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Cytogenetics and Molecular Genetics

Specific cytogenetic abnormalities are associated with a significantly inferior outcome in children and adolescents with mature B-cell non-Hodgkin's lymphoma: results of the FAB/LMB 96 international study

Leukemia volume 23, pages 323–331 (2009)Cite this article

Abstract

Clinical studies showed that advanced stage, high LDH, poor response to reduction therapy and combined bone marrow and central nervous system disease are significantly associated with a decreased event-free survival (EFS) in pediatric mature B-cell non-Hodgkin's lymphoma (B-NHL) treated on FAB/LMB96. Although rearranged MYC/8q24 (R8q24) is characteristic of Burkitt lymphoma (BL), little information is available on other cytogenetic abnormalities and their prognostic importance. We performed an international review of 238 abnormal karyotypes in childhood mature B-NHL treated on FAB/LMB96: 76% BL, 8% Burkitt-like lymphoma, 13% diffuse large B-cell lymphoma (DLBCL). The main BL R8q24-associated chromosomal aberrations were +1q (29%), +7q and del(13q) (14% each). The DLBCL appeared heterogeneous and more complex. Incidence of R8q24 (34%) was higher than reported in adult DLBCL. The prognostic value of cytogenetic abnormalities on EFS was studied by Cox model controlling for the known risk factors: R8q24, +7q and del(13q) were independently associated with a significant inferior EFS (hazard ratio: 6.1 (P=0.030), 2.5 (P=0.015) and 4.0 (P=0.0003), respectively). The adverse prognosis of R8q24 was observed only in DLBCL, whereas del(13q) and +7q had a similar effect in DLBCL and BL. These results emphasize the significant biological heterogeneity and the development of cytogenetic risk-adapted therapy in childhood mature B-NHL.

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Acknowledgements

We thank the other members of the international morphological review panel: MJ Terrier-Lacombe, C Bayle, B Felman (SFOP), M Lones (CCG) and A Wotherspoon UKCCSG). We further thank the data managers of the SFOP, CCG and UKCCSG cooperative groups, Virginia Davenport and Lauren Harrison for their active and helpful support of COG part of the study, and all the investigators who treated the patients and participated in the study. This work was supported by grants from the Division of Cancer Treatment, National Cancer Institute, National Institutes of Health, Department of Health and Human Services (COG); Cancer Research Campaign, (UKCSSG), Association pour la Recherche contre le Cancer), La Ligue Nationale Contre le Cancer, Institut Gustave Roussy (SFOP) and COG Grant CA 98543. A complete listing of grant support for research conducted by CCG and POG before initiation of the COG grant in 2003 is available online at: http://www.childrensoncologygroup.org/admin/grantinfo.htm.

Author information

Author notes

  1. H A Poirel, M S Cairo, N A Heerema, J Swansbury, A Aupérin, E Launay, W G Sanger, P Talley, S L Perkins, M Raphaël, K McCarthy, R Sposto, M Gerrard, A Bernheim and C Patte: H A Poirel and M S Cairo: These authors are considered co-primary first authors.

  2. Children's Oncology Group (COG), Arcadia, CA, USA, Société Française d’Oncologie Pédiatrique (SFOP), France, and the United Kingdom Children's Cancer Study Group (UKCCSG), Leicester, UK. A complete list of the participants in the cytogenetics study of the FAB/LMB96 International trial appears in the ‘Appendix’.

Authors and Affiliations

  1. Biological Hematological Department, CHU Avicenne—Université Paris 13, Bobigny, France

    H A Poirel, E Launay & M Raphaël

  2. Hematological Genetics and Human Molecular Genetics (GEHU), Cliniques Universitaire Saint-Luc UCL and de Duve Institute, Brussels, Belgium

    H A Poirel

  3. Division of Pediatric Blood and Marrow Transplantation, Morgan Stanley Children's Hospital of New York Presbyterian, Columbia University, New York, NY, USA

