How Important Is Unrelated Donor Human Leukocyte Antigen Disparity in the Post-Transplant Cyclophosphamide Era?
Menées à partir de données 2016-2020 portant sur 17 292 patients atteints d'une leucémie aiguë ou d'une tumeur myéloïde et ayant reçu une greffe de cellules souches hématopoïétiques issues d'un donneur non apparenté avec une incompatibilité sur un gène HLA (dont 1 523 ayant reçu du cyclophosphamide post-greffe pour prévenir une maladie du greffon contre l'hôte), ces études analysent l'association entre la non-concordance de classe I ou de classe II des gène HLA du donneur et du receveur et la survie globale des patients
The introduction of post-transplant cyclophosphamide (PTCy) as a means of graft-versus-host disease (GVHD) prevention represents a truly disruptive technology.1 Its low cost and efficacy after haploidentical bone marrow transplantation have had a major clinical effect in the field and improved access for those lacking an human leukocyte antigen (HLA)–matched donor. The original approach involved administration of pulsed, high-dose cyclophosphamide on days 3 and 4 following bone marrow infusion without additional immune suppression.1 The drug works through attenuating T-cell alloreactivity (inducing anergy or deletion) while preserving cyclophosphamide-resistant regulatory T-cell populations.2 Over the last decade, evidence has accrued that a modified PTCy strategy using additional immunoprophylactic agents (eg, a calcineurin inhibitor [CNI] and mycophenolate mofetil [MMF]) can also be applied to other settings, especially unrelated donor stem-cell transplantation using peripheral blood stem cells (PBSC).3,4 The BMT CTN-1703 trial has recently affirmed the superiority of PTCy + CNI + MMF when compared with conventional CNI-based immune prophylaxis following reduced-intensity HLA-matched related and unrelated donor PBSC transplants,5 a finding that looks set to transform clinical practice.