In 2023, the U.S. Food and Drug Administration (FDA) approved two cell-based gene therapies for sickle cell disease (SCD)1 based on hematopoietic stem cell (HSC) transplantation. Both treatments — Casgevy and Lyfgenia — are considered curative.2 And both require collecting the patient’s own blood stem cells, a process made challenging due to the nature of sickled cells. Here, we explain why and highlight six considerations for the collection procedure.
The challenge of SCD collection
Sickle cell disease results from a mutation in the beta globin of hemoglobin. This mutation produces the abnormal hemoglobin HbS. In low-oxygen conditions, HbS can form polymers, or strands, that cause the red blood cells (RBCs) to assume the sickle shape characteristic of the disease. HbS polymerization caused by that single genetic error is central to the pathophysiology of this disease.
When RBCs sickle, they develop some attributes that make blood separation difficult compared to patients who don’t have SCD. Specifically, SCD cells:
- Are fragile and can easily rupture
- Are abnormally adhesive to vascular endothelial cells
- Interact with other cells, including white blood cells (WBCs) and platelets
In addition, people with sickle cell disease may also have thrombocytosis — high levels of platelets in their blood — and their blood may be prone to clotting. These tendencies alter the density of the blood, which can affect separation and may require anticoagulant changes when using the Spectra Optia
TM Apheresis System.
SCD collection considerations
When collecting cells from a patient with SCD, you should pay closer attention to certain aspects of the procedure. Here are some key points to consider.
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Closely monitor for aggregation or clumping throughout the disposable set at a frequency greater than for patients without SCD.
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Stay vigilant regarding anticoagulation. Adequate and appropriate anticoagulation will help ensure optimal blood flow through the device for collection efficiency while maintaining patient comfort.
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Identify optimal vascular access. Assess available options, realizing that some patients may have an existing vascular access device. Then consider patient comfort and operator experience when selecting the type of vascular access to use.
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Help the patient stay hydrated. This can help optimize vascular access while also mitigating intravascular volume shifts.
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Understand timing of the collection procedure and mobilization with plerixafor. Mobilization peaks much earlier for patients with SCD than for patients who don’t have the disease.
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Keep an eye on the collect line color. Collections for patients with SCD should target a color at numbers 4 or 5 on Spectra Optia’s Collection Preference tool rather than 2 or 3.
For more information
There is exciting progress being made in treating sickle cell disease. But when therapies involve cell collection, it’s important to remember that sickled cells have unique traits that require special considerations. To learn more about collecting cells from patients with SCD, particularly when using Spectra Optia,
see these guidelines or contact your local Termo Blood and Cell Technologies representative.
1FDA. FDA approves first gene therapies to treat patients with sickle cell disease. Posted December 8, 2023. Accessed September 18, 2024. https://www.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapies-treat-patients-sickle-cell-disease. 2National Library of Medicine. Hematopoietic stem cell transplantation in sickle cell disease. Updated July 19, 2023. Accessed September 18, 2024. https://www.ncbi.nlm.nih.gov/books/NBK538515/.Spectra OptiaTM is either a registered trademark or trademark of Terumo BCT, Inc. in the United States and/or other countries. See TerumoBCT.com/trademarks for details. Casgevy is either a registered trademark or trademark of Vertex Pharmaceuticals Incorporated in the United States and/or other countries. Lyfgenia is either a registered trademark or trademark of bluebird bio, Inc. in the United States and/or other countries.