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.