CAR T-cell as an Innovative and Successful Achievement in Childhood Acute Lymphoblastic Leukaemia (ALL) Treatment

Dear editor Acute lymphoblastic leukaemia (ALL) is a prevalent and highly progressive cancer in children and adolescents, associated with an excessive production of immature lymphocytes in the bone marrow, which leads to a negative effect on the production of other blood components such as red blood cells, platelets and other white blood cells (1-3). The survival rate of this cancer was only 10% in children in the 1960s, but this had reached 90% by 2015, although still remains at 80-90% in the very young (2, 4-6). Chemotherapy is the primary treatment for ALL along with auxiliary therapies to help with its severe side effects, but hematopoietic stem cell transplantation and immunotherapy are two emerging and promising approaches in the treatment of this cancer (6-9). Immunotherapy for pediatric ALL consists of using genetically modified T cells, called chimeric antigen receptor (CAR) T-cells, which are autologous or allogeneic immune T cells that have been produced to better identify and eliminate more specific cancer cells via the targeting of one or several proteins related to cancer, notably CD19 and CD22 or both (figure 1) (6, 10). According to data presented by clinicaltrials.gov, twelve clinical studies have performed on pediatric leukaemia, especially ALL, using CAR T-cell on approximately 394 patients until 2018. However, all of these clinical trials are in the early stages (Phase I or Phase I/II) (6). Considering to data obtained from clinicaltrials.gov, ten out of twelve studies were used of CD19-targeted CAR T cells while CD22-targeted CAR T cells involved in four studies (6). Furthermore, in a Phase I clinical trial study, it was demonstrated that Bicistronic Chimeric Antigen Receptor (CAR) T-Cell Therapy which called to AUTO3, could promising as a better solve for Therapy in paediatric patients with refractory or relapse (R/R) B cell ALL, due to targeting of CD19 and CD22 at the same time (11). Similarly, a Phase I clinical trial study indicated efficiency and safety of bispecific CAR T-cell which simultaneous targeting of CD19 and CD22 in pediatric patients with ALL (12). This data along to others previously reported studies demonstrated potential capacity of CAR T-cell in leukaemia, especially ALL (6, 13, 14). In addition, tisagenlecleucel (Kymriah™), an autologous CD19-targeted CAR T cell, recently introduced as a Food and Drug Administration (FDA) and European :::::union::::: (EU) approved cell-based therapy product for use in paediatric patients with refractory or relapse (R/R) B cell precursor ALL (15-19). According to obtained results, 83% patients have demonstrated a partial or complete response to treatment using single injection of tisagenlecleucel in short period (20). Besides the high response rate to treatment, the length of time after primary treatment without certain complications or events in pediatric patients with ALL, and theirs overall survival, was higher for tisagenlecleucel-based treatment than other cancer treatment approaches (21). However, the long-term efficiency and safety of this approach, is still unclear and remains as a challenge (20). In addition, cytokine release syndrome, neurological toxicity and other toxicities are so far recognized as the most commonly known complications of this method (22). Furthermore, cardiovascular and neurodegenerative disorders can be attributed to the toxic effects of CAR T-cells on patients (23). As a result, this modern treatment should be employed along with specialized medical care by a medical group with different expertise and all the required facilities to certify optimal patient consequences (23). additionally, the cost of this treatment is very high for patients, approximately 282,000 euro per patient (24). Altogether, CAR T-cells by identifying and killing the cancer cell could help in treatment of ALL patient’s and reverse the processes of disease, which makes it as a great and new approach in cancer therapy (6). Results of clinical studies have demonstrated its potential, suggesting that CAR T-cells could be indeed used as an innovative and successful treatment for childhood ALL, where chemotherapy has failed.