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

Hany Ariffin, Syaza Ab Rahman, Leong Sheng Hoay, Edwynn Kean Hui Chiew, Hai Peng Lin, Thuan Chong Quah, Allen Eng Juh Yeoh
2020 Pediatric Hematology Oncology Journal  
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
more » ... e 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 Ma-Spore 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 anthracyclinefree induction strategy did not compromise outcome for the majority (86%) of patients. The follow-up study, Ma-Spore 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 (IKZF1 del ) and moved these patients into a higher risk category. Increasing treatment intensity for patients with IKZF1 del 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 Ma-Spore 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 (Ma-Spore 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. Background Located in South-East Asia, Malaysia and Singapore are close neighbours with a shared history of being British colonies and having a common ethnic makeup of Malay, Chinese, Indian and indigenous peoples. Despite their geographical proximity, the two countries have large economic differences. Malaysia is an upper middle-income country with a GDP per capita of USD 11,373, while Singapore is a high-income country with a GDP per capita of USD 64,581 (2018) 1 . In 2016, Malaysia allocated 3.6% of its GDP on health expenditure (USD 360 per person) whilst Singapore spent an average of USD 2,400 for each of its inhabitants. 2
doi:10.1016/j.phoj.2020.03.009 fatcat:speebxuul5hcxg5iofbesn2zmq