T-cell deplete versus T-cell replete haploidentical hematopoietic stem cell transplantation for sickle cell disease: where are we?

Abstract

Introduction: Severe sickle cell disease is associated with progressive end-organ damage and early mortality in adults. While allogeneic hematopoietic cell transplant from a matched related donor is curative, the vast majority of patients do not have a compatible sibling. Accordingly, platforms using haploidentical donors have been developed, which provide near-universal availability. Areas covered: This review focuses on the two commonly used approaches for haploidentical hematopoietic transplants, namely T-cell deplete and T-cell replete, each of which is associated with unique benefits and drawbacks. The purpose of this paper is to facilitate individualized decision-making for patients and providers by reviewing the pros-and cons of these differing approaches. Expert opinion: Individuals with sickle cell disease eligible for a hematopoietic cell transplant can be considered based on recent results. Comparable outcomes are seen with T-cell deplete and T-cell replete approaches. The choice depends largely on institutional preference.

Allogeneic hematopoietic stem cell transplantation to cure sickle cell disease: A review

“…(2) T-cell replete (TCR) grafts or un-manipulated grafts. Both approaches were increasingly tested and developed to overcome the underlying bidirectional issues of GvHD and graft rejection (94).…”

“…The use of post-transplantation cyclophosphamide completely revolutionized the field by selective deletion of alloreactive T cells. HSCs are protected from the adverse effect of cyclophosphamide due to the expression of the drug-metabolizing enzyme aldehyde dehydrogenase which is not expressed by T cells (94)(95)(96)(97). Moreover, cyclophosphamide-induced preferential expansion of regulatory T cells may also contribute to GvHD prevention (95).…”

KIR in Allogeneic Hematopoietic Stem Cell Transplantation: Need for a Unified Paradigm for Donor Selection

“…Haplo-HSCT has also shown promising results in non-malignant disorders: for example, in sickle cell disease, using both TCD and TCR platforms ( 34 – 37 ); in patients with thalassemia major, using the Baltimore strategy ( 38 ); in anaplastic anemia as salvage treatment in patients without an MSD and failing after immunotherapies ( 39 ) but also as upfront therapy using the Baltimore protocol ( 40 , 41 ); and in primary immunodeficiency disorders for patients with high-risk features ( 42 ) especially in low-income settings in which family donors are the only available option ( 43 ).…”

Debating the Future of Sickle Cell Disease Curative Therapy: Haploidentical Hematopoietic Stem Cell Transplantation vs. Gene Therapy

“…Current haplo-HSCT approaches utilize either T-cell deplete (TCD) and unmanipulated, T-cell replete (TCR) approaches, utilizing sophisticated methods for graft manipulation in the former and drug-induced immunologic tolerance in the latter to allow for engraftment while minimizing GvHD [ 12 , 32 , 33 , 34 , 35 , 36 ]. Ex vivo TCD can broadly be divided into one of two strategies: CD34 + -positive selection and CD34 + -negative selection of T-cells [ 37 ]. These techniques differ not only in the laboratory procedure but also in the composition of the product, with CD34 + selection eliminating other populations of mononuclear cells, such as B- and NK cells, that can impact post-transplant immune reconstitution.…”