Rituximab for Preventing Delayed Hemolytic Transfusion Reaction (DHTR) in Sickle CELL Adult Patients: Outcome of Transfusion and SIDE Effects in 58 CASES

Background: Transfusion is a major therapeutic of sickle cell disease (SCD); however, DHTR is one of the most feared complications . Prevention of allo immunization, by extended RBC matching is insufficient to prevent all cases of DHTR. Therefore, B cell depletion therapy should be also useful, especially in previously immunized patients to avoid the emergence of new allo-antibodies. Rituximab (RTX) is used for preventing alloimmunization for patients with a history of DHTR. Therefore, secondary prevention with rituximab prior a new exposure to transfused RBCs could be a relevant option. Here, we will report our experiences of RTX use in SCD adult patients with a previous history of DHTR. Methods: In this retrospective observational study, the data from 58 consecutive RTX infusion in 44 SCD patients with history of DHTR in our French referral center for SCD were analysed. Medical, biological and blood bank records of patients, clinical signs, rate of hemoglobin A (HbA) after transfusion (TF) were collected. To evaluate the persistence of transfused RBCs, the DHTR risk probability on days 15 and 30 after TF was evaluated according to Mekontso Dessaps nomogram. We also reported serious adverse events like infections in the year after RTX infusion. In cases of programmed surgery, 1 gramme of RTX was administred at day 1 and 15 few weeks before or one injection in emergency situation, with low dose of steroides. Adjuvant measure to avoid transfusion like EPO, Iron injection and hydroxyurea was decided in some cases. Results: We analyzed 58 cases of RTX administered to 44 adult patients with SCD, 10 of whom received two or more times this drug. A transfusion (TF) was required in 33/58 cases (56%). We distinguished three groups of patients. In the first group of 21 cases (36%), rituximab was used preventively before planned surgery at risk of bleeding, only 8 cases were transfused. In the second group of 30 cases (53%) during an acute event, in 19 cases patients received a transfusion. The third group of 7 patients received RTX during an active DHTR with hyperhemolysis requiring transfusion to protect an imminent transfusion and finally 6 of them was transfused. To evaluate the efficacy of transfusion we analyzed group 1 and 2 together and separately the third group with active DHTR and hyperhemolysis. In the first and second groups, HbA measurements was not available or interpretable in 11,1% of cases. On day 15 after TF, 77,8% of cases were classified as having a low probability of hemolysis, 7.4 % as intermediate probability and 3.7% as high probability. On day 30 after TF: 55,6% were into the low probability of hemolysis subgroup, 11,1% in the intermediate probability and 22,2% in the high probability group. (Figure 1) In group 3, HbA measurement wasn't available in 2 cases. On day 15 after TF, no cases were classified as having a low probability of hemolysis, 33,3 % as intermediate probability and 33.3% as high probability. On day 30 after TF: 33,3% were in the intermediate probability and 50 % in the high probability group. (Figure 2) Infection requiring intravenous antibiotic were observed in 19 cases/58 (32.7%) with a bacterial documentation in 73,7 %. In 63% of these cases, patients have been hospitalized in intensive care unit for acute events before RTX administration and had other risk factors of infection. The median time of apparition of infection was 28 days [11.5-46.5]. We report 4 deaths (6,8%), two patient died due to a hyperhemolysis syndrome with multiorgan failure that started before RTX administration, two other were due to an end stage cancer. These deaths are not related to the use of RTX. Conclusion: This study suggests that RTX can be safely used for preventing DHTR in patients with a previous history of DHTR and detected antibodies. We show that transfusion efficiency at day 15 post TF is better than days 30 postTF. The effectiveness of TF in active DHTR with h yperhemolysis is much lower, as most patients lose the transfused units at day 30 post TF.Beyond the use of RTX, the use of other measures such as hydroxyurea and erythropoietin to avoid the need of transfusion in these patients must be emphasized. Infection risk after RTX therapy is difficult to assess. In most cases an active inflammatory event was in process. Additional prospective studies are needed to improve the management of this challenging clinical situation. Disclosures Michel: Novartis: Consultancy; Amgen: Consultancy; Rigel: Consultancy. Galactéros:Addmedica: Membership on an entity's Board of Directors or advisory committees. Bartolucci:Novartis: Membership on an entity's Board of Directors or advisory committees; AddMedica: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; HEMANEXT: 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; Agios: Membership on an entity's Board of Directors or advisory committees.

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Crizanlizumab 5.0 Mg/Kg Exhibits a Favorable Safety Profile in Patients with Sickle Cell Disease: Pooled Data from Two Phase II Studies

Blood ◽

10.1182/blood-2019-123965 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 991-991 ◽

Cited By ~ 2

Author(s):

Julie Kanter ◽

Darla K Liles ◽

Kim Smith-Whitley ◽

Clark Brown ◽

Abdullah Kutlar ◽

...

Keyword(s):

