

pp. 89-98

Author(s):

Parul Rai ◽

Vijaya M. Joshi ◽

Jason F. Goldberg ◽

Amber M. Yates ◽

Victoria I. Okhomina ◽

...

Keyword(s):

Sickle Cell ◽

Sickle Cell Anemia ◽

Entire Cohort ◽

Disease Modifying Therapy ◽

Disease Modifying Therapies ◽

Single Center Study ◽

Adults And Children ◽

Disease Modifying ◽

Hydroxyurea Therapy ◽

Observation Period

Abstract Elevated tricuspid regurgitant velocity (TRV) ≥2.5 m/s is a predictor of disease severity in adults and children with sickle cell anemia (SCA), but how disease-modifying therapies (DMTs) affect this biomarker is incompletely understood. We investigated the effect of DMTs on TRV elevation in children. In a prospective single-center study, 204 subjects with HbSS or HbSβ0 thalassemia (mean age, 10.6 years; range, 5-18) had echocardiograms with assessment of TRV, with repeat evaluations after 2 years of observation. One-hundred and twelve participants received DMTs (hydroxyurea, n = 72; monthly erythrocyte transfusions, n = 40), 58 did not receive any DMT, and 34 were begun on hydroxyurea during this observation period. In the entire cohort, an increase in hemoglobin of 1.0 g/dL was associated with a 0.03-m/s decrease in TRV (P = .024), and a decrease in absolute reticulocyte count of 1.0 × 106/mL was associated with a 0.34-m/s decrease in TRV (P = .034). Compared with baseline, hydroxyurea exposure (continuous or newly started) was associated with an average 5% decline in mean TRV at the 2-year evaluation. Among participants newly started on hydroxyurea (mean treatment duration 1.2 ± 0.6 years), an increase in hemoglobin of 1.0 g/dL was associated with a 0.06-m/s decrease in TRV (P = .05). We conclude that hydroxyurea therapy may mitigate TRV elevation in children with SCA, possibly as a result of a reduction in hemolysis and improvement in anemia.

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Increased Hydroxyurea Prescribing Practices over Ten Years with Improved Clinical Outcomes in Children with Sickle Cell Anemia: A Single Center's Experience

Blood ◽

10.1182/blood-2020-138754 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 34-34

Author(s):

Kristine Anne Karkoska ◽

Kevin E Todd ◽

Kelly Clapp ◽

Lynette Fenchel ◽

Theodosia A. Kalfa ◽

...

Keyword(s):

Sickle Cell ◽

Sickle Cell Anemia ◽

Research Funding ◽

Group Versus ◽

First Year ◽

Prescribing Practices ◽

Clinical Complications ◽

Disease Modifying Therapy ◽

Disease Modifying ◽

First Year Of Life

Introduction: Sickle cell anemia (SCA) is a severe and life-threatening disorder that requires treatment to prevent short- and long-term complications and prolong life. The primary disease-modifying therapy for SCA remains hydroxyurea (HU). Due to 30 years of evidence demonstrating safety and efficacy culminating with BABY HUG, the 2014 National Heart, Lung, and Blood Institute (NHLBI) guidelines recommended offering HU to all children with the severe sickle cell genotypes (HbSS, HbS-0thalassemia) beginning at 9 months of age. Despite these recommendations, HU utilization in pediatric patients in the US remains with rates reported as low as 38-47% among the most severe genotypes as recently as 2017. Providers have identified a number of barriers to more widespread use, including the inability to identify which patients may benefit, concern for possible side effects, uncertainties regarding dose, and concerns regarding possible nonadherence. As complications begin as early as the first year of life, it is a disservice to withhold a proven therapy. Here, we describe the effective and nearly universal uptake of HU in our pediatric SCA population at Cincinnati Children's Hospital Medical Center (CCHMC). Methods: We performed an IRB-approved retrospective review to assess the hydroxyurea prescribing practices and clinical complications of patients with SCA treated at CCHMC from 2010-2019. Following the NHLBI guidelines' release in 2014, we changed the recommended age of HU initiation to be within the first year of life. Corresponding with this change, we have initiated HU for most young children with an individualized, pharmacokinetics (PK)-guided dosing strategy through both the Therapeutic Response Evaluation and Adherence Trial (TREAT, NCT03789591) and the Hydroxyurea Optimization through Precision Study (HOPS, NCT03789591). Due to the onset of symptoms for some patients before 9 months, we have offered HU initiation as early as 6 months of age since 2015. Our objective was to compare the rates of HU utilization, age of initiation, and hospitalization rate before (2010-13) and after (2014-19) the release of the NHLBI guidelines and the start of the TREAT study in 2014. Demographic and clinical data, including sickle cell genotype, prior/alternative therapy, SCA-related complications, HU dosing, and laboratory values were abstracted from each patient's electronic medical record (EMR). Patients were identified using the EMR's sickle cell registry. Results: We identified 439 patients with sickle cell disease followed at CCHMC from 2010-2019 (47% female, age range: 0-22 years); 275 had SCA (HbSS, HbS-0-thalassemia, or HbSD). The proportion of patients with SCA prescribed HU increased from 2010-19, from 35% in 2010 to 80% in 2019 with significantly more patients initiating HU during 2014-19 versus 2010-13 (average 20 versus 12 patients/yr, p = 0.0028, Figure 1A). The age of HU initiation was significantly lower during 2014-19 compared to 2010-13 (median = 2 y vs 6 y, p = 0.00028). Of 35 patients with SCA not on HU in 2019, 28 received chronic transfusions and the remaining 7 received no disease-modifying therapy with 3/7 patients not yet at the age to start HU. Ninety-six percent (53/55) of children with SCA born during 2014-19 were on treatment, including 52 on HU (median starting age = 10 months) and 1 on chronic transfusions; 45/52 (87%) were enrolled on TREAT or HOPS. With increased HU utilization during this study period, the number of admissions for sickle-related events was significantly lower in the 2014-19 group versus 2010-13 (2.8 vs 6.9 admissions/pt, p = 9.0 x 10-10) with no change in non-SCA related admissions, most commonly for fever (3.8 vs 4.0 admissions/pt, p = 0.8, Figure 1B). Conclusions: HU has become the standard of care for children with SCA, beginning at 6-9 months of age, prior to the onset of acute and chronic complications. Despite widespread concerns that HU will not be accepted by patients and national trends demonstrating low rates of utilization, we have shown that a deliberate, systematic, and preventive approach to HU is possible and results in nearly universal acceptance of HU for young patients with SCA. This has translated to excellent laboratory responses and significantly fewer SCA-related clinical complications in our population. Our approach and improved patient outcomes can serve as a model for other programs to expand their HU treatment for more children with SCA. Figure 1 Disclosures Kalfa: Agios Pharmaceuticals, Inc: Consultancy, Research Funding; Forma Therapeutics, Inc: Research Funding. Malik:Aruvant Sciences, CSL Behring: Patents & Royalties; Aruvant Sciences, Forma Therapeutics, Inc.: Consultancy.

