6-MP based maintenance therapy of childhood ALL in Slovenia: a retrospective study from 1970 to 2004

Abstract

Background: Maintenance therapy with 6-mercaptopurine (6-MP) as its major component has been one of the main reasons for the drastic increase in overall survival of paediatric acute lymphoblastic leukaemia (ALL) patients. In our cohort, consisting of patients receiving maintenance therapy for ALL and encompassing time period of three decades, we evaluated dosage, safety and efficiency of 6-MP in the treatment of childhood ALL according to treatment protocol, age and gender. Methods: Slovenian paediatric ALL patients diagnosed and treated from 1970 to 2004 were identified through the national oncology patients` registry. Of 414 registered paediatric ALL patients, 320 received maintenance therapy for ALL and were included into the final study cohort. Information about age, gender, treatment protocol, 6-MP related toxic events and ALL relapse was extracted from patients` files. Differences in 6-MP dose reduction, 6-MP side effects and relapse according to gender, age and treatment protocol were statistically evaluated. Results: After adjustment for gender and age incidence of 6-MP dose reduction (p<0.001) and bone marrow suppression (p = 0.019) was higher in recent treatment protocols, while relapse was more common in older protocols (p < 0.001). Younger patients had greater risk for sepsis/infection (p = 0.002), while greater age was a risk factor for osteonecrosis (p = 0.001). No statistically significant associations were found according to gender. Conclusions: In the retrospective study, encompassing three decades of maintenance treatment of childhood ALL in Slovenia, recent protocols exhibited greater effectiveness and toxicity than older protocols.