Haploidentical stem cell transplantation for patients with sickle cell disease: current status

Abstract

For patients with high-risk sickle cell disease (SCD) without any available matched sibling or unrelated donor, haploidentical stem cell transplantation (haploHCT) expands the availability of this life-saving intervention to nearly all patients who may benefit from HCT. The greatest challenge in haploHCT has been the significant risk of graft failure. Developing a treatment modality which sustains engraftment without increasing the incidence of debilitating graft-versus-host disease (GvHD) remains the ultimate goal. A number of modifications have been explored to overcome the high incidence of graft rejection and severe GvHD including: (1) ex-vivo T-cell depletion (via CD34+ selection, CD3+/CD19+, or TCRαβ+/CD19+ depletion), and (2) in vivo T-cell depletion using unmanipulated grafts followed by post-transplant cyclophosphamide (PTCy) for GvHD prophylaxis. Furthermore, the presence of donor-specific anti-HLA antibodies (DSA) has been associated with an increased risk of both graft failure and poor graft function. Several approaches for desensitization ameliorate this risk when a suitable donor without DSA is not available. In addition to advances in supportive care, the recent demonstration that stable mixed chimerism post-HCT sufficiently sustains symptom-free status has opened the door for less toxic treatment approaches yielding excellent survival outcomes. Though late effects remain uncertain, the goal of finding the least toxic conditioning regimen while providing the highest rate of donor engraftment draws closer within reach. In this review, the authors aim to present the latest findings, challenges, and treatment modalities of this life-saving modality.