Additional chromosome abnormalities in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and chemotherapy

被引：66

作者：

Cervera, Jose ^{[1
]}

Montesinos, Pau ^{[1
]}

Hernandez-Rivas, Jesus M. ^{[2
]}

Calasanz, Maria J. ^{[3
]}

Aventin, Anna ^{[4
]}

Ferro, Maria T. ^{[5
]}

Luno, Elisa ^{[6
]}

Sanchez, Javier ^{[7
]}

Vellenga, Edo ^{[8
]}

Rayon, Chelo ^{[6
]}

Milone, Gustavo ^{[9
]}

de la Serna, Javier ^{[10
]}

Rivas, Concha ^{[11
]}

Gonzalez, Jose D. ^{[12
]}

Tormo, Mar ^{[13
]}

Amutio, Elena ^{[14
]}

Gonzalez, Marcos ^{[2
]}

Brunet, Salut ^{[4
]}

Lowenberg, Bob ^{[15
]}

Sanz, Miguel A. ^{[1
]}

机构：

[1] Hosp Univ Fe, Valencia 46009, Spain

[2] Hosp Clin Univ, Salamanca, Spain

[3] Univ Navarra, E-31080 Pamplona, Spain

[4] Hosp Santa Creu & Sant Pau, Barcelona, Spain

[5] Hosp Ramon & Cajal, E-28034 Madrid, Spain

[6] Univ Oviedo, Hosp Cent Asturias, E-33080 Oviedo, Spain

[7] Hosp Univ Virgen Rocio, Seville, Spain

[8] Univ Groningen, Univ Med Ctr Groningen, Groningen, Netherlands

[9] Fundaleu, Buenos Aires, DF, Argentina

[10] Hosp 12 Octubre, E-28041 Madrid, Spain

[11] Hosp Gen Alicante, Alicante, Spain

[12] Hosp Insular, Las Palmas Gran Canaria, Spain

[13] Hosp Clin Univ, Valencia, Spain

[14] Hosp Cruces, Baracaldo, Spain

[15] Erasmus Univ, Med Ctr, Rotterdam, Netherlands

来源：

HAEMATOLOGICA-THE HEMATOLOGY JOURNAL | 2010年 / 95卷 / 03期

关键词：

acute promyelocytic leukemia; additional chromosomal abnormalities; prognostic factors; all-trans retinoic acid; anthracycline; ACUTE MYELOID-LEUKEMIA; EXTERNAL QUALITY-CONTROL; RISK-ADAPTED TREATMENT; ANTHRACYCLINE MONOCHEMOTHERAPY; CYTOGENETIC CHANGES; PETHEMA GROUP; GROUP-B; CONSOLIDATION; THERAPY; MULTICENTER;

D O I：

10.3324/haematol.2009.013243

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Background Acute promyelocytic leukemia is a subtype of acute myeloid leukemia characterized by the t(15;17). The incidence and prognostic significance of additional chromosomal abnormalities in acute promyelocytic leukemia is still a controversial matter. Design and Methods Based on cytogenetic data available for 495 patients with acute promyelocytic leukemia enrolled in two consecutive PETHEMA trials (LPA96 and LPA99), we analyzed the incidence, characteristics, and outcome of patients with acute promyelocytic leukemia with and without additional chromosomal abnormalities who had been treated with all-trans retinoic acid plus anthracycline monochemotherapy for induction and consolidation. Results Additional chromosomal abnormalities were observed in 140 patients (28%). Trisomy 8 was the most frequent abnormality (36%), followed by abn(7q) (5%). Patients with additional chromosomal abnormalities more frequently had coagulopathy (P=0.03), lower platelet counts (P=0.02), and higher relapse-risk scores (P=0.02) than their counterparts without additional abnormalities. No significant association with FLT3/ITD or other clinicopathological characteristics was demonstrated. Patients with and without additional chromosomal abnormalities had similar complete remission rates (90% and 91%, respectively). Univariate analysis showed that additional chromosomal abnormalities were associated with a lower relapse-free survival in the LPA99 trial (P=0.04), but not in the LPA96 trial. However, neither additional chromosomal abnormalities overall nor any specific abnormality was identified as an independent risk factor for relapse in multivariate analysis. Conclusions The lack of independent prognostic value of additional chromosomal abnormalities in acute promyelocytic leukemia does not support the use of alternative therapeutic strategies when such abnormalities are found.

引用

页码：424 / 431

页数：8

共 25 条

[1] Hidden abnormalities and novel classification of t(15;17) acute promyelocytic leukemia (APL) based on genomic alterations [J].

Akagi, Tadayuki ;

Shih, Lee-Yung ;

Kato, Motohiro ;

Kawamata, Norihiko ;

Yamamoto, Go ;

Sanada, Masashi ;

Okamoto, Ryoko ;

Miller, Carl W. ;

Liang, Der-Cherng ;

Ogawa, Seishi ;

Koeffler, H. Phillip .

