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2514 Prognostic Impact of MLL Partial Tandem Duplication in Acute Myeloid Leukemia of Intermediate Cytogenetic Risk: A Subgroup Analysis of Cetlam Protocol 2003 & 2012

Acute Myeloid Leukemia: Clinical Studies
Program: Oral and Poster Abstracts
Session: 613. Acute Myeloid Leukemia: Clinical Studies: Poster II
Sunday, December 6, 2015, 6:00 PM-8:00 PM
Hall A, Level 2 (Orange County Convention Center)

Marta Pratcorona1*, Ana Garrido, MD1*, Salut Brunet, MD, PhD1*, Jordi Esteve, MD, PhD2, María Camino Estivill, PhD1*, M. Paz Queipo De Llano, MD3*, Susana Vives4*, Montserrat Arnan, MD, PhD5*, David Gallardo, MD6*, Mar Tormo, MD, PhD7, Antoni Garcia-Guiñon, MD8*, Antonia Sampol, MD, PhD9*, Olga Salamero10*, Josep Ma Martí, MD11*, Joan Bargay, MD, PhD12*, M Carmen Pedro, MD13*, Montserrat Hoyos, phD1*, Marina Diaz-Beya, MD, PhD14*, Lourdes Escoda, MD, PhD15*, Ramon Guàrdia, MD, PhD16*, Josep Ribera, MD, PhD17, Jorge Sierra, MD, PhD1* and Josep F. Nomdedeu, MD, PhD1*

1Hematology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
2Hematology Department, Hospital Clínic, IDIBAPS, Institut Josep Carreras, Barcelona, Spain
3Department of Hematology, Hospital Virgen de la Victoria,, Malaga, Spain
4Hospital Universitari Germans Trias i Pujol, Badalona, Spain
5Institut Català d'Oncologia, Hospital Duran i Reynals, Barcelona, Spain
6Hematology Department, ICO-Hospital Josep Trueta, Girona, Spain
7Hospital Clínico Universitario de Valencia, Valencia, Spain
8Hematology Department, Hospital Universitari Arnau de Vilanova, Lleida, Spain
9Hospital Son Espases, Palma de Mallorca, Spain
10Hospital Universitari Vall d'Hebron, Barcelona, Spain
11Hematology Department, Hospital Mútua de Terrassa, Barcelona, Spain
12Hospital Son Llàtzer, Palma de Mallorca, Spain
13Hematology Department, Hospital del Mar, Barcelona, Spain
14Hematology Department, Hospital Clinic, IDIBAPS Barcelona. Josep Carreras Leukemia Reseach Institute, Barcelona, Spain
15ICO-Hospital Joan XXIII, Tarragona, Spain
16ICO- Hospital Josep Trueta, Girona, Spain
17Department of Hematology, ICO Badalona-Germans Trias i Pujol Hospital. Josep Carreras Leukemia Research Institute. Universitat Autonoma de Barcelona, Badalona, Spain

Background

Cytogenetics at diagnosis is the most important prognostic factor in acute myeloid leukemia (AML). Of note, intermediate cytogenetic risk group (IR-AML) is a very heterogeneous subset including normal karyotypes and all the cytogenetic abnormalities not included in the favorable or the adverse groups. Molecular alterations affecting NPM1, FLT3 and CEBPA show a prognostic impact in IR-AML. MLL partial tandem duplications (MLL-PTD) have also been described in this group of AML, but their prognostic impact have not been well established.

Aim

To analyze the prognostic relevance of MLL-PTD in the subset of patients diagnosed with IR-AML since 2003, and included in the CETLAM protocols LMA-2003 and LMA-2012.

Methods

Between 2003 and 2004 MLL-PTD were analyzed by Southern Blot (enzymes employed BglII, EcoRI, BamHI). Since 2004, a long PCR strategy was used to identify this abnormality.

Results

NPM1 mutations (NPM1mut), FLT3 internal tandem duplications (FLT3-ITD) and MLL-PTD were available for 893 patients.  No MLL-PTD was found among 111 and 161 patients of the good and poor cytogenetic risk groups, respectively. The IR-AML group included 621 patients, and 37 carried a MLL-PTD (6%), thus only this cytogenetic group of patients was analyzed. NPM1mut were found in a 41% of patients and none of them had a concomitant MLL-PTD (p<0.001). FLT3-ITD were found in a 31% of patients, and 14 patients had also an MLL-PTD. No correlation between MLL-PTD and age, leukocyte count, and percentage of blasts in bone marrow was found. There was a significant association with gender: men were more frequently mutated than women (29 vs 8; p=0.001).  Regarding outcome of IR-AML, leukemia-free survival (LFS) was significantly higher for patients without MLL-PTD (5-year LFS 44±3% vs 18±8%; p<0.001), and overall survival (OS) was also better for this subgroup of patients (5-year OS 42±2% vs 20±7%; p=0.004). There were no differences in the complete response rate, but patients with MLL-PTD had a higher risk of relapse (cumulative incidence at 5 years 39 vs 74%, p=0.000151). Among patients with MLL-PTD, no differences were observed depending on the concurrence of FLT3-ITD. When only patients with NPM1 wild-type were considered, MLL-PTD maintained a significantly poor prognostic impact (36±3% vs 21±7%; p=0.009).

Conclusions

MLL-PTD is a genetic alteration found in a 6% of IR-AML. Patients with this abnormality have a worse LFS and OS than the rest of patients of the IR-AML group.

Based on these results, patients with MLL-PTD should be considered as patients with poor cytogenetic risk AML for treatment allocation.

Disclosures: No relevant conflicts of interest to declare.

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