The predictive value of hierarchical cytogenetic classification in older adults with acute myeloid leukemia (AML): analysis of 1065 patients entered into the United Kingdom Medical Research Council AML11 trial

被引:744
作者
Grimwade, D
Walker, H
Harrison, G
Oliver, F
Chatters, S
Harrison, CJ
Wheatley, K
Burnett, AK
Goldstone, AH
机构
[1] UCL Hosp, N London Canc Network, London WC1E 6DB, England
[2] UCL, Sch Med, London W1N 8AA, England
[3] Cardiff Univ, Dept Haematol, Cardiff CF4 4XN, S Glam, Wales
[4] Guys Kings & St Thomas Sch Med, Div Med & Mol Genet, London, England
[5] Radcliffe Infirm, Clin Trial Serv Unit, Oxford OX2 6HE, England
[6] Royal Free & Univ Coll Med Sch, London, England
[7] Univ Birmingham, Clin Trials Unit, Birmingham B15 2TT, W Midlands, England
关键词
D O I
10.1182/blood.V98.5.1312
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Acute myeloid leukemia (AML) in older adults carries a poor prognosis, and the optimum treatment remains to be determined. In younger patients, treatment stratification is frequently based upon diagnostic karyotype, which was the most important prognostic factor In the UK Medical Research Council (MRC) AML10 trial. Considered here is whether karyotype is also predictive in older adults; this is done by studying 1065 cases from MRC AML11 (median age, 66 years). Three prognostic groups were distinguished on the basis of response to Induction therapy and overall survival (OS). Those with t(15;17), t(8;21), or Inv(16) composed the favor-able risk group. Overall, these abnormalities predicted a superior complete remission (CIR) rate (72%), reflecting relatively low levels of resistant disease (RD) (8%), and lower relapse risk (RR) (56%) associated with superior OS (34% at 5 years). Normal karyotype (CIR, 63%; RD, 17%; RR, 78%; OS, 15%) and other non-complex abnormalities (CR, 53%; RD, 32%; RR, 85%; OS, 10%) composed the intermediate group; while complex karyotype predicted an extremely poor prognosis (CR, 26%; RD, 56%; RR, 91 %; CS, 2%). Combining MRC AML10 and AML11 (n = 2677) revealed that the most favorable changes were rarer In older patients (younger than 55 years, 24%; 55 years or older, 7%), while complex abnormalities were more common (6% vs 13%). This study suggests that hierarchical cytogenetic classification Identifies biologically distinct subsets of AML that are represented In all age groups. Furthermore, It highlights the Importance of karyotype as a critical independent determinant of outcome in older patients with AML, providing a potential framework for stratified treatment approaches. (C) 2001 by The American Society of Hematology.
引用
收藏
页码:1312 / 1320
页数:9
相关论文
共 40 条
  • [1] Growth characteristics of acute myelogenous leukemia progenitors that initiate malignant hematopoiesis in nonobese diabetic/severe combined immunodeficient mice
    Ailles, LE
    Gerhard, B
    Kawagoe, M
    Hogge, DE
    [J]. BLOOD, 1999, 94 (05) : 1761 - 1772
  • [2] BenYehuda D, 1996, BLOOD, V88, P4296
  • [3] Presenting white blood cell count and kinetics of molecular remission predict prognosis in acute promyelocytic leukemia treated with all-trans retinoic acid:: Result of the randomized MRC trial
    Burnett, AK
    Grimwade, D
    Solomon, E
    Wheatley, K
    Goldstone, AH
    [J]. BLOOD, 1999, 93 (12) : 4131 - 4143
  • [4] AUTOLOGOUS BONE-MARROW TRANSPLANTATION FOR FIRST REMISSION ACUTE MYELOBLASTIC-LEUKEMIA IN PATIENTS OLDER THAN 50 YEARS - A RETROSPECTIVE ANALYSIS OF THE EUROPEAN-BONE-MARROW-TRANSPLANT-GROUP
    CAHN, JY
    LABOPIN, M
    MANDELLI, F
    GOLDSTONE, AH
    EBERHARDT, K
    REIFFERS, J
    FERRANT, A
    FRANKLIN, I
    HERVE, P
    GRATWOHL, A
    GORIN, NC
    [J]. BLOOD, 1995, 85 (02) : 575 - 579
  • [5] REPORT OF THE NATIONAL CANCER INSTITUTE-SPONSORED WORKSHOP ON DEFINITIONS OF DIAGNOSIS AND RESPONSE IN ACUTE MYELOID-LEUKEMIA
    CHESON, BD
    CASSILETH, PA
    HEAD, DR
    SCHIFFER, CA
    BENNETT, JM
    BLOOMFIELD, CD
    BRUNNING, R
    GALE, RP
    GREVER, MR
    KEATING, MJ
    SAWITSKY, A
    STASS, S
    WEINSTEIN, H
    WOODS, WG
    [J]. JOURNAL OF CLINICAL ONCOLOGY, 1990, 8 (05) : 813 - 819
  • [6] DASTUGUE N, 1995, LEUKEMIA, V9, P1491
  • [7] Del Poeta G, 2000, BLOOD, V96, p543A
  • [8] LOW INCIDENCE OF MDR1 EXPRESSION IN ACUTE PROMYELOCYTIC LEUKEMIA
    DRACH, D
    ZHAO, SR
    DRACH, J
    ANDREEFF, M
    [J]. BRITISH JOURNAL OF HAEMATOLOGY, 1995, 90 (02) : 369 - 374
  • [9] Lessons learned from the development of an Abl tyrosine kinase inhibitor for chronic myelogenous leukemia
    Druker, BJ
    Lydon, NB
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 2000, 105 (01) : 3 - 7
  • [10] A randomized comparison of all transretinoic acid (ATRA) followed by chemotherapy and ATRA plus chemotherapy and the role of maintenance therapy in newly diagnosed acute promyelocytic leukemia
    Fenaux, P
    Chastang, C
    Chevret, S
    Sanz, M
    Dombret, H
    Archimbaud, E
    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
    Maloisel, F
    Castaigne, S
    Preudhomme, C
    Degos, L
    [J]. BLOOD, 1999, 94 (04) : 1192 - 1200