Clinical Trial ◽

Board Of Directors ◽

Sickle Cell ◽

Research Funding ◽

Pooled Analysis ◽

Advisory Committees ◽

Phase Ii Studies ◽

Increased Risk ◽

History Of ◽

Favorable Safety

Background: Crizanlizumab, a humanized monoclonal antibody that binds P-selectin and blocks interaction with its ligands (including leukocyte PSGL-1), is under investigation for preventing vaso-occlusive crises (VOCs) in individuals with sickle cell disease (SCD). Crizanlizumab 5.0 mg/kg was shown to significantly reduce the median annual rate of VOCs by 45.3% versus placebo (Hodges-Lehmann median absolute difference of -1.01 vs placebo, 95% CI [-2.00, 0.00]; P=0.01) (Ataga et al. N Engl J Med 2017). Aims: This pooled analysis evaluated key safety endpoints in patients treated with the recommended dose of crizanlizumab (5.0 mg/kg monthly, following 2 loading doses in the first month). Methods: Data were pooled from 2 Phase II studies of SCD patients (any genotype) with a history of VOCs leading to a healthcare visit. SUSTAIN (NCT01895361) was a randomized, placebo-controlled study in patients aged 16-65 years who had experienced 2-10 VOCs in the previous 12 months. SOLACE-adults (A2202) is an ongoing, open-label PK/PD study (NCT03264989) in patients aged 16-70 years who had experienced at least 1 VOC in the previous 12 months; data cut-off for this analysis was 1 March 2019. Adverse events (AEs) were evaluated based on MedDRA v21.1. AE severity in SOLACE was assessed based on CTCAE v5; in SUSTAIN, severity was collected as mild/moderate/severe but then recategorized for this analysis to a 5-point scale similar to CTCAE grading. AEs of special interest (ie known class effects; AEs identified preclinically or in previous studies; or potentially relevant based on the mechanism of action of crizanlizumab) were also evaluated and included infections, infusion-related reactions (IRRs) and hemostatic effects. As monoclonal antibodies can induce an immune response, anti-drug antibodies (ADAs) were also measured. Results: In total, 111 patients (SUSTAIN, n=66; SOLACE, n=45) received crizanlizumab 5.0 mg/kg: 59 females (53.2%) and 52 males (46.8%). Median age was 29 years (range 16-65). The most common SCD genotypes were HbSS (n=73; 65.8%) and HbSC (n=19; 17.1%), and 75 patients (67.6%) were receiving hydroxyurea (HU). Most patients (n=67; 60.4%) had 1-4 VOCs in the previous 12 months. Median duration of exposure to crizanlizumab was 46 weeks (range 4-58). At least 1 AE was reported in 94 patients (84.7%), the most common (≥15%) being headache (n=22; 19.8%), nausea (n=18; 16.2%) and back pain (n=17; 15.3%). AEs were mild/moderate (grade 1 or 2) and resolved spontaneously in most patients; 23 patients (20.7%) had a grade 3 AE and 1 (0.9%) had a grade 4 AE (neoplasm). At least 1 serious AE was reported in 24 patients (21.6%); serious AEs with a suspected relationship to crizanlizumab were reported in 6 patients (5.4%). Twenty-eight patients (25.2%) discontinued treatment prematurely (n=23 in SUSTAIN, n=5 to date in SOLACE): discontinuations due to AEs (bradycardia and breast cancer) occurred in 2 patients (1.8%); neither was considered related to crizanlizumab. There were 2 on-treatment deaths in SUSTAIN, but neither were considered related to crizanlizumab. Infection events were reported in 51 patients (45.9%), the most common (≥5%) being upper respiratory tract infection (n=13, 11.7%) and urinary tract infection (n=11, 9.9%). There were no grade 4 infections and none led to discontinuation. Data suggest no increased risk or severity of infection in studies with crizanlizumab. Two patients (1.8%) experienced IRRs; the events were not serious and did not lead to discontinuation. Bleeding events were rare, with most observed hemostatic AEs being abnormal laboratory parameters occurring only once. Treatment-induced ADAs were transiently detected in 1 patient (0.9%) and spontaneously resolved. There were no clinically relevant laboratory (hematology, biochemistry, liver) or ECG abnormalities, or vital sign changes, and no notable differences in the AE incidence rates by gender, ethnicity or HU use. Conclusions: This pooled analysis shows that crizanlizumab 5.0 mg/kg was well tolerated, with a favorable safety profile, in patients with SCD and a history of VOCs. Most AEs were mild/moderate, and discontinuations due to AEs were infrequent. The immunogenic potential of crizanlizumab appears low and there is currently no evidence for an increased risk of infection or bleeding. SOLACE-adults and SOLACE-kids (6 months to <18 years) are ongoing, and the randomized Phase III STAND trial is recruiting. Disclosures Kanter: bluebird bio, Inc.: Consultancy; SCDAA: Membership on an entity's Board of Directors or advisory committees; NHLBI: Membership on an entity's Board of Directors or advisory committees; Rockpointe: Honoraria; Peerview: Honoraria; Jeffries: Consultancy; Medscape: Honoraria; GLG: Consultancy; Cowen: Consultancy; Guidepoint Global: Consultancy; Sangamo: Consultancy, Honoraria; Modus: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Imara: Consultancy. Liles:Novartis: Other: PI on clinical trial Sickle cell ; Shire: Other: PI on clinical trial Sickle cell ; Imara: Other: PI on Clinical trial- Sickle cell . Brown:Novartis, Inc: Research Funding. Kutlar:Bluebird Bio: Other: DSMB Member; Micelle Biopharma: Other: DSMB Chair; Novartis: Consultancy; Global Blood Therapeutics, Inc. (GBT): Research Funding; Novo Nordisk: Research Funding. Elliott:Novartis: Employment, Equity Ownership. Shah:Novartis Pharmaceuticals: Employment, Other: Shareholder. Lincy:NOVARTIS PHARMA AG: Employment. Poggio:Novartis: Employment. Ataga:Advisory Board: Global Blood Therapeutics, Novartis: Membership on an entity's Board of Directors or advisory committees, Other: VINDICO WILL FORWARD DISCLOSURES ONCE RECEIVED AND SIGNED NOT RECEIVED TO DATE; VINDICO WILL FORWARD DISCLOSURES ONCE RECEIVED AND SIGNED NOT RECEIVED TO DATE: Other: VINDICO WILL FORWARD DISCLOSURES ONCE RECEIVED AND SIGNED NOT RECEIVED TO DATE; Novartis: 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; Emmaus Life Sciences: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bioverativ: Honoraria, Membership on an entity's Board of Directors or advisory committees.

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Eversion of the Third Eyelid Cartilage in a Cat

Acta Scientiae Veterinariae ◽

10.22456/1679-9216.108850 ◽

2021 ◽

Vol 49 ◽

Author(s):

Eric Orlando Barbosa Momesso ◽

Carinne Liessi Brunato ◽

Adriana Lima Teixeira

Keyword(s):

General Anesthesia ◽

Ocular Surface ◽

Previous History ◽

Clinical Signs ◽

Sodium Hyaluronate ◽

Differential Growth ◽

Presumptive Diagnosis ◽

Ophthalmic Examination ◽

The Third ◽

History Of

Background: Eversion of the cartilage of the third eyelid is a rare congenital disease in cats. It is caused by the anterior eversion of the cartilage edge of the third eyelid. Clinical signs may be associated with secondary keratoconjunctivitis, third eyelid gland protrusion, and ocular surface irritation. The diagnosis is made by ophthalmic examination, and treatment consists of surgical resection of the everted cartilage portion. The goal of the present study was to report a case of eversion of third eyelid cartilage in a cat, given that it is an unusual abnormality in this animal species, and an important differential diagnosis to be considered in the disorders of the third eyelid.Case: A 6-year-old neutered female Persian cat was presented with a presumptive diagnosis of protrusion of the third eyelid gland, history of ocular irritation, and epiphora in the left eye. The disorder had been intermittently present since the animal was 1-year-old, with spontaneous disappearance after approximately 15 days. The owner related the reappearance of the disorder to stressful situations, with no previous history of trauma or other ocular alteration. During the ophthalmic examination, suspended solute was observed through biomiscroscopic examination in both eyes, as well as an increase in volume of the third eyelid in the left eye, without other changes. A thorough examination, under general anesthesia, indicated the protruding volume of the cartilage of the everted third eyelid. The third eyelid was pleated in its upper portion, demonstrating that the cartilage of the third eyelid was folded instead of following the curvature of the ocular surface. Under general anesthesia, the cartilage was partially removed through two parallel incisions on the bulbar conjunctival surface, divulsioning 5 mm in length in the vertical portion of the cartilage in a ‘T’ shape, and separating the conjunctiva from the underlying cartilage. The everted portion of cartilage, once removed, was in fact considered curved in its most dorsal portion, in a manner similar to what was reported in dogs. The third eyelid returned to its anatomically correct position after removing the deformed portion of the cartilage. The patient was treated postoperatively with topical drops of tobramycin and dexamethasone 3 mg/mL + 1 mg/mL (Tobradex®), and lubricant based on sodium hyaluronate 2 mg/mL (Hylo®-Gel). No complications were observed in the postoperative consultations during a 8 month follow-up.Discussion: It is suspected that the eversion of the third eyelid cartilage occurs due to a differential growth rate between the posterior and anterior portions of the cartilage; even though other theories have been proposed. The cartilage of the third eyelid can commonly be everted in large dog breeds, being classified as a disease of hereditary character. However, it has rarely been reported in cats, which can be explained by the more elastic histological constitution when compared to that of dogs. The surgical procedure performed in the present case of eversion of the third eyelid cartilage in a cat was in accordance with that described in the literature. Complete recovery of the third eyelid function was achieved, and the patient's ocular health was preserved. The reported case showed a favorable prognosis after diagnosis, associated with correct treatment and postoperative management. Although there was an effective recovery of the third eyelid, the issues related to the pathophysiology of cartilage eversion are unknown. This way, further studies are necessary to elucidate its etiology.

