Abstract
BACKGROUND: Stroke is one of the most devastating complications of sickle cell disease. The groundbreaking National Institutes of Health (NIH)-funded TWiTCH study established hydroxyurea as an effective non-inferior alternative to chronic red blood cell transfusions for primary stroke prevention in children with sickle cell disease. The study findings, published in 2016, established a protocol for transitioning patients from transfusions to hydroxyurea. It is important to evaluate how well the protocol is being implemented in clinical practice.
OBJECTIVE: The main objective of this study was to investigate the outcomes of patients who were involved in the TWiTCH study at one academic medical center and the degree of adherence to the transition protocol for patients transitioning from transfusions to hydroxyurea.
METHODS: A retrospective chart review of TWiTCH study subjects in one academic medical center. Institutional Review Board (IRB) exemption was obtained. Data was collected for the time from the end of the TWiTCH study (2014) to the most recent (2021). Data collected included: Demographics, Magnetic resonance imaging (MRA), Magnetic resonance angiography (MRA), Ferriscan, TCD, blood chemistries, Ferritin, blood counts, and stroke prevention intervention strategies.
RESULTS: Eight TWiTCH subjects were identified, seven of whom had full evaluable data. All seven patients were stroke-free and had normal TCDs as of their most recent imaging. Four patients transitioned from chronic transfusions during the TWiTCH study to hydroxyurea post-study. One patient who was on hydroxyurea stayed on hydroxyurea while two patients who were on hydroxyurea transitioned to chronic transfusions. The mean current hemoglobin F was 8.3% compared with 27% reported by the TWiTCH study for all centers. Mean current ferritin was 1981ng/mL compared to 2238.6ng/mL at end of the TWiTCH study for subjects who are on hydroxyurea, 5943ng/mL, and 1123ng/mL respectively for patients currently on transfusions. The TWiTCH study reported ferritin of 2624ng/mL and 1226ng/mL for transfusion and hydroxyurea arms, respectively. The mean hydroxyurea dose was 24.5 mg/kg compared to 27mg/kg reported from the TWiTCH study. The mean hemoglobin was 7.9g/dL compared to 8.7g/dL at end of the TWiTCH study.
CONCLUSIONS: Most patients from the TWiTCH study have been safely transitioned to hydroxyurea as part of standard clinical care at our institution. Adherence with dosing and laboratory targets was suboptimal likely due to patient noncompliance and less rigorous follow up schedule. Suboptimal compliance places patients at risk of not benefiting from all the advantages of transitioning to hydroxyurea identified on the TWiTCH study. Continued monitoring of these patients to identify any complications is warranted. Strategies to improve adherence to the transitioning protocols need to be developed.
Disclosures
No relevant conflicts of interest to declare.
Author notes
Asterisk with author names denotes non-ASH members.