BLOOD, 2009, 113 (08) :1741-1748

[2] Preliminary experience in external quality control of RT-PCR PML-RARα detection in promyelocytic leukemia [J].

Bolufer, P ;

Barragán, E ;

Sánz, MA ;

Martín, G ;

Bornstein, R ;

Colomer, D ;

Delgado, MD ;

González, M ;

Marugan, I ;

Romáan, J ;

Gómez, MT ;

Anguita, E ;

Diverio, D ;

Chomienne, C ;

Briz, M .

LEUKEMIA, 1998, 12 (12) :2024-2028

[3]

Bolufer P, 2001, HAEMATOLOGICA, V86, P570

[4] Pretreatment cytogenetic abnormalities are predictive of induction success, cumulative incidence of relapse, and overall survival in adult patients with de novo acute myeloid leukemia:: results from Cancer and Leukemia Group B (CALGB 8461) [J].

Byrd, JC ;

Mrózek, K ;

Dodge, RK ;

Carroll, AJ ;

Edwards, CG ;

Arthur, DC ;

Pettenati, MJ ;

Patil, SR ;

Rao, KW ;

Watson, MS ;

Koduru, PRK ;

Moore, JO ;

Stone, RM ;

Mayer, RJ ;

Feldman, EJ ;

Davey, FR ;

Schiffer, CA ;

Larson, RA ;

Bloomfield, CD .

BLOOD, 2002, 100 (13) :4325-4336

[5] Revised recommendations of the international working group for diagnosis, standardization of response criteria, treatment outcomes, and reporting standards for therapeutic trials in acute myeloid leukemia [J].

Cheson, BD ;

Bennett, JM ;

Kopecky, KJ ;

Büchner, T ;

Willman, CL ;

Estey, EH ;

Schiffer, CA ;

Döhner, H ;

Tallman, MS ;

Lister, TA ;

LoCocco, F ;

Willemze, R ;

Biondi, A ;

Hiddemann, W ;

Larson, RA ;

Löwenberg, B ;

Sanz, MA ;

Head, DR ;

Ohno, R ;

Bloomfield, CD .

JOURNAL OF CLINICAL ONCOLOGY, 2003, 21 (24) :4642-4649

[6]

COX DR, 1972, J R STAT SOC B, V187, P220

[7] Additional chromosomal abnormalities in patients with acute promyelocytic leukaemia (APL) do not confer poor prognosis: results of APL 93 trial [J].

de Botton, S ;

Chevret, S ;

Sanz, M ;

Dombret, H ;

Thomas, X ;

Guerci, A ;

Fey, M ;

Rayon, C ;

Huguet, F ;

Sotto, JJ ;

Gardin, C ;

Makhoul, PC ;

Travade, P ;

Solary, E ;

Fegueux, N ;

Bordessoule, D ;

San Miguel, J ;

Link, H ;

Desablens, B ;

Stamatoullas, A ;

Deconinck, E ;

Geiser, K ;

Hess, U ;

Maloisel, F ;

Castaigne, S ;

Preudhomme, C ;

Chomienne, C ;

Degos, L ;

Fenaux, P .

BRITISH JOURNAL OF HAEMATOLOGY, 2000, 111 (03) :801-806

[8] Causes and prognostic factors of remission induction failure in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and idarubicin [J].

de la Serna, Javier ;

Montesinos, Pau ;

Vellenga, Edo ;

Rayon, Chelo ;

Parody, Ricardo ;

Leon, Angel ;

Esteve, Jordi ;

Bergua, Juan M. ;

Milone, Gustavo ;

Deben, Guillermo ;

Rivas, Concha ;

Gonzalez, Marcos ;

Tormo, Mar ;

Diaz-Mediavilla, Joaquin ;

Gonzalez, Jose D. ;

Negri, Silvia ;

Amutio, Elena ;

Brunet, Salut ;

Lowenberg, Bob ;

Sanz, Miguel A. .

BLOOD, 2008, 111 (07) :3395-3402

[9] Relationship between FLT3 mutation status, biologic characteristics, and response to targeted therapy in acute promyelocytic leukemia [J].

Gale, RE ;

Hills, R ;

Pizzey, AR ;

Kottaridis, PD ;

Swirsky, D ;

Gilkes, AF ;

Nugent, E ;

Mills, KI ;

Wheatley, K ;

Solomon, E ;

Burnett, AK ;

Linch, DC ;

Grimwade, D .

BLOOD, 2005, 106 (12) :3768-3776

[10] Immunofluorescent analysis with the anti-PML monoclonal antibody PG-M3 for rapid and accurate genetic diagnosis of acute promyelocytic leukemia [J].

Gomis, F ;

Sanz, J ;

Sempere, A ;

Plumé, G ;

Senent, ML ;

Pérez, ML ;

Cervera, J ;

Moscardó, F ;

Bolufer, P ;

Barragán, E ;

Martín, G ;

Sanz, M .

ANNALS OF HEMATOLOGY, 2004, 83 (11) :687-690

← 1 2 3 →