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Workshop on Minimal Residual Disease

Treatment response and residual-disease monitoring in initial and relapsed TEL-AML1 positive childhood ALL

Leukemia volume 15, pages 280–282 (2001)Cite this article

In recently reported studies, the analyses of residual leukemic cells by sensitive and specific molecular methods or flow-cytometric techniques during multi-agent chemotherapy in childhood ALL provide measurable evidence on the effectiveness of therapy.12 Furthermore, the detection of minimal residual disease (MRD) after induction of remission has been shown to be of significant prognostic value, thus permitting the stratification of children with ALL to less toxic or more intensive treatment arms.1 In the majority of ALL, clonal rearrangements of the T-cell receptor (TCR) and immunoglobulin (Ig) gene loci represent unique clone-specific marker for MRD monitoring. However, this DNA-based approach is burdened both with high costs, and time and labor intensity. The detection of fusion transcripts by reverse transcriptase- polymerase chain reaction (RT-PCR) represents an alternative molecular surveillance method in 35–45% of childhood ALL.3

The TEL-AML1 fusion transcript [t(12;21)(p13;q22)] represents the most common genetic rearrangement in childhood ALL and is detected in 20 to 25% of initial ALL. Both at initial manifestation and at relapse, TEL-AML1+ ALL are characterized by their confinement to B cell precursor ALL, mostly leukocyte counts <50 × 109/l, age between 2 and 10 years,456 a nonhyperdiploidy, and in the event of a relapse by a long duration of remission (median 46 months).67 Another characteristic of TEL-AML1+ ALL is its association with an excellent prognosis and short-term outcome on current intensive multi-agent therapeutic regimens. This observation is currently in discussion since assessment of TEL-AML1 positivity in relapsed childhood ALL has revealed a wide range of prevalences (3.1%-28%) either supporting or contradicting its positive prognostic feature.8910 Although an effect of frontline therapeutic regimens can not be ruled out, these discrepancies are in part due to retrospective study design, low sample numbers and the lack of consideration of the long duration of remission of TEL-AML1+ ALL. Nonetheless, the TEL-AML1+ group is non-uniform and the identification of distinguishing features is required in order to stratify patients reliably to treatment arms. This molecular study analyzes response to therapy of initial and relapsed childhood TEL-AML1+ ALL during early phases of induction, assesses residual leukemia in follow-up samples, and aims at identifying children in hematologic remission with the highest risk of relapse.

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Acknowledgements

This study was supported by ‘Deutsche Kinderkrebsstiftung’, ‘Deutsche José Carreras Leukämiestiftung’, and Projects 111300001/3 from the Czech Ministry of Education.

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Authors and Affiliations

  1. Dept of Pediatric Oncology/Hematology, Charité Medical Center, Berlin, Germany

    K Seeger, D Buchwald & G Henze

  2. Dept of General Pediatrics, Children's University Hospital, Giessen, Germany

    S Viehmann & J Harbott

  3. Dept of Pediatric Oncology/Hematology, Medical School, Hannover, Germany

    M Schrappe

  4. Dept of Pediatrics, 2nd Medical School, Charles University, Prague, Czech Republic

    J Stary & J Trka

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  1. K Seeger
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Seeger, K., Viehmann, S., Buchwald, D. et al. Treatment response and residual-disease monitoring in initial and relapsed TEL-AML1 positive childhood ALL. Leukemia 15, 280–282 (2001). https://doi.org/10.1038/sj.leu.2402020

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