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Causes of Death in 198 Sickle Cell Adult Patients: Old and New Trends

Blood ◽

10.1182/blood-2019-131304 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 1031-1031

Author(s):

Anoosha Habibi ◽

Stephanie Ngo ◽

Etienne Audureau ◽

Armand Mekontso-Dessap ◽

Keyvan Razazi ◽

...

Keyword(s):

Organ Failure ◽

Board Of Directors ◽

Sickle Cell ◽

Causes Of Death ◽

Adult Patients ◽

Therapeutic Education ◽

Renal Diseases ◽

Age At Death ◽

Advisory Committees ◽

Aged Patients

Introduction: Over the past decades, there have been substantial improvements in the medical care of sickle cell patients, leading to an increase in life expectancy, despite the fact that the latest studies in adults do not see any change in age at death. Pediatric mortality has declined significantly with the introduction of systematic antibiotics, the preventive care cerebral vasculopathy and therapeutic education for families. It seems important to analyze the morbidity and mortality risks to decide the necessary preventive measures. In this study we will describe the circumstances of death, the profiles of the patients and the risk factors in SCD adult patients. Materiel and method: We retrospectively reviewed the records of patients which died between 2001 and 2019 and treated in our national referral center (Henri Mondor Hospital) where 3500 patients are followed. Basic biological parameters, chronic and acute complications present in these patients as well as their treatment, median age at death, causes and circumstances of death were identified when the information was available. Results: During this period, 198 deaths were recorded or reported by families of patients. 54% were men. Patients ranged in age from 16 to 69 years and median age at death was 37 years IQR [30-47]. Concerning the type of hemoglobinopathy there were 158 homozygous patients (77%), 28 SC (14%), 11 heterozygous Sβ0 (5%) and 4 heterozygous Sβ+(2%).The causes of death are summarized in the Table 1. Patients had chronic terminal stage organ failure in more than 30% of cases, with indication for organ transplantation (renal, hepatic or cardiac) in 60 of them and 10 precapillary PAHs. 18% of patients were dialyzed. The diagnosis of DHTR was not reported in previous studies and probably under-diagnosed but 12 (6%) patients died of hyperhemolysis with multi-organ failure in this study. Nine deaths occurred during pregnancy and 17 during a travel. Biological, echo graphics data and risk factor analysis is ongoing. Discussion: The median age of death does not seem to improve from the study of Platt et al, however our cohort appears to age, we observed an increase in the number of aged patients over 45. The causes of death have evolved compared to data avaliable from previous studies, chronic organ failures are the leading cause of mortality especially in patients with renal impairment. The prevention of the onset of these complications is one of the new challenges especially renal diseases which was associated with premature mortality. DHTR and brain hemorrhages are new entities probably previously under-diagnosed. Pregnancy remains a risk period, which should strengthen its monitoring. Table 1 Disclosures Michel: Novartis: Consultancy; Rigel: Consultancy; Amgen: Consultancy. Galactéros:Addmedica: Membership on an entity's Board of Directors or advisory committees. Bartolucci:Roche: Membership on an entity's Board of Directors or advisory committees; HEMANEXT: 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; Agios: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; AddMedica: Honoraria, Membership on an entity's Board of Directors or advisory committees.

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Implementation of Escort-HU Extension: European Sickle Cell Disease Cohort - Hydroxyurea - Extension Study : Interests and Methodology

Blood ◽

10.1182/blood-2021-152525 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 3098-3098

Author(s):

Mariane de Montalembert ◽

Ersi Voskaridou ◽

Lena Oevermann ◽

Giovanna Cannas ◽

Anoosha Habibi ◽

...

Keyword(s):