    M S Cairo

  4. Department of Pathology–Cytogenetics, The Ohio State University, Columbus, OH, USA

    N A Heerema

  5. Department of Haematology Cytogenetics, The Royal Marsden Hospital, Sutton, UK

    J Swansbury

  6. Department of Biostatistics, Institut Gustave Roussy, Villejuif, France

    A Aupérin

  7. Human Genetics Laboratory, University of Nebraska Medical Center, Omaha, NE, USA

    W G Sanger

  8. Department of Cytogenetics, Sheffield Children's Hospital, Sheffield, UK

    P Talley

  9. Department of Pathology, University of Utah Health Sciences Center, Salt Lake City, UT, USA

    S L Perkins

  10. Department of Biological Hematology, CHU Bicêtre—Assistance Publique-Hôpitaux de Paris, Université Paris-Sud 11, Le Kremlin-Bicêtre, France

    M Raphaël

  11. Department of Pathology, Gloucestershire Hospitals, NHS Foundation, Gloucestershire, UK

    K McCarthy

  12. Department of Biostatistics, Children's Hospital Los Angeles, University of Southern California, Los Angeles, CA, USA

    R Sposto

  13. Department of Paediatric Oncology, Sheffield Children's Hospital, Sheffield, UK

    M Gerrard

  14. Laboratoire de genomique cellulaire des cancers, Institut Gustave Roussy, Villejuif, France

    A Bernheim

  15. Department of Pediatric Onco-Hematology, Institut Gustave Roussy, Villejuif, France

    C Patte

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  1. H A Poirel
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Consortia

on behalf of the FAB/LMB 96 International Study Committee

Corresponding authors

Correspondence to H A Poirel or M S Cairo.

Additional information

Presented in part at the 43rd meeting of the American Society of Hematology (ASH), December 2003, Philadelphia, PA, USA, and at the 9th International Conference on Malignant Lymphoma (9-ICML), June 2005, Lugano, Switzerland.

Supplementary Information accompanies the paper on the Leukemia website (http://www.nature.com/leu)

Supplementary information

Appendix: contributing cytogeneticists and their institutions by alphabetic order (* cytogeneticists who participated on the panel of reviewers)

Appendix: contributing cytogeneticists and their institutions by alphabetic order (* cytogeneticists who participated on the panel of reviewers)

SFOP

H Avet-Loiseau (CHU, Nantes); L Baranger* (CHU, Angers); C Barin (CHU, Tours); C Bastard* (CHU, Rouen); A Bernheim* (Institut Gustave Roussy, Villejuif); MF Berthéas (Hopital Nord, St Etienne); C Bilhou-Nabera (CHU Pessac, Bordeaux); C Borie (Hopital Robert Debre, Paris); J Boyer (CHU, Brest); F Brizard (Hopital J Bernard, Poitiers); E Caillet-Bauchu* (CHU Lyon Sud); AM Capdano (Hopital De La Timone, Marseille); MA Collonge-Rame (Hopital St Jacques, Besançon); P Cornillet* (CHU, Reims); J Couturier (Institut Curie, Paris); N Dastugue (CHU Purpan, Toulouse); A Daudignon (CHU, Valenciennes); N Gachard (CHU Dupuytren, Limoges); MJ Grégoire CHRU Nancy); P Heimann (Institut Jules Bordet, Bruxelles, Belgique); C Henry (CHRU Pontchaillou, Rennes); JL Laï (CHU Jeanne de Flandre, Lille); D Leroux (Hopital Michalon, Grenoble); M Lessard (Hospices Civils, Strasbourg); I Luquet* (CHU, Reims); CHM Mellink (Emma Kinderziekenhuis EK2/AMC, Amsterdam, Netherlands); N Nadal (Hopital Nord, St Etienne); MP Pagès* (Hopital Debrousse, Lyon); D Penther (CHU, Rouen); B Perissel (Hotel Dieu, Clermont Ferrand); C Perrot (CHU Saint-Antoine, Paris); S Raynaud (CHU, Nice); P Talman (CHU, Nantes); S Taviaux* (Hopital St Charles, Montpellier); I Tigaud* (CHU E Herriot, Lyon); J Van den Akker (CHU Saint-Antoine, Paris).

