Characteristics and outcome in patients with central nervous system involvement treated in European pediatric acute myeloid leukemia study groups

• Published in: Pediatric blood & cancer 2017-12, Vol.64 (12), p.n/a
• Main Authors: Creutzig, Ursula, Dworzak, Michael N., Zimmermann, Martin, Reinhardt, Dirk, Sramkova, Lucie, Bourquin, Jan Pierre, Hasle, Henrik, Abrahamsson, Jonas, Kaspers, Gertjan, den Heuvel, Mary M., Reedijk, Ardine M. J., Moerloose, Barbara, Locatelli, Franco, Masetti, Riccardo
• Format: Article
• Language: English
• Subjects: Acute myeloid leukemia; Acute promyeloid leukemia; Adolescent; Blood cells; Central nervous system; Central Nervous System Neoplasms - mortality; Central Nervous System Neoplasms - therapy; Chemotherapy; Child; Child, Preschool; children; Clinical trials; CNS involvement; Cranial Irradiation; Cytogenetics; Cytology; Hematology; Hematopoietic Stem Cell Transplantation; Humans; Infant; Infant, Newborn; Irradiation; Leukemia; Leukemia, Myeloid, Acute - mortality; Leukemia, Myeloid, Acute - therapy; Myeloid leukemia; Neoplasms, Second Primary - epidemiology; Nervous system; Oncology; Pediatrics; Pediatrik; Promyeloid leukemia; Proportional Hazards Models; Radiation; Recurrence; Risk groups; Skull; Stem cell transplantation; Survival; Transplantation; treatment; Treatment Outcome
• ISSN: 1545-5009; 1545-5017; 1545-5017
• DOI: 10.1002/pbc.26664

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.