The American Society of Hematology (ASH) recently released 2021 guidelines for hematopoietic stem cell transplantation (HSCT) in sickle cell disease (SCD) in a publication in Blood Advances.
In the United States, SCD is the most common inherited clinically significant hemoglobinopathy, and individuals with SCD experience disease-related complications and early mortality. HSCT is the only established curative intervention for SCD.
The ASH guidelines are intended “to support patients, clinicians, and health professionals in their decisions about HSCT for SCD.”
To develop the guidelines, ASH formed a multidisciplinary guideline panel that included 2 patient representatives. The panel addressed questions on the use of HSCT for patients with SCD with neurologic injury, frequent pain, or acute chest syndrome as well as questions regarding the type of transplantation and donor used and the age of the patient.
Under the direction of the Mayo Evidence-Based Practice Research Program, the panel used updated and original systematic reviews of evidence through 2019 and followed best practices for guideline development and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to assess the certainty of the evidence and formulate recommendations. The panel’s recommendations were also subject to public comment.
Based on the questions addressed, the panel formulated 8 recommendations (readers are advised to consult the full publication to read the detailed recommendations with the qualifying remarks):
- In patients with SCD who have experienced an overt stroke or have an abnormal transcranial Doppler ultrasound, consider HLA-matched related HSCT rather than standard of care (hydroxyurea [HU]/transfusion).
- For patients with frequent pain, consider related matched allogeneic transplantation rather than standard of care.
- For patients with recurrent episodes of acute chest syndrome, consider matched related allogeneic transplantation over standard of care.
- For patients with SCD with an indication for HSCT who lack a matched sibling donor, consider transplants from alternative donors in the context of a clinical trial.
- For allogeneic HSCT, consider either total-body irradiation ≤400 cGy or chemotherapy-based conditioning regimens.
- For both children and adults with SCD who have an indication for allogeneic HSCT and a matched sibling donor, consider myeloablative conditioning over reduced-intensity conditioning that contains melphalan/fludarabine regimens.
- In patients with an indication eligible for HSCT, consider allogeneic transplantation at an earlier age rather than an older age.
- Consider the use of HLA-identical sibling cord blood when available over bone marrow.
The guidelines were limited by the nonexistence of any randomized controlled clinical trials for HSCT in SCD. Thus, the panel deemed all recommendations to be based on very low or low certainty in the evidence.
Because of the substantial lack of evidence for HSCT in SCD, the panel highlighted key needs for future improvement to recommendations:
- A clinical longitudinal registry to serve as a comparator for HSCT studies
- For individuals living with SCD, increased access to care by SCD specialists
- Greater evaluation of newer disease-modifying therapies and their impact on quality and length of life for individuals living with SCD
- Predictive biomarkers of mortality in SCD
- Updated data to evaluate newer alternative donor transplantation regimens
Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Kanter J, Liem RI, Bernaudin F, et al. American Society of Hematology 2021 guidelines for sickle cell disease: stem cell transplantation. Blood Adv. 2021;5(18):3668-3689. doi:10.1182/bloodadvances.2021004394C