The ethics of a proposed study of hematopoietic stem cell transplant for children with “less severe” sickle cell disease

Abstract

Hematopoietic stem cell transplant (HSCT) is the only cure for sickle cell disease (SCD). HSCT using an HLA-identical sibling donor is currently an acceptable treatment option for children with severe SCD, with expected HSCT survival >95% and event-free survival >85%. HSCT for children with less severe SCD (children who have not yet suffered overt disease complications or only had mild problems) is controversial. It is important to consider the ethical issues of a proposed study comparing HLA-identical sibling HSCT to best supportive care for children with less severe SCD. In evaluating the principles of nonmaleficence, respect for individual autonomy, and justice, we conclude that a study of HLA-identical sibling HSCT for all children with SCD, particularly hemoglobin SS and Sβ0-thalassemia disease, is ethically sound. Future work should explore the implementation of a large trial to help determine whether HSCT is a beneficial treatment of children with less severe SCD.

Improved Splenic Function After Hematopoietic Stem Cell Transplant for Sickle Cell Disease

“…This study is the first to investigate factors associated with splenic recovery post‐HSCT for SCD. Our finding that older age at time of HSCT was associated with poor splenic function post‐HSCT adds support to the idea that it may be preferable to transplant patients with SCD at a young age before irreversible organ damage occurs . Nonetheless, most patients (21/25, 84%) with absent splenic uptake pre‐HSCT did acquire uptake post‐HSCT, including a few patients with Hb SS disease older than 18 years.…”

Sickle cell disease: an international survey of results of HLA-identical sibling hematopoietic stem cell transplantation

“…11 Although several reports have demonstrated that HLA-identical sibling transplantation with bone marrow (BM) or umbilical cord blood (CB) establishes normal hematopoiesis and is associated with excellent survival, most studies were conducted at single institutions or in the context of clinical trials. [12][13][14][15][16][17] The current study sought to describe outcomes after HLA-identical sibling transplantation for SCD worldwide.…”

Hematopoietic stem cell transplantation for sickle cell disease: Progress and challenges

“…An additional consideration is whether prevention of recurrent pain, hospitalizations, reduced HRQL, and other complications throughout childhood balances the risks of MSD‐HSCT. In our view, there is equipoise to support a clinical trial of MSD‐HSCT in younger children with less severe SCD; this should include a control group of untransplanted children and a long follow‐up duration …”

“…Participants will be “biologically randomized” to HSCT or standard care based on the availability of an HLA‐identical sibling or unrelated donor, and all participants’ healthcare expenditures will be tracked. A proposed study of early MSD‐HSCT in young, less severely affected children could determine the long‐term impact on outcomes and healthcare costs …”