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EBMT 2025 | Patient selection for gene therapy in sickle cell disease
Akshay Sharma, MBBS, MSc, St. Jude Children’s Research Hospital, Memphis, TN, comments on the importance of patient selection for gene therapy in sickle cell disease (SCD). Dr Sharma emphasizes that the selection and preparation process, which can take 6 to 12 months, requires a thorough evaluation of patients’ organ function, medical history, and current health status to ensure their suitability for gene therapy. This includes assessing cardiac, pulmonary, and renal function; history of stroke or cerebral infarct; as well as considering the potential risks associated with myeloablative busulfan conditioning and the need to manage chronic blood transfusions. This interview took place at the 51st Annual Meeting of the EBMT in Florence, Italy.
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Transcript
Patient selection is very important for gene therapy, just as it is for allogeneic hematopoietic cell transplantation. Gene therapy is a very, very long process for patients with sickle cell disease. It starts with selection of the ideal patient, preparation for collection of hematopoietic stem cells, harvesting the hematopoietic stem cells, and then conditioning the patients with chemotherapy to then administer the cells back to them...
Patient selection is very important for gene therapy, just as it is for allogeneic hematopoietic cell transplantation. Gene therapy is a very, very long process for patients with sickle cell disease. It starts with selection of the ideal patient, preparation for collection of hematopoietic stem cells, harvesting the hematopoietic stem cells, and then conditioning the patients with chemotherapy to then administer the cells back to them. From start to finish, this process can take anywhere from 6 to 12 months. And at each step of the way, patients have to be in a certain good health to be able to collect the cells and then to receive chemotherapy.
And so the first step involves performing a thorough organ function evaluation, looking at their cardiac function, pulmonary function, renal function, making sure that there is no history of stroke or cerebral infarct, which would preclude these patients from receiving gene therapy. And once that has been done, we can move forward with the different steps.
It is essential to perform all these evaluations upfront because many patients, because of their underlying conditions, especially if they have pulmonary dysfunction or if they’ve had a history of stroke for which they’re receiving chronic blood transfusions, they may be at higher risk after gene therapy. For example, patients who are receiving gene therapy currently, they all need to undergo myeloablative busulfan conditioning. And we know that myeloablative busulfan conditioning is associated with a certain degree of pulmonary toxicity and neurotoxicity. And so if somebody really has diffuse pulmonary fibrosis already, perhaps giving them busulfan is not a good idea.
Also, patients who have severe vaso-occlusive crises for which they are getting admitted to the hospital on a very frequent basis, it may become very challenging to collect hematopoietic stem cells from them in adequate quantities.
And lastly, as I alluded to, patients who are receiving chronic blood transfusions for CNS disease, we may not be able to adequately discontinue or safely discontinue their blood transfusions after gene therapy. We just don’t have evidence to do that right now. And so these are the conditions that we need to pay special attention to, to select the patients for undergoing gene therapy.
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Disclosures
Consultant: Medexus Inc., Vertex Pharmaceuticals, Editas Medicine, Pfizer, BioLineRx; Clinical Trial site-PI: CRISPR Therapeutics, Vertex Pharmaceuticals, Novartis, Beam Therapeutics; Honoraria: Blackwood CME.
