Treatment of childhood cancer is a success story, particularly for acute lymphoblastic leukaemia (ALL).
More than 90% of ALL patients below 18 years of age are rescued with contemporary chemotherapy.
However, the remaining 10% have resistant or reoccurring leukaemia and require alternative treatment regimens.
One of the most powerful leukaemia therapies is haematopoietic stem cell transplantation from a donor (allogeneic HSCT).
Approximately 50-80% of paediatric ALL patients that receive allogeneic HSCT are cured, 20% experience leukaemic reoccurrence (relapse), and 10% die from complications.
Allogeneic HSCT is a multistep procedure:
- Identify a suitable donor, i.e., a compatible sibling or unrelated person.
- Reduce the patient’s leukaemia to an undetectable level with chemotherapy, antibodies, or genetically modified cells from the patient (“CAR-T-cells”).
- Collect a donor graft by harvesting bone marrow, peripheral blood stem cells, or umbilical cord blood.
- Prepare the patient for transplantation (“conditioning”).
- Perform the stem cell transplantation.
For high-risk leukaemia, the gold standard conditioning procedure is a combination of total body irradiation (TBI) and high dose chemotherapy.
This approach is very effective in controlling leukaemia in the conditioning step, but patients may experience highly negative consequences of this procedure later in life: sterility, growth retardation, lung problems, and secondary cancer.
Therefore, a large consortium of paediatric transplant experts initiated a global study to investigate whether chemotherapy-based conditioning could substitute TBI.
The study is called FORUM (For Omitting Radiation Under Majority Age) and had to be stopped because chemotherapy-based conditioning had significantly poorer outcomes (i.e., lower overall survival rates) than the combination of TBI and chemotherapy.
The researchers will now perform prospective monitoring to better define the advantages and limitations of various conditioning approaches.