(ORLANDO, Dec. 6, 2025) Patients who underwent hematopoietic cell transplantation for sickle cell disease saw high rates of survival without disease symptoms and low rates of severe side effects or complications years after their procedure, according to a new study . The study included over 1,000 patients, representing the largest and most comprehensive analysis of long-term transplant outcomes to date in people living with sickle cell disease.
"A majority of patients in this cohort are alive; the transplant worked so they no longer show symptoms of their sickle cell disease, and most have had no late effects post-transplant," said lead study author Elizabeth Stenger, MD, associate professor in the department of pediatrics at Emory University School of Medicine and pediatric hematologist/oncologist at the Aflac Cancer and Blood Disorders Center of Children's Healthcare of Atlanta in Georgia. "There are families that really want to know the data, and this will be among the largest and most statistically well-powered studies that can provide this information to patients we are counseling about transplant."
Hematopoietic cell transplantation can eliminate symptoms of sickle cell disease by giving patients the ability to make healthy blood cells instead of ones prone to sickling. For the procedure, patients first undergo a chemotherapy-based conditioning regimen to clear the bone marrow of their own stem cells. Stem cells from a healthy donor are then infused and migrate to the bone marrow, where they begin producing healthy blood cells.
This procedure has been in use for several decades, but strategies for donor matching and conditioning have evolved over time. Long-term outcomes from hematopoietic cell transplantation, as it is currently practiced, have not been well studied in people living with sickle cell disease. In particular, it is unknown whether patients may face unique long-term effects of chemotherapy conditioning due to sickle cell disease-related organ damage.
Researchers analyzed data from 1,013 patients who received a hematopoietic cell transplant at 112 medical centers in the United States and internationally between 1996 to 2022. About half were female and just over half had a matched related donor. Procedures that resulted in primary graft failure (meaning that the donor stem cells did not persist early after transplant) were excluded from the data set.
At seven years post-transplant, 90% of transplant recipients remained alive, 83% were alive and had experienced no issues with transplant rejection, and 63% were alive without having experienced any late rejection or severe graft-versus-host disease (GVHD), a condition in which the transplanted donor cells attack the recipient's body.
Sickle cell disease outcomes, which were assessed at a median of five years post-transplant, were also largely positive. Most patients (86%) remained free from sickle cell disease symptoms with hemoglobin S levels at or below 50%, and most (74%) had no sickle cell disease-related complications reported at any time point post-transplant.
Excluding infections, the most common late effects of transplant were those affecting the liver (seen in 10% of patients at seven years post-transplant), lungs (8%), reproductive organs (6%), and pancreas (i.e., diabetes; 6%). Of the 9% of patients who died, the most common causes of death were organ failure, infection, and GVHD.
Factors associated with better outcomes included being younger at the time of transplant, having a matched related donor instead of a genetically mismatched or unrelated donor, and having bone marrow instead of peripheral blood as the source of donated cells.
Remaining free of GVHD was also significantly associated with better long-term outcomes. At a median of five years, 26% of patients had experienced chronic GVHD and 30% had experienced acute GVHD, both of any severity.
Given its uniquely large sample with heterogenous transplant characteristics, researchers said that the study findings can help families and doctors make informed decisions about whether – and when – to pursue a transplant. "This study can provide more concrete data about [the risks and benefits] if transplant is undertaken early versus waiting," said Dr. Stenger. "Right now, allogeneic hematopoietic cell transplantation is the only known and available option for this population capable of eliminating the full spectrum of disease symptoms. Especially if we do it while patients are young or before the onset of organ damage, these patients can go on to live much more normal lives."
The study also underscores the importance of ongoing health monitoring following a transplant. "From a clinical standpoint, [it reinforces] the need to make sure these patients are having the recommended annual follow-up to screen and monitor for late effects so that if they are happening, we can catch them early and hopefully prevent them from becoming symptomatic and more clinically significant," said Dr. Stenger.
Since the study relied on data provided to a registry, researchers noted that the level of detail is somewhat limited for some factors.
Researchers are now working to compare survival outcomes among people living with sickle cell disease who received a hematopoietic cell transplant versus those who did not receive a transplant including those who received disease-modifying treatment. Dr. Stenger said that additional insights on potential late effects could be gained through future studies with a longer follow-up period.
Elizabeth Stenger, MD, of Emory University School of Medicine and the Aflac Cancer and Blood Disorders Center of Children's Healthcare of Atlanta, will present this study on Monday, December 8, 2025, at 4:30 p.m. Eastern time in W331 of the Orange County Convention Center.
