Outcome of children with high-risk acute lymphoblastic leukemia (HR-ALL): Nordic results on an intensive regimen with restricted central nervous system irradiation

Background. Improvement in outcome of childhood high-risk (HR) ALL was sought with a very intensive Nordic protocol leaving most patients without CNS-RT. Methods. A total of 426 consecutive children entered the NOPHO-92 HR-ALL program. HR criteria included WBC >= 50 x 10(9)/L, CNS or testicular involvement, T-cell, lymphomatous features, t(9;22), t(4;1 1), or slow response. Of these, 152 children had very high risk (VHR) with special definitions. CNS consolidation was based on high-dose MTX (8 g/m(2)) and ARA-C (12 g/m(2)) alternating. VHR patients also received cranial RT. Results. The 9-year EFS was 61 +/- 3%, OS 74 +/- 2%, and EFS for T-ALL 62 +/- 4%. Cumulative incidence of isolated CNS relapse was 4.7 +/- 1%, and CNS relapse in total 9.9 +/- 2%. Poor prognostic factors were WBC >= 200 x 10(9)/ L and a very slow response. Conclusions. HR-ALL was successfully treated on the NOPHO-92 regimen, with a relatively low CNS relapse rate for non-irradiated children. WBC >= 200 x 10(9)/L and very slow response emerged as strong poor prognostic factors. (c) 2003 Wiley-Liss, Inc.