Sickle Cell Disease: Stem Cell Transplantation
Consideration for transplantation should occur in all patients with neurologic injury who have a matched related sibling donor.
When considering transplantation for neurologic injury, children younger than age 16 years who receive matched sibling donor (MSD) HSCT have better outcomes than those older than age 16 years.
For patients with frequent pain, the ASH guideline panel suggests using related matched allogeneic transplantation rather than standard of care.(C, ⨁○○○)
Consideration for transplantation should be given to patients who do not respond or have an inadequate response to standard of care, such as HU, new targeted therapies, or chronic transfusion therapies.
Consideration for transplantation should be given to patients who continue to have recurrent ACS despite optimal standard of care (eg, HU, L-glutamine, crizanlizumab, and chronic transfusion therapy).
Alternative donor transplantation has the potential to improve or resolve disease manifestations in patients with severe SCD. The risks related to transplantation complications should be balanced with benefits derived from successful transplantation.
Recommendations could not be made if an MSD was not available because of the paucity of available data.
The impact of age on HSCT outcome may also be affected by the conditioning regimen used.
Potential harms (complications and adverse effects) of HSCT
|Death||Survival after HLA-identical sibling donor HSCT varies by age. In a large retrospective analysis of HSCT in patients with SCD, mortality occurred in 5%-20% depending on age. The probabilities of OS and EFS are summarized below:
For patients <16 y of age:
For patients ≥16 y of age:
In a more recent analysis of the data by CIBMTR, a higher incidence of mortality was observed in patients >13 y of age following myeloablative conditioning and MSD HSCT.
|GVHD||The development of GVHD after HSCT was a significant concern voiced by some patient representatives. The thought of dealing with a new chronic disease, like chronic GVHD, might be perceived as worse than SCD for some patients, although it is possible that some may consider this an acceptable risk, depending on severity, if balanced by cure from SCD. The incidence of GVHD after MSD HSCT and myeloablative conditioning is summarized below:
For patients ≤16 y of age:
acute GVHD (grade 2-4), 12.6%
chronic GVHD, 14.6%
For those >16 y of age:
acute GVHD (grade 2-4), 16%
chronic GVHD, 23%
|Graft failure||For some individuals considering HSCT, the biggest risk is that the procedure fails, and they have recurrent SCD. Graft failure is most often manifested as autologous recovery and therefore recurrence of the SCD manifestations. Risk of graft failure varies by conditioning intensity, donor type, GVHD prophylaxis (eg, use of T-cell depletion), and HLA match. After MSD HSCT, graft failure occurs in 5%-10% of patients.
The risk of graft rejection increases as the conditioning regimen intensity decreases and if an alternative donor (HLA mismatched or unrelated) is used. Although less frequent than GVHD, the risk of graft failure may carry a larger emotional burden than other HSCT complications and should be thoroughly discussed with potential patients and families as well as familial donors if applicable.
|Infection||Infection is a common complication of SCT but is usually manageable. In many instances, infection may prolong hospitalization or cause additional hospitalizations in individuals who have undergone SCT. In rare instances, infections might not respond to available treatment and could be fatal. The risk decreases over time after SCT and as immune suppression is stopped. Infection is a common complication of GVHD.|
|Infertility||Infertility risk after HSCT is an important consideration for all patients and in those with SCD. Infertility occurs frequently after myeloablative conditioning and is nearly universal in postpubertal patients. However, with the advent of less intense conditioning, the risk of infertility is likely lower. The option of gamete retrieval and cryopreservation is an increasingly considered option, although it is expensive and not universally available. This is an important consideration in patient decision making|
|Malignancy||The incidence of a therapy-related malignancy, particularly after myeloablative allogeneic HSCT, seems to be low overall. Risks after less intense conditioning regimens are not known at this time. This risk should be discussed with potential patients and families.|
Sickle Cell Disease: Stem Cell Transplantation
September 28, 2021
Last Updated Month/Year
July 14, 2023
Supplemental Implementation Tools
Country of Publication
Male, Female, Adolescent, Adult, Child, Older adult
Health Care Settings
Nurse, nurse practitioner, physician, physician assistant
D000755 - Anemia, Sickle Cell, D018380 - Hematopoietic Stem Cell Transplantation
sickle cell disease, stem cell transplantation, SCD, Hematopoietic stem cell transplantation, HSCT
Kanter J, Liem RI, Bernaudin F, Bolaños-Meade J, Fitzhugh CD, Hankins JS, Murad MH, Panepinto JA, Rondelli D, Shenoy S, Wagner J, Walters MC, Woolford T, Meerpohl JJ, Tisdale J. American Society of Hematology 2021 guidelines for sickle cell disease: stem cell transplantation. Blood Adv. 2021 Sep 28;5(18):3668-3689. doi: 10.1182/bloodadvances.2021004394C. PMID: 34581773.