This Article Full Text Full Text (PDF) Erratum (v26,p2238) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Einsiedel, H. G. Articles by Henze, G. Search for Related Content PubMed PubMed Citation Articles by Einsiedel, H. G. Articles by Henze, G.

Long-Term Outcome in Children With Relapsed ALL by Risk-Stratified Salvage Therapy: Results of Trial Acute Lymphoblastic Leukemia-Relapse Study of the Berlin-Frankfurt-Münster Group 87

From the Department of Pediatric Oncology/Hematology, Charité Universitätsmedizin Berlin; Departments of Pediatric Oncology/Hematology of Universities in Hannover, Hamburg, Düsseldorf, Frankfurt, Germany; St. Anna Kinderspital, Wien, Austria; Erasmus MC Sophia Children's Hospital, Rotterdam, the Netherlands; and Department of Oncology/Hematology and Tumorimmunology, Berlin-Buch, Germany

Address reprint requests to Arend v. Stackelberg, Charité Universitätsmedizin Berlin Campus Virchow-Klinikum Otto-Heubner-Centrum für Kinder und Jugendmedizin Klinik für Pädiatrie, m.S. Onkologie/Hämatologie Augustenburger Platz 1 13353 Berlin, Germany; e-mail: arend.stackelberg{at}charite.de

PURPOSE: Approximately 20% of children with acute lymphoblastic leukemia (ALL) suffer a relapse, and their prognosis is unfavorable. Between 1987 and 1990, the multicenter trial Acute Lymphoblastic Leukemia-Relapse Study of the Berlin-Frankfurt-Münster Group (ALL-REZ BFM) 87 was conducted to establish a uniform treatment for these children in Germany and Austria.

PATIENTS AND METHODS: Of 207 registered patients, 183 patients were stratified into three groups according to the protocol: A, early bone marrow (BM) relapse (n = 56); B, late BM relapse (n = 101); C, isolated extramedullary relapse (n = 26). Treatment consisted of risk-adapted alternating short-course multiagent systemic and intrathecal chemotherapy, cranial irradiation, if indicated, and conventional maintenance therapy. Additionally, 24 patients with an exceptionally poor prognosis (early BM or any relapse of T-cell ALL) were treated with individual regimens. In 35 patients, stem-cell transplantation was performed.

RESULTS: The probability of event-free survival (EFS) and overall survival of all registered patients at 15 years was 0.30 ± 0.03 and 0.37 ± 0.03, respectively, with significant differences between the strategic groups (A, 0.18 ± 0.05 and 0.20 ± 0.05; B, 0.44 ± 0.05 and 0.52 ± 0.05; C, 0.35 ± 0.09 and 0.42 ± 0.10). Despite risk-adapted treatment, an early time point of relapse and T-lineage immunophenotype were significant predictors of inferior EFS in uni- and multivariate analyses.

CONCLUSION: With the ALL-REZ BFM 87 protocol, more than one-third of patients may be regarded as cured from recurrent ALL with second complete remissions lasting more than 10 years. Immunophenotype and time point of relapse are important prognostic factors that allow us to adapt more precisely treatment intensity to individual prognosis in future trials.

Supported by Deutsche Krebshilfe, Bonn, Germany.

Both authors contributed equally to this work.

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

This article has been cited by other articles:

				E. A. Raetz, M. J. Borowitz, M. Devidas, S. B. Linda, S. P. Hunger, N. J. Winick, B. M. Camitta, P. S. Gaynon, and W. L. Carroll Reinduction Platform for Children With First Marrow Relapse in Acute Lymphoblastic Lymphoma J. Clin. Oncol., August 20, 2008; 26(24): 3971 - 3978. [Abstract] [Full Text] [PDF]

				E. A. Raetz, M. S. Cairo, M. J. Borowitz, S. M. Blaney, M. D. Krailo, T. A. Leil, J. M. Reid, D. M. Goldenberg, W. A. Wegener, W. L. Carroll, et al. Chemoimmunotherapy Reinduction With Epratuzumab in Children With Acute Lymphoblastic Leukemia in Marrow Relapse: A Children's Oncology Group Pilot Study J. Clin. Oncol., August 1, 2008; 26(22): 3756 - 3762. [Abstract] [Full Text] [PDF]

