Patients with de novo acute myeloid leukaemia and complex karyotype aberrations show a poor prognosis despite intensive treatment: a study of 90 patients
- PMID: 11167792
- DOI: 10.1046/j.1365-2141.2001.02511.x
Patients with de novo acute myeloid leukaemia and complex karyotype aberrations show a poor prognosis despite intensive treatment: a study of 90 patients
Abstract
The clinical significance of complex chromosome aberrations for adults with acute myeloid leukaemia (AML) was assessed in 920 patients with de novo AML who were karyotyped and treated within the German AML Cooperative Group (AMLCG) trials. Complex chromosome aberrations were defined as three or more numerical and/or structural chromosome aberrations excluding translocations t(8;21)(q22;q22), t(15;17)(q22;q11-q12) and inv(16)(p13q22). Complex chromosome anomalies were detected in 10% of all cases with a significantly higher incidence in patients > or = 60 years of age (17.8% vs. 7.8%, P < 0.0001). Clinical follow-up data were available for 90 patients. Forty-five patients were < 60 years of age and were randomly assigned to double induction therapy with either TAD-TAD [thioguanine, daunorubicin, cytosine arabinoside (AraC)] or TAD-HAM (high-dose AraC, mitoxantrone). Twenty-one patients achieved complete remission (CR) (47%), 20 patients (44%) were non-responders and 9% of patients died during aplasia (early death). The median overall survival (OS) was 7 months and the OS rate at 3 years was 12%. Patients receiving TAD-HAM showed a significantly higher CR rate than patients receiving TAD-TAD (56% vs. 23%, P = 0.04). Median event-free survival was less than 1 month in the TAD-TAD group and 2 months in the TAD-HAM group, respectively (P = 0.04), with a median OS of 4.5 months vs. 7.6 months (P = 0.13) and an OS after 3 years of 7.6% vs. 19.6%. Forty-five patients were > or = 60 years of age: 28 of these patient were treated for induction using one or two TAD courses and 17 cases received TAD-HAM with an age-adjusted reduction of the AraC dose. The CR rate was 44%, 38% were non-responders and 18% experienced early death. The median OS was 8 months and the OS rate at 3 years was 6%. In conclusion, complex chromosome aberrations in de novo AML predicted a dismal outcome, even when patients were treated with intensive chemotherapy. Patients under the age of 60 years with complex aberrant karyotypes may benefit from HAM treatment during induction. However, long-term survival rates are low and alternative treatment strategies for remission induction and consolidation are urgently needed.
Similar articles
-
6-Thioguanine, cytarabine, and daunorubicin (TAD) and high-dose cytarabine and mitoxantrone (HAM) for induction, TAD for consolidation, and either prolonged maintenance by reduced monthly TAD or TAD-HAM-TAD and one course of intensive consolidation by sequential HAM in adult patients at all ages with de novo acute myeloid leukemia (AML): a randomized trial of the German AML Cooperative Group.J Clin Oncol. 2003 Dec 15;21(24):4496-504. doi: 10.1200/JCO.2003.02.133. J Clin Oncol. 2003. PMID: 14673036 Clinical Trial.
-
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. 1999 Jun 15;93(12):4116-24. Blood. 1999. PMID: 10361108 Clinical Trial.
-
The prognostic value of cytogenetics is reinforced by the kind of induction/consolidation therapy in influencing the outcome of acute myeloid leukemia--analysis of 848 patients.Leukemia. 2001 Jun;15(6):903-9. doi: 10.1038/sj.leu.2402142. Leukemia. 2001. PMID: 11417475 Review.
-
Early blast clearance by remission induction therapy is a major independent prognostic factor for both achievement of complete remission and long-term outcome in acute myeloid leukemia: data from the German AML Cooperative Group (AMLCG) 1992 Trial.Blood. 2003 Jan 1;101(1):64-70. doi: 10.1182/blood-2002-02-0532. Epub 2002 Jun 28. Blood. 2003. PMID: 12393605 Clinical Trial.
-
A systematic overview of chemotherapy effects in acute myeloid leukaemia.Acta Oncol. 2001;40(2-3):231-52. doi: 10.1080/02841860151116321. Acta Oncol. 2001. PMID: 11441935 Review.
Cited by
-
Acute myeloid leukemias with reciprocal rearrangements can be distinguished by specific gene expression profiles.Proc Natl Acad Sci U S A. 2002 Jul 23;99(15):10008-13. doi: 10.1073/pnas.142103599. Epub 2002 Jul 8. Proc Natl Acad Sci U S A. 2002. PMID: 12105272 Free PMC article.
-
Speciation Theory of Carcinogenesis Explains Karyotypic Individuality and Long Latencies of Cancers.Genes (Basel). 2018 Aug 9;9(8):402. doi: 10.3390/genes9080402. Genes (Basel). 2018. PMID: 30096943 Free PMC article.
-
Cytogenetics in acute myeloid leukemia.Curr Oncol Rep. 2002 Sep;4(5):390-7. doi: 10.1007/s11912-002-0032-0. Curr Oncol Rep. 2002. PMID: 12162912 Review.
-
Prognostic implications of chromosome 17 abnormalities in the context of monosomal karyotype in patients with acute myeloid leukemia and complex cytogenetics.Clin Lymphoma Myeloma Leuk. 2014 Apr;14(2):163-71. doi: 10.1016/j.clml.2013.07.009. Epub 2014 Jan 22. Clin Lymphoma Myeloma Leuk. 2014. PMID: 24461514 Free PMC article.
-
Gemcitabine and cytosine arabinoside cytotoxicity: association with lymphoblastoid cell expression.Cancer Res. 2008 Sep 1;68(17):7050-8. doi: 10.1158/0008-5472.CAN-08-0405. Cancer Res. 2008. PMID: 18757419 Free PMC article.
Publication types
MeSH terms
Substances
Supplementary concepts
LinkOut - more resources
Full Text Sources