An article published Online First and in the October edition of The Lancet Oncology reports that a dexamethasone-based treatment reduces the risk of relapse and improves the rate of cure in children with acute lymphoblastic leukaemia (ALL). This can be achieved without the use of cranial radiation and some commonly used chemotherapy drugs, therefore minimising the risk of unnecessary side-effects. This very effective treatment approach gives results equalling with the best international protocols.

Childhood ALL is the most common type of childhood cancer and is curable in the majority of patients. However, many children with ALL are over-treated. As a result, they are exposed to unnecessary side-effects. In a prior study, the ALL-6 protocol (1984-88), the Dutch Childhood Oncology Group (DCOG) indicated that by replacing prednisone by dexamethasone and cranial radiation by moderately intensive intrathecal chemotherapy, the most effective treatment protocol to date was reached. Non-high risk (NHR) patients with a five year event-free survival ranged to 83 percent. However, high risk (HR) patients who were on institutional protocols had an event-free survival of just 53 percent.

The DCOG present in this study the results of the ALL-9 protocol. It is identical in design to ALL-6 for the NHR group, in order to confirm the results in a new cohort of patients. At the same time, it introduces a new treatment strategy for the HR group with the aim of improving on the results achieved in ALL-6.

Between January 1997 and November 2004, a total of 859 patients with ALL aged 1 to18 years were recruited from eight oncology centres in the Netherlands. They were monitored for more than six years. Patients were divided into two treatment groups: NHR (70 percent) and HR (30 percent) by conventional criteria. Patients in the NHR group were treated with a basic induction of three drugs (dexamethasone, vincristine, and L-asparaginase) and medium-dose methotrexate (3×2 g/m²). The HR group received a four-drug induction (as for the NHR group plus four doses of daunorubicin), consolidation with methotrexate 4×2 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. None of the patients underwent cranial irradiation.

In general, the ALL-9 protocol showed similar event-free survival in the NHR group. There was an improvement in 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 general event-free survival was 81 percent compared to 76 percent in the ALL-6 period. In the NHR group, the five year event-free survival was 84 percent in ALL-9. This was a similar result to the 83 percent reported in ALL-6. However, in the HR group, the five year event-free survival was 72 percent in the ALL-9 treated protocol. This compared with 53 percent in the ALL-6 period when they were on institutional protocols. Also, overall survival in the ALL-9 protocol was 90 percent for patients in the NHR group and 78 percent for HR patients.

The authors write in conclusion: “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.”

“Dexamethasone-based therapy for childhood acute lymphoblastic leukaemia: results of the prospective Dutch Childhood Oncology Group (DCOG) protocol ALL-9 (1997-2004)”
Anjo J Veerman, Willem A Kamps, Henk van den Berg, Eva van den Berg, Jos P M Bökkerink, Marrie C A Bruin, Marry M van den Heuvel-Eibrink, Carin M Korbijn, Elisabeth T Korthof, Karin van der Pal, Theo Stijnen, Margreet H van Weel Sipman†, J Fransje van Weerden, Elisabeth R van Wering, Anna van der Does-van den Berg, for the Dutch Childhood Oncology Group
DOI: 10.1016/S1470-2045(09)70228-1
The Lancet Oncology

Written by Stephanie Brunner (B.A.)