T-Cell Depletion and No Post-Transplant Immune Suppression Provides Better Immune Recovery to Aspergillus Than Conventional T Cell-Replete Hematopoietic Transplants.
Authors: Perruccio Katia , Cesaro Simone , Topini Fabiana , Gazzola Maria Vittoria , Burchielli Emanuela , Barzan Alessandra , Aversa Franco , Messina Chiara , Martelli Massimo F. , Velardi Andrea 
Published: October 2019

Abstract
After hematopoietic transplantation invasive aspergillosis is one of the most lethal infections. Susceptibility to invasive aspergillosis may be due to GvHD and its prophylaxis and treatment in T cell-replete transplants, and to T-cell-depletion in haploidentical transplants. Studies in mice and humans show that adaptive T-helper type-1 immune effector mechanisms are involved in control of invasive aspergillosis (Hebart et al. Blood, 2002; Cenci et al. J Immunol, 2000). In vivo T-cell priming induced by DCs pulsed with A. fumigatus conidia protects bone marrow transplanted mice from invasive aspergillosis (Bozza et al. Blood, 2000). This study monitored recovery of anti-Aspergillus immune competence in recipients of T cell-replete matched transplants and of T cell-depleted matched or haploidentical transplants for acute leukaemia. Patients: 32 pediatric recipients of matched T-replete transplants from unrelated donors (n=21), unrelated cord blood (n=2), and matched siblings (n=9) (median age: 10.5 years; range: 0.5–24); 20 adult recipients of matched T cell-depleted transplants (median age: 43 years; range 18–65), and 46 adult recipients of haploidentical transplants (median age: 34 years; range: 9–64). In all we monitored recovery of CD4+ T-cells and Aspergillus-specific CD4+ T-cells (by LDA) monthly for 18 months after transplant. Total CD4+ T-cell counts were higher after T-replete matched than after T-depleted matched or haploidentical transplant. At 9 months, CD4+ cells were: 1332±337 in T-cell replete transplant recipients, 364±62 in T cell-depleted matched transplant recipients, and 218±186 in haploidentical transplant recipients (p=0.000). Incidence of acute GvHD > grade II was 60% after T-replete transplantation, 0% after T cell-depleted matched and 9% after haploidentical transplantation. Aspergillus-specific T cells were first detected 15–18 months after T-replete matched transplantation (when immune suppressive GvHD prophylaxis/therapy was being withdrawn); 7–9 months after T cell-depleted matched transplantation and 9–12 months after haploidentical transplantation (p=0.000). Incidence of invasive aspergillosis was 21%, with a 10% mortality after T-replete transplants, 0% after T cell-depleted matched (p=0.000) and 7% with 4% mortality after haploidentical transplants (p=0.000). Although T cell counts were significantly higher after T-replete transplants their function appeared to be impaired by post-transplant immune suppression/GvHD. T-replete transplants were associated with a higher incidence of invasive aspergillosis and aspergillosis-related deaths. Specific Aspergillus immune competence recovered faster after T cell-depleted transplants, whether matched or haploidentical. These results show that T-cell depletion and no post-transplant immune suppression may provide a better pattern of immune recovery than T cell-replete transplantation and challenge the widely held belief that immune recovery after T cell-depleted transplants, particularly the haploidentical, is unduly delayed.