CCG

J Beigel* (Children's Hospital of Philadelphia, Philadelphia, PA); P Benn (University of Connecticut, Farmington, CT); E Cantu, (Children's Hospital Medical Center, Akron, OH); K Carlson (University of Chicago, Chicago, IL); L Cooley (Children's Mercy Hospital, Kansas City, KS); A Dawson (Cancer Care Manitoba, Winnipeg, MB); VG Dev (Genetics Associates, Nashville, TN); G Dewald (Mayo Clinic, Rochester, MN); T Drumheller (Valley Children's Hospital, Fresno, CA); J Fink (Hennepin, Minneapolis, MN); I Gadi (Genetics Associates, Nashville, TN); J Hanna (Sacred Heart Hospital, Spokane, WA); A Glassman (MD Anderson, Houston, TX); K Harrison (Loyola University, Chicago, IL); N Heerema* (Indiana University, Indianapolis, IN); J Higgins (Spectrum Health, Grand Rapids, MI); R Higgins (Allina Health System, Minneapolis, MN); B Hirsch* (University of Minnesota, Minneapolis, MN); D Horsman (British Columbia Cancer Agency, Vancouver, BC); D Kalousek (British Columbia Children's Hospital, Vancouver, BC); P Koduru (Winthrop, New York, NY); R Lebo (Children's Hospital Medical Center, Akron, OH); X Li (Kaiser Permenente, anta Clara, CA); RE Magenis* (Oregon Health Sciences University, Protland, OR); K McFadden (British Columbia Children's Hospital, Vancouver, BC); L McGavron* (University of Colorado Health Science Center, Denver, CO); L McMorrow (Thomas Jefferson University, Philadelphia, PA); A Murch (King Edward Memorial Hospital, Melbourne, Australia); K Opheim (University of Washington, Seattle, WA); D Panzar (British Columbia Children's Hospital, Vancouver, BC); L Pasztor (Palo Verde Laboratory, Phoenix, AZ); A Pettigrew (University of Kentucky, Lexington, KY); C Philips (Emory University, Atlanta, GA); K Rao* (University of North Carolina, Durham, NC); PN Rao (University of California at LosAngeles, Los Angeles, CA); D Rouston* (University of Michigan, Ann Arbor, MI); W Sanger* (University of Nebraska, Omaha, NB); KL Satya-Prakash (Medical College of Georgia, Augusta, GA); S Schwartz (Case Western Reserve University, Cleveland, OH); GS Sekhon (University of Wisconsin, Madison, WI); G Shaw (Marshfield Laboratories, Marshfield, WI); S Shekter-Levin (Magee Women's Hospital, Pittsburg, PA); N Spinner (Children's Hospital of Philadelphia, Philadelphia, PA); W Stanley (Genetics IVF, Fairfax, VA); P Storto (Michigan State University, Lansing, MI); M Thangavelu (Genzyme, Orange County, CA); K Theil* (The Ohio State University, Columbus, OH); G Vance (Indiana University, Indianapolis, IN); D VanDyke (Henry Ford Hospital, Detroit, MI); T Zadeh (Genetics Center, CA, Orange, CA).

UKCCSG

Cytogeneticists belong to the UK Cancer Cytogenetics Group (UKCCG).

K Andrews (Addenbrookes Hospital, Cambridge); M Booth (University Hospital of Wales, Cardiff); N Bown (Institute of Human Genetics, Newcastle); T Davies (Southmead Hospital, Bristol); E Grace (Western General Hospital, Edinburgh); M Griffiths (Birmingham Women's Hospital, Birmingham); P Howard (Liverpool Women's Hospital, Liverpool); D Hughes (The Churchill Hospital, Oxford); H Kempski (The Hospital for Sick Children, Great Ormond Street, London); D Lillington (St Barts Hospital, London); G Lowther (Yorkhill Hospital, Glasgow); K Martin (Nottingham City Hospital, Nottingham); P Roberts (St James Hospital, Dublin); F Ross (Salisbury District Hospital, Salisbury); J Sadler (Leicester Royal Infirmary, Leicester); R Stallings (St James Hospital, Dublin); D Stevenson (Grampian University Hospitals, Aberdeen); J Swansbury* (The Royal Marsden Hospital, Sutton); P Talley* (Sheffield Children's Hospital, Sheffield); N Telford (The Christie Hospital, Manchester); H Walker (University College Hospital, London).

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Poirel, H., Cairo, M., Heerema, N. et al. Specific cytogenetic abnormalities are associated with a significantly inferior outcome in children and adolescents with mature B-cell non-Hodgkin's lymphoma: results of the FAB/LMB 96 international study. Leukemia 23, 323–331 (2009). https://doi.org/10.1038/leu.2008.312

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