Sickle Cell Disease ◽

Board Of Directors ◽

Sickle Cell ◽

Research Funding ◽

Steering Committee ◽

Leg Ulcers ◽

Cell Disease ◽

Advisory Committees ◽

History Of

Abstract The efficacy and long-term effectiveness of hydroxycarbamide/hydroxyurea (HU) in the prevention of painful crises and in the decrease of mortality and morbidity in sickle cell disease (SCD) patients have been established (Charache et al. 1992; Steinberg et al 2010, Voskaridou et al 2010). From January 2009 to March 2019, the non-interventional prospective cohort study ESCORT-HU was conducted to evaluate the use of HU in real-life conditions and to collect information on the long-term safety of HU when used in current practice for the prevention or treatment of symptomatic complications in patients with sickle cell disease (SCD) (Montalembert et al 2021). A total of 1906 patients, 55% of adults, were enrolled in this study in 62 centres (Germany, Greece, Italy and France). The mean exposure to HU in this cohort was 30 months, for a cumulative exposure of 7310 patient-per year. The main objectives of ESCORT-HU have been fulfilled as regards the collection of data on the most common concerns associated with the use of HU in SCD patients: myelosuppression, child growth, concomitant administration of live vaccines, safety in population with renal and hepatic impairment and frequency of SCD events (painful crises, acute chest syndrome, stroke, acute splenic sequestration, infections, blood transfusions and hospitalizations) (Montalembert et al 2021). In order to better identify potential long-term risks and specific concerns of HU therapy, ESCORT-HU extension is being implemented in Europe with the goal of 2500 patients enrolled. Main risks targeted by the study are leg ulcers, one of the most limiting factors to continue a treatment with HU. Patients will be recruited over a 5-year period. In addition to patients already involved in the first ESCORT-HU study, new at-risk patients might be added such as patients with a history of HU exposure of at least 5 years, to allow a follow-up of patients treated with long-term HU to fully estimate the incidence of potential risk of malignancies prepubescent children aged more than 10 years for girls and more than 13 years for boys in order to document impact or not of HU on puberty and realisation of cryopreservation,patients with a history of leg ulcers, to search for discriminating criteria between leg ulcer caused by the disease and HU-induced leg ulcer,pregnant women without interruption of HU 3 months before the beginning of the pregnancy and males treated with HU whose partner is pregnant and without discontinuation of HU 3 months before the beginning of the pregnancy. To date, there is a limited number of pregnancies exposed to HU with documented outcome. Despite no adverse effects on pregnancy or on the health of the foetus/new-born have been registered, an increase of the number of pregnancies with documented outcomes will allow for meaningful assessment of foetal outcome following exposure to HU during pregnancy, 10 months after the beginning of ESCORT-HU extension, 818 patients have been enrolled in 70 investigational sites in 4 countries (Greece, Italy, Germany and France) (see Graph below). A first steering committee was hold in June 2021. Its conclusions were that distribution of patients (genotype, sex, age) was consistent with the first study and the number of events reported until now was coherent with what was expected per year, with no occurrence of major concern. This extension study involves most of competence centres which manage SCD patients. SC patients have become increasingly well cared for in recent decades and have seen their life expectancy increase. HU treatment is now a chronic treatment possibly for life in many patients with SCD, better its knowledge of its efficiency and tolerance, better patient adherence to treatment will be. Figure 1 Figure 1. Disclosures de Montalembert: Addmedica: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bluebird Bio: Consultancy, Membership on an entity's Board of Directors or advisory committees; Vertex: Consultancy. Voskaridou: ADDMEDICA: Consultancy, Research Funding; BMS: Consultancy, Research Funding; GENESIS: Consultancy, Research Funding; NOVARTIS: Research Funding; PROTAGONIST: Research Funding; IMARA: Research Funding. Oevermann: NOVARTIS: Consultancy; GBT: Consultancy. Joseph: bluebird bio: Consultancy. Colombatti: BlueBirdBio: 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; Novartis: Membership on an entity's Board of Directors or advisory committees; Novo Nordisk: Membership on an entity's Board of Directors or advisory committees. Bartolucci: INNOVHEM: Other: Co-founder; Jazz Pharma: Other: Lecture fees; AGIOS: Consultancy; Addmedica: Consultancy, Other: Lecture fees, Research Funding; Fabre Foundation: Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Lecture fees, Steering committee, Research Funding; Bluebird: Consultancy, Research Funding; F. Hoffmann-La Roche Ltd: Consultancy; GBT: Consultancy; Emmaus: Consultancy; Hemanext: Consultancy. Brousse: BLUEBIRDBIO: Consultancy; ADDMEDICA: Consultancy. Galactéros: Addmedica: Membership on an entity's Board of Directors or advisory committees.

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High Rate of Recurrent Venous Thromboembolism Is Children with Sickle Cell Disease and History of VTE: Analysis of the Trinetx Research Network Database

Blood ◽

10.1182/blood-2021-154003 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 778-778

Author(s):

Marisol Betensky ◽

Ernest Amankwah ◽

Jane S Hankins ◽

Neil Goldenberg

Keyword(s):

Risk Factors ◽

Venous Thromboembolism ◽

Sickle Cell Disease ◽

Board Of Directors ◽

Sickle Cell ◽

Research Network ◽

Cell Disease ◽

Advisory Committees ◽

History Of ◽

Recurrent Vte

Abstract Background: Sickle Cell Disease (SCD) is associated with a chronic prothrombotic state that increases the risk of venous thromboembolism (VTE). The rate of VTE in hospitalized children with SCD is nearly 2%, substantively higher than the 0.2-0.6% rate seen in the general pediatric population. 1-3 The frequency and risk factors associated with the development of recurrent VTE in this population are vastly unknown. This knowledge gap hinders the development of disease-specific guidelines for the management and secondary prevention of VTE in pediatric SCD. Aim: To investigate the frequency of recurrent VTE in children birth to 21 years of age (inclusive) with SCD and history of prior VTE. Methods: We analyzed patient-level data from the TriNetX Research Network Database, a global federated network of electronic medical record (EMR) data from 42 health care organizations. Children ≤21 years of age with a diagnosis of SCD and history of VTE between January 1 2008 to March 31 2021 were included in the analysis. Index VTE was defined as the first diagnosis of VTE in the patient's EMR. Recurrent VTE was defined as an acute VTE diagnosis that occurred 90 days after the index VTE discharge date in a different anatomic location from the index VTE. Patient demographic and clinical characteristics were summarized using counts and percentages. Missing values were not imputed. Overall, one year and five-year recurrence VTE are reported with the corresponding 95% confidence intervals (CI). Results: A total of 119 children with SCD and VTE were included. Table 1 shows the patients baseline characteristics. Mean age at the time of index VTE diagnosis was 16.7 years (standard deviation 5.5 years). The majority of patients were Black (87%) and female (61%). The most frequent index VTE diagnosis was pulmonary embolism (42%) followed by lower (23%) and upper (22%) extremity VTE. Of the 119 patients,10 (8.4%, 95%CI=4-15%) developed recurrent VTE within 1-year and 25 (21.0%, 95%CI=14-29%) developed recurrent VTE within 5-years from index VTE. Compared to patients without recurrent VTE, patients with recurrent VTE were more frequently female (50% vs. 68%, respectively), and slightly older (mean age 16.6 years vs. 17.2 years, respectively). The most frequent anatomic location for VTE recurrence was the upper extremity (32%) Conclusions: This retrospective database analysis identified, for the first time, high rates of recurrent VTE of 8.4% and 21% at 1- and 5-years post-VTE in children with SCD. These rates stand in contrast with the 3% VTE recurrence at 1-year reported for the general pediatric VTE population. 4 Further analyses of the database are ongoing to identify risk factors for recurrent VTE in this population. These initial findings highlight the need for cooperative multicenter prospective studies to reliably establish rates of- and prognostic factors associated with recurrent VTE in children with SCD, in order to generate evidence for disease-specific treatment guidelines, and to inform future prognostically-stratified interventional trials designed to optimize VTE outcomes in pediatric SCD. 1.Kumar R, Stanek J, Creary S, et al. Prevalence and risk factors for venous thromboembolism in children with sickle cell disease: an administrative database study. Blood Adv 2018;2:285-291. 2. Raffini L, Huang YS, Witmer C, Feudtner C. Dramatic increase in venous thromboembolism in children's hospitals in the United States from 2001to 2007. Pediatrics 2009;124:1001-8. 3. Setty BA, O'Brien SH, Kerlin BA. Pediatric venous thromboembolism in the United States: a tertiary care complication of chronic diseases. Pediatr Blood Cancer 2012;59:258-64. 4. Goldenberg NA, Schulman S, Kittelson JM, et al, Kids-DOTT Trial Investigators and the ATLAS Group. A Six-week versus Three-month Duration of Anticoagulation for Acute Provoked Venous Thromboembolism in Patients < 21 Years Old: Results of the Multinational Kids-DOTT Randomized Controlled Trial. [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 1). Figure 1 Figure 1. Disclosures Hankins: Global Blood Therapeutics: Consultancy; Vindico Medical Education: Consultancy; UpToDate: Consultancy; Bluebird Bio: Consultancy. Goldenberg: Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Daiici: Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Anthos: Membership on an entity's Board of Directors or advisory committees.

