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Blood, 15 October 2004, Vol. 104, No. 8, pp. 2444-2451.
Prepublished online as a Blood First Edition Paper on March 23, 2004; DOI 10.1182/blood-2003-04-1299.


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NEOPLASIA

A report from the LALA-94 and LALA-SA groups on hypodiploidy with 30 to 39 chromosomes and near-triploidy: 2 possible expressions of a sole entity conferring poor prognosis in adult acute lymphoblastic leukemia (ALL)

Christiane Charrin, Xavier Thomas, Martine Ffrench, Quoc-Hung Le, Joris Andrieux, Marie-Joelle Mozziconacci, Jean-Luc Laï, Chrystele Bilhou-Nabera, Lucienne Michaux, Alain Bernheim, Christian Bastard, Hossein Mossafa, Christine Perot, Odile Maarek, Claude Boucheix, Véronique Lheritier, André Delannoy, Denis Fière, and Nicole Dastugue

From the Hôpital Edouard Herriot, Lyon, France; Département de biostatistique, Centre Hospitalier Lyon Sud, Pierre-Bénite, France; Centre Hospitalier, Lille, France; Institut Paoli Calmettes, Marseille, France; Hôpital du Haut Levêque, Bordeaux, France; Cliniques St Luc, Brussels, Belgium; Institut Gustave Roussy, Villejuif, France; Centre Henri Becquerel, Rouen, France; Laboratoire CERBA, Val d'Oise, France; Hôpital Saint Antoine, Paris, France; Hôpital Saint-Louis, Paris, France; INSERM U268, Villejuif, France; Hôpital de Jolimont, Haine St Paul, Belgium; and Hôpital Purpan, Toulouse, France.

To reveal the relationship between hypodiploidy with 30 to 39 chromosomes and near-triploidy in acute lymphoblastic leukemia (ALL), we studied 24 patients presenting with one of these aneuploidies among 623 adults with ALL registered in the Leucémie Aigüe Lymphoblastique de l'Adulte (LALA) protocols. The 2 ploidy groups presented a striking similarity of their cytogenetic profiles: chromosomes 2, 3, 4, 7, 13, 15, 16, and 17, significantly monosomic in hypodiploidy 30 to 39, were also frequently disomic in near-triploidy, whereas those retained in pairs in hypodiploidy 30 to 39 were frequently tetrasomic in near-triploidy. DNA content data revealed the simultaneous presence of 2 aneuploid peaks in most tested cases (DNA indexes: 0.72-0.87/1.39-1.89) and a multiple correspondence analysis applied on cytogenetic profiles ascertained their strong relationship. We thus assumed that near-triploidy derives from the duplication of hypodiploidy with 30 to 39 chromosomes and that both aneuploid groups are 2 expressions of the same disease. These 24 patients presented with B-cell phenotype, low leukocytoses (median white blood cell count, 4.2 x 109/L), and poor prognosis (complete remission, 57%; median disease-free-survival, 8 months; median survival, 10.4 months) comparable to that of Ph+ patients treated according to the same protocol. We suggest that hypodiploidy with 30 to 39 chromosomes or near-triploidy should be regarded as a new high-risk factor in the risk stratification of adult ALL protocols.


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