1. ¹Department of Pediatric Hematology and Oncology, CLIP, Second Medical School, Charles University and University Hospital Motol, Prague, Czech Republic
2. ²Pediatric Hematology Oncology Department, Schneider Children's Medical Center of Israel, Petah Tikva, Israel
3. ³Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
4. ⁴Department of Pediatrics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China
5. ⁵Servicio Hemato Oncológico, Centro Hospitalario Pereira Rossell, Montevideo, Uruguay
6. ⁶Department of Pediatrics, Regional Hospital, Ceske Budejovice, Czech Republic
7. ⁷Department of Pediatrics, University Hospital Schleswig-Holstein, Kiel, Germany
8. ⁸Department of Pediatrics, University of Milano-Bicocca, Ospedale San Gerardo, Monza, Italy
9. ⁹Pediatric Hemato-Oncology, Cancer Research Center, Sheba Medical Center, Tel Hashomer, Israel
10. ¹⁰Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

Correspondence: Dr J Trka, Department of Pediatric Hematology and Oncology, Charles University, 2nd Medical School, V uvalu 84, 150 06—Prague 5, Czech Republic. E-mail: jan.trka@lfmotol.cuni.cz

Received 2 January 2008; Accepted 17 January 2008; Published online 28 February 2008.

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 l^{- 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.