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MRD levels during the first months of treatment indicate relapses in children with t(12;21)-positive ALL

Leukemia volume 14, pages 1707–1708 (2000)Cite this article

The TEL-AML1 fusion gene created by the t(12;21) is the most common translocation in childhood acute lymphoblastic leukemia. Although this subgroup of leukemias seems to be associated with an excellent prognosis in most studies, controversial data exist regarding the incidence of TEL-AML1 at relapse varying from 10 to 24% (reviewed in Ref. 1). Although the prognostic significance of MRD in such cases has already been addressed previously in several studies, the use of the TEL-AML1 fusion transcript as a clonal disease marker for MRD detection prevented a direct comparison of the respective results with those obtained in cases lacking such transcripts.1 In a large prospective trial, we recently showed that the determination of the MRD by means of clonotypic antigen receptor gene rearrangement analysis provides important prognostic clues in patients treated according to ALL-BFM 90 protocols.23 We were therefore interested whether this holds also true for t(12;21)-positive ALL and whether we are able to discriminate between children, who are likely to be cured from those, who are at risk for a relapse.

In the present study, we selected 57 children with B cell precursor (BCP) ALL according to the availability of bone marrow samples at diagnosis, during the course of therapy and at relapse. Eight patients had high risk leukemia according to BFM criteria (prednisone poor response, t(4;11), or t(9;22)). None of the prednisone poor responders had a t(12;21)-positive leukemia and they were therefore excluded from further analysis. The remaining 49 children with non-high risk BCP ALL were treated in Austria according to current BFM protocols4 (ALL-BFM 90: n = 43, ALL-BFM 95: n = 6) between January 1992 and November 1996. Age at diagnosis ranged from 3 months to 14 years (median 5 years). Clinical characteristics of the patients did not deviate from those of the additional 189 children with non-high risk BCP-ALL enrolled in the ALL-BFM studies in Austria during the study period. To increase the number of relapses from t(12;21)-positive leukemias two additional patients with a late relapse of their t(12;21)-positive ALL, one isolated in the ovary after 4.1 years and the other in the bone marrow after 4.5 years, from whom follow-up samples for MRD analysis were available, have been included.

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References

  1. Rubnitz JE, Pui C-H, Downing JR . The role of TEL fusion genes in pediatric leukemias Leukemia 1999 13: 6–13

    Article  CAS  Google Scholar 

  2. Van Dongen JJ, Seriu T, Panzer-Grümayer ER, Biondi A, Pongers-Willemse MJ, Corral L, Stolz F, Schrappe M, Masera G, Kamps WA, Gadner H, van-Wering ER, Ludwig WD, Basso G, de Bruijn MA, Cazzaniga G, Hettinger K, van der Does van den Berg A, Hop WC, Riehm H, Bartram CR . Prognostic value of minimal residual disease in acute lymphoblastic leukemia in childhood Lancet 1998 352: 1731–1738

    Article  CAS  Google Scholar 

  3. Panzer-Grümayer ER, Schneider M, Panzer S, Fasching K, Gadner H . Rapid molecular response during early induction chemotherapy predicts a good outcome in childhood acute lymphoblastic leukemia Blood 2000 95: 790–794

    PubMed  Google Scholar 

  4. Pongers-Willemse MJ, Seriu T, Stolz F, d’Aniello E, Gameiro P, Pisa P, Gonzalez M, Bartram CR, Panzer-Grümayer ER, Biondi A, San Miguel JF, van Dongen JJM . Primers and protocols for standardized detection of minimal residual disease in acute lymphoblastic leukemia using immunoglobulin and T cell receptor gene rearrangements and TAL1 deletions as PCR targets. Report of the BIOMED-1 CONCERTED ACTION: investigation of minimal residual disease in acute leukemia Leukemia 1999 13: 110–118

    Article  CAS  Google Scholar 

  5. Schrappe M, Reiter A, Sauter S, Ludwig WD, Wörmann B, Harbott J, Bender-Götze C, Dörffel W, Dopfer R, Frey E, Havers W, Henze G, Kühl J, Richter R, Ritter J, Treuner J, Zintl F, Odenwald E, Welte K, Riehm H . Konzeption und Zwischenergebnis der Therapiestudie ALL-BFM 90 zur Behandlung der akuten lymphoblastischen Leukämie bei Kindern und Jugendlichen: die Bedeutung des initialen Therapieansprechens in Blut und Knochenmark Klin Pädiatr 1994 206: 208–227

    Article  CAS  Google Scholar 

  6. Zuna J, Hrusak O, Kalinova M, Muzikova K, Stary J, Trka J for the Czech Paediatric Haematology Working Group . TEL-AML1 positivity in childhood ALL: average or better prognosis? Leukemia 1999 13: 22–24

    Article  CAS  Google Scholar 

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Acknowledgements

This work was supported in part by the ‘Österreichische Kinderkrebshilfe’ and by private donations to the CCRI. We thank M Konrad and S Fischer for excellent technical assistance, also the physicians B Ausserer, FM Fink, N Jones, G Müller, I Mutz, R Ployer, N Pobegen, K Schmitt and O Stöllinger for providing bone marrow samples. Production of the probes was supported by the Biomed 1 Concerted Action CT94-1703.

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  1. Children’s Cancer Research Institute and St Anna Kinderspital, Vienna, Austria

    K Fasching, M König, K Hettinger, G Mann, H Gadner, OA Haas & ER Panzer-Grümayer

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  1. K Fasching
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  2. M König
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Fasching, K., König, M., Hettinger, K. et al. MRD levels during the first months of treatment indicate relapses in children with t(12;21)-positive ALL. Leukemia 14, 1707–1708 (2000). https://doi.org/10.1038/sj.leu.2401882

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