Karyotypic analysis predicts outcome of preremission and postremission therapy in adult acute myeloid leukemia: a Southwest Oncology Group/Eastern Cooperative Oncology Group study

Blood - Tập 96 Số 13 - Trang 4075-4083 - 2000
Marilyn L. Slovak1, Kenneth J. Kopecky1, Peter A. Cassileth1, David H. Harrington1, Karl S. Theil1, Anwar N. Mohamed1, E Paietta1, Cheryl L. Willman1, David R. Head1, Jacob M. Rowe1, Stephen J. Forman1, Frederick R. Appelbaum1
1From the City of Hope National Medical Center, Duarte, CA.

Tóm tắt

Abstract The associations of cytogenetics with complete remission (CR) rates, overall survival (OS), and outcomes after CR were studied in 609 previously untreated AML patients younger than 56 years old in a clinical trial comparing 3 intensive postremission therapies: intensive chemotherapy, autologous transplantation (ABMT), or allogeneic bone marrow transplantation (alloBMT) from matched related donors. Patients were categorized into favorable, intermediate, unfavorable, and unknown cytogenetic risk groups based on pretreatment karyotypes. CR rates varied significantly (P < .0001) among the 4 groups: favorable, 84% (95% confidence interval [CI], 77%-90%); intermediate, 76% (CI, 71%-81%); unfavorable, 55% (CI, 48%-63%); and unknown, 54% (CI, 33%-74%). There was similar significant heterogeneity of OS (P < .0001), with the estimated relative risk of death from any cause being 1.50 (CI, 1.10-2.05), 3.33 (CI, 2.43-4.55), and 2.66 (CI, 1.59-4.45) for the intermediate, unfavorable, and unknown risk groups, respectively, compared with the favorable group. In multivariate analyses, the effects of cytogenetic risk status on CR rate and OS could not be explained by other patient or disease characteristics. Among postremission patients, survival from CR varied significantly among favorable, intermediate, and unfavorable groups (P = .0003), with significant evidence of interaction (P = .017) between the effects of treatment and cytogenetic risk status on survival. Patients with favorable cytogenetics did significantly better following ABMT and alloBMT than with chemotherapy alone, whereas patients with unfavorable cytogenetics did better with alloBMT. Cytogenetic risk status is a significant factor in predicting response of AML patients to therapy; however, to tighten treatment correlates within genetically defined AML subsets, a significantly larger leukemia cytogenetic database is warranted.

Từ khóa


Tài liệu tham khảo

Mrozek, 1997, Clinical significance of cytogenetics in acute myeloid leukemia., Semin Oncol., 24, 17

Raimondi, 1999, Chromosomal abnormalities in 478 children with acute myeloid leukemia: clinical characteristics and treatment outcome in a cooperative pediatric oncology group study - POG 8821., Blood., 94, 3707

Tallman, 1997, All-trans-retinoic acid in acute promyelocytic leukemia., N Engl J Med., 337, 1021, 10.1056/NEJM199710093371501

Fenaux, 1997, Acute promyelocytic leukemia: biology and treatment., Semin Oncol., 24, 92

Bloomfield, 1998, Frequency of prolonged remission duration after high-dose cytarabine intensification in acute myeloid leukemia varies by cytogenetic subtype., Cancer Res., 58, 4173

Buchner, 1999, Double induction strategy for acute myeloid leukemia: the effect of high-dose cytarabine with mitoxantrone instead of standard dose cytarabine with daunorubicin and 6-thioguanine: a randomized trial by the German AML Cooperative Group., Blood., 93, 4116

Zittoun, 1995, Autologous or allogeneic bone marrow transplantation compared with intensive chemotherapy in acute myelogenous leukemia., N Engl J Med., 332, 217, 10.1056/NEJM199501263320403

Harousseau, 1997, Comparison of autologous bone marrow transplantation and intensive chemotherapy as postremission therapy in adult acute myeloid leukemia., Blood., 90, 2978

Cassileth, 1998, Chemotherapy compared with autologous or allogeneic bone marrow transplantation in the management of acute myeloid leukemia in first remission., N Engl J Med., 339, 1649, 10.1056/NEJM199812033392301

Grimwade, 1998, The importance of diagnostic cytogenetics on outcome in AML: analysis of 1,612 patients entered into the MRC AML 10 trial., Blood., 92, 2322, 10.1182/blood.V92.7.2322

Mitelman, 1995, ISCN (1995): An International System for Human Cytogenetic Nomenclature.

Slovak, 1995, Trisomy 11: an association with stem/progenitor cell immunophenotype., Br J Haematol., 90, 266, 10.1111/j.1365-2141.1995.tb05146.x

Dastugue, 1995, Prognostic significance of karyotype in de novo adult acute myeloid leukemia., Leukemia., 9, 1491

Behm, 1996, Rearrangement of the MLL gene confers a poor prognosis in childhood acute lymphoblastic leukemia, regardless of presenting age., Blood., 87, 2870, 10.1182/blood.V87.7.2870.bloodjournal8772870

Schoch, 1996, Fifty-one patients with acute myeloid leukemia and translocation t(8;21)(q22;q22): an additional deletion in 9q is an adverse prognostic factor., Leukemia., 10, 1288

Alsabeh, 1997, Acute myeloid leukemia with t(6;9)(p23;q34): association with myelodysplasia, basophilia, and initial CD34 negative immunophenotype., Am J Clin Pathol., 107, 430, 10.1093/ajcp/107.4.430

Cheson, 1990, Report of the National Cancer Institute–sponsored workshop on definitions of diagnosis and response in acute myeloid leukemia., J Clin Oncol., 8, 813, 10.1200/JCO.1990.8.5.813

Kaplan, 1958, Nonparametric estimation from incomplete observations., J Am Stat Assoc., 53, 457, 10.1080/01621459.1958.10501452

Burnett, 1998, Randomised comparison of addition of autologous bone-marrow transplantation to intensive chemotherapy for acute myeloid leukemia in first remission: results of MRC AML 10 trial., Lancet., 351, 700, 10.1016/S0140-6736(97)09214-3

Caligiuri, 1998, Rearrangement of ALL1 (MLL) in acute myeloid leukemia with normal cytogenetics., Cancer Res., 58, 55

Romana, 1995, The (12;21) of acute lymphoblastic leukemia results in a TEL-AML1 gene fusion., Blood., 85, 3662, 10.1182/blood.V85.12.3662.bloodjournal85123662

Veldman, 1997, Hidden chromosome abnormalities in haematological malignancies detected by multicolour spectral karyotyping., Nat Genet., 15, 406, 10.1038/ng0497-406

Zhang, 2000, 24-color spectral karyotyping reveals chromosome aberrations in “cytogenetically normal” acute myeloid leukemia., Genes Chromosomes Cancer., 28, 318, 10.1002/1098-2264(200007)28:3<318::AID-GCC10>3.0.CO;2-M

Martinez-Climent, 1995, Abnormalities of chromosome band 11q23 and the MLL gene in pediatric myelomonocytic and monoblastic leukemias: identification of the t(9;11) as an indicator of long survival., J Pediatr Hematol Oncol., 17, 277, 10.1097/00043426-199511000-00001

Peniket, 1999, Del(9q) AML: clinical, cytological and cytogenetic characteristics and prognostic implications for patients entering the MRC AML trials., Blood., 94, 496a