1 Introduction
Acute lymphoblastic leukaemia (ALL) is a leading haematological malignancy diagnosed in children all over the world. Although the long-term survival rate for paediatric ALL is approaching and even over 90%, there are still 10~15% relapsed ALL considered as one of the leading causes of cancer mortality in children1,2. Although the relapses are mainly detected in bone marrow, it occurs occasionally that extramedullary tissues are involved accounting for 15-20% of all the relapses3. To patients with extramedullary relapsed, the central nervous system leukemia and testicular leukaemia are the most identified4,5. However, the natural history of extramedullary relapse generally correlates with poor prognosis and limited overall survival6. Conventional chemotherapy, radiation, or even allogeneic hematopoietic stem cell transplantation (allo-HSCT) have presented less successful in dealing with these patients, especially with multiple relapses7,8. Therefore, ALL patient with extramedullary diseases remains a great challenge and new therapeutic strategies are urgently required.
Recently, chimeric antigen receptor T-cell immunotherapy (CAR-T) is getting a wide attention and becoming an increasingly hot spot on the treatment of r/r B-ALL. CAR-T cells were first identified by Dr. Zelig Eshhar in the late 1980s and early 1990s9. It refers to harnessing the cytotoxicity ability of genetically modified T cells with high specificity and cytotoxicity to tumour cells. CAR-T cells contain an antigen-specific single-chain antibody fragment (scFv) linked to intracellular signalling domains independent of MHC restriction and antigen processing10. There is no doubt that 19CAR-T has achieved impressive clinical achievements in both adult and paediatric r/r B-ALL with an amazing disease remission rate, which is emerging as a standard strategy for r/r B-ALL patients11–14. Nevertheless, the application and effect of CAR-T in B-ALL patients with extramedullary relapses are rarely issued even disqualified in some cohorts11,13.
Here we reported our experiences of anti-CD19 CAR-T cells on the treatment of 8 pediatric B-ALL patients with extramedullary tissue and bone marrow relapse simultaneously.