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Minimal Risidual Disease

Minimal residual disease (MRD) analysis in the non-MRD-based ALL IC-BFM 2002 protocol for childhood ALL: is it possible to avoid MRD testing?

Leukemia volume 22, pages 989–997 (2008)Cite this article

Abstract

The ALL IC-BFM 2002 protocol was created as an alternative to the MRD-based AIEOP-BFM ALL 2000 study, to integrate early response criteria into risk-group stratification in countries not performing routine PCR-based MRD testing. ALL IC stratification comprises the response to prednisone, bone marrow (BM) morphology at days 15 and 33, age, WBC and BCR/ABL or MLL/AF4 presence. Here, we compared this stratification to the MRD-based criteria using MRD evaluation in 163 patients from four ALL IC member countries at days 8, 15 and 33 and week 12. MRD negativity at day 33 was associated with an age of 1–5 years, WBC<20 000 μl−1, non-T immunophenotype, good prednisone response and non-M3 morphology at day 15. There were no significant associations with gender or hyperdiploidy in the study group, or with TEL/AML1 fusion within BCP-ALL. Patients with M1/2 BM at day 8 tended to be MRD negative at week 12. Patients stratified into the standard-risk group had a better response than intermediate-risk group patients. However, 34% of them were MRD positive at day 33 and/or week 12. Our findings revealed that morphology-based ALL IC risk-group stratification allows the identification of most MRD high-risk patients, but fails to discriminate the MRD low-risk group assigned to therapy reduction.

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Acknowledgements

This work was supported by MSM0021620813, MZO00064203, MZdNR8269-3/2005, Israel Cancer Association and Children's Cancer Foundation of Hong Kong. We thank the following participating clinical centers for clinical management and sample collection: Czech Republic: Brno (J Sterba), Ceske Budejovice (Y Jabali), Hradec Králové (J Hak), Olomouc (V Mihál), Ostrava (B Blazek), Plzeň (Z Černá), Prague (J Stary), Ústí nad Labem (D Prochazkova); Israel: Afula (H Gavriel), Beer-Sheva (J Kapelushnik), Haifa Bnei-Zion (D Attias), Haifa Rambam (R Elhasid), Holon (A Ballin), Jerusalem Hadassah (M Weintraub), Jerusalem Shaarei Zedek (H Miskin), Petah-Tikva (G Avrahami), Rehovot (D Sthoeger), Tel Aviv (Y Burstein), Tel Hashomer (B Bielorai). We also thank S Bendova for sequencing and A Vrzalova for data management.

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Authors and Affiliations

  1. Department of Pediatric Hematology and Oncology, CLIP, Second Medical School, Charles University and University Hospital Motol, Prague, Czech Republic

    E Fronkova, E Mejstrikova, L Reznickova, T Valova, K Zdrahalova, O Hrusak, J Stary & J Trka

  2. Pediatric Hematology Oncology Department, Schneider Children's Medical Center of Israel, Petah Tikva, Israel

    S Avigad, S Manor & B Stark

  3. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

    S Avigad, S Manor & B Stark

  4. Department of Pediatrics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China

    K W Chik & C K Li

  5. Servicio Hemato Oncológico, Centro Hospitalario Pereira Rossell, Montevideo, Uruguay

    L Castillo

  6. Department of Pediatrics, Regional Hospital, Ceske Budejovice, Czech Republic

    Y Jabali

  7. Department of Pediatrics, University Hospital Schleswig-Holstein, Kiel, Germany

    M Schrappe

  8. Department of Pediatrics, University of Milano-Bicocca, Ospedale San Gerardo, Monza, Italy

    V Conter

  9. Pediatric Hemato-Oncology, Cancer Research Center, Sheba Medical Center, Tel Hashomer, Israel

    S Izraeli

  10. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

    S Izraeli

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  1. E Fronkova
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Correspondence to J Trka.

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Fronkova, E., Mejstrikova, E., Avigad, S. et al. Minimal residual disease (MRD) analysis in the non-MRD-based ALL IC-BFM 2002 protocol for childhood ALL: is it possible to avoid MRD testing?. Leukemia 22, 989–997 (2008). https://doi.org/10.1038/leu.2008.22

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