HEMATOPOIETIC STEM CELL TRANSPLANTATION FOR HEMOGLOBINOPATHIES

Abstract

In 2021 the Brazilian society of stem cell transplantation and cell therapy published the consensus guidelines regarding hematopoietic stem cell transplantation (HSCT) for hemoglobinopathies. No changes have been added for thalassemia. HSCT with a matched sibling donor (MSD) or a related cord blood is the treatment of choice for young patients with transfusion dependent thalassemia. Matched unrelated and haploidentical HSCT, using bone marrow graft, are a clinical option. For sickle cell disease (SCD), conditioning regimen should be myeloablative for patients < 16 years old. For adults, fludarabine, busulfan and ATG is a safe and effective regimen. The chemo-free regimen with alemtuzumab and TBI, pioneered by the NIH group, was successfully reproduced by other centers and is a good option for adults and patients with established organ damage. Haploidentical HSCT with post-transplant cyclophosphamide showed high rejection rates in the beginning but improvements in the conditioning regimen were performed, including the use of pre-transplant immunosuppression, the increase in TBI dose from 2 cGy to 4 cGy and the addition of thiotepa, which significantly reduced rejection rates. We consider haploidentical transplant as a clinical option in children with significant neurological alteration and in adults with the established indications. The optimal timing for HSCT in SCD children with MSD is not well established. Previous international reports showed excellent outcomes in young children. The risk of grade 2-4 acute graft-versus-host disease (GVHD) and chronic GVHD is significantly higher in patients older than 15 years old.  Despite potential complications of HSCT (GVHD, gonadal dysfunction), transplantation at an earlier age may prevent organ dysfunction, strokes, iron overload and improve patients’ quality of life. Therefore, an early referral to HSCT is strongly recommended. The medical dilemma in older SCD patients, will be the assessment of established organ damage and the risk of transplantation. The clinical course of SCD is extremely variable and no validated genetic risk score has been established so far. Most of the risk scores use phenotypic characteristics together with laboratory biomarkers and imaging parameters to define outcomes in SCD.