Treatment
Patients were uniformly treated on a modified protocol based on the ALL-MB 91 protocol, as detailed in table 1. This protocol was developed by professor Günther Henze for the treatment of patients in Russia at a time when less than 10 percent of children with ALL were surviving with the aim to reduce toxicity in consolidation treatment and costs, without affecting overall survival (OS) 7. Compared to the BFM protocol that was broadly used in Europe, the dose of anthracyclines was reduced in induction and in consolidation. In consolidation Capizzi methotrexate courses were introduced to replace the high-dose methotrexate elements of the BFM protocol. Furthermore, preventive radiation of the central nervous system (CNS) was only performed in high-risk patients. Instead, triple intrathecal chemotherapy with methotrexate, cytarabine and prednisone was administered. The main difference of the protocol used in Cambodia was the suppression of cranial radiation therapy. Also, a cumulative dose of daunorubicin of 120 mg/m2 was given to patients with standard risk (SR, see below) which was more than the SR arm of the ALL-MB-91 protocol (45 mg/m2, only one dose during induction), but a reduction of half of the cumulative dose compared to the standard BFM protocol 7. Compared to current ALL protocols, this regimen did neither include cyclophosphamide nor cytarabine and used non-pegylated asparaginase to reduce costs.