Improving outcome through two decades in childhood ALL in the Nordic countries: the impact of high-dose methotrexate in the reduction of CNS irradiation

Abstract

In this population-based material from the five Nordic countries (Denmark, Finland, Iceland, Norway and Sweden), 2860 children below 15 years of age were diagnosed with acute lymphoblastic leukemia (ALL) from July 1981 to June 1998. 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 with multidrug chemotherapy, including pulses of methotrexate in high doses and avoidance of cranial irradiation in most children. The overall event-free survival (EFS) at 5 years has increased from 56.5 ± 1.7% in the early 1980s to 77.6 ± 1.4% during the 1990s. The main improvements were seen in children with non-high risk leukemia. In high-risk patients, progress has been moderate, especially in children with high WBC (у100 × 10 9 /l) at diagnosis. During the last time period (January 1992-June 1998), only 10% of the patients have received cranial irradiation in first remission, while 90% of the patients have received pulses of high dose methotrexate (5-8 g/m 2 ) isolated or combined with high-dose cytosine arabinoside (total dose 12 g/m 2 ) plus multiple intrathecal injections of methotrexate as CNS-targeted treatment, not translating into increased cumulative incidence of CNS relapse. Leukemia (2000) 14, 2267-2275.

Cell death induced by dexamethasone in lymphoid leukemia is mediated through initiation of autophagy

“…Chart represents quantification of p-Thr308-Akt band intensity in relation to the total protein levels Materials and Methods Patients. The study included leukemic cells from two precursor-B ALL patients (2 boys, 13 and 16 years old), who were treated according to the NOPHO-ALL 2000 protocol, 36,37 and from 11 patients (5 males, 6 females) with CLL for whom the median age was 77 (50-85) years. The diagnosis was established according to the World Health Organization classification.…”

Long-term results of NOPHO ALL-92 and ALL-2000 studies of childhood acute lymphoblastic leukemia

“…The study showed the feasibility of reduced use of cranial irradiation, 4 emphasized that host pharmacogenetics influence the cure rate, 5 confirmed the importance of myelosuppression during maintenance therapy, 6 showed that MTX/6MP maintenance therapy is important for high-risk (HR) ALL, 7 and allowed mapping of the epidemiological and clinical characteristics of several cytogenetically defined subsets of ALL. [8][9][10][11][12][13][14] The goals of the subsequent common NOPHO ALL-2000 protocol were to examine the efficacy of Vincristine (VCR)/Dexamethasone reinductions during maintenance therapy and to examine the feasibility of non-centralized minimal residual disease (MRD) monitoring by flow cytometry and PCR.…”

“…3 During the following decade the therapy became harmonized, and since January 1992 Nordic children 1.0-14.9 years of age have been treated according to common protocols. The details and treatment results of two previous non-uniform protocol periods 1981-1985 and 1986-1991 were reported in the December 2000 issue of Leukemia together with those of 11 other study groups, 4 and their overall results are presented in Table 1.…”

Adverse health events and late mortality after pediatric allogeneic hematopoietic SCT—two decades of longitudinal follow-up

“…11,12 Singlefraction TBI (sTBI) 10-12 Gy with CY (120 mg/kg) was used at the University Hospital in Huddinge during 1978-1995 and at the Helsinki University Hospital during [1978][1979][1980][1981][1982][1983]. Fractionated TBI (fTBI) was introduced in Helsinki in 1984 (10)(11)(12) Gy in 5-6 fractions) and in Huddinge in 1993 (12 Gy in 4 fractions). Patients with SAA have received CY (200 mg/kg) with or without TLI 6 Gy or fTBI 10 Gy.…”