Relapsed childhood acute lymphoblastic leukemia in the Nordic countries: prognostic factors, treatment and outcome.
Relapse is the main reason for treatment failure in childhood acute lymphoblastic leukemia. Despite improvements in the up-front therapy, survival after relapse is still relatively poor, especially for high-risk relapses. The aims of this study were to assess outcomes following acute lymphoblastic leukemia relapse after common initial Nordic Society of Paediatric Haematology and Oncology protocol treatment; to validate currently used risk stratifications, and identify additional prognostic factors for overall survival. Altogether, 516 of 2735 patients (18.9%) relapsed between 1992 and 2011 and were included in the study. There were no statistically significant differences in outcome between the up-front protocols or between the relapse protocols used, but an improvement over time was observed. The 5-year overall survival for patients relapsing in the period 2002-2011 was 57.5±3.4%, but 44.7±3.2% (P<0.001) if relapse occurred in the period 1992-2001. Factors independently predicting mortality after relapse included short duration of first remission, bone marrow involvement, age ten years or over, unfavorable cytogenetics, and Down syndrome. T-cell immunophenotype was not an independent prognostic factor unless in combination with hyperleukocytosis at diagnosis. The outcome for early combined pre-B relapses was unexpectedly poor (5-year overall survival 38.0±10.6%), which supports the notion that these patients need further risk adjustment. Although survival outcomes have improved over time, the development of novel approaches is urgently needed to increase survival in relapsed childhood acute lymphoblastic leukemia.
Department of Pediatric Oncology, Astrid Lindgren Children's Hospital, Stockholm, Sweden Childhood Cancer Research Unit, Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden trausti.oskarsson@ki.se.
Trausti
T
Oskarsson
Department of Pediatric Oncology, Astrid Lindgren Children's Hospital, Stockholm, Sweden Childhood Cancer Research Unit, Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.
Stefan
S
Söderhäll
Department of Pediatric Oncology, Uppsala University Hospital, Sweden.
Johan
J
Arvidson
Department of Pediatrics, Umeå University Hospital, Sweden.
Erik
E
Forestier
Clinical Epidemiology and Biostatistics, Faculty of Medicine and Health, Örebro University, Sweden Clinical Epidemiology Unit, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden Department of Epidemiology and Public Health, University College London, UK.
Scott
S
Montgomery
Unit of Biostatistics, IMM, Karolinska Institutet, Stockholm, Sweden.
Matteo
M
Bottai
Department of Pediatric Oncology, Rigshospitalet University Hospital, Copenhagen, Denmark.
Birgitte
B
Lausen
Department of Pediatrics, Odense University Hospital, Denmark.
Niels
N
Carlsen
Department of Pediatrics, Ullevål Hospital, Oslo, Norway.
Marit
M
Hellebostad
Department of Pediatrics, Turku University Hospital, Turku, Finland.
Päivi
P
Lähteenmäki
Children's Hospital, University of Helsinki and Helsinki University Central Hospital, Finland.
Ulla M
UM
Saarinen-Pihkala
Children's Hospital, Landspitali University Hospital, Reykjavik, Iceland.
Ólafur G
ÓG
Jónsson
Department of Pediatric Oncology, Astrid Lindgren Children's Hospital, Stockholm, Sweden Childhood Cancer Research Unit, Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.
Mats
M
Heyman
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000401:mortality* / Q000628:therapy*; D012008:Recurrence; D018570:Risk Assessment; D015996:Survival Rate