Optimizing Stem Cell Transplantation in Children and Adolescents with Acute Lymphoblastic Leukemia (ALL)

Acute lymphoblastic leukemia (ALL) is a form of blood cancer in which immature white blood cells in the bone marrow multiply uncontrollably. This disease often affects children. A stem cell transplant (HSCT) is often used when the disease carries a high risk of relapse or a relapse has already occurred. In this procedure, the diseased bone marrow is replaced with healthy stem cells from another person (allogeneic). This therapy can lead to a cure, but it is also associated with significant risks. These include severe infections, organ failure, or a condition known as graft-versus-host disease (GvHD), in which the new immune system attacks the body.

The goal of the Phase 2/3 study is to improve the treatment surrounding the stem cell transplant so that fewer side effects occur while maintaining efficacy. To this end, there are several study groups examining different treatment regimens based on age, donor status, and post-transplant condition. In the R1 sub-study, two dosages of pre-transplant chemotherapy are being compared. Whole-body radiation at 8 Gy or 12 Gy, both in combination with the chemotherapy drug etoposide. The goal is to determine whether the lower radiation dose provides equally effective protection against relapse while causing fewer short- and long-term side effects. The R2 sub-study focuses on children and young adults who develop a grade 2–4 acute graft-versus-host disease (aGvHD) for the first time after transplantation. Here, two treatment strategies are being compared: the immunotherapy drug ruxolitinib combined with corticosteroids versus corticosteroids alone. The goal is to determine whether the additional administration of ruxolitinib controls aGvHD more quickly or more reliably and reduces complications. The S1 sub-study involves patients who receive a transplant from a family donor who is not a perfect match. In this group, two approaches are being compared to reduce rejection, severe immune reactions, and GvHD. Either the chemotherapy drug cyclophosphamide is administered after transplantation, or the graft is processed in the laboratory prior to administration by removing certain immune cells through a process known as αβ-T-cell depletion. The P1 sub-study examines children under 2 years of age with B-cell ALL who do not receive total-body irradiation as part of their pre-transplant treatment. After transplantation, these children receive additional relapse prevention with up to four treatment cycles of blinatumomab as maintenance therapy. Blinatumomab is an immunotherapy (bispecific antibody) that very specifically “guides” the body’s own immune cells to remaining leukemia cells so that they can be better recognized and eliminated. The goal is to reduce the risk of relapse in this particularly young and vulnerable group.

Children and young adults between the ages of 3 months and 25 years are eligible to participate. The disease must be in complete remission prior to the planned stem cell transplant, and a suitable donor source must be available (e.g., a compatible relative, unrelated donor, or umbilical cord blood). Patients with an active infection, severe organ damage, or a history of transplantation (except for certain sub-studies) are not eligible to participate.