AUTOLOGOUS ANTI-CD19 CHIMERIC ANTIGEN RECEPTOR T-CELLS IMMUNO-THERAPY IN RELAPSED/REFRACTORY ACUTE LYMPHOBLASTIC LEUKEMIA PATIENTS: A SYSTEMATIC REVIEW

Introduction: Acute Lymphoblastic Leukemia (ALL) is the most prevalent malignant neoplasm in children; but, when it happens in adults, ALL becomes a devastating disease. Although, chemotherapy produces positive results in patients first contact with the disease, the possibility of cure is practically null when ALL becomes relapsed/refractory. Objective: To systematically review the anti-tumor efficacy of Anti-CD19 Chimeric Antigen Receptor (CAR) T-Cells Immunotherapy in the treatment of patients diagnosed with relapsed/refractory ALL, as well as to discuss its advantages and disadvantages, according to the current literature. Methodology: The study consisted in a systematic review based on analysis of manuscripts retrieved, from 2015 to 2019, in the databases PubMed, Cochrane Libery and LILACS, and also in the journals BLOOD, NATURE, Journal of the American Medical Association (JAMA) and New England Journal of Medicine (NEJM). The searches were made by using the key words: CD19-specific chimeric antigen receptor, relapsed/refractory acute lymphoblastic leukemia and treatment outcome. Results: Only 18 (19,15%) of 94 retrieved papers met the inclusion criteria and were selected for the review (which totalized 637 participants). In the responses, 81,47% (95% CI, 80,19% 82,75%) of the patients had a Complete Response; 10,91% (95% CI, 10,23% 11,59%) did not respond to the treatment; the neoplasm relapsed in 28,18% (95% CI 27,63% 28,73%) of the cases; and 12,88% (95% CI, 12,12% 13,63%) of the patients died. The most common side effects found were Cytokine Release Syndrome (CRS) and Neurotoxicity; they occurred, respectively, in 71,11% (95% CI, 70,72% -71,50%) and 26,79% (95% CI, 26,39% 27,19%) of the patients. The average risk of bias of the analyzed studies was considered low. Conclusion: Despite the side effects related to CRS and Neurotoxicity, the Anti-CD19 CAR T-Cells Immunotherapy is shown as a promising and highly effective therapy, which is able to generate high rates of Complete Response in the treatment of relapsed/ refractory ALL. This legacy starts to consolidate now and reveals new perspectives, so that, in the next years, it becomes possible to benefit from new advances and from increasingly encouraging data.