Abstract 1003

Poster Board I-25

Introduction:

Recently, the cooperative group HOVON-SAKK has refined the prognostic impact of cytogenetic abnormalities in acute myeloid leukemia (AML) by introducing the concept of monosomal karyotype (MK). This consists of ≥ 2 autosomal monosomies or one autosomal monosomy in addition to a structural alteration. In their experience, MK would explain the poor prognosis of AML with a complex karyotype.

Objective:

To investigate the prognostic impact of MK in patients with primary (de novo) AML enrolled in the Spanish CETLAM group protocols (AML 94/99/03). Also, to determine whether considering MK added predictive value to the cytogenetic classification of the Medical Research Council (MRC).

Methods:

Retrospective analysis of data from 1149 AML patients. Chromosomal formula was centrally reviewed with karyotypes being classified by the presence of MK and allocated into the MRC risk categories. Complete remission (CR) rate, disease-free survival (DFS) and overall survival (OS) were calculated.

Results:

The karyotype was assessable in 904 (79%) of the 1149 cases. In 145 of the 904 cases (16%), abnormalities involving CBF gene were detected and in 437 (48%) the karyotype was normal (NK). In 253 (28%) additional patients the karyotype was not monosomal; of them, 61 (24%) belonged to the unfavorable MRC with 17 cases harboring a complex karyotype ≥ 5 abnormalities, 7 cases with rearrangements 3q, 13 cases with -7, 9 cases with 5q abnormalities and 16 cases with t(6;9)). The remaining 69 (7.7%) patients had a MK; of them, 59 (85.5%) were from the unfavorable MRC category and included 43 cases with complex karyotype ≥ 5 abnormalities, 6 cases with rearrangements 3q, 5 cases with -7, 5 cases with alterations of 5q). The following table summarizes the results in terms of CR rate, DFS and OS:

CBFNKMK- (IP)*MK- (UP)**MK+***p
CR 92% 82% 76% 68% 52% < 0,001 
DFS (4 years) median (month) 58%± 5114.8 45%± 322.6 38%± 516.3 20%± 812.3 15%± 74.73 <0,001 
OS (8 years) median (month) 62%± 4- 35%± 321.2 34%± 416.0 16%± 612.8 3%± 36.6 <0,001 
CBFNKMK- (IP)*MK- (UP)**MK+***p
CR 92% 82% 76% 68% 52% < 0,001 
DFS (4 years) median (month) 58%± 5114.8 45%± 322.6 38%± 516.3 20%± 812.3 15%± 74.73 <0,001 
OS (8 years) median (month) 62%± 4- 35%± 321.2 34%± 416.0 16%± 612.8 3%± 36.6 <0,001 
*

MK- (IP): Non-monosomal karyotype in the intermediate prognosis MRC cytogenetic group.

**

MK -(UP): Non-monosomal karyotype in the unfavorable prognosis MRC cytogenetic group.

***

MK+ : Cases with MK

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Conclusions:

The addition of MK to the MRC cytogenetic classification refines the prognostic prediction. In our series, the dismal outcome of patients with MK is confirmed; these patients had worse prognosis than those with adverse cytogenetics without MK. Alternative treatment strategies are mandatory for MK+ patients.

Supported in part by grants: GR1-01075, ECO07/90065, PI080672 and RD06/0020/0101.

Disclosures:

No relevant conflicts of interest to declare.

Topics:
karyotype determination procedure, leukemia, myelocytic, acute, magnetic resonance cholangiography, complete remission, monosomy, chromosome abnormality, clinical trials cooperative groups, medical research

Author notes

*

Asterisk with author names denotes non-ASH members.

© 2009 by The American Society of Hematology
2009
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