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Blood, 15 January 2004, Vol. 103, No. 2, pp. 442-450.
Prepublished online as a Blood First Edition Paper on September 22, 2003; DOI 10.1182/blood-2003-05-1495.
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CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
Clinical significance of HOX11L2 expression linked to t(5;14)(q35;q32), of HOX11 expression, and of SIL-TAL fusion in childhood T-cell malignancies: results of EORTC studies 58881 and 58951
Hélène Cavé,
Stefan Suciu,
Claude Preudhomme,
Bruce Poppe,
Alain Robert,
Anne Uyttebroeck,
Michèle Malet,
Patrick Boutard,
Yves Benoit,
Laurent Mauvieux,
Patrick Lutz,
Françoise Méchinaud,
Nathalie Grardel,
Françoise Mazingue,
Madeleine Dupont,
Geneviève Margueritte,
Marie-Pierre Pages,
Yves Bertrand,
Emmanuel Plouvier,
Ghislaine Brunie,
Christian Bastard,
Dominique Plantaz,
Isabel Vande Velde,
Anne Hagemeijer,
Frank Speleman,
Michel Lessard,
Jacques Otten,
Etienne Vilmer, and
Nicole Dastugue, the EORTC-CLG
From the Laboratoire de Biochimie Génétique, Hôpital Robert Debré (Assistance Publique-Hôpitaux de Paris [AP-HP]), Paris, France; Institut National de la Santé et de la Recherche Médicale (INSERM) U417, Hôpital Robert Debré, Paris, France; European Organization for Research and Treatment of Cancer (EORTC) Data Center, Brussels, Belgium; Laboratoire d'Hématologie A, Hôpital Calmette, Lille, France; Universitair Ziekenhuis Ghent, Ghent, Belgium; Unité d'Hématologie Infantile, Hôpital Purpan, Toulouse, France; U. Z. Gasthuisberg, Leuven, Belgium; Unité d'Onco-Hématologie Pédiatrique, Centre Hospitalier Universitaire (CHU), Caen, France; Hôpital Universitaire Hautepierre, Strasbourg, France; CHR Hôtel Dieu, Nantes, France; CHR de Lille, Lille, France; Hôpital Arnaud de Villeneuve, Montpellier, France; Hôpital Debrousse, Lyon, France; CHR de Besançon-Hôpital Saint Jacques, Besançon, France; Centre Henri Becquerel, Rouen, France; CHU de Grenoble, La Tronche, France; Akademisch Ziekenhuis - Vrije Universiteit Brussel (VUB), Brussels, Belgium; Service d'Immuno-Hématologie Pédiatrique, Hôpital Robert Debré (AP-HP), Paris, France; and Laboratoire d'Hématologie, Hôpital Purpan, Toulouse, France.
In a series of 153 children with T-cell malignancies enrolled in 2 consecutive European Organization for Research and Treatment of Cancer (EORTC) trials, we assessed the HOX11L2 expression and/or the presence of a t(5;14)(q35;q32). Additionally, in 138 of these patients, HOX11 expression and SIL-TAL rearrangement were also assessed. These alterations were mutually exclusive, and their frequency was 23% (n = 35), 7% (n = 10), and 12% (n = 17), respectively. HOX11L2/t(5;14) positivity was more frequent in acute lymphoblastic leukemia (ALL) with cortical T immunophenotype and in children aged between 6 and 9 years. In contrast with previously reported data, patients positive and negative for HOX11L2/t(5;14) were comparable with regard to clinical outcome as well as to the response to a 7-day prephase treatment or to residual disease at completion of induction therapy. The 3-year event-free survival (EFS) rate (± SE percentage) for patients positive and negative for HOX11L2/t(5;14) was 75.5% (± 8.1%) and 68.3% (± 5.0%), respectively; the hazard ratio was 0.84 (95% confidence interval, 0.40-1.80). Patients with HOX11-high expression and those with SIL-TAL fusion had low levels of residual disease at the end of induction and a favorable prognosis: the 3-year EFS rate was 83.3% (± 8.5%) and 75.3% (± 12.6%), respectively. The results obtained in HOX11L2/t(5;14) patients in this study do not confirm the unfavorable prognosis reported in previous studies.
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