Clinical Importance of Morphological Multilineage Dysplasia in Acute Myeloid Leukemia with Myelodysplasia Related Changes

Sang Hyuk Park; Hyun-Sook Chi; Seo-Jin Park; Seongsoo Jang; Chan-Jeoung Park

doi:10.3343/kjlm.2010.30.3.231

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Park, Chi, Park, Jang, and Park: Clinical Importance of Morphological Multilineage Dysplasia in Acute Myeloid Leukemia with Myelodysplasia Related Changes

Original Article

Korean J Leg Med 2010;30(3):231-238.

Published online: 14 January 2010

DOI: https://doi.org/10.3343/kjlm.2010.30.3.231

Clinical Importance of Morphological Multilineage Dysplasia in Acute Myeloid Leukemia with Myelodysplasia Related Changes

Sang Hyuk Park, M.D., Hyun-Sook Chi, M.D., Seo-Jin Park, M.D., Seongsoo Jang, M.D., Chan-Jeoung Park, M.D.

Department of Laboratory Medicine, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea

Corresponding author: Hyun-Sook Chi, M.D. Department of Laboratory Medicine, Asan Medical Center and University of Ulsan College of Medicine, 388-1 Pungnap 2-dong, Songpa-gu, Seoul 138-736, Korea Tel: +82-2-3010-4502, Fax: +82-2-478-0884 E-mail: hschi@amc.seoul.kr

Revised 9 November 200923 March 2010 Accepted 30 April 2010

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background:

AML with myelodysplasia related changes (AML MRC) is known to show a poor prognosis compared with de novo AML, but controversies exist about the prognostic impact of multilineage dysplasia (MLD) among MRC. We investigated the prognostic impact of MLD in AML MRC.

Methods:

A total of 357 patients newly diagnosed as AML at Asan Medical Center from January 2001 to December 2005 were analyzed. They were diagnosed and classified as AML with recurrent genetic abnormalities, AML MRC, and AML not otherwise specified (AML NOS). Prognostic markers including overall survival (OS) and event free survival (EFS) were obtained through retrospective analysis of electronic medical records.

Results:

AML MRC patients showed a lower complete remission (CR) rate (44.7% vs. 64.9%, P= 0.002) and shorter OS (297 vs. 561 days, P=0.004) and EFS (229 vs. 374 days, P=0.004) than AML NOS patients. Patients with MLD among AML MRC also showed a lower CR rate (37.7%, P=0.001) and shorter OS (351 days, P=0.036) and EFS (242 days, P=0.076) than AML NOS patients. However, among AML MRC patients, there were no differences in OS, EFS and CR between patients with and without MLD.

Conclusions:

AML MRC patients showed a lower CR rate and shorter OS and EFS than AML NOS patients. AML MRC patients with MLD showed similar results and their prognosis was not different from those without MLD. MLD findings among AML MRC could be an independent poor prognostic factor in de novo AML.

Keywords: Prognosis, Multilineage, Dysplasia, AML, Myelodysplasia, Related, Changes

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Fig. 1.

Comparison of overall survival and event free survival in 357 patients among 3 AML groups according to revised 2008 WHO classification. Abbreviations: RGA, recurrent genetic abnormalities; MRC, myelodysplasia related changes; NOS, not otherwise specified.

Fig. 2.

Fig. 2. Comparison of overall survival and event free survival of AML MRC patients among 3 subgroups. Abbreviation: MLD, multilineage dysplasia.

Fig. 3.

Comparison of overall survival and event free survival of AML MLD patients compared with other AML. Abbreviation: MLD, multilineage dysplasia.

Table 1.

Clinical characteristics and prognosis in 3 AML groups

Clinical variables	AML RGA (N=115)	AML NOS (N=148)	AML MRC (N=94)	P value∗
Age, median (range)	42 (2-80)	45 (1-82)	53 (2-79)	0.362
Hb (g/dL), median (range)	8.8 (2.6-14.7)	9.0 (3.6-15.1)	8.5 (3.2-11.6)	0.09
WBC (×1,000 /μL), median (range)	8.4 (0.4-239.4)	10.8 (0.7-333.4)	5.1 (0.3-246.0)	<0.001
Platelet (×1,000 /μL), median (range)	44.0 (5.0-511.0)	57.0 (2.9-302.0)	42.5 (6.0-433.0)	0.992
Blast (%), median (range)	66.8 (20.2-96.2)	66.1 (5.2-98.8)	50.5 (16.4-96.2)	<0.001
FLT3 ITD mutation	100.0%	17.4%	5.1%	0.011
FLT3 D835 mutation	14.7%	7.6%	5.0%	0.605
CR	79.1%	64.9%	44.7%	0.002
Relapse	26.1%	30.4%	29.8%	0.919
Death	26.1%	64.9%	76.6%	0.054
OS (days), median	1,455.0, P<0.001^†	561	297	0.004
EFS (days), median	1,294.0, P<0.001^†	374	229	0.004

^∗ P value, NOS compared with MRC;

^† P value compared with MRC.

