Risk-stratified therapy and the impact on long-term toxicity in patients with childhood acute lymphoblastic leukemia

This study aimed to investigate the impact of risk-stratified therapy on long-term toxicity in patients with childhood acute lymphoblastic leukemia.  

This study concluded that risk-stratified therapy has reduced late complications and mortality among survivors of standard-risk acute lymphoblastic leukemia. 

Risk-stratified therapy is a method that modifies treatment on the basis of clinical and biological features of patients. It has improved the 5-year overall survival of childhood acute lymphoblastic leukemia (ALL) patients to 90%. However, the impact of risk-stratified therapy on long-term toxicity in childhood ALL patients remains unknown. 

This study involved 6148 survivors of childhood ALL. They were compared to 5051 healthy siblings. Mortality rate, secondary cancers (SCs), chronic health conditions, and neurocognitive (related to the nervous system and thinking and reasoning capabilities) outcomes were measured. Patients were grouped according to the decade of diagnosis. This influenced the treatment intensity and combinations. The 6 groups were 1970s-like (70s), standard-risk (SR) or high-risk (HR) 1980s like (80sSR, 80sHR), SR or HR 1990s like (90sSR, 90sHR), and relapse/transplantation (R/BMT). Patients were followed up for an average of 27.9 to 35.9 years. 

The 20-year all-cause mortality rate for all patients was 6.6%. The 90sHR and 90sSR groups had lower health-related late mortality when compared to the 70s group. The health-related late mortality of the 90sHR and 90sSR groups was similar to the general US population.  

The 90sSR group had a lower rate of SCs when compared to the 70s group. The 90sSR group had a similar rate of SCs to the general US population. 

11% of the 90sSR group had severe chronic health conditions compared to 22.5% of the 70s group. The 90sSR group had a 30% lower occurrence of impaired memory and a 50% better task efficiency when compared to the 70s group. 

This study concluded that risk-stratified therapy has reduced late complications and mortality among survivors of SR-ALL (as seen in the 90sSR group). It was also concluded that health-related late mortality and SC risks among survivors of SR childhood ALL are similar to the general population. 

Follow-up was significantly higher for the 70s group compared to the 90s group. This might have impacted the results. Further studies are needed.