Exploring the State of the Science of Stem Cell Transplantation and Posttransplant Disability Proceedings of a Workshop (2022) / Chapter Skim
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5 The Future Outlook for Stem Cell Transplantation and Disability
5 The Future Outlook for Stem Cell Transplantation and Disability
Pages 53-64
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From page 53... ...
GENE THERAPY John Tisdale, chief of the Cellular and Molecular Therapeutics Branch at the National Institutes of Health said that allogeneic hematopoietic stem cell transplantation (HSCT) can cure sickle cell disease by replacing the patient's stem cells with another person's stem cells.
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From page 54... ...
We know that allogenic transplantation works for curing sickle cell disease, said Tisdale; risk of stroke, pain, acute chest syndrome, and other symptoms are drastically reduced. Gene therapy is demonstrating efficacy in sickle cell disease and other diseases, and "we are hopeful" that the improvements seen in allogenic transplants will also be seen with the gene therapy approach.
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From page 55... ...
–CRISPR-associated 9 (Cas9) nucleases; HSC: hematopoietic stem cell; HSCT: hematopoietic stem cell transplantation; NHP: nonhuman primate; SCID: severe combined immunodeficiency; TALEN: transcription activator-like effector nuclease; ZFN: zinc finger nuclease.
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From page 56... ...
These cells consist of different parts, explained Porter: an antibody to target the specific protein on the cancer cell, sequences to bring and stabilize the protein on the surface of the T cell, and signals for T-cell activation, growth, and survival. Similar to gene therapy, lentivirals are used to bring new coding into the T cell.
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From page 57... ...
The major unique toxicity of CAR T cells is cytokine release syndrome, in which inflammatory molecules are released because of immune cell activation. Although severe, the syndrome can be managed quite effectively in most patients with the use of an antibody called tocilizumab, he said.
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From page 58... ...
Porter said that with these results, "it is time that we can say" that CAR T cells are indeed curing patients who previously had incurable, rapidly progressing, life-threatening malignancies. PREVENTING AND MITIGATING HSCT COMPLICATIONS Steven Devine, chief medical officer at the National Marrow Donor Program (NMDP)
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From page 59... ...
. If transplants could be conducted successfully with 7/8 donors, this would increase donor availability for patients who are African American to 72 percent, and if 6/8 donors were added, it would increase TABLE 5-2 Increase in Use of Posttransplant Cyclophosphamide in Patients Receiving Hematopoietic Stem Cell Transplants Year Donor Source 2016 2020 Matched sibling 7% 24% Haploidentical related 85% 94% Matched unrelated 6% 28% Mismatched unrelated 14% 63% SOURCES: As presented by Steven Devine, November 15, 2021; CIBMTR®a; The views expressed in this publication are that of the authors and do not reflect the position of the Center for International Blood and Marrow Transplant Research.
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From page 60... ...
Given this potential, the NMDP sought to evaluate PTCy in HSCT patients with a mismatched or unrelated donor (Shaw et al., 2021)
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From page 61... ...
1 The FDA-approved abatacept (Orencia) in December 2021 for the prophylaxis of acute GVHD, in combination with a calcineurin inhibitor and methotrexate, in adults and pediatric patients 2 years of age and older undergoing HSCT from a matched or 1 allelemismatched unrelated donor: https://www.fda.gov/drugs/resources-information-approveddrugs/fda-approves-abatacept-prophylaxis-acute-graft-versus-host-disease (accessed March 3, 2022)
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From page 62... ...
Further, said Thompson, preexisting disparities and social determinants of health can perpetuate and exacerbate disparities. For example, while gene therapy can be used to cure sickle cell anemia, patients with existing organ damage will likely still have a degree of disability.
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From page 63... ...
The fields of gene therapy and CAR T cells are in their infancy, said Porter, so there is a lack of long-term outcomes data. More than 1,000 different cell therapies are currently in development, and the field is set to "explode." Now is the time, he emphasized, to set up a mechanism to collect long-term data in this area.
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From page 64... ...
64 STEM CELL TRANSPLANTATION AND POSTTRANSPLANT DISABILITY CLOSING REMARKS To conclude the workshop, Rosenbaum thanked the speakers, the workshop participants, the planning committee, the staff, and the Social Security Administration for their part in putting together this "rich discussion." The workshop presentations and discussions, she said, offered an incredible amount of insight into the promises and challenges of hematopoietic stem cell transplantation therapy and what is on the horizon. After these remarks, Rosenbaum adjourned the workshop.
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