Donor leukocyte infusions (DLI) can be used after bone marrow transplant (BMT) for nonmalignant diseases when chimerism is decreasing to avoid graft rejection, but GvHD must also be avoided. Sickle cell disease (SCD) is the most common hemoglobinopathy in Brazil, curable by BMT. With an HLA identical BMT, data suggest that at least 35% of donor cells are sufficient to avoid rejection. In haploidentical BMT, mixed chimerism leads to higher risk of graft failure. The management of mixed chimerism for SCD is still a matter of debate.

To describe a case series of DLI to reverse decreasing chimerism in SCD.

Retrospective analysis of SCD patients after BMT receiving DLI in two institutions. For haplo transplants, conditioning was ATG 4,5 mg/kg, Flu 150 mg/m² and Cy 29 mg/kg, TBI 200-400 cGy and TT 10 mg/kg in all but one patient. The matched sibling donor (MSD) BMT, used ATG 6,2 mg/kg, busulfan 18mg/kg and Flu 150 mg/m². GVHD prophylaxis was PT-Cy, sirolimus or tacrolimus + MMF and CsA + MTX for MSD BMT. Serial chimerism was evaluated monthly by VNTR or STR. Fresh donor peripheral blood was used for DLI in all cases. Data was collected from medical records.

From 2016 to 2025, 49 BMT for SCD were performed by the group, in 48 patients, 13 MSD and 33 haplo. One patient had BMT in another institution and had the follow up done in our center. Five patients received DLI due to mixed chimerism. These patients were 6,6-19,9 years of age. Four of them had haplo and one MSD. The DLI infusion was considered when the chimerism was around 70% and progressively decreasing. The average follow-up time before the indication of DLI was 163 days. They received 2-9 DLIs, 5 × 105-5 × 10⁶ CD3/kg. The reasons for interruption were stabilization or improvement of chimerism (4/5), development of GVHD (1/5) and one graft rejection, later undergoing a second BMT with complete donor engraftment. All donors had sickle cell trait and the HbS remained around 50%. One patient is still under evaluation and had planned additional DLI infusion due to chimerism of 82% in mononuclear cells. One important limitation is the lack of split chimerism availability in all patients.

DLI is a feasible strategy to avoid rejection after BMT for sickle cell disease.