Current Results and Future Research Priorities in Late Effects after Hematopoietic Stem Cell Transplantation for Children with Sickle Cell Disease and Thalassemia: A Consensus Statement from the Second Pediatric Blood and Marrow Transplant Consortium International Conference on Late Effects after Pediatric Hematopoietic Stem Cell Transplantation
Biology of Blood and Marrow Transplantation
A B S T R A C T Sustained donor engraftment after allogeneic hematopoietic cell transplantation (HCT) converts to healthy donor hemoglobin synthesis and halts disease symptoms in patients with sickle cell disease and thalassemia major. A diseasefree survival probability that exceeds 90% has been reported when HCT using an HLA-matched sibling donor is performed in young patients with low-risk disease or treatment-related risk factors. Alternate donor HCT and HCT in adults is performed
... y because of a higher risk profile. Transplant-specific risks include conditioning regimen-related toxicity, graft-versus-host disease, graft rejection with marrow aplasia or disease recurrence, and infections associated with immunosuppression and delayed immune reconstitution. The magnitude of risk depends on patient age, clinical status of the underlying disease (eg, organ injury from vasculopathy and iron overload), donor source, and intensity of the conditioning regimen. These risks are commonly monitored and reported in the short term. Documenting very late outcomes is important, but these data are rarely reported because of challenges imposed by patient drop-out and insufficient resources. This report summarizes long-term follow-up results after HCT for hemoglobin disorders, identifies gaps in knowledge, and discusses opportunities for future investigations. This consensus summary will be followed by a second article detailing comprehensive long-term follow-up recommendations to aid in maintaining health in these individuals and identifying late complication risks that could facilitate interventions to improve outcomes. j o u r n a l h o m e p a g e : w w w. b b m t . o r g a cessation of the acute signs and symptoms of the underlying disorder after stable engraftment of donor cells. The assumption that a successful transplant will extend lifespan and stop disease-related complications is central to decision-making about HCT. The goal of this summary article is to define and address current gaps in knowledge to create a roadmap of clinical investigation in this field. In a subsequent article we will suggest comprehensive monitoring guidelines to inform clinical decision-making that might facilitate health maintenance after HCT for these disorders. These efforts follow an international working group that convened at the Second Pediatric Blood and Marrow Transplant International Consensus Conference on Late Effects after HCT in Minneapolis, Minnesota, USA in May 2016. CURRENT RESULTS OF HCT FOR HEMOGLOBIN DISORDERS Thalassemia More than 4000 individuals with thalassemia major have received HCT, with most reports focused on results in children and young adults. Risk category assignments have been developed in several transplant series, determined by recipient age, liver size, liver histology, and whether or not there is compliance with iron chelation therapy     . Outcomes are best in young patients who lack risk factors and receive HLA-identical sibling HCT. Among 1493 consecutive transplant registry cases reported to the European Group for Blood and Marrow Transplantation hemoglobinopathy database, the 2-year overall survival (OS) and event-free survival (EFS) rates were 88% and 81%, respectively. However, among children < 2 years of age who received an HLA-identical sibling allograft, the OS and EFS rates at 2 years were 95% and 93%, respectively. Conversely, recipients > 18 years of age had OS and EFS rates of of 80% and 76%, respectively  . Results after HLA-identical sibling umbilical cord blood transplantation are very similar, with lower rates of acute and chronic graftversus-host disease (GVHD) after umbilical cord blood compared with bone marrow transplantation  . Thus, most clinicians agree that HCT for thalassemia should be considered in young patients with favorable risk profiles who have an HLA-identical sibling donor  .