• Benefits of immunotherapy in the treatment of pediatric acute lymphoblastic leukemia
  • Batol Abbasi,1,*
    1. Tabriz University of Medical Sciences


  • Introduction: Abstract: Acute lymphoblastic leukemia (ALL) is a subtype of leukemia that is common in childhood. The disease is characterized by the abnormal proliferation and accumulation of immature lymphoid cells in the bone marrow. Today, 5-year survival rates are greater than 90% for children with ALL in high-income countries. Despite therapeutic advances, further intensification of chemotherapy is associated with significant short-term and long-term side effects. There are still subsets of patients who are refractory to treatment after hematopoietic stem cell transplantation (HSCT) and chemotherapy. Given these challenges, new approaches are essential. Since the immune system plays a crucial role in the progression and relapse of ALL, immunotherapies have been demonstrated to be effective in treating relapsed or refractory disease and are now being investigated in frontline treatment regimens. In this article, we will review emerging immunotherapies for the treatment of pediatric ALL, as well as side effects and new developments.
  • Methods: Introduction: Acute lymphocytic leukemia (ALL) is a blood malignancy characterized by the overproduction of immature white blood cells called lymphoblasts (1). ALL is divided into T-cell, B-cell, and T-cell tumors (2). The environmental and/or genetic factors influence the development of ALL. Among these, genetic conditions such as Down syndrome or ataxia telangiectasia, ionizing radiation, pesticide exposure, childhood infections are included (3,4). Occurrence varies by sex, age, and race (5). The incidence of ALL is highest in children aged 1 to 4 years and in adults aged 55 years or older (6), with a male-to-female ratio of 1.2:1 (7). Although ALL occurs in both adults and children, children account for up to 80% of cases (8). Currently, modern treatment regimens have increased the 5-year survival rate to over 90% for children with ALL (9). Approximately 20% of patients are refractory to initial therapy or relapse after an initial complete remission (CR), resulting in a poor prognosis (10). Therefore, it is essential to explore new therapeutic approaches for these patients.
  • Results: review
  • Conclusion: Conclusion: Immunotherapy is a promising new therapeutic weapon against pediatric B-cell ALL. As noted in this article, T-cell engagers and CAR T-cell therapies have been successful in treating refractory and relapsed pediatric B-cell ALL. Today, blinatumomab is approved for the treatment of refractory and relapsed pediatric ALL. Blinatumomab is a bispecific T-cell receptor (BiTE) that targets CD19. Currently, researchers are further investigating the use of blinatumomab in MRD elimination as a post-reinduction consolidation therapy, which is believed to be more effective and less toxic than chemotherapy. Also, inotuzumab ozogamicin, a humanized antibody-drug conjugate to CD22, has shown the most promise. In addition, tisagenlecleucel, a typical representative of CAR T cell therapies, marked a change in treatment at a time when no treatment was available for children and young adults with refractory and or relapsed B-cell ALL. It is predicted that immunotherapy targeting multiple antigens, such as trispecific CD3/CD19/CD20 T-cell engagers and dual CD19 and CD22-targeting CAR T-cell therapy, in addition to overcoming antigen modulation, can also significantly enhance therapeutic efficacy. Despite all these advances, further studies on resistance and toxicity should be conducted to develop new ways to improve some of the toxicities and prevent relapse. Variable mechanisms, including antigen depletion/loss and antigen escape through lineage switching, influence responses to immunotherapy and lead to resistance or disease relapse. In summary, as noted in the text, the successful results of immunotherapy in clinical trials have proven the efficacy of immunotherapy in the treatment of pediatric B-cell ALL and have led to dramatic improvements in outcomes in the refractory or relapsed subgroup of patients. We believe that integrating and expanding these therapeutic approaches into frontline therapy and discovering novel modifications of multiple antigens will further enhance efficacy and reduce toxicity, thereby improving long-term outcomes in pediatric B-cell ALL patients.
  • Keywords: Acute lymphoblastic leukemia (ALL), Immunotherapy, pediatric, treating refractory, relapsed