PATIENTS AND METHODS: Three hundred sixty-nine children with favorable-risk BCP-ALL (age 1-9 years, no extramedullary disease, and no high-risk genetics) who cleared minimal residual disease (≤0.01%) at the end of remission induction were enrolled into Ma-Spore (MS) ALL trials. One hundred sixty-seven standard-risk (SR) patients (34% of Malaysia-Singapore ALL 2003 study [MS2003]) were treated with the MS2003-SR protocol and received 120 mg/m2 of anthracyclines during delayed intensification while 202 patients (42% of MS2010) received an anthracycline-free successor protocol. The primary outcome was a noninferiority margin of 1.15 in 6-year event-free survival (EFS) between the MS2003-SR and MS2010-SR cohorts.
RESULTS: The 6-year EFS of MS2003-SR and MS2010-SR (anthracycline-free) cohorts was 95.2% ± 1.7% and 96.5% ± 1.5%, respectively (P = .46). The corresponding 6-year overall survival was 97.6% and 99.0% ± 0.7% (P = .81), respectively. The cumulative incidence of relapse was 3.6% and 2.6%, respectively (P = .42). After adjustment for race, sex, age, presenting WBC, day 8 prednisolone response, and favorable genetic subgroups, the hazard ratio for MS2010-SR EFS was 0.98 (95% CI, 0.84 to 1.14; P = .79), confirming noninferiority. Compared with MS2003-SR, MS2010-SR had significantly lower episodes of bacteremia (30% v 45.6%; P = .04) and intensive care unit admissions (1.5% v 9.5%; P = .004).
CONCLUSION: In comparison with MS2003-SR, the anthracycline-free MS2010-SR protocol is not inferior and was less toxic as treatment for favorable-risk childhood BCP-ALL.
METHODS: We systematically searched multiple databases to identify studies reporting incidence of antineoplastic-related cardiovascular toxicity in Asia published from inception to November 2018. Pre-specified subgroups were performed to explore heterogeneity and study quality assessed and reported according to PRISMA guidelines.
RESULTS: A total of 61 studies across 11 countries in Asia reported 8 types of cardiovascular toxicities were included. These studies mostly reported on adult populations, and usually examined cardiotoxicities related to anthracycline use. The most frequently reported cardiotoxicities were heart failure, electrocardiogram abnormalities and left ventricular dysfunction. The pooled estimated incidence of cardiotoxicity was 4.27% (95% CI: 3.53-5.07). Subgroup analysis showed higher incidence in middle income countries compared to high income countries.
CONCLUSIONS: Although robust incidence studies are sparse, cardiovascular complications affects approximately one in twenty cancer patients in Asia. This highlights a unique opportunity of cancer patients caring that need cardiologists and oncologist to become familiar with this emerging sub-specialty.