CNS-3 status remains an independent adverse prognosis factor in children with acute lymphoblastic leukemia (ALL) treated without cranial irradiation: Results of EORTC Children Leukemia Group study 58951 |
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| Authors: | N. Sirvent S. Suciu B. De Moerloose A. Ferster F. Mazingue G. Plat K. Yakouben A. Uyttebroeck C. Paillard V. Costa P. Simon C. Pluchart M. Poirée O. Minckes F. Millot C. Freycon P. Maes C. Hoyoux Y. Benoit |
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| Affiliation: | 1. Department of Pediatric Hematology-Oncology, CHU, Montpellier, France;2. University Montpellier, Montpellier, France;3. EORTC Headquarters, Brussels, Belgium;4. Department of Pediatric Hematology-Oncology and Stem Cell Transplantation, Ghent University Hospital, Ghent University, Ghent, Belgium;5. Department of Pediatric Hematology-Oncology, Children''s University Hospital Queen Fabiola, Université Libre de Bruxelles (ULB), Brussels, Belgium;6. Department of Pediatric Hematology-Oncology, CHRU, Lille, France;7. Department of Pediatric Hematology-Oncology, CHU-Hôpital Purpan, Toulouse, France;8. Department of Pediatric Hematology, Robert-Debré Hospital, AP–HP, Paris, France;9. Department of Pediatric Hematology-Oncology, University Hospital Gasthuisberg, Leuven, Belgium;10. Department of Pediatric Hematology-Oncology, University Hospital Hautepierre, Strasbourg, France;11. Department of Pediatrics, Portuguese Oncology Institute, Porto, Portugal;12. Pediatric Hematology Unit, CHU Jean-Minjoz Hospital, Besançon, France;13. Department of Pediatric Hematology-Oncology, American Memorial Hospital, Reims, France;14. Department of Pediatric Hematology-Oncology, CHU Nice, Nice, France;15. Department of Pediatric Hematology-Oncology, CHU, Caen, France;p. Pediatric Oncology Unit, University Hospital, Poitiers, France;q. Department of Pediatric Oncology, University Hospital, Grenoble, France;r. Department of Pediatrics, University Hospital Antwerp, Antwerp, Belgium;s. Department of Pediatrics, CHR de la Citadelle, Liège, Belgium;t. Department of Genetics, Assistance publique–Hôpitaux de Paris (AP–HP), Robert-Debré Hospital, Paris, France;u. INSERM UMR 1131, University Institute of Hematology, University Paris-Diderot, Paris Sorbonne Cité, Paris, France;v. Institute of Pediatric Hematology and Oncology (IHOP), Hospices Civils de Lyon, University Lyon 1, Lyon, France;1. Neonatology Intensive Care Unit, University Hospital of Grenoble, CS 10217, 38043 Grenoble Cedex 9, France;2. Neonatal Intensive Care Unit, University Hospital of Amiens, France–PériTox UMR_I 01, University of Picardy Jules Verne, 1, rond point du Professeur Christian Cabrol, 80054 Amiens, France;3. Neonatal and Pediatric Intensive Care Unit, University Hospital of Trousseau, AP–HP, 26, avenue du Dr Arnold Netter, 75012 Paris, France;4. NICU of Port-Royal, AP–HP Centre–Université de Paris, Cochin Hospital, 123, boulevard de Port-Royal, 75014 Paris, France;5. Neonatal Intensive Care Unit, University Hospital of Nantes, 38, boulevard Jean Monnet, 44000 Nantes, France;1. University Children''s Hospital, Vandoeuvre-lès-Nancy, France;2. Independent Pediatric Practice of Dr. Lapp/Guillaume/Watelet, Vandoeuvre-lès-Nancy, France;3. Pediatric Emergency Department, CHRU, Vandoeuvre-lès-Nancy, France;4. DRI Research and Innovation Unit, CHRU, Vandoeuvre-lès-Nancy, France;5. Methodology, Data Management and Statistics Unit, DRCI, CHRU, Vandoeuvre-lès-Nancy, France;6. Department of Dermatology, Regional University Hospital (CHRU), 5, rue du Morvan, 54500 Vandoeuvre-lès-Nancy, France;1. Association Clinique et Thérapeutique Infantile du Val de Marne (ACTIV), 94000 Créteil, France;2. Université Paris Est, IMRB- GRC GEMINI, 31, rue Le Corbusier, 94000 Créteil, France;3. Clinical Research Center (CRC), Centre Hospitalier