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'- Response to Pan etal.

Abstract

We have read the letter by Pan et al (2018) that posed two interesting questions. The first question was whether the chimerism status before the patients received a donor-derived chimeric antigen receptor-modified (CAR-T) cell infusion should be considered. The second question asked whether the use of corticosteroids influenced the efficacy of CAR-T therapy. For the first question, as shown in Table IV of our article (Chen et al, 2017), 4 of 6 patients had mixed chimerism and the chimerism analysis data for the other 2 patients were not available. It seems that full chimerism or mixed chimerism is commonly observed in relapsed patients whereas complete rejection is unusual. Brudno et al (2016) evaluated 20 patients with human leucocyte antigen-matched sibling donor or unrelated donor allogeneic blood or marrow transplantation, in which no new-onset graft-versus-host- disease (GVHD) occurred after CAR-T cells infusion. On the other hand, in-vitro experiments showed that GVHD caused by CAR-T from the allogeneic source was primarily triggered by CD4 + cells in CAR-T cells, and only occurred in the presence of leukaemic cells. (Jacoby et al, 2016). Taken together, chimerism status may not be a determinant that affects the severity of GVHD after CAR-T therapy. With reference to the second question, methylprednisolone was used as a first-line drug to treat patients with GVHD. Even so, the CAR-T cells infusion was generally effective in our study (in which 5 of 6 patients achieved minimal residual disease-negative remission). Actually, the association between the glucocorticoid dose and the efficacy of CAR-T has not been well defined. Therefore, this issue merits further investigations. In brief, Pan et al's questions are helpful; however, data for CAR-T cells therapy after haploidentical haematopoietic stem cell transplantation are scarce. More, larger studies are required to confirm the efficacy and determine the mechanism of CAR-T cells, especially in the setting of allogeneic haematopoietic transplantation.