LAUSR

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has remarkably improved the dismal prognosis of many aggressive hematological malignancies. However, post-transplant relapse remains a major challenge [1]. As there are limited treatment options for the patients relapsed after allo-HSCT, these populations often have poor prognosis. Donor lymphocyte infusions (DLIs) are routinely used as a preemptive measure or therapeutic modality for recurrence. The engraftment of donor T cells is able to eradicate tumor cells and mediate antitumor activity mainly through graftversus-lymphoma (GVL) effect. However, DLI has met with limited success as these allogeneic lymphocytes can also target normal tissues, thus leads to high risk of clinically significant GVHD [2]. For this reason, new therapeutic interventions are urgently needed for relapsed B-cell malignancies. CD19-chimeric antigen receptor (CAR19) T-cell therapy has emerged as a promising immunotherapy for relapsed and/or refractory B-cell malignancies. It has been considered both as an ideal bridge leading to a transition to allo-HSCT [3], and as a potential salvage therapy for progressive malignancy [4]. However, this therapeutic modality is not yet fully mastered owing to the risk of acute GVHD (aGVHD) or chronic GVHD (cGVHD) after introducing of CAR19 T cells, which is the Achilles heel of CAR-T therapy. CAR19 T-cell immunotherapy mainly exerts antitumor activity through the GVL effect mediated by adoptively transferred T cells. A subset of allo-reactive T cells do not specifically target tumor cells but also mediate allogeneic immune responses against normal recipient tissues, which may potentially leading to fatal complication of GVHD. Currently, available treatment approaches for GVHD has ranged from steroids to many other immune-suppressants, immunotoxins