				M. H. Cohen, J. R. Johnson, R. Justice, and R. Pazdur FDA Drug Approval Summary: Nelarabine (Arranon(R)) for the Treatment of T-Cell Lymphoblastic Leukemia/Lymphoma Oncologist, June 1, 2008; 13(6): 709 - 714. [Abstract] [Full Text] [PDF]

				A. von Stackelberg, R. Hartmann, C. Buhrer, R. Fengler, G. Janka-Schaub, A. Reiter, G. Mann, K. Schmiegelow, R. Ratei, T. Klingebiel, et al. High-dose compared with intermediate-dose methotrexate in children with a first relapse of acute lymphoblastic leukemia Blood, March 1, 2008; 111(5): 2573 - 2580. [Abstract] [Full Text] [PDF]

				S. Malempati, P. S. Gaynon, H. Sather, M. K. La, and L. C. Stork Outcome After Relapse Among Children With Standard-Risk Acute Lymphoblastic Leukemia: Children's Oncology Group Study CCG-1952 J. Clin. Oncol., December 20, 2007; 25(36): 5800 - 5807. [Abstract] [Full Text] [PDF]

				N. Hagedorn, C. Acquaviva, E. Fronkova, A. von Stackelberg, A. Barth, U. zur Stadt, A. Schrauder, J. Trka, N. Gaspar, K. Seeger, et al. Submicroscopic bone marrow involvement in isolated extramedullary relapses in childhood acute lymphoblastic leukemia: a more precise definition of "isolated" and its possible clinical implications, a collaborative study of the Resistant Disease Committee of the International BFM study group Blood, December 1, 2007; 110(12): 4022 - 4029. [Abstract] [Full Text] [PDF]

				U. M. Saarinen-Pihkala, C. Heilmann, J. Winiarski, A. Glomstein, J. Abrahamsson, J. Arvidson, A. N. Bekassy, E. Forestier, G. Jonmundsson, H. Schroeder, et al. Pathways Through Relapses and Deaths of Children With Acute Lymphoblastic Leukemia: Role of Allogeneic Stem-Cell Transplantation in Nordic Data J. Clin. Oncol., December 20, 2006; 24(36): 5750 - 5762. [Abstract] [Full Text] [PDF]

				M. H. Cohen, J. R. Johnson, T. Massie, R. Sridhara, W. D. McGuinn Jr., S. Abraham, B. P. Booth, M. A. Goheer, D. Morse, X. H. Chen, et al. Approval summary: nelarabine for the treatment of T-cell lymphoblastic leukemia/lymphoma. Clin. Cancer Res., September 15, 2006; 12(18): 5329 - 5335. [Abstract] [Full Text] [PDF]

				R. Kirschner-Schwabe, C. Lottaz, J. Todling, P. Rhein, L. Karawajew, C. Eckert, A. von Stackelberg, U. Ungethum, D. Kostka, A. E. Kulozik, et al. Expression of Late Cell Cycle Genes and an Increased Proliferative Capacity Characterize Very Early Relapse of Childhood Acute Lymphoblastic Leukemia Clin. Cancer Res., August 1, 2006; 12(15): 4553 - 4561. [Abstract] [Full Text] [PDF]

				P. S. Gaynon, R. E. Harris, A. J. Altman, B. C. Bostrom, J. C. Breneman, R. Hawks, D. Steele, T. Zipf, D. O. Stram, D. Villaluna, et al. Bone Marrow Transplantation Versus Prolonged Intensive Chemotherapy for Children With Acute Lymphoblastic Leukemia and an Initial Bone Marrow Relapse Within 12 Months of the Completion of Primary Therapy: Children's Oncology Group Study CCG-1941 J. Clin. Oncol., July 1, 2006; 24(19): 3150 - 3156. [Abstract] [Full Text] [PDF]