Prognostic Value of Complex Karyotype and Monosomal Karyotype in Patients with Adult Acute Lymphoblastic Leukemia Treated with Risk-Adapted Protocols
Authors: Motlló Cristina , Ribera Josep-Maria , Morgades Mireia , Granada Isabel , Grau Javier , Montesinos Pau , González-Campos José , Fernández-Abellán Pascual , Tormo Mar , Bethencourt Concha , Brunet Salut , Hernández-Rivas Jesús M , Moreno MJ , Sarra Jose , Del Potro Eloy , Barba Pere , Bernal Teresa , Amigo Maria-Luz , Grande Carlos , Bermudez Arancha , Guardia Ramon , Llorente Andrés , Peñarrubia Maria Jesús , Arias Jesús , Sanz Miguel Angel , Feliu Evarist 
Published: October 2019

Abstract
Abstract 4785

Background
The karyotype is an important predictor of outcome in adults with acute lymphoblastic leukemia (ALL). Some groups have reported the negative prognostic value of complex karyotype (CK, defined as ≥5 unrelated chromosomal abnormalities) in adult ALL (Moorman et al, Blood. 2007:109;3189-97). On the other hand, monosomal karyotype (MK, defined as ≥2 distinct autosomal chromosome monosomies or 1 single monosomy in the presence of structural abnormalities) has been associated with a worse outcome in patients with acute myeloid leukemia. We aimed to assess the prognostic value of cytogenetic abnormalities, especially CK and MK, in adults with ALL treated with protocols of the Spanish PETHEMA Group.

Patients and Methods
The karyotypes of 783 adult ALL patients from 63 Spanish centers treated according to the protocols of the PETHEMA Group between 1993 and 2011 were reviewed. The several PETHEMA protocols were risk-adapted (standard-risk –SR–, high-risk –HR–) or subtype-oriented (Philadelphia chromosome [Ph+] ALL -with or without imatinib-, and Burkitt's ALL [BL]). The impact of the main cytogenetic abnormalities as well as of the CK and MK on complete remission (CR) rate, CR duration, overall survival (OS) and event-free survival (EFS) was analyzed.

Results
The median age of the series was 33 years (range 15–82) and 448 patients (57.2%) were male. The karyotypes of 560 out of 783 patients were evaluable after review: normal karyotype 153 patients, t(9;22) 120, t(v;11q23) 30, t(8;14), t(8;22) or t(2;8) 47, high hyperdiploidy (>50 chromosomes) 53, low hyperdiploidy (47–50 chromosomes) 52, hypodiploidy (45–39 chromosomes) 32 and extreme hypodiploidy (<39 chromosomes) 2. Twenty-eight patients (8.3% of the 338 evaluable karyotypes) had CK and 54 (11.2% of the 481 evaluable karyotypes) had MK. The CR rate, probability of CR duration, the OS probability and the EFS probability are described in table 1. In our study the CK and the MK did not have any impact on CR, CR duration, OS and EFS. Analysis of OS probabilities at 4 years of the most important cytogenetic abnormalities showed: normal karyotype: 46±5%, t(9;22): 20±12%, t(v;11q23): 26±17%, hyperdiplody: 54±15%, hypodiploidy: 47±27%, t(1;19): 44±31% and t(8;14)/t(8;22)/t(2;8): 48±16% (p<0.001).

Conclusions
Our study confirms that cytogenetics is a very important tool for risk assessment in adult ALL. Patients with t(9;22) and t(v;11q23) had the worst prognosis and the t(1;19) did not have prognostic significance. The introduction of imatinib in patients with t(9:22) ALL significantly improved their outcome. The CK and the MK were not associated with a worse prognosis in patients treated with risk-adapted or subtype-oriented protocols of the PETHEMA group.

Disclosures:
No relevant conflicts of interest to declare.