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Prognostic Factors for Developing Thrombosis in Polycytemia Vera: A Retrospective Analysis of 331 Patients with Long-Term Follow-up Highlights the Importance of White Blood Cells Levels

Blood ◽

10.1182/blood-2020-139431 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 48-49

Author(s):

Samantha Ferrari ◽

Chiara Pagani ◽

Mariella D'Adda ◽

Nicola Bianchetti ◽

Annamaria Pelizzari ◽

...

Keyword(s):

Risk Factors ◽

Multivariate Analysis ◽

High Risk ◽

Board Of Directors ◽

Advisory Board ◽

Advisory Committees ◽

Risk Status ◽

History Of ◽

Wbc Count

Polycythemia Vera (PV) is a chronic myeloproliferative neoplasm characterized by erythrocytosis, constitutively active mutations in JAK2 and an increased susceptibility to thrombotic events (TEs). There is still controversy about the role of increased hematocrit and of other variables including elevated white blood cell count as risk factors for the occurrence of TEs. A better definition of the relative prognostic importance of hematologic parameters would help us to better tailor the therapeutic approach to PV patients (pts), which is currently mainly based on the use of acetilsalycilic acid (ASA), venesection and hydroxyurea . The aim of our study was to analyze if any clinical or laboratory variables were significantly associated to the occurrence of TEs both at PV diagnosis and during the course of the disease in a large series of PV pts uniformly followed at a single Center over a period of 29.5 years from January 1986 to June 2019. Clinical and laboratory data were obtained from the time of diagnosis until death, progression to acute leukemia or last follow-up. Hematocrit (Hct), hemoglobin (Hb), white blood cell (WBC) and platelet (PLT) levels were recorded for each patient at least every 6 months. Among a total of 331 pts, the median age was 65 years (range 30-92 years), and 56% were male. "High risk" features (age ≥ 60 years and/or history of prior thrombosis) were present in 221 pts (66.7%). The incidence of cardiovascular risk factors was: hypertension 64%, diabetes 15%, hyperlipidemia 28%, history of active or remote smoking 41%. Patients on ASA were 279 (84%), 19 (6%) were on oral anticoagulation, while 27 (8%) were on ASA+oral anticoagulant. At PV diagnosis 54 pts (16%) presented with thrombosis, arterial in 32 (59%) and venous in 22 (41%). A previous TE was recorded in 57 pts (17%): in 43 (75%) arterial, in 12 (22%) venous and in 2 (3%) mixed (arterial+venous). Previous thrombosis was the only variable significantly associated with the presence of a TE at PV diagnosis (P=0.02). After PV diagnosis, with a median follow-up of 81 months (range 1-374 months), 63 pts (19%) experienced a TE and 11 of them a further episode, for a total of 74 TEs. The incidence rate (pts/year) of TEs was 2.7%. Forty-two events were arterial (57%), 31 were venous (42%) and 1 (1%) was mixed. It was the first TE for 37 pts. Cerebrovascular accidents and deep-venous thrombosis were the most frequent arterial and venous TEs both at PV diagnosis and throughout the disease course, with a relative incidence of 50% and 32% respectively. The table compares the characteristics of patients who did or did not develop a TE after PV diagnosis. At univariate analysis, PV high risk status, a previous TE and hyperlipidemia at PV diagnosis were significantly associated with a subsequent TE. Among hematologic variables an elevated WBC count at the time of thrombosis, but not Hct or PLT levels, was highly significantly associated with the development of a TE. At multivariate analysis, WBC count ≥10.4 x 10^9/L and hyperlipidemia maintained their independent prognostic value, while high risk status and a previous TE lost their prognostic significance. Both at univariate and multivariate analysis, hyperlipidemia at diagnosis (P=0.009 and P=0.002) and high WBC count at thrombosis (P=0.001 and P=<0.0001) predicted for arterial thromboses, while only a history of prior thrombosis (P=0.03) predicted for venous ones. In conclusion, our analysis confirms that elevated WBC count at the moment of the event more than increased hematocrit is associated to the development of thrombosis in PV pts. We also found that hyperlipidemia was an independent risk factor for arterial thrombosis, calling for an accurate management of increased lipid levels. Whether a reduction of the WBC count during the course of PV may reduce the frequency of TE remains to be demonstrated by prospective studies. Table Disclosures D'Adda: Novartis: Other: Advisory board; Incyte: Other: Advisory board; Pfizer: Other: Advisory board. Rossi:Daiichi Sankyo: Consultancy, Honoraria; Sanofi: Honoraria; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; Novartis: Other: Advisory board; Alexion: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria; Celgene: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Jazz: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees.

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Identifying Factors That Predict for Unplanned Readmissions for Acute Myeloid Leukemia Patients Receiving Consolidation Cytarabine Based Therapies

Blood ◽

10.1182/blood-2019-128807 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 3433-3433

Author(s):

Caitlin Siebenaller ◽

Madeline Waldron ◽

Kelly Gaffney ◽

Brian P. Hobbs ◽

Ran Zhao ◽

...

Keyword(s):

