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The Eleventh International Childhood Acute Lymphoblastic Leukemia Workshop Report: Ponte di Legno, Italy, 6–7 May 2009

Leukemia volume 23, pages 2318–2324 (2009)Cite this article

Induction failure attributed to refractory disease is a rare event in pediatric ALL,1, 2, 3, 4 and hence there is only scanty information on this topic in the literature. To identify the clinical, biological and prognostic features of these patients, Dr Martin Schrappe and Dr Martin Zimmermann analyzed a large cohort of patients enrolled in the clinical trials of 14 cooperative study groups between 1985 and 2000. Induction failure, as defined by the morphological persistence of leukemic blasts in bone marrow (M2 or M3 marrow) or at extramedullary site(s), was found in 1041 (2.3%) of 44 554 patients. Not surprisingly, patients with induction failure were more likely to have adverse risk factors, such as older age, high leukocyte count, T-cell ALL, or the presence of Philadelphia chromosome or 11q23 rearrangements, compared with the other patients. In spite of the resistance to induction chemotherapy, about one-third of patients were alive at 10 years. Treatment results were particularly poor for patients aged <1 or ⩾10 years, males, and those with leukocyte count >100 × 109/l at diagnosis or large post-induction tumor burden in the bone marrow. Additional analyses are underway to determine the heterogeneity in clinical outcome according to the genetic features and treatment with or without hematopoietic stem cell transplantation.

In a previous retrospective analysis of 326 children with Philadelphia chromosome-positive ALL treated by 10 major study groups between 1986 and 1996, the group showed that there was substantial heterogeneity among this subset of leukemia and that transplantation from matched related donor, but not from unrelated donor, was superior to chemotherapy, in terms of disease-free survival and survival.5 To evaluate the impact of improvements in chemotherapy and stem cell transplantation, the group performed a second survey of patients treated by 14 major study groups between 1995 and 2005. The study was limited to the 647 patients who had not received imatinib or other tyrosine kinase inhibitors. Preliminary results were presented at the 50th annual meeting of the American Society of Hematology in December 2008. Dr Maurizio Aricü reported that the treatment results of this cohort were significantly better than those of the previous cohorts in terms of complete remission rate (89 vs 82%), 7-year event-free survival (31 vs 25%), and 7-year survival (44 vs 36%). Prognostic factors found in the early study remained important, including age, initial leukocyte count, and early treatment response. Final analysis of outcomes for patients treated with chemotherapy versus various types of stem cell transplant is underway. The results will serve as baseline data for future comparison with patients treated with contemporary therapy including the tyrosine kinase inhibitors.

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Acknowledgements

This work was supported in part by the Osterreichische Kinderkrebshilfe and private donations to the Associazione Italiana Ricerca sul Cancro, Fondazione Tettamanti, Consiglio Nazionale Ricerche-Ministero Istruzione Universitá Ricerca; by a grant from the US National Institutes of Health (CA21765); and by the American Lebanese Syrian Associated Charities (ALSAC). The meeting was supported by generous grants from the Comitato Maria Letizia Verga and the Zegna Foundation.

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Authors and Affiliations

  1. Pediatric Department, University of Milano-Bicocca, San Gerardo Hospital, Monza, Italy

    A Biondi & G Masera

  2. Department of Pediatric Hematology, H,

    A Baruchel

  3. ô,

    A Baruchel

  4. pital Saint Louis and Robert Debré, University Paris Diderot, Paris, France

    A Baruchel

  5. Pediatric Hematology/Oncology/Bone Marrow Transplantation, University of Colorado College of Medicine, Aurora, CO, USA

    S Hunger

  6. Pediatric Clinic, the National University Hospital, Copenhagen, Denmark

    K Schmiegelow

  7. Department of Pediatrics, University Medical Center, Kiel, Germany

    M Schrappe

  8. Departments of Oncology and Pathology, St Jude Children's Research Hospital and the University of Tennessee Health Science Center, Memphis, TN, USA

    C H Pui

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Correspondence to A Biondi.

Appendix

Appendix

Participating groups/institutions (participants): Associazione Italiana di Ematologia ed Oncologia Pediatrica (Aricó M, Biondi A, Conter V, Locatelli F, Masera G, Valsecchi MG), Berlin-Frankfurt-Münster Group (Gadner H, Haas O, Izraeli S, Mann G, Moericke A, Riehm H, Schrappe M, Stanulla M, Zimmermann M), German Co-operative Study Group (Escherich G, Horstmann M), Children's Oncology Group (Camitta B, Carroll W, Devidas M, Gaynon P, Hunger S, Nachman J, Raetz E, Whitlock J), Czech Pediatric Hematology (Stary J, Trka J), Dutch Childhood Oncology Group (Pieters R), Dana-Farber Cancer Institute (Sallan S, Silverman L), European Organization for Research and Treatment of Cancer—Childhood Leukemia Cooperative Group (Benoit Y, Bertrand Y), French Acute Lymphoblastic Leukaemia Group (Baruchel A), Japanese Pediatric Leukemia/Lymphoma Study Group (Horibe K), Nordic Society of Paediatric Haematology and Oncology (Schmiegelow K), St Jude Children's Research Hospital (Evans W, Jeha S, Pui C-H, Relling M), United Kingdom Acute Lymphoblastic Leukemia (Gibson B, Harrison C, Mitchell C), Taiwan Pediatric Oncology Group (Liang D-C, Shih L-Y).

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Biondi, A., Baruchel, A., Hunger, S. et al. The Eleventh International Childhood Acute Lymphoblastic Leukemia Workshop Report: Ponte di Legno, Italy, 6–7 May 2009. Leukemia 23, 2318–2324 (2009). https://doi.org/10.1038/leu.2009.211

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