A dexamethasone-based treatment reduces the risk of relapse and improves the cure rate in children with acute lymphoblastic leukaemia (ALL) without the use of cranial radiation and some routinely used chemotherapy drugs, thus minimising the risk of unnecessary side-effects. This highly effective treatment strategy produces results on a par with the best protocols worldwide. These are the conclusions of an Article published Online First and in the October edition of the Lancet Oncology.
Childhood ALL is the most common type of childhood cancer and is curable in most patients. However, many children with ALL are over-treated and as such are exposed to unnecessary side-effects. In a previous study, the ALL-6 protocol (1984), the Dutch Childhood Oncology Group (DCOG) showed that the use of dexamethasone instead of prednisone and moderately intensive intrathecal chemotherapy instead of cranial radiation was their most effective treatment protocol to date. In non-high risk (NHR) patients 5-year event-free survival reached 83%, but high risk (HR) patients who were on institutional protocols, had an event-free survival of just 53%.
In this study, the DCOG present the results of the ALL-9 protocol, which is identical in design to ALL-6 for the NHR group—in order to confirm the results in a new cohort of patients—while introducing a new treatment strategy for the HR group with the aim of improving on the results achieved in ALL-6.
In total, 859 patients with ALL aged 1 years were recruited from eight oncology centres in the Netherlands between January, 1997, and November, 2004, and followed-up for more than 6 years. Patients were stratified into two treatment groups—NHR (70%) and HR (30%) by conventional criteria. Patients in the NHR group were treated with a basic three-drug induction (dexamethasone, vincristine, and L-asparaginase) and medium-dose methotrexate (3x2 g/m²). The HR group received a four-drug induction (as for the NHR group plus four doses of daunorubicin), consolidation with methotrexate 4x2 g/m², and two intensification courses before maintenance, which was 109 weeks for all patients. Triple intrathecal medication was given 13 times in NHR patients and 15 times in HR patients and 17 times in those with initial central nervous system involvement. No patient received cranial irradiation.
Overall, the ALL-9 protocol showed similar event-free survival in the NHR group and better event-free survival in the HR group compared with the ALL-6 protocol. The results were also better than the previous DCOG ALL-7 and ALL-8 protocols.
In the ALL-9 protocol overall event-free survival was 81% compared to 76% in the ALL-6 period. 5-year event-free survival in the NHR group was 84% in ALL-9 which is similar to 83% reported in ALL-6. Yet, in the HR group, 5-year event-free survival was 72% in the ALL-9 treated protocol compared with 53% in the ALL-6 period when they were on institutional protocols. In addition, overall survival in the ALL-9 protocol was 90% for patients in the NHR group and 78% for HR patients.
The authors conclude: "The results for NHR patients [70% of all newly diagnosed patients] were achieved with high cumulative doses of dexamethasone and vincristine, but without the use of anthracyclines, etoposide, cyclophosphamide, or cranial irradiation, therefore minimising the risk of side-effects…The 5-year event-free survival of 72% in the ALL-9 HR group without the use of cranial irradiation and with limited use of anthracyclines and cyclophosphamide can be regarded as a favourable result in this group of patients."
See also Reflection and Reaction.
Dutch Childhood Oncology Group, The Hague, Netherlands. T) +31-70-3674545 E) info@skion.nl
Professor Anjo Veerman, VU University Medical Centre, Amsterdam, Netherlands. T) +31-20-4442420 E) ajp.veerman@vumc.nl
For full Article and Reflection and Reaction see: http://press.thelancet.com/tlochildall.pdf
Journal
The Lancet Oncology