Immunotherapy for Pediatric Acute Lymphoblastic Leukemia: Recent Advances and Future Perspectives

Abstract

Pediatric acute lymphoblastic leukemia (ALL) is the most common subtype of childhood leukemia, which is characterized by the abnormal proliferation and accumulation of immature lymphoid cell in the bone marrow. Although the long-term survival rate for pediatric ALL has made significant progress over years with the development of contemporary therapeutic regimens, patients are still suffered from relapse, leading to an unsatisfactory outcome. Since the immune system played an important role in the progression and relapse of ALL, immunotherapy including bispecific T-cell engagers and chimeric antigen receptor T cells has been demonstrated to be capable of enhancing the immune response in pediatric patients with refractory or relapsed B-cell ALL, and improving the cure rate of the disease and patients’ quality of life, thus receiving the authorization for market. Nevertheless, the resistance and toxicities associated with the current immunotherapy remains a huge challenge. Novel therapeutic options to overcome the above disadvantages should be further explored. In this review, we will thoroughly discuss the emerging immunotherapeutics for the treatment of pediatric ALL, as well as side-effects and new development.

Prevalence and Treatment Outcomes of Childhood Acute Lymphoblastic Leukemia in Kosovo

“…It is essential that these measurements are adopted in Kosovar healthcare to improve childhood ALL treatment outcomes. Finally, ALL clinical outcomes could be improved by lowering toxicity from previous chemotherapeutical regimens and infections through implementing therapeutic novelties in the ALL field, such as intensified chemotherapy schemes, targeted therapies including tyrosine kinase inhibitors and chimeric antigen receptors, and reducing the frequency of blood transfusions [ 31 , 41 , 42 , 43 ].…”

Oral Manifestations: A Warning-Sign in Children with Hematological Disease Acute Lymphocytic Leukemia

“…The latter is associated with speaking and swallowing problems, difficulty with facial movements and xerostomia. Thus, these are all transient conditions [ 56 , 57 ]. The Food and Drug Administration (FDA)-approved therapies for children with ALL can be found in Figure 1 .…”

“…After treatment, the follow-up should be short—with 3 to 6 months between each appointment—and the medical dentist should manage any manifestations and advice about good oral hygiene practice. After 2 years, the appointments can be conducted at more spaced-out intervals [ 56 ].…”

“…Orthodontic treatment can begin or resume after completion of all antineoplastic treatments, at least after 2 years of remission, when the risk of relapse is reduced, and the patient is no longer taking immunosuppressive drugs [ 56 ]. Thus, the risk of developing complications is always increased due to the disease and its treatments, especially if there are alterations in bone metabolism and oral mucosa sensitivity that can cause ulcerations [ 67 , 68 ].…”

miR-539-5p targets BMP2 to regulate Treg activation in B-cell acute lymphoblastic leukemia through TGF-β/Smads/MAPK

“…However, 20% of ALL are still at risk for relapse, and treatment outcomes after relapse are unsatisfactory and are the leading cause of death in ALL [ 4 ]. With the rise of immunotherapy, immunotherapies targeting ALL antigen-associated monoclonal antibodies and chimeric antigen receptor T cells have been shown to be effective against ALL and can significantly improve the prognosis of patients with relapsed/refractory ALL [ 5 ]. In addition, miRNAs have been described as modulators of a large number of different immune processes and have the potential to be key to the future development of immunotherapy [ 6 ].…”