Malaysia-Singapore (MASPORE) leukaemia study group: From common history to successful collaboration

Abstract

The 1970s marked the beginning of childhood cancer services in Malaysia and Singapore, two neighbours in South-East Asia. Between 1995 and 2002, Malaysia utilized a treatment regimen based on the Dutch DCOG 7 and German BFM protocols for children with acute lymphoblastic leukaemia (ALL), whilst Singapore in collaboration with Hong Kong employed the HK-ALL 1997 protocol, based on BFM ALL 95. In 2002, the overall 6-year event-free survival (EFS) for childhood ALL in Malaysia stood at 56%, while the 5-year EFS for HK-ALL 1997 was 79%. Formal collaboration between Malaysia and Singapore for the treatment of childhood ALL began in 2003. The first collaborative trial was the seminal MASPORE ALL2003 study which utilized a single PCR-based minimal residual disease marker to risk stratify patients according to disease severity, and used a 3-drug induction regimen for non-high-risk patients. This effort resulted in an improvement in 6-year EFS for both countries, at 80%, with an overall survival of 88%. The study showed that treatment could be appropriately tailored to disease risk, and that an anthracycline-free induction strategy did not compromise outcome for the majority (86%) of patients. The follow-up study, MASPORE ALL2010 focused on delivering therapy that was more intensive for those in high-risk group while reducing intensity for standard and intermediate risk groups. The study also took into consideration patients with IKZF1 gene deletion (IKZF1del) and moved these patients into a higher risk category. Increasing treatment intensity for patients with IKZF1del resulted in a reduction in 5-year cumulative incidence of relapse (CIR) from 30 to 13%, and improved overall 5-year survival from 69 to 91%. The MASPORE ALL2010 trial also studied TPMT and NUDT15 gene variants in its patient population to optimize thiopurine dosing. As the study moves into its next phase (MASPORE ALL2020), precision medicine and risk-adapted therapy remain the cornerstone strategies for childhood ALL, especially in the era of increased recognition of late effects amongst survivors of childhood cancer. Future therapies will likely focus on further targeted treatment for childhood ALL as more molecularly distinct subtypes become known.