Characteristics and outcome in patients with central nervous system involvement treated in European pediatric acute myeloid leukemia study groups. Issue 12 (9th June 2017)

• Record Type: Journal Article
• Authors: Creutzig, Ursula; Dworzak, Michael N.; Zimmermann, Martin; Reinhardt, Dirk; Sramkova, Lucie; Bourquin, Jan Pierre; Hasle, Henrik; Abrahamsson, Jonas; Kaspers, Gertjan; van den Heuvel, Mary M.; Reedijk, Ardine M. J.; De Moerloose, Barbara; Locatelli, Franco; Masetti, Riccardo
• Is Part Of: Pediatric blood & cancer. Volume 64:Issue 12(2017)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2017-06-09
• Subjects: acute myeloid leukemia -- children -- CNS involvement -- treatment; Tumors in children -- Periodicals; Blood -- Diseases -- Periodicals; Cancer in children -- Periodicals; 618.92
• DOI: 10.1002/pbc.26664
• Languages: English
• ISSNs: 1545-5009

Abstract

Abstract: Background: There is no consensus on the treatment for pediatric patients with acute myeloid leukemia and initial central nervous system (CNS) involvement. Methods: To evaluate different CNS‐directed treatment options (intrathecal [IT] therapy, CNS irradiation, hematopoietic stem cell transplantation [HSCT]), 261 patients (excluding acute promyelocytic leukemia) with initial CNS involvement treated in trials with similar intensive chemotherapy by four cooperative European study groups (1998–2013) were studied and compared with CNS‐negative patients from the Berlin–Frankfurt–Münster group. Results: Patient characteristics in the different study groups were comparable. Young age, high white blood cell count, extramedullary involvement other than the CNS, monoblastic morphology, and inv(16) were associated with CNS involvement (each P < 0.0001). There were no major differences in outcome between the study groups. The cumulative incidence of relapse (CIR) regarding the CNS was higher in initially CNS‐positive versus initially CNS‐negative patients (all: 8 ± 2% vs. 3 ± 1%, P (Gray) = 0.001; isolated: 4 ± 1% vs. 1 ± 0%, P (Gray) = 0.03). However, global outcome of the CNS‐positive cohort (overall survival, 64 ± 3%; event‐free survival 48 ± 3%; and CIR 33% ± 3%) did not differ significantly from CNS‐negative patients. Risk groups defined by cytogenetics were of likewise prognostic significance in CNS‐positive and ‐negative patients. CNS treatment with cranial irradiation was not superior compared to IT therapy and systemic chemotherapy (± HSCT). Conclusion: Although CNS relapses occurred more frequently in initially CNS‐positive patients, their global outcome was similar as in CNS‐negative patients. Intensified IT therapy was heterogeneous; however, at least eight applications, preferably with triple IT chemotherapy, seem to be appropriate to accompany dose‐intensive systemic chemotherapy.