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Klin Padiatr 2013; 225(S 01): S50-S56
DOI: 10.1055/s-0033-1337964
Zum 80. Geburtstag von Prof. Riehm
© Georg Thieme Verlag KG Stuttgart · New York

Prediction of Outcome by Early Response in Childhood Acute Lymphoblastic Leukemia

Das frühe Ansprechen auf die Therapie als prognostischer Faktor bei der akuten lymphoblastischen Leukämie im Kindesalter
A. Möricke
1   Department of Pediatrics, University Hospital Schleswig-Holstein, Campus Kiel, Germany
,
M. Lauten
2   Pediatric Hematology and Oncology, University Hospital Schleswig-­Holstein, Campus Lübeck, Germany
,
R. Beier
3   Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany
,
E. Odenwald
3   Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany
,
M. Stanulla
1   Department of Pediatrics, University Hospital Schleswig-Holstein, Campus Kiel, Germany
,
M. Zimmermann
3   Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany
,
A. Attarbaschi
4   St. Anna Children’s Hospital, Vienna, Austria
,
F. Niggli
6   Kinderspital, University Hospital Zürich, Switzerland
,
M. Schrappe
1   Department of Pediatrics, University Hospital Schleswig-Holstein, Campus Kiel, Germany
› Author Affiliations
Further Information

Publication History

Publication Date:
22 May 2013 (online)

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Abstract

Background:

In the ALL-BFM studies for treatment of acute lymphoblastic leukemia, reduction of leukemic blasts in peripheral blood after a one-week prednisone pre-phase – the so-called prednisone response – has been used for risk stratification since the 1980s and has been one of the most relevant factors for identification of high-risk patients. In the trial ALL-BFM 95, early cytomorphological marrow response on day 15 of induction therapy was prospectively evaluated and its prognostic value was analyzed in comparison to the prednisone response and other established prognostic factors.

Results:

Compared to prednisone response, day 15 marrow response was superior in outcome prediction – yet with differential effect depending on blast lineage. Outcome was poor in T cell leukemia patients with prednisone poor-response independent of day 15 marrow response, whereas among patients with prednisone good-response different risk groups could be identified by day 15 marrow response. In contrast, prednisone response lost prognostic significance in precursor B cell leukemia when stratified by day 15 marrow response.

Conclusions:

Selective addition of day 15 marrow response to conventional stratification criteria applied on ALL-BFM 95 may significantly improve risk-adapted treatment delivery. Even though cutting-edge trial risk stratification is meanwhile dominated by minimal residual disease evaluation, an improved conventional risk assessment, as presented here, could be of great importance to countries lacking the technical and/or financial resources associated with the application of minimal residual disease analysis.

Zusammenfassung

Hintergrund:

Die Blastenreduktion im peri­pheren Blut nach einer einwöchigen Prednison-Vorphase – der sogenannte Prednison-Response – wird in den ALL-BFM-Studien zur Behandlung von Kindern mit akuter lymphoblastischer Leukämie seit den 1980er Jahren für die Risikostratifizierung herangezogen und stellt einen der wichtigsten Faktoren für die Identifizierung von Hochrisikopatienten dar. In der Studie ALL-BFM 95 wurde zusätzlich das frühe zytomorphologische Ansprechen auf die Therapie am Tag 15 der Induktionstherapie im Knochenmark pro­spektiv untersucht und dessen prognostischer Wert im Vergleich zum Prednison-Response und anderen etablierten Prognosefaktoren analysiert.

Ergebnisse:

Das zytomorphologische Ansprechen im Knochenmark am Tag 15 war als prognostischer Faktor dem Prednison-Response insgesamt überlegen, jedoch mit unterschiedlichem Effekt in Abhängigkeit vom Immunphänotyp der Blasten. Während bei Patienten mit B-Vorläuferzell-Leukämie der Prednison-Reponse in Kombination mit dem Ansprechen am Tag 15 seine prognostische Wertigkeit komplett verlor, war bei Patienten mit T-Zell-Leukämie ein ­schlechter Prednison-Response auch bei gutem Ansprechen am Tag 15 prognostisch ungünstig.

Schlussfolgerung:

Die Verwendung des zytomorphologischen Therapieansprechens am Tag 15 in der Induktionstherapie für die Risikostra­tifizierung kann im Vergleich zur konventionellen Stratifizierung der Studie ALL-BFM 95 eine bessere Risikoadaptierung der Therapie ermöglichen. Auch wenn mittlerweile in vielen aktuellen Therapiestudien die zytomorphologische Evaluation des Therapieansprechens weitgehend durch Methoden zur Erfassung der minimalen Resterkrankung abgelöst wurde, kann insbesondere in Ländern, in denen keine ausreichenden Mittel für Analysen der minimalen Resterkrankung ­verfügbar sind, eine verbesserte konventionelle Risikoeinschätzung entscheidend zur Qualität der Therapie beitragen.

Key words

childhood acute lympho­blastic leukemia - early treatment response - clinical trial

Schlüsselwörter

akute lymphomblastische Leukämie in der Kindheit - frühes Therapieansprechen - klinische Studie
 

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