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1553 Characteristics and Outcome of Early T Cell Precursor ALL (ETP-ALL) Patients Treated with High-Risk Spanish Pethema ProtocolsClinically Relevant Abstract

Program: Oral and Poster Abstracts
Session: 618. Acute Lymphoblastic Leukemia: Biology, Cytogenetics, and Molecular Markers in Diagnosis and Prognosis: Poster I
Hematology Disease Topics & Pathways:
Clinically relevant
Saturday, December 1, 2018, 6:15 PM-8:15 PM
Hall GH (San Diego Convention Center)

Eulalia Genesca, PhD1*, Mireia Morgades, M.Prob.S2*, Pau Fernandez3*, Pere Barba, MD4*, Cristina Gil, MD, PhD5*, Ramon Guàrdia, MD6*, Maria Jose Moreno, MD7*, Daniel Martínez-Carballeira, MD8*, Irene García-Cadenas9*, Susana Vives, MD10*, Jordi Ribera11*, José González-Campos, MD12*, Marina Diaz-Beyá, MD13*, Santiago Mercadal, MD14*, Maria Teresa Artola, MD15*, Antonia Cladera, MD16*, Mar Tormo, MD, PhD17, Arancha Bermudez, MD18*, Ferran Vall-Llovera, MD19*, Pilar Martinez, MD20*, María-Luz Amigo, MD21*, Juan-Miguel Bergua, MD22*, María Calbacho, MD23*, Jesús-María Hernández-Rivas, MD, PhD24*, Silvia Monsalvo25*, Andrés Novo, MD26*, Marta Cervera, MD27*, Antonio Garcia-Guiñon, MD28*, Jordi Junca, MD29*, Juana Ciudad, PhD30*, Alberto Orfao, MD, PhD31 and Josep-Maria Ribera, MD, PhD32

1Josep Carreras Leukaemia Research Institute (IJC), Badalona, Spain
2ICO Badalona-Hospital Germans Trias i Pujol. Josep Carreras Leukemia Research Institute. Universitat Autònoma de Barcelona, Badalona, Spain
3Hospital Universitari i Politècnic La Fe, Valencia; CIBERONC, Instituto Carlos III, Madrid, Spain
4Department of Hematology. Vall d’Hebron Institute of Oncology (VHIO), University Hospital Vall d’Hebron. Barcelona, Spain, BARCELONA, Spain
5Haematology department, Alicante General Hospital, Alicante, Spain
6ICO Girona- Hospital Josep Trueta, Girona, Spain
7Haematology department, Virgen de la victoria Hospital, Malaga, Spain
8Haematology department, Asturias Central Hospital, Oviedo, Spain
9Hematology Department, Hospital Sant Creu i Sant Pau, Barcelona, Spain
10Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain
11ICO-Hospital Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras, Barcelona, Spain
12Hospital Universitario Virgen del Rocío, Sevilla, Spain
13Hematology department, Hospital Clínic de Barcelona, Barcelona, Spain
14Haematology, Institut Catala d'Oncologia. Hospital Duran i Reynals. IDIBELL, Hospitalet De Llobregat, Spain
15Haematolgy department, Hospital de Donostia, Donostia, Spain
16Haematology department, Hospital Son Llatzer, Palma, Spain
17Haematology department, Hospital Clinico de Valencia, Valencia, Spain
18Haematology department, Marques de Valdecilla Universitary Hospital, Santander, Spain
19Haematology department, Hospital Mutua de Terrassa, Terrassa, Spain
20Haematology department, 12 Octubre Hospital, Madrid, Spain
21Haematology department, Morales Meseguer Hospital, Murcia, Spain
22Haematology department, San Pedro de Alcantara Hospital, Caceres, Spain
23Hematology and Hemotherapy, Hospital 12 de Octubre, Madrid, Spain
24Haematology department, University Hospital of Salamanca, Salamanca, Spain
25Haematology department, Gregorio Marañon Hospital, Madrid, Spain
26Haematology department, Hospital Son Espases, Palma, Spain
27Haematology department, ICO Tarragona-Hospital Joan XXIII, Tarragona, Spain
28Haematology department, Arnau de Vilanova Hospital, LLEIDA, ESP
29Haematology department, Germans Trias i Pujol Hospital-ICO, Badalona, Spain
30University of Salamanca, Salamanca, Spain
31Cancer Research Centre (IBMCC, USAL-CSIC), Department of Medicine and Cytometry Service (NUCLEUS), University of Salamanca and IBSAL, Salamanca, Spain
32Haematology department, Hospital Universitari Germans Trias i Pujol-ICO, Josep Carreras Research Institute(IJC), Badalona, Spain

