Predictors of response to reinduction chemotherapy for patients with acute myeloid leukemia who do not achieve complete remission with frontline induction chemotherapy

被引:21
作者
Brandwein, Joseph M. [1 ]
Gupta, Vikas [1 ]
Schuh, Andre C. [1 ]
Schimmer, Aaron D. [1 ]
Yee, Karen [1 ]
Xu, Wei [2 ]
Messner, Hans A. [1 ]
Lipton, Jeffrey H. [1 ]
Minden, Mark D. [1 ]
机构
[1] Univ Toronto, Univ Hlth Network, Princess Margaret Hosp, Dept Med Oncol & Hematol, Toronto, ON M5G 2M9, Canada
[2] Univ Toronto, Univ Hlth Network, Princess Margaret Hosp, Dept Biostat, Toronto, ON M5G 2M9, Canada
关键词
D O I
10.1002/ajh.21034
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Eighty-one patients with acute myeloid leukemia who had persistent leukemia following standard induction therapy with cytarabine plus daunorubicin (7+3 regimen) underwent reinduction therapy with a combination of mitoxantrone, etoposide, and high-dose cytarabine (HiDAC). Patients. achieving complete remission (CR) then received consolidation therapy with HiDAC plus mitoxantrone. Patients with matched sibling donors were referred for allogeneic bone marrow transplantation (BMT) in CR-1. The overall response rate to reinduction was 53%. The major adverse predictors of CR on multivariate analysis were poor risk cytogenetics, a higher % bone marrow blasts prior to reinduction therapy and increased age. The median relapse-free survival (RFS) was 9 months and the estimated 2-year RFS was 30%. No significant predictors of RFS or overall survival (OS) were found among the patients achieving CR. Patients undergoing allogeneic BMT in CR-1 after double induction had a 50% 2-year OS. Patients relapsing after achieving CR with double induction had a poor outcome with a 4% 1-year OS. The results indicate that patients with poor risk cytogenetics or marrow blast percentage >= 60% following 7+3 induction have a low probability of achieving CR with reinduction and should be considered for novel approaches to improve CR rates. Patients achieving CR are at high risk of relapse and should be considered for allogeneic BMT or novel strategies to attempt to reduce relapse rates.
引用
收藏
页码:54 / 58
页数:5
相关论文
共 16 条
  • [1] Phase III randomized multicenter study of a humanized anti-CD33 monoclonal antibody, lintuzumab, in combination with chemotherapy, versus chemotherapy alone in patients with refractory or first-relapsed acute myeloid leukemia
    Feldman, EJ
    Brandwein, J
    Stone, R
    Kalaycio, M
    Moore, J
    O'Connor, J
    Wedel, N
    Roboz, GJ
    Miller, C
    Chopra, R
    Jurcic, JC
    Brown, R
    Ehmann, WC
    Schulman, P
    Frankel, SR
    De Angelo, D
    Scheinberg, D
    [J]. JOURNAL OF CLINICAL ONCOLOGY, 2005, 23 (18) : 4110 - 4116
  • [2] Prognostic significance of activating FLT3 mutations in younger adults (16 to 60 years) with acute myeloid leukemia and normal cytogenetics:: a study of the AML Study Group Ulm
    Fröhling, S
    Schlenk, RF
    Breitruck, J
    Benner, A
    Kreitmeier, S
    Tobis, K
    Döhner, H
    Döhner, K
    [J]. BLOOD, 2002, 100 (13) : 4372 - 4380
  • [3] The importance of diagnostic cytogenetics on outcome in AML: Analysis of 1,612 patients entered into the MRC AML 10 trial
    Grimwade, D
    Walker, H
    Oliver, F
    Wheatley, K
    Harrison, C
    Harrison, G
    Rees, J
    Hann, I
    Stevens, R
    Burnett, A
    Goldstone, A
    [J]. BLOOD, 1998, 92 (07) : 2322 - 2333
  • [4] 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
    Grimwade, D
    Walker, H
    Harrison, G
    Oliver, F
    Chatters, S
    Harrison, CJ
    Wheatley, K
    Burnett, AK
    Goldstone, AH
    [J]. BLOOD, 2001, 98 (05) : 1312 - 1320
  • [5] Disease biology rather than age is the most important determinant of survival of patients ≥60 years with acute myeloid leukemia treated with uniform intensive therapy
    Gupta, V
    Chun, K
    Yi, QL
    Minden, M
    Schuh, A
    Wells, R
    Brandwein, J
    [J]. CANCER, 2005, 103 (10) : 2082 - 2090
  • [6] Histone deacetylase inhibitors are the potent inducer/enhancer of differentiation in acute myeloid leukemia: a new approach to anti-leukemia therapy
    Kosugi, H
    Towatari, M
    Hatano, S
    Kitamura, K
    Kiyoi, H
    Kinoshita, T
    Tanimoto, M
    Murate, T
    Kawashima, K
    Saito, H
    Naoe, T
    [J]. LEUKEMIA, 1999, 13 (09) : 1316 - 1324
  • [7] Lancet JE, 2003, BLOOD, V102, p176A
  • [8] Levis M, 2005, BLOOD, V106, p121A
  • [9] Löwenberg B, 1998, J CLIN ONCOL, V16, P872
  • [10] Phase 1 and pharmacodynamic studies of G3139, a Bcl-2 antisense oligonucleotide, in combination with chemotherapy in refractory or relapsed acute leukemia
    Marcucci, G
    Byrd, JC
    Dai, GW
    Klisovic, MI
    Kourlas, PJ
    Young, DC
    Cataland, SR
    Fisher, DB
    Lucas, D
    Chan, KK
    Porcu, P
    Lin, ZP
    Farag, SF
    Frankel, SR
    Zvviebel, JA
    Kraut, EH
    Balcerzak, SP
    Bloomfield, CD
    Grever, MR
    Caligiuri, MA
    [J]. BLOOD, 2003, 101 (02) : 425 - 432