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Pathways Through Relapses and Deaths of Children With Acute Lymphoblastic Leukemia: Role of Allogeneic Stem-Cell Transplantation in Nordic Data

Ulla M. Saarinen-Pihkala, Carsten Heilmann, Jacek Winiarski, Anders Glomstein, Jonas Abrahamsson, Johan Arvidson, Albert N. Békássy, Erik Forestier, Gudmundur Jonmundsson, Henrik Schroeder, Kim Vettenranta, Finn Wesenberg, Göran Gustafsson

From the Hospital for Children and Adolescents, University of Helsinki, Finland; Department of Pediatrics, Juliane Marie Center, Rigshospitalet, Copenhagen; Aarhus University Hospital, Skejby, Aarhus, Denmark; Karolinska University Hospital, Huddinge; University Children's Hospital, Uppsala; Queen Silvia Children's Hospital, University of Göteborg, Göteborg; University Children's Hospital, Lund; Childrens Hospital, University of Umeå, Umeå; Childhood Cancer Research Unit, Karolinska Institute, Stockholm, Sweden; Rikshospitalet, Oslo, Norway; and Landspitalinn, Reykjavik, Iceland

Address reprint requests to Ulla M. Saarinen-Pihkala, Hospital for Children and Adolescents, University of Helsinki, PO Box 281, 00029 HUS, Helsinki, Finland; e-mail: ulla.pihkala{at}hus.fi

PURPOSE: Our focus was on patients with pediatric acute lymphoblastic leukemia (ALL) who experienced relapse or died without becoming transplantation candidates. The purpose was to outline measures needed to improve the outcome.

PATIENTS AND METHODS: We analyzed our population-based 20-year data on 3,385 Nordic children with ALL treated on Nordic Society for Pediatric Hematology and Oncology ALL protocols, and described the flow of these patients through relapses, remissions, and deaths as a result of toxicity, demonstrating where major patient losses occurred.

RESULTS: In total, 854 patients (25%) had a first and 274 patients (8%) had a second ALL relapse. P for survival after the first relapse was .35 ± .02. The induction mortality (2.2%, primary; 10.3%, first relapse; 26.3%, second relapse) and remission mortality (1%, first complete remission [1CR]; 19%, second CR [2CR]) were significant; transplantation-related mortality (TRM) only represented 15% (69 of 459) of the deaths as a result of toxicity. Of the 766 patients entering 2CR, 29% underwent transplantation (P for survival, .46 ± .04), whereas 71% continued receiving chemotherapy (P for survival, .39 ± .02). Children with stem-cell transplantation indications in 2CR, if they did not undergo transplantation, generally died or had a second relapse. The patient groups that underwent transplantation in 1CR (n = 84), 2CR (n = 220), and 3CR (n = 62) represented different risk profiles. Those with allogeneic stem-cell transplantation (allo-SCT) in 3CR (P for survival, .37 ± .07) had an ALL and first relapse with favorable features.

CONCLUSION: Major patient losses occurred through mortality as a result of toxicity and resistant disease during the pathways before allo-SCT. After relapse, more patients were lost to mortality as a result of toxicity during conventional chemotherapy compared with TRM. After second relapse, the chance for rescue by allo-SCT in 3CR was minimal. The question of whether transplantation is recommended after ALL relapse should be carefully addressed, and more efficient relapse protocols should be launched.

Supported by Research Funding of the Helsinki University Hospitals, Helsinki, Finland (U.S.-P.), Foundation for Pediatric Research, Helsinki, Finland (U.S.-P.), and by Swedish Child Cancer Foundation, Stockholm, Sweden (G.G.).

Presented in part at the Annual Nordic Society for Pediatric Hematology and Oncology Meeting, May 7-9, 2006, Tampere, Finland.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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