Long-term Follow-up After Mixed Donor Myeloid Chimerism at 1 Year Post Transplantation for Sickle Cell Disease

Hematopoietic cell transplantation (HCT) for sickle cell disease (SCD) is an established cure, but mixed donor chimerism is common even with myeloablative conditioning regimens. With many North American centers using less intensive conditioning regimens, rates of mixed donor chimerism may increase. The clinical long-term outcomes of these patients are not well described in combination with laboratory markers of hemolysis and hemoglobin S percentage. The objective of this study was to describe long-term graft integrity and clinical outcomes in survivors of HCT for SCD with mixed donor chimerism at 1-year post-HCT. A retrospective multi-center observational analysis of 33 children and adolescents with sickle cell disease and mixed donor chimerism at 1-year post-HCT and at least 2 years of follow-up was performed. Descriptive statistics and a linear mixed-effects model (LMM) were used. Longer time to follow-up was predictive of lower myeloid chimerism but not lymphoid chimerism. Higher chimerism at 1-year post-HCT were associated with higher chimerism at last follow-up (myeloid and lymphoid). Hemolysis was noted when donor myeloid chimerism was 25% or less. No secondary neoplasms were noted. In this cohort of children and adolescents who have undergone HCT for SCD with mostly reduced intensity or nonmyeloablative conditioning, lower myeloid chimerism was seen with longer follow-up, highlighting the need for lifetime surveillance of chimerism and clinical outcomes. A higher donor myeloid chimerism at one year is preferable and associated with higher long-term values. No secondary malignancies were observed.