Comments on the article 'Donor-derived CD19-targeted T cell infusion induces minimal residual disease-negative remission in relapsed B-cell acute lymphoblastic leukaemia with no response to donor lymphocyte infusions after haploidentical haematopoietic stem cell transplantation'.

Abstract

We read the recent article by Chen et al (2017) with great interest. They demonstrated that donor-derived CD19-directed chimeric antigen receptor-modified T (CAR-T) cells can potentially cure relapsed acute lymphocytic leukaemia (ALL) cases after haploidentical haematopoietic stem cell transplantation (haplo-HSCT). Among these cases, 83·33% patients achieved a minimal residual disease (MRD) negative remission and without grade 4 acute graft-versus-host disease (aGVHD). Their study agrees with a previous investigation (Brudno et al, 2016), but more information needs to be provided. Firstly, before the patient receives a donor-derived CAR-T cell infusion, the data about chimerism analysis should be taken into account. In particular, post-transplant donor/recipient chimerism should be taken into consideration in the assessment of aGVHD. If matched, autologous CAR in patients may be replaced by the donor-derived CAR, which is more enduring and determines the efficiency of therapy (Davila et al, 2014). Otherwise, donor-derived CAR-T cell infusion may deteriorate GVHD. Secondly, Chen et al (2017) reported that methylprednisolone was administered for patients who were suspected to have aGVHD. As is well known, corticosteroids can improve GVHD and cytokine release syndrome (Xu & Tang, 2014). However, short intensive corticosteroid courses, such as methylprednisolone, cause a profound reduction in naive T-lymphocyte production (Flinn & Gennery, 2017), affecting CAR-T cell efficacy. Perhaps, the molecular monitoring of CAR-T copies should become a routine surveillance in patients. We are interested in whether the use of corticosteroids may influence the efficacy of CAR-T therapy. In summary, the work by Chen et al (2017) sheds new light on the efficiency of donor-derived CAR-T cell infusions in relapsed ALL after haplo-HSCT. Further studies on whether donor cells are superior to autologous cells and how to balance between corticosteroids usage and CAR-T efficacy in cytokine release syndrome and GVHD cases are certainly warranted.