Immune reconstitution post allogeneic transplant and the impact of immune recovery on the risk of infection

Abstract

Infection is the leading cause of non-relapse mortality after allogeneic haematopoietic cell transplantation (HCT). This occurs as a result of dysfunction to the host immune system from the preparative regimen used prior to HCT, combined with a delay in reconstitution of the donorderived immune system after HCT. In this article, we elaborate on the process of immune reconstitution post-HCT that begins with the innate system and is followed by recovery of adaptive immunity. Simultaneously, we describe how the tempo of immune reconstitution influences the risk of various infections. We explain some of the key differences in immune reconstitution and the consequent risk of infections in recipients of peripheral blood stem cell, bone marrow or umbilical cord blood grafts. Other factors that impact on immune recovery are also highlighted. Finally, we allude to various strategies that are being tested to enhance immune reconstitution post-HCT.

The QuantiFERON Monitor® assay is predictive of infection post allogeneic hematopoietic cell transplantation

“…In addition, results cannot be extrapolated to haploidentical and cord blood patients as, at the time of performance of the study, there were few such donors utilized at our center. Assessing what impact these alternative donors have on the QFM assay would be important, given the different immune recovery profiles of these alternative transplants . Finally, immune function in later phases of an alloHCT has not been explored in this study; however, a cross‐sectional study assessing IFN‐γ levels in QFM assay at later time points post‐transplant is currently underway at our center.…”

Superior immune reconstitution using Treg-expanded donor cells versus PTCy treatment in preclinical HSCT models

“…Following aHSCT, patients experience increased rates of infection due to neutropenia and delays in recovery of quantitative and functional lymphoid immunity (32)(33)(34). This immune impairment occurs in part as a consequence of slow lymphoid reconstitution, which can delay effective antiviral and other immune responses for months or years following aHSCT (35)(36)(37)(38)(39).…”

Dynamics of BKPyV reactivation and risk of hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation

“…Referring to this three‐phase hypothesis, the urinary mucosal damage (phase I) and the immunosuppression (phase II), induced by the conditioning regimen, would create the best conditions for BKPyV replication, while the inflammatory reaction following immune recovery of BKPyV‐specific lymphoid cells (phase III) would be the main cause for the onset of HC. Considering that, differently from innate immune cells, the lymphoid reconstitution generally starts after some weeks post‐allo‐HSCT, the unexpectedly more protracted progression of infection observed in patients affected by HC of grade II/III (over those with grade I) could be reconciled by a necessary involvement of lymphocytes (or even GVHD) in the full picture of epithelial damage …”