American Society of Hematology 2021 guidelines for sickle cell disease: stem cell transplantation

Abstract

Background: Sickle cell disease (SCD) is a life-limiting inherited hemoglobinopathy that results in significant complications and affects quality of life. Hematopoietic stem cell transplantation (HSCT) is currently the only curative intervention for SCD; however, guidelines are needed to inform how to apply HSCT in clinical practice. Objective: These evidence-based guidelines of the American Society of Hematology (ASH) are intended to support patients, clinicians, and health professionals in their decisions about HSCT for SCD. Methods: The multidisciplinary guideline panel formed by ASH included 2 patient representatives and was balanced to minimize potential bias from conflicts of interest. The Mayo Evidence-Based Practice Research Program supported the guideline development process, including performing systematic evidence reviews (through 2019). The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, including GRADE Evidence-to-Decision frameworks, to assess evidence and make recommendations, which were subject to public comment. Results: The panel agreed on 8 recommendations to help patients and providers assess how individuals with SCD should consider the timing and type of HSCT. Conclusions: The evidence review yielded no randomized controlled clinical trials for HSCT in SCD; therefore, all recommendations are based on very low certainty in the evidence. Key recommendations include considering HSCT for those with neurologic injury or recurrent acute chest syndrome at an early age and to improve nonmyeloablative regimens. Future research should include the development of a robust SCD registry to serve as a comparator for HSCT studies.

Consensus definition of essential, optimal, and suggested components of a pediatric sickle cell disease center

“…Collaboration with a hematopoietic stem cell transplant (HSCT) team is essential to offer curative therapy, especially since early consideration of HSCT for children with Hb SS and S-β 0 thalassemia who have an unaffected human leukocyte antigen-identical sibling was suggested by ASH in 2021. 21 Since the goal of pediatric SCD care is survival into adulthood and continued lifespan care, a partnership with an adult SCD program is essential. 16 Transition requires not only a referral to an adult hematologist/center, but also communication with the receiving team to convey essential knowledge about the patient's prior care and complications.…”

“…Collaboration was defined as regular communication and availability. Collaboration with a hematopoietic stem cell transplant (HSCT) team is essential to offer curative therapy, especially since early consideration of HSCT for children with Hb SS and S‐β 0 thalassemia who have an unaffected human leukocyte antigen‐identical sibling was suggested by ASH in 2021 21 . Since the goal of pediatric SCD care is survival into adulthood and continued lifespan care, a partnership with an adult SCD program is essential 16 .…”

Sickle Cell Disease

“…With some exceptions, such as sepsis and stroke prevention in children, preoperative transfusions, and hydroxyurea therapy, much of the evidence for managing SCD comes from observational cohorts, small RCTs, extrapolation from other populations, and expert opinion . Lack of research funding likely contributes to this paucity of high-quality evidence.…”

Development of curative therapies for sickle cell disease

“…Unfortunately, <20% of patients have HLA-matched donors. In the absence of a matched sibling donor, HLA-matched unrelated donors and HLA-identical sibling cord blood (CB) donors are alternatives ( 24 ).…”