In-vivo or ex-vivo T cell depletion or both to prevent graft-versus-host disease after hematopoietic stem cell transplantation

ABSTRACT

Introduction: Hematopoietic stem cell transplantation (HSCT) represents a widely accepted therapeutic strategy for the treatment of hematologic disorders which are otherwise considered incurable. Alloreactive T cells infused with the stem cell inoculum may generate graft-versus-host disease (GVHD) representing one the most relevant obstacles to the successful outcome of patients receiving allogeneic HSCT.

Areas covered: In this review, the authors provide an overview of the most recent approaches of T-cell depletion (TCD) including ex-vivo αβ+ TCD and in-vivo TCD with anti-thymocyte globulin (ATG).

Expert opinion: Ex vivo depletion of donor T-cells prevents both acute and chronic GVHD without the need for any additional posttransplant immunological prophylaxis either in haploidentical HSCT and HLA matched transplants. Three prospective trials evaluating the efficacy of ATG in matched unrelated donor transplant recipients demonstrated that ATG reduces the incidence of both acute and chronic GVHD without a significant increase of relapse rate, and similar results have been reported in the setting of blood stem cell grafts from matched sibling donors.

KEYWORDS:

• Stem cell transplantation
• graft-versus-host disease
• infections
• immune reconstitution

Article highlights

• Prospective clinical trials have demonstrated that ATG may reduce the incidence of both acute and chronic GVHD without a significant increase of relapse rate in patients receiving grafts from unrelated donors. Similar results have been reported in the setting of blood stem cell grafts from matched sibling donors, where the risk of chronic GVHD may be significantly high in absence of T-cell manipulation.

• Two ATG preparations are currently licensed for prevention of GVHD: Thymoglobulin and ATG-F. Target antigens of the two ATG preparations differ each other, as well as the pharmacokinetic profile which is remarkably influenced by the dose of ATG.

• The optimal dosing and timing of administration of ATG has not been established. In general, we can say that ATG should be administered as part of the preparative regimen, avoiding the infusion on day 0.

• Ex vivo depletion of donor T-cells prevents both acute and chronic GVHD without the need for any additional posttransplant immunological prophylaxis, even in recipients of haploidentical stem cell transplantation.

• Recipients of HLA-identical sibling transplants may still benefit from the more recent TCD-based strategies because the age of patients is gradually increasing and, with all the age-related co-morbidities, patients are less able to tolerate GVHD and its treatments.

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This manuscript has not been funded.