Board Of Directors ◽

Myeloid Leukemia ◽

Research Funding ◽

Smoking Status ◽

Consolidation Therapy ◽

Peripheral Vascular ◽

Consolidation Chemotherapy ◽

Advisory Committees ◽

History Of ◽

Acute Myeloid

Background: Younger patients (pts) with acute myeloid leukemia (AML) who enter a remission after intensive induction chemotherapy routinely receive at least one cycle of consolidation therapy with high dose cytarabine (HiDAC). This is commonly administered over a five-day inpatient stay, after which pts are discharged home as their blood counts nadir. It is thus a natural consequence of therapy that readmission for febrile neutropenia (FN) occurs, which can impact measures of quality and value in this population. Precise descriptions of incidence, type, and severity of infection, if identified, are lacking, and thus it is unknown to what standard cancer centers should be held for anticipated readmission. We measured these rates, and attempted to identify predictive factors for readmission. Methods: Adult AML pts ≥ 18 years of age who received at least one cycle of HiDAC consolidation (1000-3000 mg/m2 for six doses) in 2009-2019 were included. Our primary aim was to identify predictive factors for readmission after the first cycle of consolidation chemotherapy. The following pt characteristics and co-morbid conditions were analyzed: age, gender, body mass index (BMI), smoking status, AML cytogenetic risk status, history of diabetes, peripheral vascular disease, cardiovascular disease, chronic pulmonary disease, hepatic impairment, and other cancers. Secondary aims included: estimating rates of all-cause readmissions among all HiDAC cycles, defining the rate of FN readmissions, estimating rates of intensive care unit (ICU) admissions, clinical (e.g., probable pneumonia per imaging) and microbiologically-documented infections, prophylactic (ppx) medications used, and mortality. Statistical analyses interrogated potential risk factors for evidence of association with hospital readmission after the first cycle of consolidation chemotherapy. Results: We identified 182 AML pts who fit inclusion criteria. The median age was 50 years (range 19-73); 55% were female and 45% were male. Statistical analyses revealed no association with readmission after cycle 1 for cytogenetic risk (p=0.85), history of heart failure (p= 0.67), chronic pulmonary disease (p=1), connective tissue disease (p=0.53), cerebrovascular accident (p=0.63), diabetes (p=0.63), gender (p=0.07), history of lymphoma (p=0.53), other solid tumors (p=0.53), liver disease (p=1), myocardial infarction (p=0.71), peripheral vascular disease (p=1), or smoking status (p= 0.52). For 480 HiDAC cycles analyzed (88% at 3000 mg/m2), the overall readmission rate was 50% (242/480), of which 85% (205/242) were for FN. Those readmissions which were not FN were for cardiac complications (chest pain, EKG changes), non-neutropenic fevers or infections, neurotoxicity, bleeding or clotting events, or other symptoms associated with chemotherapy (nausea/vomiting, pain, etc.). Median time to FN hospital admission was 18 days (range 6-27) from the start of HiDAC. Of the 205 FN readmissions, 57% had documented infections. Of these infections, 41% were bacteremia, 23% fungal, 16% sepsis, 12% other bacterial, and 8% viral. Of 480 HiDAC cycles, ppx medications prescribed included: 92% fluoroquinolone (442/480), 81% anti-viral (389/480), 30 % anti-fungal (142/480), and 3% colony stimulating factor (14/480). Only 7% (14/205) of FN readmissions resulted in an ICU admission, and 1% (3/205) resulted in death. Conclusions: Approximately half of patients treated with consolidation therapy following intensive induction therapy can be expected to be readmitted to the hospital. The majority of FN readmissions were associated with clinical or microbiologically documented infections and are not avoidable, however ICU admission and death associated with these complications are rare. Readmission of AML pts following HiDAC is expected, and therefore, should be excluded from measures of value and quality. Disclosures Waldron: Amgen: Consultancy. Hobbs:Amgen: Research Funding; SimulStat Inc.: Consultancy. Advani:Macrogenics: Research Funding; Abbvie: Research Funding; Kite Pharmaceuticals: Consultancy; Pfizer: Honoraria, Research Funding; Amgen: Research Funding; Glycomimetics: Consultancy, Research Funding. Nazha:Incyte: Speakers Bureau; Abbvie: Consultancy; Daiichi Sankyo: Consultancy; Jazz Pharmacutical: Research Funding; Novartis: Speakers Bureau; MEI: Other: Data monitoring Committee; Tolero, Karyopharma: Honoraria. Gerds:Imago Biosciences: Research Funding; Roche: Research Funding; Celgene Corporation: Consultancy, Research Funding; Pfizer: Consultancy; CTI Biopharma: Consultancy, Research Funding; Incyte: Consultancy, Research Funding; Sierra Oncology: Research Funding. Sekeres:Syros: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Millenium: Membership on an entity's Board of Directors or advisory committees. Mukherjee:Partnership for Health Analytic Research, LLC (PHAR, LLC): Consultancy; McGraw Hill Hematology Oncology Board Review: Other: Editor; Projects in Knowledge: Honoraria; Celgene Corporation: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Honoraria; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Speakers Bureau; Takeda: Membership on an entity's Board of Directors or advisory committees.

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Splenomegaly in Children with Sickle Cell Anemia Receiving Hydroxyurea in Sub-Saharan Africa

Blood ◽

10.1182/blood-2019-129937 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 993-993

Author(s):

Leon Tshilolo ◽

George A. Tomlinson ◽

Patrick T. McGann ◽

Teresa S. Latham ◽

Peter Olupot-Olupot ◽

...

Keyword(s):