Background:

ETP-ALL was included as a provisional identity in the 2016 WHO classification of ALL. This subtype was first identified by Coustan-Smith et al. in 2009. However, this immunophenotype-based classification does not fully enclose all ETP-ALL cases identified by gene expression profile (GEP). Although early studies in small series of ETP-ALL suggested a very poor outcome for ETP ALL more recent and larger series have showed improvement in outcome treating children with a contemporary protocol based on chemotherapy schedules, or after allogeneic stem cell transplantation (allo-SCT) in adults.

Aim:

To investigate the clinical and biological features of ETP-ALL cases in the Spanish cohort of adult T-cell ALL (T-ALL) patients and to assess the potential impact of high-risk therapy on their outcome.

Method:

One hundred eighty-five adults with T-ALL treated according to two consecutive MRD-oriented high-risk adult PETHEMA protocols -ALL-HR-2003 (NCT00853008) and ALL-HR-11 (NCT01540812; still ongoing)- were included in this study. The EGIL criteria were used to define the immunologic subtype of T-ALL after central review of immunophenotype reports, and the criteria proposed by Zuurbier et al. (Zuurbier L. et al. Haematologica 2014; 99:94-102) were used to define ETP-ALL. These later criteria consist of a combination of immunophenotypic markers (absence of CD1a-/CD4-/CD8-, cut-off <10%, and expression of the stem cell marker CD34+and/or at least one myeloid marker such as CD13+or CD33+, cut-off >25%), that resemble those published by Coustan-Smith, with the advantage that include most ETP-ALL cases, as identified by GEP, avoiding the use of partial expression of CD5 marker to immuno-classify these patients.

Results:

Thirty-four out of 167 evaluable patients (20%) with T-ALL showed an ETP-ALL immunophenotype. Patients with ETP-ALL were older (mean 39 [SD 12] vs. 33 [12] yr; p=0.011), showed more frequently lymph node involvement (79% vs. 56%; p=0.021) and lower WBC counts at diagnosis (mean, 72 [155] vs. 97 [112] x109/L; p=0.004). At genetic level, ETP-ALL patients were associated with the absence of deletions in CDKN2A/B gene cluster (91% vs. 26%; p<0.001) (10/11 cases) and with the absence of bi-allelic deletions in TCRG gene (67% vs. 5%; p=0.001) (6/9 cases). In turn, ETP-ALL patients showed poorer response to induction therapy: 82% of ETP-ALL had poorer early cytologic response (>10% BM blasts on day+14) vs. 37% of non-ETP (p<0.001), and 23% of ETP-ALL patients did not reach CR vs. 6% non-ETP T-ALL cases (p=0.005). Flow-MRD data at CR (available in 141/167 patients) showed MRD levels ≥0.1% in 65% of ETP-ALL vs. 18% of non-ETP ALL (p<0.001), and MRD level ≥0.01% in 85% vs. 37%, respectively (p<0.001). Forty-six percent of ETP-ALL patients required a second induction treatment compared to 8% of non-ETP-ALL (p<0.001). Consequently, more ETP-ALL patients underwent allo-SCT (70% vs. 21%, p<0.001). The OS of ETP-ALL patients was poorer after censoring or not the follow-up at the time of transplant (Figures 1A and B).

Conclusions:

ETP-ALL accounts for 20% of adult T-ALL in the PETHEMA cohort and it is associated with a poorer initial response to treatment (lower CR rate, poorer MRD clearance) than the remaining T-ALL patients. Such poorer outcome is not overcome by allo-SCT in our series.

Supported by grants from: Asociación Española Contra el Cáncer, AECC (GC16173697BIGA), Instituto Carlos III (PI14/01971 FI), 2017-SGR288 (GRC), CERCA Program from Generalitat de Catalunya, and “La Caixa” Foundation.

Disclosures: Fernandez: Daiichi Sankyo: Consultancy, Speakers Bureau; Novartis: Research Funding, Speakers Bureau.

*signifies non-member of ASH