Highlights
- •Haploidentical transplantation expands the donor pool for sickle cell anemia patients.
- •GVHD is mitigated by two methods: 1. ex-vivo and 2. in vivo T-cell depletion.
- •Graft failure is reduced by the modifications to the conditioning regimens.
- •New desensitization protocols can reduce levels of donor-specific anti-HLA antibodies.
- •Reduced intensity conditioning, mixed chimerism reduce toxicities with good outcomes.
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.
Keywords
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Published online: August 28, 2022
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