In all, 447 children with acute myeloid leukaemia (AML) have been treated on three consecutive NOPHO studies from July 1984 to December 2001. NOPHO-AML 84 was of moderate intensity with an induction of three courses of cytarabine, 6-thioguanine and doxorubicin followed by four consolidation courses with high-dose cytarabine. The 5-year event-free survival (EFS), disease free survival (DFS) and overall survival (OS) were 29, 37 and 38%. NOPHO-AML 88 was of high intensity with the addition of etoposide and mitoxantrone in selected courses during induction and consolidation. The interval between the induction courses should be as short as possible, that is, time intensity was introduced. The 5-year EFS, DFS and OS were 41, 48 and 46%. In NOPHO-AML 93, the treatment was stratified according to response to first induction course. The protocol utilised the same induction blocks as NOPHO-AML 88, but after the first block, children with a hypoplastic, nonleukaemic bone marrow were allowed to recover before the second block. Consolidation was identical with NOPHO-AML 88. The 5-year EFS, DFS and OS in NOPHO-AML 93 were 48, 52 and 65%. The new NOPHO-AML protocol has been based on experiences from previous protocols with stratification of patients with regard to in vivo response and specific cytogenetic aberrations.

From July 1984 the five Nordic countries (Denmark, Finland, Iceland, Norway and Sweden) have registered all children with acute myeloid leukaemia (AML) and treated them on two consecutive protocols of different intensity (NOPHO-84 and NOPHO-88). We probably have information on every child with this diagnosis in our region. We found an annual incidence of AML of 0.7 new cases per 100,000 children < 16 years of age. We observed a distinct peak of incidence in the first 2 years of life. Children with Down's syndrome accounted for 13% of all cases. Eighty of 105 cases treated on NOPHO-84 achieved remission (78%). In NOPHO-88, 100/118 patients entered remission (85%). The overall event-free survival (p-EFS) for the two studies was 0.32 for NOPHO-84 and 0.42 for NOPHO-88. The majority of relapses occurred within 2 years of diagnosis. When looking for prognostic factors the strongest significant adverse factor found was male sex. Children with Down's syndrome (n = 35) had a very favourable outcome if they received therapy according to protocol, and infants (n = 26) had a superior outcome compared to children 1-2 years or > 10 years of age at diagnosis.

In a multinational, population‐based study from the five Nordic countries (Denmark, Finland, Iceland, Norway and Sweden), 2648 children below 15 y of age were diagnosed with acute lymphoblastic leukaemia (ALL) in the years 1981‐1996. The annual incidence was 3.9/100 000 children and was stable throughout the study period. The development from regional or national protocols to common Nordic treatment protocols for all risk groups was completed in 1992 through a successive intensification of therapy, based on multidrug chemotherapy including pulses of methotrexate in high doses and avoidance of cranial irradiation in most children. For children with non‐B‐cell ALL (n= 2602), the event‐free survival (p‐EFS) increased from 0.53 ± 0.02 (diagnosed 7/81‐6/86) to 0.67 ± 0.02 (7/86‐12/91) to 0.78 ± 0.02 (1/92‐12/96). The corresponding p‐EFS values at 5 y were 0.57, 0.70 and 0.78, respectively. The main improvements were seen in the group of children with non‐high risk leukaemia, with 5‐y p‐EFS values increasing from 0.60 to 0.76 and 0.85 for the three periods. In high‐risk patients, progress has been moderate, especially in children with high white blood cell values at diagnosis. During the last 5‐y period, only 10% of the patients received cranial irradiation in first remission while 90% of the patients received high doses of cytostatic infusions (methotrexate isolated or combined with cytarabinoside) and multiple intrathecal injections of methotrexate as CNS‐adjusted treatment without any indication of an increased CNS relapse rate.

Six hundred and fifty-six children with acute lymphoblastic leukemia (ALL) have been diagnosed in the five Nordic countries (Denmark, Finland, Iceland, Norway and Sweden) during the period from July 1981 through June 1985. Annual incidence of ALL was 3.6/100,000 children aged less than 15 years, with an incidence for males of 3.8 and for females of 3.4 respectively. Half of the children were younger than 5 years of age at diagnosis, with a peak incidence between 2-3 years of age. The leukemias were classified as Standard Risk (SR), Intermediate Risk (IR) or High Risk (HR) leukemia according to prognostic criteria at diagnosis. The remission rate was 95%. In children greater than or equal to 1 year of age with non-B-cell ALL at diagnosis, the Event-Free Survival (EFS) was 0.58; 0.65 for SR-children, 0.51 for IR-children and 0.52 for HR-children. WBC count at diagnosis was the most important prognostic factor and a WBC count of 11-20 X 10(9)/l was associated with the worst prognosis of all WBC values (EFS = 0.30), independent of other prognostic factors. Male sex was the second most important adverse prognostic criterion. The follow-up in January 1986 (observation time 6-54 months), showed that 442 of the 656 children (67%) were in complete continuous remission. The total results indicate a possibility to improve the prognosis for most of the risk groups of ALL with a more intensive treatment.