Intercommunal de Créteil, 40, avenue de Verdun, 94000 Créteil, France;4. Groupe de pathologie infectieuse pédiatrique (GPIP), CHU Lenval, 57, avenue de la Californie, 06200 Nice, France;1. Service des Urgences Pédiatriques, University Hospital of Strasbourg, 1, avenue Molière, 67200 Strasbourg, France;2. Service de Santé Publique, University Hospital of Strasbourg, 1, avenue Molière, 67200 Strasbourg, France;3. Service de Néonatalogie, University Hospital of Strasbourg, 1, avenue Molière, 67200 Strasbourg, France;4. Service de Pédiatrie I, University Hospital of Strasbourg, 1, avenue Molière, 67200 Strasbourg, France;1. Brest University Hospital, Pediatrics Department, Brest, France;2. Brest University Hospital, neonatal Intensive Care Unit, Brest, France;3. Laboratory of Lymphocyte Activation and Susceptibility to EBV infection, Inserm UMR 1163, Paris, University Paris Descartes Sorbonne Paris Cité, Imagine Institute, Paris, France;4. CHU de Nantes, Pediatric Hematology-Oncology Unit, Nantes, France;5. University Hospital of Angers, Department of Pediatric Onco-hematology, Angers, France;6. Department of Pediatric Onco-Hematology, Poitiers University Hospital, Poitiers, France;7. Department of Pediatric Hematology/Oncology, University Hospital of Rennes, Rennes, France;8. Centre Hospitalo-universitaire de Tours, Service de réanimation pédiatrique, Tours, France;9. CHU de Nantes, Department of Pediatric Emergency, Nantes, France;10. CHU de Nantes, Department of Pediatrics, Nantes, France;1. Department of Paediatric Intensive Care, DMU 3 Santé de l’enfant et de l’adolescent, Bicêtre Hospital, APHP Paris Saclay University, France;2. Department of Paediatric Surgery, DMU 3 Santé de l’enfant et de l’adolescent, Bicêtre Hospital, APHP Paris Saclay University, France;3. Department of Paediatric Hepatology and National Reference Centre for Rare Paediatric Liver Diseases, DMU 3 Santé de l’enfant et de l’adolescent, Bicêtre Hospital, APHP Paris Saclay University, France;4. Department of Paediatric Radiology, Bicêtre Hospital, DMU 14 Imagerie–Médecine nucléaire - Pathologie, APHP Paris Saclay University, France |
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| Abstract: | AimTo evaluate the prognostic significance of initial central nervous system (CNS) involvement of children with acute lymphoblastic leukemia (ALL) enrolled in the EORTC 58951 trial.Patients and methodsFrom 1998 to 2008, 1930 ALL patients were included in the randomized EORTC 58951 trial. Overall treatment intensity was adjusted according to known prognostic factors including the level of minimal residual disease after induction treatment. CNS-directed therapy comprised four to 11 courses of i.v. methotrexate (5 g/m2), and 10 to 19 intrathecal chemotherapy injections, depending on risk group and CNS status. Cranial irradiation was omitted for all patients.ResultsThe overall 8-year event-free survival (EFS) and overall survival (OS) rates were 81.3% and 88.1%, respectively. In the CNS-1, TPL+, CNS-2, and CNS-3 groups, the 8-year EFS rates were 82.1%, 77.1%, 78.3%, and 57.4%, respectively. Multivariable analysis indicated that initial CNS-3 status, but not CNS-2 or TLP+, was an independent adverse predictor of outcome. The 8-year incidence of isolated CNS relapse was 1.7% and of isolated or combined CNS relapse it was 3.7%. NCI high-risk group, male sex, CNS-2 and CNS-3 status were independent predictors for a higher incidence of any CNS relapse.ConclusionsCNS-3 status remains associated with poor prognosis and requires intensification of both systemic and CNS-directed therapy.This trial was registered at https://clinicaltrials.gov/under/NCT00003728. |
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| Keywords: | Children Acute lymphoblastic leukemia Central nervous system |
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