Study aid only. Verify against current guidelines, primary literature, staging manuals, and prescribing information before clinical use.

← All algorithms  ·  Related notes →

Sickle Cell Disease: Disease-Modifying Therapy

First-line Second-line Later-line SECOND-LINE THIRD-LINE / LATER Sickle cell disease (HbSS / Sβ0) Foundation Add-on (recurrent VOC / anemia) Curative All with VOC Hydroxyurea ↑ HbF, ↓ crises · BABY HUG ↗ ↓ VOC Crizanlizumab SUSTAIN ↗ ↓ VOC L-glutamine adjunct Transplant Allogeneic HSCT matched donor Gene therapy exa-cel / lovo-cel CLIMB-SCD-121 / HGB-206 ↗

Sickle Cell Disease: Disease-Modifying Therapy: overview

This algorithm covers disease-modifying therapy for sickle cell disease (HbSS or S beta-zero thalassemia), structured as foundation therapy, add-on agents and curative options.

Hydroxyurea is the foundation for all patients with vaso-occlusive crises (VOC), acting by raising fetal hemoglobin (HbF) and reducing crises. For recurrent VOC or anemia, add-on options include crizanlizumab to reduce VOC (SUSTAIN) and L-glutamine as an adjunct to reduce VOC. Voxelotor (HOPE), which raised hemoglobin, was withdrawn from the market in 2024 and is no longer an option. Curative approaches are reserved for later in the sequence: allogeneic hematopoietic stem cell transplantation for patients with a matched donor, and gene therapy with exa-cel or lovo-cel for selected patients. The chart therefore places agents that reduce crisis frequency before curative therapy, with transplantation and gene therapy as the only options intended to cure the disease.

Trials behind this algorithm

Background reading: Sickle Cell Disease board review notes.

Sickle Cell Disease: Disease-Modifying Therapy: the algorithm in words

Starting point: Sickle cell disease (HbSS / Sβ0). Full background: Sickle Cell Disease notes.