ALLOGENEIC HEMATOPOIETIC CELL TRANSPLANTATION (HCT) FOR ACTIVATED PI3K DELTA SYNDROME: ENHANCING HOST LYMPHODEPLETION AND AVOIDING POST-TRANSPLANTATION SIROLIMUS IMPROVES ENGRAFTMENT
- Dimana Dimitrova, United States of America
Abstract
Background and Aims
Activating PIK3CD mutations confer increased lifetime risk of EBV-associated lymphoma, recurrent infections, and immune cytopenias. Allogeneic HCT is curative, but risk of graft failure is high across transplantation platforms, and comorbidities may preclude myeloablative conditioning (MAC). We compare the outcomes of 3 PIK3CD patients transplanted using a serotherapy-free reduced-intensity-conditioning (RIC) platform including sirolimus for graft-versus-host disease (GVHD) prophylaxis and 3 subsequent patients who received a modified RIC platform designed to reduce graft failure.
Methods
Six PIK3CD patients received one of two HCT platforms (Figure 1).
Results
All patients are alive (Figure 2). P1 has phenotype reversal despite ongoing mixed donor chimerism. P2 has full donor chimerism and resolution of pre-HCT chronic infections, but a course complicated by CMV pneumonitis and focal segmental glomerulosclerosis requiring ongoing immunosuppression. P3 had primary graft failure requiring a second, alemtuzumab-containing RIC HCT, with threatened secondary graft failure but increased donor chimerism upon withdrawal of sirolimus. He developed Grade III acute GVHD following donor lymphocyte infusion but is currently clinically well, off immunosuppression. P4, P5, and P6 are engrafted, with early signs of phenotype reversal and no GVHD in P4 and P5.
Conclusions
Our experience suggests that enhancing host lymphodepletion pre-HCT and avoiding post-HCT exposure to sirolimus, which may provide survival advantage to host cells, improves engraftment outcomes in PIK3CD patients. While follow up is short for the patients receiving our modified platform, their robust donor chimerism and lack of GVHD to date are encouraging and show MAC is not necessary to ensure engraftment in this high-risk population.