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How I approach disease‐modifying therapy in children with sickle cell disease in an era of novel therapies

Pediatric Blood & Cancer ◽

10.1002/pbc.29363 ◽

2021 ◽

Author(s):

Kristine Karkoska ◽

Patrick T. McGann

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Novel Therapies ◽

Cell Disease ◽

Disease Modifying Therapy ◽

Disease Modifying

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Assessing Efficacy of Provider and Family Education, Electronic Health Record Documentation Tools, and Information Technology to Increase Use of Hydroxyurea in Children with Sickle Cell Anemia

Blood ◽

10.1182/blood-2019-127770 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 2288-2288

Author(s):

Kyle Hickman ◽

Steve McCalley ◽

Vinay Vaidya ◽

Esteban Gomez ◽

Christine M. Knoll ◽

...

Keyword(s):

Information Technology ◽

Sickle Cell ◽

Sickle Cell Anemia ◽

Family Education ◽

Cell Phenotype ◽

Daily Routine ◽

Intervention Period ◽

Post Intervention ◽

Modifying Agent ◽

Disease Modifying

Background: Hydroxyurea (HU) is an imperative disease-modifying agent in the treatment of sickle cell anemia (SCA). Over the past 30 years, numerous clinical trials have demonstrated both safety and efficacy of this medication in prevention of acute and long-term complications of SCA; however HU continues to be under-utilized in clinical practice. Possible reasons include a lack of provider and family education on the drug, a family's belief in the lack of severity of their child's disease, families not wanting to add additional medications to daily routine and fear of side effects. We sought to increase HU use by a multi-pronged approach of using provider and family education, information technology (IT) tools and weekly reinforcement at pre-visit planning (PVP) team meetings. Methods: We conducted provider education sessions to disseminate knowledge about HU. These included review of NHLBI guidelines, dosing guidelines and tips to optimize HU use and merits of escalating to maximum tolerated dose. The target audience was physicians, fellows, mid-level providers and nurses. ECHO sessions provided by a regional collaborative augmented this effort. A consensus HU guideline document was readily available electronically. The IT team in collaboration with the sickle cell team modified the clinic visit electronic note. The new note included check boxes to document eligibility for HU (based on sickle cell phenotype and severity of disease), and initial and ongoing HU counselling. A table in the clinic note tracked HU dose modifications. A practical algorithm regarding initiation, escalation and monitoring of HU was available as a pop-up in the note to assist providers. An electronic "Sickle Cell Dashboard" was created using real-time data. The dashboard flagged HU eligible patients not yet started on HU. Strategies to successfully initiate HU therapy for these patients were discussed at weekly PVP meetings. We provided HU counselling early and often during first months of life. Successful counselling strategies were shared among providers at PVP meetings. Ancillary staff was trained in utilization of dashboard. Percentage of HU eligible patients who were prescribed HU was measured for two periods: August 1, 2017 to July 31, 2018 (pre-intervention) and August 1, 2018 to July 31, 2019 (post-intervention). A two-sided Fisher's exact test measured statistical significance. Results: In the pre-intervention period 94 of 138 (68%) HU eligible patients were prescribed HU. In the post-intervention period 131 of 164 (80%) HU eligible patients received HU prescription. The 12% increase was statistically significant (p=0.021). Increased education and counselling fostered provider enthusiasm and confidence in prescribing HU. An early start of HU therapy resulted in better compliance with treatment. The collaboration with IT team and creation of electronic "Sickle Cell Dashboard" identified several areas of improvement and inspired additional quality improvement projects. Discussion: Aggressive provider and family education, enhanced electronic records, weekly PVP meetings, readily available HU dosing guidelines and an automated dashboard to flag eligible patients for targeted counselling improved the utilization of this important disease-modifying agent in a significant way. Further improvements can be made by monitoring pharmacy database for prescription fill rates, flagging patients who are overdue for follow-up visits and providing ongoing counselling. Infrastructure established for and lessons learned from this project can be applied to improve comprehensive care for SCA in a sustainable and cost-effective fashion. Figure Disclosures Gomez: Alnylam: Consultancy; Novo Nordisk, Novartis, Pfizer, Sanofi, Takeda, UniQure: Research Funding.

