Nashville, Tennessee – Among adult patients with severe sickle cell disease (SCD), favorable outcomes were reported with use of a modified transplantation procedure, according to results from a multicenter study presented at the 65th American Society of Hematology (ASH) Annual Meeting & Exposition in December 2023.
Although the use of stem cell transplantation is a potentially curable option for patients with SCD, the procedure is not feasible for most individuals because of a shortage of suitable donors or a failure to tolerate the effects of the intensive chemotherapy required prior to the transplant. Using a modified transplantation technique, however, can broaden the possible donor pool and involves a “gentler conditioning regimen,” thus permitting a larger group of individuals to derive benefit from this treatment.
According to Adetola A. Kassim, MD, MS, professor of medicine at Vanderbilt University Medical Center in Nashville, Tennessee, and the lead author of the study, “This is a pragmatic approach for adults with SCD, and the results are fantastic.” He noted, “This study has clearly shown that you can take selected patients with significant comorbidities to transplant, and hopefully change the trajectory of their disease.”
In patients with the inherited blood disorder SCD, red blood cells (RBCs) become misshapen, thus lessening their ability to carry oxygen throughout the body. Among those with the condition, episodes of severe pain, known as vaso-occlusive crises, are reported often, along with damage to organs and tissues over time, leading to premature mortality.
In SCD, a stem transplant can help to cure the disorder by deleting those stem cells that generate the misshapen RBCs and replacing them with donor stem cells that will produce healthy RBCs.
In the standard SCD stem cell transplantation procedure, the donor must be a sibling with a high level of genetic similarity to the recipient. Further, the stem cell recipient must be healthy enough to be able to tolerate an intensive chemotherapy regimen. In the modified transplant procedure, which is referred to as “related, reduced intensity haploidentical bone marrow transplantation,” it is necessary for the donor only to be only “half-matched genetically to the recipient.”
Utilization of such a technique thus expands the donor pool, with not only siblings considered possible donors, but parents, children, cousins, aunts, and uncles as well. Although fewer than 25% of individuals with SCD have a matched sibling who might possibly be a donor, approximately 90% do have a relative who might be a half-matched donor. This modified approach is also more easily tolerated by those with SCD-related medical issues, including organ damage.
In the present study, among a group of 54 patients with SCD and a history of frequent blood transfusions, stroke, decreased cardiac function, and pain episodes, 42 received a modified stem cell transplant. At 2 years, the overall rate of survival after transplantation was 95% and the estimated rate of event-free survival was 88%.
At 100 days post-transplant, 4.8% of recipients had a primary graft failure and 4.8% experienced grade 3 or higher adverse events. Infections were common, and 78.6% of participants reported 1 or more hospitalization(s). Although 2 of the patients died, most of the recipients had significant improvements in markers of blood functioning, reduced pain and fatigue, and improved lung and cardiac function.
“In future studies, the researchers plan to focus on opportunities to reduce rates of infection, enhance supportive care, and preserve fertility among people undergoing the procedure.”
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