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City of Hope researchers assess novel stem cell transplant procedure
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The California Institute for Regenerative Medicine awarded a $5.7 million grant to City of Hope to fund a trial of a novel hematopoietic stem cell transplant procedure for adults with severe sickle cell disease.
“The City of Hope transplant program in sickle cell disease has vast experience in the field and has completed hematopoietic stem cell transplantation in 27 patients to date,” Joseph Rosenthal, MD, chief of the division of pediatric hematology/oncology at City of Hope, said in a press release. “The California Institute for Regenerative Medicine funding will now allow us to conduct a phase 1 trial in six adult patients with severe sickle cell disease.
“City of Hope believes this treatment will improve the quality of life for patients while also reducing the risk for graft-versus-host disease and transplant-related complications,” Rosenthal added. “Our hope is that this treatment can be eventually offered to sickle cell disease patients as a curative therapy.”
HemOnc Today spoke with Rosenthal about this novel approach; the efficacy and safety observed so far; how the trial will be conducted; and the potential implications if this approach is proven safe and effective.
Question: How was this novel approach developed?
Answer: One of our basic research labs headed by Defu Zeng, MD, has long been interested in exploring the mechanisms for achieving immune tolerance. Zeng and colleagues developed this procedure in mouse models, including mice with auto-immune disorders. Results showed that the human leukocyte antigen barrier can be crossed without any rejection of GVHD when the cells are manipulated in a certain way. This was the basis of our research now underway.
Q: How will the trial be conducted?
A: The patient population includes those with sickle cell disease, especially those who have suffered significant organ injury secondary to sickle cell disease. It is relatively not that difficult to find patients with an adequate identical donor, and we rarely face a situation in which a patient does not have an identical donor. Approximately 90% of patients will have an adequate identical donor. In the first phase of the trial, we will collect cells from the donor and manipulate them to be ready to achieve mixed chimerism. Once we have the cells stored and frozen, the patient will start 21 days of a nontoxic treatment regimen. On day 0 — the day of the procedure — the patient will be given the stored cells. The treatment will take place in a specially designed clinic.
Q: Why are new approaches needed for this patient population ?
A: Sickle cell disease is a devastating disorder. In West Africa, there are roughly 400,000 children born with sickle cell disease, nearly 80% of whom will die of their disease within 2 years. This is not a problem anymore in the United States. Here, the adverse effects of sickle cell disease have shifted to young adulthood and adulthood. Although the life expectancy for someone with this disease has been extended in the Western world, the suffering associated with the condition is a result of vaso-occlusive crisis, such as stroke, bone issues and general organ failure. These patients have a very poor quality of life. Even though their life is extended, it is not a good life. Much of the treatment for this disease in the United States is focused on providing supportive care with hydroxyurea. However, there are ways to achieve complete cure of the condition and this is what we are focused on — finding treatment that is easy to deliver, is associated with less transplant-associated toxicities and is resulting in cure of the condition.
Q: What are the potential implications if this approach is proven safe and effective?
A: If successful, it can potentially change from a life of misery and suffering from sickle cell disease to a life that is sickle cell disease free and without the common complications often associated with the disease. There even are potential implications beyond sickle cell disease. If we can achieve immune tolerance with sickle cell disease, it can lead to achievements for other autoimmune disorders for which immune tolerance is key to long-term survival. This could be a possibility if this trial is successful.
Q: Is there anything else that you would like to mention?
A: Trying to find a curative treatment is only the tip of the iceberg of sickle cell disease treatment. Currently, the focus is on providing the best supportive care for patients with sickle cell disease to minimize their suffering. Our approach looks at the next generation of treatment aimed at cure of this disease. – by Jennifer Southall
For more information:
Joseph Rosenthal, MD, can be reached at City of Hope, 1500 E. Duarte Road, Duarte, CA 91010; email: jrosenthal@coh.org.
Disclosure: Rosenthal reports no relevant financial disclosures.