¹Department of Hemato-Immunology, Robert Debré Hospital, Paris, France

²European Organisation for Research and Treatment of Cancer (EORTC), Data Center, Brussels, Belgium

³Department of Hemato-Oncology, HUDE, Brussels, Belgium

⁴Department of Immuno-Hemato-Pediatry, Debrousse Hospital, Lyon, France

⁵Laboratory of Genetic Biochemistry, Robert Debré Hospital, Paris, France

⁶Department of Hemato-Oncology, A Lacasagne Center, Nice, France

⁷Department of Pediatric Hemato-Oncology, Universitair Ziekenhuis, Gent, Belgium

⁸Laboratory of Hematology, CHU Purpan, Toulouse, France

⁹Laboratory of Hematology, CHR, Lille, France

¹⁰Laboratory of Hematology, Debrousse Hospital, Lyon, France

¹¹Department of Hematology, Children's Hospital, Toulouse, France

¹²Department of Hematology, CHR, Lille, France

¹³Department of Hematology, J Bernard Hospital, Poitiers, France

¹⁴Department of Hematology, Hautepierre, Strasbourg, France

¹⁵Department of Hematology, CHU, Angers, France

¹⁶Department of Hematology, CHR Hotel-Dieu, Nantes, France

¹⁷Department of Hematology, CHRU, Caen, France

¹⁸Department of Hematology, American Hospital, Reims, France

¹⁹Department of Pediatry, CHR La Citadelle, Liège, Belgium

²⁰Department of Hematology, Saint Jacques Hospital, Besançon, France

²¹Department of Pediatrics, UZ Gasthuisberg, Leuven, Belgium

²²Department of Onco-Hematology, A Villeneuve Hospital, Montpellier, France

²³Department of Pediatrics, CHR La Tronche, Grenoble, France

²⁴Department of Pediatrics, Escolar San Joao Hospital, Porto, Portugal

²⁵Department of Pediatrics, Esperance Clinic, Montegnée, Belgium

²⁶Department of Pediatrics, AZ Middelheim, Antwerpen, Belgium,

²⁷Department of Pediatrics, AZ-VUB, Brussels, Belgium

Correspondence to: E Vilmer, Robert Debré Hospital, 48 bd Serrurier, 75019 Paris, France; Fax: 331 40 03 47 40

The first two authors contributed equally to this paper

We present here the long-term results of three randomized clinical trials conducted on children with newly diagnosed acute lymphoblastic leukemia (ALL) between 1983 and 1998 by the Children Leukemia Cooperative Group (CLCG) from EORTC. In study 58831/32, the overall event-free survival (EFS) rates (± s.e.) at 6 and 10 years were 66% ± 1.8% and 65% ± 1.8%, respectively, and the risk of isolated central nervous system (CNS) relapse was 6% ± 1% and 7% ± 1%, respectively. In patients with a standard risk of relapse the omission of cyclophosphamide had no adverse effect on disease-free survival rates at 10 years (trial 58831). In medium- and high-risk patients the omission of radiotherapy did not increase the risk of CNS or systemic relapse (trial 58832). In study 58881 (1989-1998) the overall EFS rate at 8 years was 68.4% ± 1.2% and the risk of isolated CNS relapse was 4.2% ± 0.5%. In this trial which adressed three randomized questions, the following results were obtained: the combination of cytarabine at high doses with methotrexate at high doses during interval therapy did not improve prognosis. The addition of 6-mercaptopurine iv during maintenance increased the risk of late relapse. E. coli asparaginase was more toxic and has a higher efficacy than erwinia asparaginase. leukocyte counts >100 ´ 10⁹/l, specific genetic abnormalities, a poor initial response to steroids or a high level of minimal residual disease at early time points were consistently associated with an adverse prognosis in the 58881 trial. Leukemia (2000) 14, 2257-2266.

long-term follow-up; acute lymphoblastic leukemia; childhood; EORTC