Chemotherapy Alone Versus Total-Body Irradiation Before Allogeneic Stem Cell Transplantation in Children and Adolescents with Acute Lymphoblastic Leukemia

Acute lymphoblastic leukemia (ALL) is a malignant disease of the white blood cells characterized by uncontrolled production of white blood cell precursors (blasts) in the bone marrow and blood. The overproduction of blasts disrupts normal blood formation and the immune system. In ALL, other organs or the central nervous system may also be affected. Consequently, fatigue, anemia, an increased tendency to bleed, fever, and an increased susceptibility to infections may occur. The exact cause of ALL is not fully understood, but genetic mutations and environmental factors play a role. In many cases, treatment for ALL is based on chemotherapy administered in several phases. However, there may be instances where the treatment is not effective enough or where unfavorable factors affect the disease’s prognosis. In such cases, allogeneic stem cell transplantation is performed. In this procedure, the diseased blood system is destroyed through intensive therapy, and a new blood system is subsequently transplanted. This is done using cells from a donor whose blood system is highly compatible with that of the patient. To date, total-body irradiation has often been part of the intensive pre-transplant therapy; however, this can lead to significant long-term side effects, especially in growing children. It may be possible to avoid radiation by using intensive chemotherapy instead.

The goal of this Phase 3 study is to investigate the efficacy and safety of total-body irradiation compared to various chemotherapy regimens as pre-treatment for an allogeneic stem cell transplant. In addition, the study will examine the extent to which the match between the donor cells and those of the recipients affects the treatment outcome. To this end, participants will first be divided into three main groups based on the type of donor cells. These groups consist of either a sibling donor (matched sibling donor, MSD), an unrelated donor with a high degree of genetic compatibility in the blood system (matched donor, MD), or a donor with a lower degree of genetic compatibility (mismatched donor, MMD). The study divides patients into four groups. Within the main groups, patients are randomly assigned to receive either total-body irradiation with a total dose of 12 Gy over six treatments or chemotherapy prior to transplantation. The study is open-label, meaning that both the medical staff and the patient know which medications are being administered. The study will initially run for 1.5 years and then for up to 10 years, during which the effectiveness of the therapy and the occurrence of side effects from the various medications will be evaluated. The key factors are whether or when the disease recurs during therapy or when side effects occur.

Patients with acute lymphoblastic leukemia (ALL) are eligible to participate in this study. The initial diagnosis or diagnosis of relapse must have occurred before the age of 19, and patients must be no older than 21 at the time of transplantation. Before the start of the stem cell transplant, complete remission (full recovery) must be achieved through pre-treatment.