Hydroxyurea Use Among Infants with Sickle Cell Disease: A Survey of Pediatric Hematologists-Oncologists In the United States
Authors: Singh Arun L , Lastra Carlos , Mahadeo Kris M. 
Published: October 2019

Abstract
Abstract 1640
A National Institutes of Health expert panel concluded that barriers to hydroxyurea (HU) therapy for patients with sickle cell disease (SCD) exist at multiple levels, including that of healthcare providers.1 Despite calls for more widespread use of HU among infants with SCD, only a small fraction of those who meet currently accepted criteria for HU administration are actually prescribed therapy.1 To address this disparity, we assessed barriers to HU therapy as perceived by Pediatric Hematologists-Oncologists in the United States. This study was approved by the institutional review board. We surveyed 400 Pediatric Hematologists/Oncologists from varying regions in the United States. Prospective participants were emailed a link to an anonymous online survey. To ensure an optimal response rate, two-follow up emails were sent at two week intervals to those who did not initially respond. Our survey instrument was evaluated for content validity by 5 Pediatric subspecialists from geographically diverse areas of the country and included both public and private settings. Response rate was equal to (complete responses+ partial responses)/(complete responses + partial responses + nonresponse + implicit refusals). In this study, a complete response was defined as 80% or more of questions answered and a partial response as less than 80% of questions answered. The response rate for this survey was 25% (n=99). Respondents’ primary areas of practice included pediatric hematology (27.5%; n=22), general pediatric hematology oncology (57.5%, n=46) and pediatric oncology (15%, n=12). Respondents’ practices ranged in the size of their sickle cell populations from 3 to 1600 (median=300). The vast majority of respondents agreed or strongly agreed that HU was an effective treatment for children with SCD (98%, n= 83). Most respondents (55%, n=45) reported the age range of 1–5 years as the youngest age at which they initiated HU therapy among their patients, 17% (n=14) had initiated therapy in a patient between 6months and 1 year of age. Common independent criteria for HU initiation included recurrent acute chest syndromes (94%, n=78), vaso-occlusive crises (93%, n=77), other pulmonary disease (including increased tricuspid regurgitation velocities) (66%, n=55) and priapism (58%, n=48). Interestingly, 30% (n=25) of respondents used patient/family request as an independent criterion for HU therapy. Compliance/adherence (89%, n=72), need for frequent monitoring (78%, n=68) and family concerns regarding toxicity (76%, n= 63) were the most commonly reported barriers to the effective use of HU therapy among patients with SCD. While, 57.8% (n=48) of respondents agreed/strongly agreed that HU is an effective drug for the prevention of organ damage among infants with SCD, only 32% (n= 26) supported the prophylactic use of HU for infants (>6 months) with severe sickle genotypes (SS, SB0), regardless of disease severity. Respondents were most concerned about cytopenias (68%, n=55), fertility (46%, n=37), risk of malignancy (27%, n=22), gastrointestinal disturbances (26%, n=21) and avascular necrosis (17%, n=14). The majority of respondents agreed/strongly agreed that a prospective randomized controlled clinical trial is needed to establish the long-term safety and efficacy profile of HU treatment before prophylactic therapy is offered to infants with severe sickle cell genotypes, irrespective of their disease severity (78%, n=63), or to infants with SCD regardless of genotype and disease severity (82%, n=67). Respondents identified lack of funding for (71%, n=73) and family/patient mistrust towards a clinical trial (45%, n=46) as the major barriers to conducting a prospective study. The majority of respondents (94%, n=78) supported the establishment of a registry for all patients with SCD who are on HU therapy. While most respondents believe HU to be an effective drug for the treatment of patients with SCD and for prevention of associated organ damage, there is concern for potential toxicities of therapy. Most respondents support a prospective randomized controlled clinical trial and/or establishment of a registry for the use of prophylactic HU therapy among infants with SCD.
1. Brawley OW, Conrelius LJ, Edwards LR, et al. National Institutes of Health Consensus Development Conference statement: hydroxyurea treatment for sickle cell disease. Ann Internal Med. 2008; 148:932-938.

Disclosures:
Off Label Use: off-label use of hydroxyurea in children.