Immune Monitoring After Allogeneic Hematopoietic Cell Transplantation: Toward Practical Guidelines and Standardization

Abstract

Hematopoietic cell transplantation (HCT) is often a last resort, but potentially curative treatment option for children suffering from hematological malignancies and a variety of non-malignant disorders, such as bone marrow failure, inborn metabolic disease or immune deficiencies. Although efficacy and safety of the HCT procedure has increased significantly over the last decades, the majority of the patients still suffer from severe acute toxicity, viral reactivation, acute or chronic graft-versus-host disease (GvHD) and/or, in case of malignant disease, relapses. Factors influencing HCT outcomes are numerous and versatile. For example, there is variation in the selected graft sources, type of infused cell subsets, cell doses, and the protocols used for conditioning, as well as immune suppression and treatment of adverse events. Moreover, recent pharmacokinetic studies show that medications used in the conditioning regimen (e.g., busulphan, fludarabine, anti-thymocyte globulin) should be dosed patient-specific to achieve optimal exposure in every individual patient. Due to this multitude of variables and site-specific policies/preferences, harmonization between HCT centers is still difficult to achieve. Literature shows that adequate immune recovery post-HCT limits both relapse and non-relapse mortality (death due to viral reactivations and GvHD). Monitoring immune parameters post-HCT may facilitate a timely prediction of outcome. The use of standardized assays to measure immune parameters would facilitate a fast comparison between different strategies tested in different centers or between different clinical trials. We here discuss immune cell markers that may contribute to clinical decision making and may be worth to standardize in multicenter collaborations for future trials.

Dynamics of recent thymic emigrants in pediatric recipients of allogeneic hematopoetic stem cell transplantation

“…Delayed immune reconstitution with absent RTE generation is associated with increased risks for infection, treatment-related mortality, and chronic GvHD 47 . Markers of immune reconstitution including initiation and maintenance of RTE production are therefore important predictors of overall outcome 48 . The assessment of thymic function in pediatrics is not standardized and previous reports mainly rely on reaching specific absolute numbers of CD45RA+expressing CD4 T cells independent of the age of the child 49 .…”

“…In summary, there is a unique opportunity to standardize conditioning protocols for NMD 54 and MD 55 and to use longitudinal RTE-reconstitution assessment tools -as suggested herein pediatric allo-HSCT to further analyze the impact of underlying disease, toxicity of conditioning, serotherapy and GvHD on long-term thymic function after allo-HSCT which is of great relevance to detect and prevent precocious immunosenescence, malignancy and autoimmune disease 48 .…”

T Cell Subsets During Early Life and Their Implication in the Treatment of Childhood Acute Lymphoblastic Leukemia

“…Children considered for CD19-targeted immunotherapy are to a large extent in post-HSCT and possibly in their immune-reconstitution phase. There are several parameters that will impact on the kinetics of T-cell recovery after HSCT, such as the conditioning regimens, donor type and age, graft manipulation, type of graft-vs-host disease (GvHD), as well as treatment and prophylaxis [reviewed in ( 73 )]. In children followed for T cell recovery after HSCT for hematological malignancies, studies suggest that recent thymic emigrants and TRECs recover within 6–12 months post-HSCT ( 11 , 74 , 75 ).…”

The dynamics of B‐cell reconstitution post allogeneic hematopoietic stem cell transplantation: A real‐world study

“…Previous studies have shown that immune reconstitution is a dynamic process that involves different subpopulations of immune cells, each with its own reconstitution pattern and kinetics. Moreover, immune reconstitution varies greatly among individuals and is influenced by multiple factors related to the donor, the recipient, and the transplantation procedure [4][5][6][7][8]. Most of the previous studies have focused on the reconstitution of T cells and natural killer (NK) cells, which play key roles in cellular immunity [9][10][11].…”