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HLA Typing Status of Hospitalized Pediatric Patients with Sickle Cell Disease: Impact of Socioeconomics and an Initiative to Offer Typing to All Patients with Siblings

Blood ◽

10.1182/blood-2021-153807 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 2969-2969

Author(s):

Arrey-Takor Ayuk-Arrey ◽

Isha Darbari ◽

Allistair Abraham ◽

Robert Sheppard Nickel

Keyword(s):

Socioeconomic Status ◽

Sickle Cell Disease ◽

Sickle Cell ◽

Pediatric Patients ◽

Hospitalized Patients ◽

Hla Typing ◽

Cell Disease ◽

Full Sibling ◽

Disease Modifying Therapy ◽

Disease Modifying

Abstract Background: Hematopoietic stem cell transplant (HSCT) using an HLA-identical sibling donor is a well-established cure for sickle cell disease (SCD). Historically, HSCT was only offered to patients with SCD who had suffered severe complications; however, given improved HSCT outcomes, it is now reasonable to consider HSCT for most patients with SCD who have an HLA-identical sibling. Thus, HLA typing of all full siblings of patients with SCD should be a clinical priority to ensure patients are aware of and have access to this therapeutic option. The primary objectives of this study are to describe the baseline prevalence of HLA typing among a cohort of hospitalized pediatric patients with SCD and to evaluate whether having had HLA typing is associated with certain characteristics. Secondarily, the study describes the acceptability of HLA typing among patients with a healthy (non-SCD) full sibling who had not already had HLA typing at baseline after dedicated outreach to these families. Methods: Between January 1, 2020 and December 31, 2020 a REDCap database of all hospitalized patients with SCD was prospectively maintained. Patient demographic and clinical information was abstracted via retrospective chart review. To evaluate socioeconomic status, a neighborhood area deprivation index (ADI) was determined for each patient using their home address and the Neighborhood Atlas website (https://www.neighborhoodatlas.medicine.wisc.edu/). ADI is a validated ranking (0-100) of Census Block Groups, considering income, education, employment, and housing quality. A higher ADI represents greater socioeconomic disadvantage. As part of a clinical outreach initiative, patients' families who had not already had typing at the time of their hospitalization were contacted to determine if the patient has a healthy full sibling and, if applicable, offer sibling HLA typing. This outreach was originally planned to occur in person at the time of hospitalization or clinic follow-up, but due the COVID-19 pandemic it was paused and when resumed conducted mostly via telephone. Results: During the 52-week study period, 291 patients with SCD were hospitalized at the study pediatric institution. Seventy-one patients (24%) had already completed HLA typing at the time of their first hospitalization during the study period. These patients with HLA typing at baseline were significantly more likely to have a diagnosis of sickle cell anemia (HbSS/HbSβ 0 genotype) and be on disease-modifying therapy (hydroxyurea or chronic transfusion) compared to patients without typing at baseline (Table). Age and sex were not significantly different between patients with and without typing (Table). The group of patients who did not have HLA typing at baseline had a significantly greater ADI (mean 29.7 vs. 24.0, p=.008) and proportion of patients with a high disadvantage ADI score ≥40 (23% vs. 10%, p=.02), Figure. Of the 220 patients with no history of HLA typing, the sibling status of 187 patients was determined via outreach to these families as of July 2021. Among these 187 patients, 81 (43%) reported having a healthy full sibling. Among these 81 patients with siblings, after being offered family HLA typing, 42 (52%) were interested and referred for HLA typing, 29 (36%) were undecided, and 10 (12%) declined typing. Conclusion: Hospitalized pediatric patients with SCD who had already been HLA typed were more likely to have a severe SCD genotype and be on disease-modifying therapy as expected. Patients who had not had HLA typing were more likely to live in a socioeconomically disadvantaged neighborhood. This finding suggests that dedicated outreach to all families regarding HLA typing is needed. Our clinical initiative to offer typing to all hospitalized patients with healthy full siblings was feasible, with a majority of families interested in pursuing HLA typing. Continued work is needed to ensure patients with SCD have equal access to curative therapy regardless of socioeconomic status. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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