1. ¹CLIP (Childhood Leukaemia Investigation Prague), Department of Paediatric Haematology and Oncology, Charles University, 2nd Medical School, Prague, Czech Republic
2. ²Laboratoire de Biochimie Génétique, Hôpital Robert Debré, Paris, France
3. ³Department of Paediatric Oncology/Haematology, Charite Medical University Berlin, Berlin, Germany
4. ⁴Department of Immunology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
5. ⁵Department of Paediatric Haematology and Oncology, Silesian Medical Academy, Zabrze, Poland
6. ⁶Institute of Pharmaceutical Biology/DCAL, University of Frankfurt, Frankfurt/Main, Germany
7. ⁷Department of Paediatric Oncology, University Hospital, Brno, Czech Republic
8. ⁸Paediatric Onco-Haematology Unit, University Hospital, Caen, France
9. ⁹Department of Paediatrics, University Hospital, Kiel, Germany

Correspondence: Dr Jan Zuna, CLIP, Department of Paediatric Haematology and Oncology, Charles University Prague, 2nd Medical School, V Uvalu 84, Prague 5 – 150 06, Czech Republic. E-mail: jan.zuna@lfmotol.cuni.cz

Received 5 March 2007; Revised 27 March 2007; Accepted 28 March 2007; Published online 26 April 2007.

Abstract

Data on secondary acute lymphoblastic leukaemia (sALL) following ALL treatment are very rare. However, the incidence might be underestimated as sALLs without a significant lineage shift might automatically be diagnosed as relapses. Examination of immunoglobulin and T-cell receptor gene rearrangements brought a new tool that can help in discrimination between relapse and sALL. We focused on the recurrences of childhood ALL to discover the real frequency of the sALL after ALL treatment. We compared clonal markers in matched presentation and recurrence samples of 366 patients treated according to the Berlin–Frankfurt–Munster (BFM)-based protocols. We found two cases of sALL and another three, where the recurrence is suspicious of being sALL rather than relapse. Our proposal for the 'secondary ALL after ALL' diagnostic criteria is as follows: (A) No clonal relationship between diagnosis and recurrence; (B) significant immunophenotypic shift – significant cytogenetic shift – gain/loss of a fusion gene. For the sALL (A) plus at least one (B) criterion should be fulfilled. With these criteria, the estimated frequency of the sALL after ALL is according to our data 0.5–1.5% of ALL recurrences on BFM-based protocols. Finally, we propose a treatment strategy for the patients with secondary disease.