Stem cell transplantation for sickle cell disease: ASH 2021 guideline

Recommendation 1

The ASH guideline panel suggests HLA-matched related HSCT rather than standard of care (hydroxyurea (HU)/transfusion) in patients with SCD who have experienced an overt stroke or have an abnormal transcranial Doppler ultrasound (TCD) (conditional recommendation. very low certainty in the evidence).

Remarks

• 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.

Recommendation 2

For patients with frequent pain, the ASH guideline panel suggests using related matched allogeneic transplantation rather than standard of care (conditional recommendation, very low certainty in the evidence about effects).

Remark

• 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.

Recommendation 3

For patients with recurrent episodes of ACS, the ASH guideline panel suggests using matched related allogeneic transplantation over standard of care (conditional recommendation, very low certainty in the evidence about effects).

Remark

• 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).

Recommendation 4

For patients with SCD with an indication for HSCT who lack an MSD, the ASH guideline panel suggests using transplants from alternative donors in the context of a clinical trial (conditional recommendation, very low certainty in the evidence about effects).

Remark

• 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.

Recommendation 5

For allogeneic HSCT, the ASH guideline panel suggests using either total-body irradiation (TBI) ≤400 cGy or chemotherapy-based conditioning regimens (conditional recommendation, very low certainty in the evidence about effects).

Recommendation 6a

For children with SCD who have an indication for allogeneic HSCT and an MSD, the ASH guideline panel suggests using myeloablative conditioning over RIC that contains melphalan/fludarabine regimens (conditional recommendation, very low certainty in the evidence about effects).

Recommendation 6b

For adults with SCD who have an indication for allogeneic HSCT and an MSD, the ASH guideline panel suggests nonmyeloablative conditioning over RIC that contains melphalan/fludarabine regimens (conditional recommendation, very low certainty in the evidence about effects).

Recommendation 7

In patients with an indication eligible for HSCT, the ASH guideline panel suggests using allogeneic transplantation at an earlier age rather than an older age (conditional recommendation, low certainty in the evidence about effects).

Remarks

• 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.

Recommendation 8

The ASH guideline panel suggests the use of HLA-identical sibling cord blood when available (and associated with an adequate cord blood cell dose and good viability) over bone marrow (BM) (conditional recommendation, very low certainty in the evidence about effects).

"The use of HSCT for SCD is evolving," the authors write. "The conditional nature of the recommendations for all questions results from the short duration of accumulated data and the reliance on evaluation of noncomparative data."

Reference:

"American Society of Hematology 2021 guidelines for sickle cell disease: stem cell transplantation," is published in the journal Blood Advances.