Recent Advances in Treatment Options for Childhood Acute Lymphoblastic Leukemia

Abstract

Acute lymphoblastic leukemia is the most common blood cancer in pediatric patients. There has been enormous progress in ALL treatment in recent years, which is reflected by the increase in the 5-year OS from 57% in the 1970s to up to 96% in the most recent studies. ALL treatment is based primarily on conventional methods, which include chemotherapy and radiotherapy. Their main weakness is severe toxicity, which prompts dose reduction, decreases the effectiveness of the treatment, and, in some cases, can lead to death. Currently, numerous modifications in treatment regimens are applied in order to limit toxicities emerging from conventional approaches and improve outcomes. Hematological treatment of pediatric patients is reaching for more novel treatment options, such as targeted treatment, CAR-T-cells therapy, and immunotherapy. These methods are currently used in conjunction with chemotherapy. Nevertheless, the swift progress in their development and increasing efficacity can lead to applying those novel therapies as standalone therapeutic options for pediatric ALL.

Keywords: CAR-T; acute lymphoblastic leukemia; chemotherapy; conventional therapy; immunotherapy; pediatric; radiotherapy; targeted therapy.

Figure 1

Current therapeutic options for acute lymphoblastic leukemia in children. Starting with conventional therapies: (a)—chemotherapy and (b)—radiotherapy; through targeted treatment via kinase inhibitors—(c); ending with the latest treatment methods—(d). Image created with biorender.com (accessed on 14 March 2022).

Figure 2

Steps of the CART-cell therapy. 1—Peripheral blood mononuclear cells are collected from the patient by plasmapheresis. 2—The leukapheresis material is cryopreserved and transported to the laboratory. 3—T-cells are activated with beads that are coated with anti-CD3/CD28 antibodies. They are then transduced with a self-activating vector containing an anti-CD19 CAR transgene. 4—There is a CD19 antigen on the tumor cell. Opposite the tumor cell is the CAR tisagenlecleucel. It consists of a single-chain CD19-specific mouse antibody fragment (FMC63), a CD8-a hinge, and a transmembrane region linked to domains: CD3-zeta (signaling) and 4-1BB (costimulatory) domain. The 4-1BB domain serves as a costimulatory signal for cell activation. 5—Cell multiplication is carried out until sufficient numbers are reached. 6—The finished product, which has the ability to attack blastic cells, is administered to the patient. Image created with biorender.com (accessed on 14 March 2022).