Board Of Directors ◽

Sickle Cell ◽

Sickle Cell Anemia ◽

Growth Parameters ◽

Sub Saharan Africa ◽

Advisory Committees ◽

Splenic Enlargement ◽

Hydroxyurea Treatment ◽

Lower Blood ◽

Sub Saharan

Introduction. Children with sickle cell anemia enrolled in Realizing Effectiveness Across Continents with Hydroxyurea (REACH, NCT01966731) received open-label hydroxyurea at maximum tolerated dose (MTD) in four countries within sub-Saharan Africa (Tshilolo et al, NEJM 2019;380:121-131). Unlike children in the United States or Europe, a substantial proportion of REACH participants had splenomegaly at enrollment, and more developed splenomegaly while receiving hydroxyurea. Splenic enlargement in association with hydroxyurea treatment in sub-Saharan Africa is previously unrecognized, and its causes and consequences remain unclear. Methods. Palpable splenomegaly was evaluated at both the mid-clavicular and mid-axillary lines at each scheduled and unscheduled sick visit. The size of the spleen, defined as the greatest distance (cm) below the subcostal margin, was recorded in the REDCap trial database at all four clinical sites. Cross-sectional analysis was performed at baseline enrollment using four spleen categories (Not Palpable, 1-4 cm, ≥5 cm, or Splenectomy) with correlations for age, sex, site, growth parameters, alpha-thalassemia trait and G6PD deficiency. This analysis was repeated using the largest spleen size over the first two years on hydroxyurea, but examining two-year laboratory values and also the hydroxyurea dose at MTD, time to MTD, dose-limiting toxicities, and clinical outcomes including acute splenic sequestration, malaria infections, and sepsis. Results. A total of 606 children started hydroxyurea study treatment, including 6 (1.0%) with previous splenectomy, 59 (9.7%) with previous splenic sequestration, and 99 (16.3%) with palpable splenomegaly at enrollment (52 children with 1-4 cm and 47 with ≥5 cm). Large spleens (≥5 cm) were commonly observed at baseline at all clinical sites except Uganda, which identified only 1 child. Compared to those with no palpable spleen, children with large spleens at baseline had similar age and growth parameters, but were significantly more likely to have alpha-thalassemia (78.7% versus 56.2%, P=0.004) and also G6PD deficiency among males (28.0% versus 17.6%, P=0.32). Children with large spleens at enrollment also had a lower hemoglobin (Hb = 6.5 versus 7.3 g/dL, P<0.001) and lower platelet count (platelets = 227 versus 410 x 109/L, P<0.001), but equivalent fetal hemoglobin (HbF = 10.2 versus 9.4%, P=0.82). On hydroxyurea treatment with escalation to MTD, 262 children (43.7%) had palpable splenomegaly recorded, including 120 (20.0%) with spleens ≥5 cm. These large spleens were observed at all four clinical sites, with DRC having the most (52) and Uganda with the least (14). After 24 months of hydroxyurea treatment, laboratory differences were noted according to the cumulative occurrence of splenomegaly including a significantly lower hemoglobin and platelet count, higher absolute reticulocyte count, and lower hydroxyurea dose at MTD (Table). Large spleens were associated with a high cumulative incidence of laboratory dose-limiting toxicities, as well as a significantly higher risk of having clinically symptomatic malaria and receiving blood transfusions (Table). A total of 31 children (5.2%) on hydroxyurea treatment received elective splenectomy, including one partial splenectomy using arterial embolization. Conclusion. Children with sickle cell anemia living in sub-Saharan Africa have an increased risk of having palpable splenomegaly, which is further increased while receiving hydroxyurea treatment. Large spleen at baseline were associated with lower blood counts, consistent with hypersplenism. On hydroxyurea treatment, children with large spleens had significantly lower blood counts and more dose-limiting toxicities, which lowered their eventual hydroxyurea dose at MTD but still led to robust HbF responses. Children with large spleens were also at higher risk of developing malaria infections, receiving transfusions, and requiring surgical splenectomy. Splenic enlargement in association with hydroxyurea treatment was common in children with sickle cell anemia in the REACH trial; its cause remains unclear but the consequences include substantial laboratory toxicity and clinical morbidity. Investigating the etiologies and management of children with chronically enlarged spleens is crucial before expanding hydroxyurea access across Africa for sickle cell anemia. Disclosures Ware: Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Other: Research Drug Donation; Nova Laboratories: Membership on an entity's Board of Directors or advisory committees; CSL Behring: Membership on an entity's Board of Directors or advisory committees; Novartis: Other: DSMB; Agios: Membership on an entity's Board of Directors or advisory committees; Addmedica: Other: Research Drug Donation.

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BCX9930, a Potent, Selective, Oral Factor D Inhibitor, Demonstrates Proof-of-Concept As Monotherapy in Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH)

Blood ◽

10.1182/blood-2020-138838 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 14-15

Author(s):

Austin Kulasekararaj ◽

Jacques Le Roux Malherbe ◽

Andrew McDonald ◽

Melanie Cornpropst ◽

Phil Collis ◽

...

Keyword(s):

South Africa ◽

Board Of Directors ◽

Research Funding ◽

Total Bilirubin ◽

Proof Of Concept ◽

Advisory Committees ◽

Clone Size ◽

The Past ◽

History Of ◽

Pre Treatment

INTRODUCTION: PNH, a rare, chronic, life-threatening disease, is characterized by hemolytic anemia due to uncontrolled activity of the complement alternative pathway (AP), bone marrow failure, and thrombosis. Inhibition of C5 by intravenously administered eculizumab and ravulizumab reduces intravascular hemolysis, but PNH red blood cells (RBCs) become opsonized and susceptible to extravascular hemolysis (Risitano et al, Blood 2009). Only approximately half of PNH patients become transfusion independent with eculizumab treatment (Hillmen et al, NEJM 2006). BCX9930 is a potent, selective, orally administered inhibitor of complement factor D. Inhibition of factor D may prevent both intravascular and extravascular hemolysis in PNH. In healthy subjects, BCX9930 showed linear pharmacokinetics and dose-related AP suppression, and was safe and generally well-tolerated over a wide dose range. Here we describe safety and laboratory data establishing proof-of-concept for BCX9930 monotherapy in PNH patients in Study BCX9930-101 (NCT04330534). METHODS: Ongoing Study BCX9930-101 includes an open-label, dose-ranging evaluation of BCX9930 in PNH subjects who may either be naïve to C5 inhibitors (and receive BCX9930 as monotherapy) or have an incomplete treatment response to eculizumab or ravulizumab (with BCX9930 added to existing treatment). Up to 4 sequential cohorts each use a forced titration design for the first 28 days (Figure 1). Subjects enrolled in South Africa can participate in an individualized 48-week extension if they derive benefit at Day 28. Clinical benefit from BCX9930 is evaluated using laboratory monitoring and symptom assessment. Safety and tolerability are evaluated via clinical and laboratory monitoring, causality of adverse events is assessed by investigators, and the study is overseen by an independent Data Monitoring Committee. Data from Cohort 1 through 28 days is reported; data from the extension and subsequent cohorts will be subsequently summarized as available. RESULTS: To date, four C5 inhibitor naïve PNH subjects in South Africa have enrolled in Cohort 1. These subjects had PNH for a median of 4.5 years; 2 subjects had a history of transfusions in the past year; 1 subject each had a history of aplastic anemia or major thrombosis. Pre-treatment lactate dehydrogenase (LDH), total bilirubin, hemoglobin (Hb), reticulocyte count, and RBC PNH Type III clone size ranged from 3.7-11.1 × ULN, 0.61-3.3 mg/dL, 6.1-11.6 g/dL, 0.13-0.29 × 106/µL, and 41.4%-88.6% respectively. Treatment over 28 days with 50 mg twice daily (BID; Days 1-14) and 100 mg BID (Days 15-28) of BCX9930 produced dose-dependent, clinically meaningful improvements across hemolysis biomarkers (Figure 2). Decreases were observed in LDH (4/4), reticulocytes (4/4), and total bilirubin (2/2 subjects with elevated pre-treatment values). Increases were observed in Hb (3/4) and PNH RBC clone size (4/4). One subject showed an initial response to BCX9930 50 mg BID, followed by worsening indicators of hemolysis temporally associated with an upper respiratory tract infection (URTI; onset on Day 7). With an increase in dose to 100 mg BID and resolution of the URTI, LDH and reticulocytes fell and Hb rose. All four subjects reported one or more PNH-associated symptoms, including hemoglobinuria, jaundice, fatigue, erectile dysfunction, headache and abdominal pain, prior to enrollment. With the exception of one subject with persistent hemoglobinuria, all symptoms resolved by Day 28 on BCX9930. Three subjects experienced moderate headache that resolved in < 3 days after initiating BCX9930. One subject developed a rash during treatment with amoxicillin for an URTI; the rash resolved while continuing BCX9930 dosing. One subject on concomitant chronic corticosteroids and azathioprine had an unrelated fatal serious adverse event of disseminated varicella during the study extension. Based on review of safety data, Cohort 2 opened at doses of 200 mg BID and 400 mg BID and, in the 3 subjects who continued into the extension, the dose was titrated to ≥ 200 mg BID. CONCLUSIONS: Oral BCX9930 elicited rapid changes in laboratory parameters indicative of reduced hemolysis and clinical benefit and was safe and generally well-tolerated over a 28-day dosing interval. These interim results establish proof of concept for monotherapy with BCX9930 in the treatment of C5-inhibitor naïve PNH patients and support evaluation of higher doses. Disclosures Kulasekararaj: Alexion:Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel grants, Speakers Bureau;Ra Pharma:Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel grants, Speakers Bureau;BioCryst Pharmaceuticals, Inc.:Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees;Apellis:Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel grants, Speakers Bureau;Roche:Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Novartis:Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel grants, Speakers Bureau;Celgene:Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel grants, Speakers Bureau.Malherbe:Key Oncologics:Honoraria, Other: Conference sponsor;Novartis:Other: Conference sponsor;Astellas:Honoraria, Other: Conference sponsor;Takeda:Consultancy;Acino:Honoraria;Shire:Other: Conference sponsor;BioCryst Pharmaceuticals, Inc.:Consultancy;Janssen:Consultancy, Honoraria, Other: Conference sponsor;Roche:Honoraria, Other: Conference sponsor.McDonald:venetoclax advisory board in South Africa (in CLL context):Consultancy;Alberts Cellular Therapy:Current Employment.Cornpropst:BioCryst Pharmaceuticals, Inc.:Current Employment.Collis:BioCryst Pharmaceuticals, Inc.:Current Employment.Davidson:BioCryst Pharmaceuticals, Inc.:Current Employment.Chen:BioCryst Pharmaceuticals, Inc.:Current Employment.Tower:BioCryst Pharmaceuticals, Inc.:Current Employment.Gesty-Palmer:BioCryst Pharmaceuticals, Inc.:Current equity holder in publicly-traded company, Ended employment in the past 24 months.Sheridan:BioCryst Pharmaceuticals, Inc.:Current Employment.Risitano:Alexion:Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau;Alnylam:Research Funding;Novartis:Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau;Pfizer:Speakers Bureau;Achillion:Membership on an entity's Board of Directors or advisory committees;Apellis:Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Biocryst:Membership on an entity's Board of Directors or advisory committees;RA pharma:Research Funding;Amyndas:Consultancy;Samsung:Membership on an entity's Board of Directors or advisory committees;Roche:Membership on an entity's Board of Directors or advisory committees;Jazz:Speakers Bureau.

