Frequency and prognostic significance of additional cytogenetic abnormalities to the Philadelphia chromosome in young and older adults with acute lymphoblastic leukemia

Abstract

About 25–35% of adult patients with acute lymphoblastic leukemia show the Philadelphia (Ph) chromosome. Few series have evaluated the prognosis of additional cytogenetic alterations (ACA) to the Ph chromosome. We analyzed the frequency, type and prognostic significance ofACA in adults (18–60 years) treated in the ALL-Ph-08 trial. Fifty-two out of 74 patients (70%) showed ACA and 19 (26%) presented monosomies associated with t(9;22) (monosomal karyotype, MK). Similar complete response (CR) rate, CR duration, overall survival and event-free survival (EFS) were observed in patients with or without ACA, but patients with MK showed shorter CR duration and EFS than the remaining. On multivariate analysis, the only variable with prognostic impact for CR duration and EFS was the presence of MK (p = .003 and p = .036, respectively). Although ACA associated with the Ph chromosome are frequent, only monosomies were associated with poor prognosis in this group of patients.

Keywords:

• Acute lymphoblastic leukemia
• Philadelphia chromosome
• additional cytogenetic alterations
• monosomies
• prognosis

Acknowledgments

We want to thank to the following Spanish hospitals that have participated in the PETHEMA protocols and have included patients in this study. ICO-Hospital Germans Trias i Pujol, Badalona. Hospital Universitario y Politécnico La Fe, Valencia. ICO-Hospital Duran i Reynals, L’Hospitalet del Llobregat. Hospital Virgen Del Rocío, Sevilla. Hospital Clínico Universitario Virgen de la Victoria, Málaga. Hospital Vall d’Hebron, Barcelona. Hospital Joan XXIII, Tarragona. Hospital Carlos Haya, Málaga. Hospital Son Espases, Palma de Mallorca. Hospital Universitario Central, Asturias. Hospital Clínico Universitario, Salamanca. Hospital del Mar, Barcelona. Hospital Morales Meseguer, Murcia. Hospital Clínico Universitario, Valencia. Hospital de Sant Pau, Barcelona. Hospital San Pedro de Alcántara, Cáceres. Hospital Xeral, Lugo. Hospital de Fuenlabrada, Madrid. Hospital Clínico Universitario, Valladolid. ICO-Hospital Josep Trueta, Girona. Hospital La Zarzuela, Madrid. Hospital Sanchinarro, Madrid. Hospital Xeral Cies, Vigo. Hospital General Universitario, Alicante. Hospital Universitario, Las Palmas de Gran Canaria. Hospital Marqués de Valdecilla, Santander. Hospital Ramón y Cajal, Madrid. Hospital Meixoeiro, Vigo. Complexo Hospital Universitario, Orense, and Hospital del Galdakao, Bizkaia.

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article online at https://doi.org/10.1080/10428194.2017.1326596.

Additional information

Funding

Supported in part by grants PI10/01417 (F.I.S.), RD12-0036-0029 from RTICC, Instituto Carlos III and RD14-SGR225 (GRE), Generalitat de Catalunya, and ‘La Caixa’.