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Klin Padiatr 2014; 226(06/07): 338-343
DOI: 10.1055/s-0034-1387795
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

Minimal Residual Disease–based Treatment is Adequate for Relapse-prone Childhood Acute Lymphoblastic Leukemia with an intrachromosomal amplification of chromosome 21: The experience of the ALL-BFM 2000 trial

Eine auf der minimalen Resterkrankung basierende Risikostratifizierung ist adäquat zur Behandlung von Kindern mit akuter lymphoblastischer Leukämie und einer intrachromosomalen Amplifikation am Chromosom 21: Erfahrungen aus der ALL-BFM 2000 Studie
A. Attarbaschi
1   Department of pediatric Hematology and Oncology, St. Anna Children’s Hospital, Medical University of Vienna, Vienna, Austria
,
R. Panzer-Grümayer
2   Children’s Cancer Research Institute (CCRI), Vienna, Austria
,
G. Mann
1   Department of pediatric Hematology and Oncology, St. Anna Children’s Hospital, Medical University of Vienna, Vienna, Austria
,
A. Möricke
3   Department of Pediatric Hematology and Oncology, Children’s University Hospital, University Hospital Schleswig-Holstein, Campus Kiel, Germany
,
M. König
2   Children’s Cancer Research Institute (CCRI), Vienna, Austria
,
A. Mecklenbräuker
2   Children’s Cancer Research Institute (CCRI), Vienna, Austria
,
A. Teigler-Schlegel
4   Department of Pediatric Hematology and Oncology, Oncogenetic Laboratory, Justus-Liebig-University, Giessen, Germany
,
J. Bradtke
5   Institute of Pathology, Justus-Liebig-University, Giessen, Germany
,
J. Harbott
4   Department of Pediatric Hematology and Oncology, Oncogenetic Laboratory, Justus-Liebig-University, Giessen, Germany
,
G. Göhring
6   Institute of Cell and Molecular Pathology, Medical School of Hannover, Hannover, Germany
,
M. Stanulla
7   Department of Pediatric Hematology and Oncology, Medical School of Hannover, Hannover, Germany
,
M. Schrappe
3   Department of Pediatric Hematology and Oncology, Children’s University Hospital, University Hospital Schleswig-Holstein, Campus Kiel, Germany
,
M. Zimmermann
7   Department of Pediatric Hematology and Oncology, Medical School of Hannover, Hannover, Germany
,
O. A. Haas
1   Department of pediatric Hematology and Oncology, St. Anna Children’s Hospital, Medical University of Vienna, Vienna, Austria
2   Children’s Cancer Research Institute (CCRI), Vienna, Austria
,
on behalf of the Austrian and German ALL-BFM (Berlin-Frankfurt-Münster) Study Group › Author Affiliations
Further Information

Publication History

Publication Date:
28 November 2014 (online)

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Abstract

Background: Recently, the UK CCLG and COG reported that an intrachromosomal amplification of chromosome 21 (iAMP21) in acute lymphoblastic leukemia (ALL) loses its adverse prognostic impact with intensified therapy.

Patient and Methods: We evaluated the prognosis of iAMP21 among patients from the ALL-BFM (Berlin-Frankfurt-Münster) 2000 trial with 46 of 2 637 (2%) patients iAMP21+.

Results: 8-year event-free-survival (EFS, 64±8% vs. 81±1%, p=0.0026) and cumulative incidence of relapse (CIR, 29±8% vs. 14±1%, p=0.008) of the iAMP21 cases were significantly worse compared with non-iAMP21 patients. Within the MRD low-risk group, iAMP21 cases (n=14) had an inferior 8-year EFS (76±12% vs. 92±1%, p=0.0081), but no increased CIR (10±10% vs. 6±1%, p=0.624). Within the MRD intermediate-risk group, iAMP21 cases (n=27) had a worse 8-year EFS (56±11% vs. 78±2%, p=0.0077) and CIR (44±11% vs. 20±2%, p=0.003) with 6/10 relapses occurring after 2 years.

Conclusions: Conclusively, we believe that there is no necessity for enrolling all iAMP21 patients into the high-risk arm of ongoing ALL-BFM trials because MRD low-risk patients have a moderate relapse risk under current therapy. Whether the increased relapse risk in MRD intermediate-risk patients can be avoided by late treatment intensification remains to be answered by the AIEOP-BFM ALL 2009 trial randomly using protracted pegylated L-asparaginase during delayed intensification and early maintenance.

Zusammenfassung

Hintergrund: In 2 rezenten Publikationen der UK CCLG und der COG ist gezeigt worden, dass die intrachromosomale Amplifikation am Chromosom 21 (iAMP21) ihre ungünstige Prognose mit einer intensivierten Therapie verliert.

Patients und Methoden: Wir evaluierten die Prognose von iAMP21 innerhalb einer Kohorte von 2 637 Patienten aus der ALL-BFM (Berlin-Frankfurt-Münster) 2000 Studie, wobei 46 Patienten (2%) iAMP21+ waren.

Ergebnisse: Das 8-Jahres Ereignisfreie Überleben (EFS) (64±8% vs. 81±1%, p=0.0026) und die kumulative Inzidenz an Rezidiven (29±8% vs. 14±1%, p=0.008) der iAMP21 Patienten waren signifikant schlechter im Vergleich zu den non-iAMP21 Patienten. Innerhalb der MRD Low-risk Gruppe (n=14) hatten iAMP21 Patienten eine ungünstigere 8-Jahres EFS Rate (76±12% vs. 92±1%, p=0.0081), aber keine erhöhte Rezidivinzidenz (10±10% vs. 6±1%, p=0.624). Innerhalb der MRD Intermediate-risk Gruppe (n=27) hatten iAMP21 Patienten eine ungünstigere 8-Jahres EFS Rate (56±11% vs. 78±2%, p=0.0077) und erhöhte Rezidivinzidenz (44±11% vs. 20±2%, p=0.003), wobei 6 von 10 Rezidiven nach 2 Jahren zu beobachten waren.

Schlussfolgerungen: Schlussfolgernd glauben wir, dass derzeit kein Anlass besteht, sämtliche iAMP21 Patienten in den Hochrisikoarm laufendender ALL-BFM Studien einzuschließen, da MRD Low-risk Patienten mit der derzeitigen Therapie nur ein moderates Rezidivrisiko haben. Ob sich das erhöhte Rezidivrisiko der MRD Intermediate-risk Patienten mittels einer späten Therapieintensivierung vermeiden lässt, wird sich vielleicht innerhalb der AIEOP-BFM ALL 2009 zeigen können, in welcher pegylierte L-Asparaginase protrahiert während der späten Intensivierung und frühen Dauertherapie randomisiert verwendet wird.

Key words

iAMP21 - minimal residual disease - relapse - prognosis

Schlüsselwörter

iAMP21 - minimale Resterkrankung - Rezidiv - Prognose

Supplementary Material

 

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