Abbreviations: RGA, recurrent genetic abnormalities; NOS, not otherwise specified; MRC, myelodysplasia related changes; WBC, white blood cells; FLT3, Fms-related tyrosine kinase 3; ITD, internal tandem duplication; CR, complete remission; OS, overall survival; EFS, event free survival.

Table 2.

Comparison of OS, EFS, CR and death rate among subgroups of AML MRC

Type and description	Median (days)		CR	Death
Type and description	OS	EFS	CR	Death
Prior MDS history (N=9)	113.0	97.0	33.3%	22.2%
(P value compared with MLD)	P=0.712	P=0.504	P=0.800	P<0.001
MDS related cytogenetic abnormality (N=32)	234.0	184.0	59.4%	84.3%
(P value compared with MLD)	P=0.749	P=0.391	P=0.052	P=0.704
MLD (N=53)	351.0	242.0	37.7%	81.1%

Abbreviations: OS, overall survival; EFS, event free survival; CR, complete remission; MRC, myelodysplasia related changes; MLD, multilineage dysplasia.

Table 3.

Comparison of OS, EFS, CR and death rate between MLD and other MRC

	Median (days)		CR	Death
	OS	EFS	CR	Death
MLD	351.0	242.0	37.7%	81.1%
(P value compared with other MRC)	P=0.342	P=0.154	P=0.124	P=0.238
Other MRC	212.0	162.0	53.7%	70.7%

Abbreviations: OS, overall survival; EFS, event free survival; CR, complete remission; MLD, multilineage dysplasia; MRC, myelodysplasia related changes.

Table 4.

Comparison of OS, EFS, CR and death rate between AML MRC and other AML

	Median (days)		CR	Death
	OS	EFS	CR	Death
Other AML (N=263) (P value compared with AML MRC)	994.0	579.0	71.1%	47.9%
	P<0.001	P<0.001	P<0.001	P<0.001
Other AML, good prognostic cytogenetics excluded (N=156) (P value compared with AML MRC)	556.0	373.0	65.4%	64.7%
	P=0.004	P=0.007	P=0.001	P=0.049
AML MRC (N=94)	297.0	229.0	44.7%	76.6%

Abbreviations: OS, overall survival; EFS, event free survival; CR, complete remission; MRC, myelodysplasia related changes.

Table 5.

Comparison of OS, EFS, CR and death rate between AML MLD and other AML

Type and description	Median (days)		OS	EFS
Type and description	CR	Death	OS	EFS
Other AML (N=304)	858.0	463.0	68.8%	51.0%
(P value compared with MLD)	P=0.002	P=0.011	P<0.001	P<0.001
Other AML, good prognostic cytogenetics excluded (N=197)	517.0	309.0	62.9%	66.0%
(P value compared with MLD)	P=0.125	P=0.274	P=0.001	P=0.034
AML NOS (N=148)	561.0	374.0	64.9%	64.9%
(P value compared with MLD)	P=0.036	P=0.076	P=0.001	P=0.028
MLD (N=53)	351.0	242.0	37.7%	81.1%

Abbreviations: OS, overall survival; EFS, event free survival; CR, complete remission; MLD, multilineage dysplasia.

Table 6.

Factors associated with OS, EFS, CR and relapse rate

Variables	OS			EFS			CR			Relapse
Variables	HR (95% CI)	P value	Adverse effect	HR (95% CI)	P value	Adverse effect	HR (95% CI)	P value	Adverse effect	HR (95% CI)	P value	Adverse effect
Age (≤60 vs. >60)	2.49	0.001	>60	2.80	<0.001	>60	0.20	0.004	>60	2.02	0.192	-
	(1.42-4.36)			(1.67-4.70)			(0.06-0.61)			(0.70-5.82)
WBC (≤20,000/μL vs. >20,000/μL)	1.31	0.308	-	1.10	0.706	-	0.61	0.336	-	0.38	0.072	≤20,000
	(0.78-2.20)			(0.67-1.80)			(0.22-1.67)			(0.13-1.10)		/μL
Blasts (≤60% vs. >60%)	0.74	0.213	-	0.58	0.019	≤60%	1.17	0.748	-	0.57	0.228	-
	(0.46-1.20)			(0.37-0.91)			(0.45-3.01)			(0.23-1.42)
MRC (Yes vs. No)	1.95	0.023	Yes	1.86	0.025	Yes	0.28	0.030	Yes	1.47	0.475	-
	(1.10-3.46)			(1.08-3.20)			(0.09-0.88)			(0.51-4.23)
MLD (Yes vs. No)	1.87	<0.001	Yes	1.69	0.002	Yes	0.25	<0.001	Yes	0.73	0.384	-
	(1.33-2.64)			(1.20-2.38)			(0.13-0.46)			(0.37-1.47)

Abbreviations: OS, overall survival; EFS, event free survival; CR, complete remission; HR, hazard ratio; WBC, white blood cells; MRC, myelodysplasia related changes; MLD, multilineage dysplasia.

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