Why, Who, When, and How? Rationale for Considering Allogeneic Stem Cell Transplantation in Children with Sickle Cell Disease

Abstract

Considering the progress made in the management of sickle cell disease during the past 30 years, along with the excellent results obtained with hematopoietic stem cell transplantation (SCT), it is important to reexamine why, who, when and how to recommend allogeneic SCT in children with sickle cell disease. While sickle cell disease has a low risk of death in children and a high risk for morbidity during aging, SCT carries an early risk of death, graft-vs-host disease and infertility. Nevertheless, SCT offers at least 95% chance of cure with low risk of chronic graft-vs-host disease when a matched-sibling donor is available and the risks of infertility can be reduced by ovarian, sperm or testis cryopreservation. Thus, all available therapies such as hydroxyurea, transfusions and SCT should be presented to the parents, providers, and affected children and discussed with them from infancy. Furthermore, the use of these therapies should be adjusted to the severity of the disease and to local availabilities in order to choose the treatment offering the best benefit/risk ratio.

Keywords: acute-chest syndrome; cerebral silent infarct; cerebral vasculopathy; hematopoïetic stem cell transplantation; hydroxyurea; sickle cell anemia; sickle cell disease; stroke; transfusion; vaso-occlusive crisis.

Figure 1

Difference between a transfused sickle-cell anemia (SCA)-patient who has a double population of sickle SS cells and transfused normal AA red cells and a transplanted patient who has only normal red blood cells as the donor (AS or AA) and no more sickle cells.

Figure 2

When to recommend SCT in children with sickle cell disease?

Figure 3

Indications of the different treatments: hydroxyurea, chronic transfusion and. type of SCT to recommend in children with cerebral vasculopathy. Abbreviations: HU = hydroxyurea, MSD = matched-sibling donor, SCT = stem cell transplantation, Haplo = related haplo-identical, URD = unrelated stem cell-transplantation.

Figure 4

Indications of the different treatments: hydroxyurea, chronic transfusion and. which kind of stem cell transplantation to propose in children with frequent vaso-occlusives or recurrent acute chest syndrome Abbreviations: VOC = vaso-occlusive crisis, ACS = acute-chest syndrome, HU = hydroxyurea, MSD = matched-sibling donor, SCT = stem cell transplantation, Haplo = related haplo-identical, URD = unrelated stem cell-transplantation, MAC = myeloablative conditioning.