Background Aims Results Conclusions Maria ...

3 downloads 0 Views 1MB Size Report
immaturity cell surface markers (CD34, CD117, CD7, and CD123) on leukemic blasts in adult de novo. AML patients (pts) by multiparametric flow cytometry ...
PROGNOSTIC IMPACT OF THE LEVELS OF EXPRESSION OF CELL SURFACE PROTEINS COMMONLY EXPRESSED BY BLASTS AND HEMATOPOIETIC PRECURSOR CELLS IN DE NOVO ACUTE MYELOID LEUKEMIA: A REPORT FROM THE SPANISH CETLAM STUDY

Maria Concepción García-Dabrio1, Montserrat Hoyos2, Salut Brunet2, Mar Tormo3, Josep-Maria Ribera, MD, PhD4, Carme Talarn5, Jordi Esteve, MD, PhD6, Ramon Guardia7, Rafael F Duarte, MD, PhD8, M. Paz Queipo De Llano, MD9, Joan Bargay10, Josep M. Marti-Tutusaus11, Inmaculada Heras12, Carmen Pedro13, Antoni Garcia14, Juan Besalduch15, Olga Salamero16, Pio Torres17, Dolores Hernández18, Llorenç Font19, Natalia Lloveras7, Marta Pratcorona6, Lourdes Escoda5,Susana Vives4, Ana Garrido2, Anna Aventin, MD1, Quentin Lecrevisse20, Alberto Orfao20, Jorge Sierra2, MD, PhD and Josep F. Nomdedeu, MD1 1

Department of Hematology and Laboratory, Hospital de la Santa Creu i Sant Pau, Universitat Autónoma Barcelona, Spain; 2Hematology Division, Hospital de la Santa Creu I Sant Pau, Barcelona, Universitat Autónoma Spain; 3Department of Hematology, Hospital Clinic, Valencia, Spain; 4Department of Hematology, Hospital ICO Germans Trias i Pujol, Badalona, Spain; 5Hematology Service, Hospital Joan XXIII, Tarragona, Spain; 6Hematology Service, Hospital Clínic, IDIBAPS, Barcelona, Spain; 7Hematology Department, Institut Català d'Oncologia. Hospital Josep Trueta, Girona, Spain; 8Clinical Hematology, Hospital ICO Duran i Reynals, Barcelona, Spain; 9Department of Hematology, Hospital Virgen de la Victoria, Málaga, Spain; 10Department of Hematology, Hospital Sont Llatzer, Palma de Mallorca, Spain; 11Hematology Service, Hospital Mutua de Terrassa, Terrassa, Spain; 12Hematology Service Hospital la Reixaca, Murcia, Spain; 13Hematology Service, Hospital del Mar, Barcelona, Spain; 14Hematology Service, Hospital Arnau de Vilanova, Lleida, Spain; 15Department of Hematology, Hospital Sont Dureta, Palma de Mallorca, Spain; 16Department of Hematology, Hospital Vall d’Hebrón, Barcelona, Spain; 17Hematology Service, A Coruña, Spain; 18Hematology Service, Hospital Universitario de la Paz, Madrid, Spain; 19Hematology Service, Hospital Verge de la Cinta, Tortosa, Spain; 20Cytometry Service, Department of Medicine and Cancer Research Center (IBMCC, University of Salamanca-CSIC), University of Salamanca, Salamanca, Spain

[email protected]

Blast cells were gated as well-delineated clusters of SSC low/int/CD45dimevents (“blast gate”) using residual normal lymphocytes as internal quality control.

Background The prognostic impact of immunophenotypic markers in acute myeloid leukemias (AML) has been long controversial. Few studies have analyzed the prognostic value of the intensity of cell surface markers (Sm) expression commonly expressed on AML blasts.

Aims Fig. 1: The left panel shows gating strategy. The upper-right panel shows the intensity of CD34 MFI expression in two AML pts, (A) low, and (B) high CD34 MFI. The dotted line indicates the MFI CD34 threshold values (143.39). The lower-right panel shows CD117 MFI expression in two AML pts, (A) low, and (B) high CD117 MFI. The dotted line indicates the MFI CD117 threshold values (284.01).

We analyzed the prognostic impact of the mean fluorescence intensity (MFI) expression of several immaturity cell surface markers (CD34, CD117, CD7, and CD123) on leukemic blasts in adult de novo AML patients (pts) by multiparametric flow cytometry (MPFC) treated according to the multicenter CETLAM AML-03 protocol. We also determined its correlation with other clinical and biological variables and the prognostic significance in terms of overall survival (OS), leukemia-free survival (LFS) and cumulative incidence of relapse (CIR).

Patients and methods 592 adult de novo AML pts (M3 excluded) were treated according to the CETLAM AML-03 trial between 2003 and 2011. Patients characteristics is displayed in Table 1. Table 1. Patient´s characteristics on the whole de novo AML series. N=592 Follow-up, median (range, months) Age, median (range, years) 50 Gender (%) Male Female WBC (x109/l) Median (range) 20 FAB classification (n, %) M0 M1 M2 M4 and M4Eo M5 M6 M7 AML with dysplasia Not classified MRC (n, %) Favorable Intermediate Adverse Molecular/Favorable Genotype (FG) (n, %) NPM1mut/CEBPAmut (FG) CEBPAmut NPM1mut FLT3-ITD/no-mut FLT3-ITD No mutations MLL (n, %) Wild type MLL-PTD MFI CD34 (n, %) 143.39 MFI CD117 (n, %) 284.01 MFI CD7 (n, %) 15.61 MFI CD123 (n, %) 164.75 Outcome (n, %) Complete Remission (CR) 1 cycle 2 cycles Refractoriness Exitus

17 (0.03-100) 52 (16-70) 263 (44%) 329 (56%) 324 (55%) 268 (45%) 12.70 (0.23-408) 340 (58%) 249 (42%) 41 (7%) 111 (19%) 118 (20%) 144 (24%) 110 (19%) 23 (4%) 6 (1%) 28 (4%) 11 (2%) 71 (13%) 380 (70%) 91 (17%) 98 (22%) 17 (17%) 81 (83%) 340 (78%) 136 (40%) 204 (60%) 502 (93%) 35 (7%) 231 (39%) 360 (61%) 460 (78%) 123 (22%) 486 (82%) 106 (18%) 325 (55%) 267 (45%) 447 (76%) 387 (87%) 60 (13%) 65 (11%) 77 (13%)

Results The results are shown in Table 2. Table 2. Univariate and Multivariate analysis. Results at 5-years. Univariate Survival Age 50years Gender Male Female WBC 20 x 109/l MRC classification Favorable Intermediate Adverse Favorable Genotype (FG) NPM1/CEBPAmut and FLT3-wt FLT3-ITD/no mutations MLL Wild type MLL-PTD MFI CD34 143.39 MFI CD117 284.01 MFI CD123 164.75 MFI CD7 15.61

n

OS

592

39±2%

263 329

53±3% 28±3%

325 268

P-value

LFS

n

CIR

P-value

P-value

448

42±2%