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Simple Summary: Donor lymphocyte infusions (DLIs) are immune cells of the donor. They can potentially directly target leukemic cells. Thus, DLIs can be given to acute myeloid leukemia (AML) patients after allogeneic hematopoietic cell transplantation (alloHCT) in order to prevent or treat relapse. Measurable residual disease (MRD) describes very low levels of disease. Currently, it is still not well described how we can use MRD assessment for predicting response and outcome after DLI. This is a retrospective study looking at 76 AML patients receiving DLI treatment. MRD was evaluated prior to DLI treatment as well as 30 and 90 days after DLI. It was observed that within 90 days after DLI treatment, 73% of MRD+ patients converted to MRD−. Furthermore, MRD and remission status at the time of DLI were highly prognostic for the outcome (both for the relapse rate and also for relapse-free survival). Donor lymphocyte infusions (DLIs) can directly target leukemic cells through a graft-versus-leukemia effect and play a key role in the prevention and management of relapse after allogeneic hematopoietic cell transplantation (alloHCT). Predictors of response to DLIs are not well established. We evaluated measurable residual disease (MRD) before, 30 and 90 days after DLI treatment as biomarkers of response. MRD was assessed by next-generation sequencing in 76 DLI-treated acute myeloid leukemia patients. MRD status before DLI treatment was independently prognostic for event-free survival (EFS, p < 0.001) and overall survival (OS, p < 0.001). Within 90 days of DLI treatment, 73% of MRD+ patients converted to MRD− and 32% of patients without remission achieved remission. MRD status 90 days after DLI treatment was independently prognostic for the cumulative incidence of relapse (CIR, p = 0.011) and relapse-free survival (RFS, p = 0.001), but not for OS. To evaluate the role of DLI treatment in MRD− patients, 23 MRD− patients who received DLIs were compared with a control cohort of 68 MRD− patients not receiving DLIs. RFS (p = 0.23) and OS (p = 0.48) were similar between the two cohorts. In conclusion, MRD is prognostic before (EFS, OS) and after (CIR, RFS) DLI treatment and may help in the selection of patients who benefit most from DLIs. [ABSTRACT FROM AUTHOR]

Donor lymphocyte infusion (DLI) can (re-)induce durable remission in relapsing patients after allogeneic hematopoietic stem-cell transplantation (alloHSCT). However, DLI harbors the risk of increased non-relapse mortality due to the co-occurrence of graft-versus-host disease (GVHD). GVHD onset may be caused or accompanied by changes in the clonal T-cell receptor (TCR) repertoire. To investigate this, we analyzed T cells in a cohort of 21 patients receiving DLI after alloHSCT. We performed deep T-cell receptor β (TRB) sequencing of sorted CD4+CD25+CD127low regulatory T cells (Treg cells) and CD4+ conventional T cells (Tcon cells) in order to track longitudinal changes in the TCR repertoire. GVHD following DLI was associated with less diverse but clonally expanded CD4+CD25+CD127low Treg and CD4+ Tcon TCR repertoires, while patients without GVHD exhibited healthy-like repertoire properties. Moreover, the diversification of the repertoires upon GVHD treatment was linked to steroid-sensitive GVHD, whereas decreased diversity was observed in steroid-refractory GVHD. Finally, the unbiased sample analysis revealed that the healthy-like attributes of the CD4+CD25+CD127low Treg TCR repertoire were associated with reduced GVHD incidence. In conclusion, CD4+CD25+CD127low Treg and CD4+ Tcon TRB repertoire dynamics may provide a helpful real-time tool to improve the diagnosis and monitoring of treatment in GVHD following DLI. [ABSTRACT FROM AUTHOR]

Simple Summary: CD19+ Chimeric antigen receptor (CAR) T-cells are used against CD19+ hematologic malignancies, such as high-grade B-cell lymphoma and acute lymphoblastic leukemia. Since this is a relatively new treatment approach, not all potential side effects are well described, and the underlying pathobiology is often not well defined. Here, we summarize current data on the incidence and the current management of CD19+ CAR T-cell complications. We discuss frequently occurring toxicities and we highlight evidence for the occurrence of rarer side effects affecting different organ systems. In addition, we highlight new findings that shed light on the pathophysiology of CAR T-cell-related complications. Clinical trials demonstrated that CD19+ chimeric antigen receptor (CAR) T-cells can be highly effective against a number of malignancies. However, the complete risk profile of CAR T-cells could not be defined in the initial trials. Currently, there is emerging evidence derived from post approval studies in CD19+ CAR T-cells demonstrating both short-term and medium-term effects, which were unknown at the time of regulatory approval. Here, we review the incidence and the current management of CD19+ CAR T-cell complications. We highlight frequently occurring events, such as cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, cardiotoxicity, pulmonary toxicity, metabolic complications, secondary macrophage-activation syndrome, and prolonged cytopenia. Furthermore, we present evidence supporting the hypothesis that CAR T-cell-mediated toxicities can involve any other organ system and we discuss the potential risk of long-term complications. Finally, we discuss recent pre-clinical and clinical data shedding new light on the pathophysiology of CAR T-cell-related complications. [ABSTRACT FROM AUTHOR]