Abstract 3563

The distinctive features of the World Health organization (WHO) classification compared to French-America-British Co-operative group (FAB) classification of acute myeloid leukemia is the new morphological entity “AML with multilineage dysplasia (MLD)”, and now this subgroup has been renamed as 'AML with myelodysplasia-related change (MRC)”. It generally accepted that dysplasia was most frequently noted in older individual, is often associated with an unfavorable cytogenetic profiles and unfavourable response to therapy. However it is still controversial. Therefore, we evaluated the impact of MRC on overall survival (OS) and leukemia free survival (LFS) in acute myeloid leukemia patients.

A total of 644 adult AML patients diagnosed at Samsung Medical Center (SMC) between Sep.1994 and Oct. 2010 were enrolled. We reviewed their medical histories, clinical parameters, hemogram data, bone marrow aspirate and cytogenetic studies, and reclassified them into AML with of MRC and without MRC groups. Of 664 patients, 543 patients were received induction chemotherapy, among them, 84 patients demonstrated MRC and 451 patients did not. Median age was 50 (15–88) years old, and 57.1% of patients were male. Median follow up period was 77.3 [0–191] months.

AML without MRC group had more favorable cytogenetic risk, higher WBC counts and LDH levels than those with MRC. However, other variable such as age, sex, hemoglobin level, absolute neutrophil, and peripheral blast count, induction chemotherapy regimen, hematopoietic stem cell transplantation, CR1 (complete response after induction chemotherapy), CRp (complete recovery of platelet), and relapse rate were not different between two groups. Since FLT3-ITD and NPM1 tests were introduced into laboratory work after 2005, results of these tests were available only in 158 and 75 patients respectively, and these were not different between two groups.

In univariate analysis, advanced age (>65 years) predicted worse LFS (median LFS [95% C.I.]; ° Â65 years vs >65 years; 9.3[7.2–11.4] vs 5.9[4.6–7.2] months, p =0.014). In terms of OS, young age (p=0.000), female (p=0.000), favorable cytogenetic risk (p=0.000), CR1 (p=0.000), CRp (p=0.000), absence of relapse (p=0.000), and HSCT (p=0.000) showed a higher probability of longer OS (Table 1). The presence of MRC, FLT3-ITD, and NPM1 did not affect OS (Table 1).

Table 1.

Summary of univariate analysis for overall survival.

Median OS (months) [95% C.I.] or mean OS ± SD (months)p
Age °Â65 years 47.9 [17.1 – 78.6] 0.000 
 >65 years 13.1 [5.9 – 20.4]  
Sex Male 23.2 [16.5 – 30.0] 0.000 
 ¢Female 112.2 [ – ]  
Cytogenetic risk ¢Favorable 107.0±7.4 0.000 
 Intermediate 28.0 [19.0 – 36.9]  
 Unfavorable 10.8 [7.8 – 13.7]  
 Unknown 17.5 [6.8 – 28.1]  
MRC Absence 35.9 [6.6 – 65.2] 0.081 
 Presence 19.0 [6.9 – 31.0]  
CR1 ¢Yes 112.2 [–] 0.000 
 No 3.6 [1.1 – 6.1]  
CRp ¢Yes 70.9±4.4 0.000 
 No 54.8 [18.5 – 91.1]  
Relapse Yes 21.5 [17.2 – 25.9] 0.000 
 No 17.5 [–]  
HSCT ¢Auto 86.2±5.6 0.000 
 ¢Allo 83.8±6.5  
 Not done 17.5 [10.8 – 24.1]  
FLT3-ITD Positive 8.2 [0–26.1] 0.595 
 Negative 29.5 [20.9–38]  
NPM1 ¢Positive 104.1±11.0 0.978 
 ¢Negative 78.9±15.0  
Median OS (months) [95% C.I.] or mean OS ± SD (months)p
Age °Â65 years 47.9 [17.1 – 78.6] 0.000 
 >65 years 13.1 [5.9 – 20.4]  
Sex Male 23.2 [16.5 – 30.0] 0.000 
 ¢Female 112.2 [ – ]  
Cytogenetic risk ¢Favorable 107.0±7.4 0.000 
 Intermediate 28.0 [19.0 – 36.9]  
 Unfavorable 10.8 [7.8 – 13.7]  
 Unknown 17.5 [6.8 – 28.1]  
MRC Absence 35.9 [6.6 – 65.2] 0.081 
 Presence 19.0 [6.9 – 31.0]  
CR1 ¢Yes 112.2 [–] 0.000 
 No 3.6 [1.1 – 6.1]  
CRp ¢Yes 70.9±4.4 0.000 
 No 54.8 [18.5 – 91.1]  
Relapse Yes 21.5 [17.2 – 25.9] 0.000 
 No 17.5 [–]  
HSCT ¢Auto 86.2±5.6 0.000 
 ¢Allo 83.8±6.5  
 Not done 17.5 [10.8 – 24.1]  
FLT3-ITD Positive 8.2 [0–26.1] 0.595 
 Negative 29.5 [20.9–38]  
NPM1 ¢Positive 104.1±11.0 0.978 
 ¢Negative 78.9±15.0  
¢

“median survival not reached

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Next, we analyzed MRC effect in each variable to OS. The presence MRC did not affect OS of each group which divided according to the age (Figure 1. A and B), sex, cytogenetic risk groups (Figure 1. C and D), relapse, CR1, HSCT, and FLT3-ITD, though AML with MRC group had tendancy to have poor survival rate in intermediate cytogenetic risk group (Figure 1. C). However in patients who did not acheived CRp or showed NPM1, the presence of MRC correlated with shorter OS.
Figure 1.
Figure 1. Overall survival (OS) according to the presence of MRC in age ° Â65 group (A), age>65 group (B), intermediate cytogenetic risk group (C)), and unfavorable cytogenetic risk group (D).
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Overall survival (OS) according to the presence of MRC in age ° Â65 group (A), age>65 group (B), intermediate cytogenetic risk group (C)), and unfavorable cytogenetic risk group (D).

Figure 1.
Figure 1. Overall survival (OS) according to the presence of MRC in age ° Â65 group (A), age>65 group (B), intermediate cytogenetic risk group (C)), and unfavorable cytogenetic risk group (D).
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Overall survival (OS) according to the presence of MRC in age ° Â65 group (A), age>65 group (B), intermediate cytogenetic risk group (C)), and unfavorable cytogenetic risk group (D).

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In this study, patients with MRC did not show inferior outcomes than those without MRC. Therefore it is not necessary to decide different treatment strategy according to the presence of MRC

Disclosures:

No relevant conflicts of interest to declare.

Topics:
leukemia, myelocytic, acute, magnetic resonance cholangiography, medical reserve corps, myelodysplastic syndrome, preleukemia, c-reactive protein, cyclic amp receptor protein, epley maneuver, hematopoietic stem cell transplantation, impedance threshold device

Author notes

*

Asterisk with author names denotes non-ASH members.

© 2011 by The American Society of Hematology
2011
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