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Sickle Stroke Screen: A Patient-Centered Educational Initiative for Children with Sickle Cell Anemia in the Displace Consortium

Blood ◽

10.1182/blood-2020-141963 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 43-44

Author(s):

Alyssa M Schlenz ◽

Shannon Phillips ◽

Martina Mueller ◽

Cathy L Melvin ◽

Robert J Adams ◽

...

Keyword(s):

Needs Assessment ◽

Board Of Directors ◽

Sickle Cell ◽

Sickle Cell Anemia ◽

Stroke Prevention ◽

Stroke Risk ◽

Advisory Board ◽

Educational Initiative ◽

Advisory Committees ◽

Board Membership

Introduction: The NHLBI funded Dissemination and Implementation of Stroke Prevention Looking at the Care Environment (DISPLACE) study was designed to improve implementation of stroke prevention guidelines in children with sickle cell anemia (SCA), particularly implementation of transcranial Doppler (TCD) ultrasound for identifying individuals at risk of stroke. The study consists of 3 phases: 1) evaluating current stroke risk screening practices, 2) exploring barriers and facilitators to guideline implementation (needs assessment), and 3) designing and implementing interventions to improve stroke risk screening. A key barrier identified through qualitative methods during the needs assessment was a gap in education, including an overall lack of understanding among patients and caregivers of the purpose of TCD screening. This abstract describes the process of developing one of the interventions for phase 3, a rebranding and educational initiative. Methods: During the needs assessment, 27 key informant interviews and 173 complete surveys were conducted with individuals with SCA and their caregivers. Transcripts from the interviews and survey responses were reviewed to better understand the extent of educational gaps described by families as well as to guide initial rebranding prototypes. Prototypes were developed by the study team, including a new name and logo for TCD as well as an infographic. An interview guide was then created to obtain feedback on the prototypes from individuals with SCA and/or the parent or primary caregiver from two sites in the consortium. Cue cards with prototypes were included with prompts for the "think aloud" method to be applied during interviews. Cue cards were presented first with prototypes for the new name in black font on a white background to solicit feedback on the wording alone. Then, cue cards included various layouts, fonts, and graphics with the prototype names for in-depth feedback on the logo appearance. Finally, participants were asked questions pertaining to the infographic. Results: Twenty interviews were conducted with individuals with SCA and/or the parent/caregiver at two DISPLACE sites. Almost all participants (95%) made the connection between the wording prototypes and TCD without prompting. Many participants expressed that the word "stroke" in both options was "scary," and sometimes chose the option that was "less scary to them." However, many participants also felt that the word "stroke" was necessary to explain the reason for the procedure and would prompt families to ask about the screening as opposed to making them more fearful. The majority of participants (60%) chose "Sickle Stroke Screen" over "Stroke Risk Screen." Participants reported preferring this wording because it is specific to SCA, was easier to remember and represented a less "scary" option. The most commonly preferred logo is presented in Figure 1. Participant reasons for selecting this option were: it is easier to read; they preferred the stacked layout; it is less spread out; they liked the bold letters; it is more eye catching; and it includes the words "sickle cell" in the logo. When asked about preferences for an infographic, the majority described including a picture of a brain. Nearly all participants believed a reassuring message was needed to balance out the fear of the word "stroke." The message, "knowledge is power" provided this balance and resonated with nearly all participants (95%). Figure 2 presents the infographic developed based on participant feedback. Conclusions: Results from this educational rebranding effort highlight the importance of understanding patient and family educational gaps and incorporating their perspective and feedback into educational campaigns. The new logo and infographic were integrated into an educational pamphlet, informative posters and other material designed by the DISPLACE site principal investigators. Part 3 of the study is underway including implementation of the educational initiative at the DISPLACE sites. The new terminology and logo have also been broadly distributed throughout the US through community-based organizations to other patients, families, and stakeholders. Disclosures Kanter: AGIOS: Membership on an entity's Board of Directors or advisory committees; NHLBI Sickle Cell Advisory Board: Membership on an entity's Board of Directors or advisory committees; SCDAA Medical and Research Advisory Board: Membership on an entity's Board of Directors or advisory committees; Wells Fargo: Honoraria; Jeffries: Honoraria; Cowen: Honoraria; bluebird bio, inc: Consultancy, Honoraria; Novartis: Consultancy; Sanofi: Consultancy; Medscape: Honoraria; Guidepoint Global: Honoraria; GLG: Honoraria; BEAM: Membership on an entity's Board of Directors or advisory committees.

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