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Value of cytogenetic abnormalities in adults with Ph-negative B-cell precursor acute lymphoblastic leukemia

Marina Lafage-Pochitaloff, Laurence Baranger, Mathilde Hunault, Wendy Cuccuini, Christine Lefebvre, Audrey Bidet, Isabelle Tigaud, Virginie Eclache, Eric Delabesse, Chrystèle Bilhou-Nabéra, Christine Terré, Elise Chapiro, Nathalie Gachard, Marie-Joelle Mozziconacci, Geneviève Ameye, Sarah Porter, Nathalie Grardel, Marie C. Béné, Yves Chalandon, Carlos Graux, Françoise Huguet, Véronique Lhéritier, Norbert Ifrah and Hervé Dombret

Key points

  • Combined use of global and targeted analyses allows the cytogenetic classification of 88% of adult patients with Ph-negative BCP-ALL.

  • In GRAALL trials, t(4;11)/KMT2A-AFF1 and t(v;14q32)/IGH are the two cytogenetic anomalies significantly associated with a worse outcome.

Abstract

Multiple cytogenetic subgroups have been described in adult Philadelphia chromosome (Ph)-negative B-cell precursor (BCP) acute lymphoblastic leukemia (ALL), often comprising small numbers of patients. In this study, we aimed to reassess the prognostic value of cytogenetic abnormalities in a large series of 617 adult patients with Ph-negative BCP-ALL (median age, 38 years), treated in the intensified GRAALL-2003/2005 trials. Combined data from karyotype, DNA index, FISH and/or PCR screening for relevant abnormalities were centrally reviewed and were informative in 542 cases (88%), allowing classification in ten exclusive primary cytogenetic subgroups and in secondary subgroups including complex and monosomal karyotypes. Prognostic analyses focused on cumulative incidence of failure (including primary refractoriness and relapse), event-free survival and overall survival. Only two subgroups, namely t(4;11)/KMT2A-AFF1 and 14q32/IGH translocations, displayed a significant worse outcome in this context, still observed after adjustment for age and after censoring patients who received allogeneic stem cell transplantation (SCT) in first remission at SCT time. A worse outcome was also observed in patients with low-hypodiploidy/near-triploidy, but this was likely related to their higher age and worse tolerance to therapy. The other cytogenetic abnormalities, including complex and monosomal karyotypes, had no prognostic value in these intensive protocols designed for adult patients up to the age of 60 years.

  • Submitted May 9, 2017.
  • Accepted July 17, 2017.