Clinical Significance of Co-expression of Aberrant Antigens in Acute Leukemia

Seong Hyun Jeong; Hyun Woo Lee; Seok Yun Kang; Mi Sun Ahn; Yoon Ho Hwang; Jin Hyuk Choi; Hugh Chul Kim; Sung Ran Cho; Joon Seong Park

doi:10.5045/kjh.2009.44.2.67

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Jeong, Lee, Kang, Ahn, Hwang, Choi, Kim, Cho, and Park: Clinical Significance of Co-expression of Aberrant Antigens in Acute Leukemia

Original Article

Korean J Hematol 2009;44(2):67-73.

Published online: 20 June 2009

DOI: https://doi.org/10.5045/kjh.2009.44.2.67

Clinical Significance of Co-expression of Aberrant Antigens in Acute Leukemia

Seong Hyun Jeong, M.D., Hyun Woo Lee, M.D., Seok Yun Kang, M.D., Mi Sun Ahn, M.D., Yoon Ho Hwang, M.D., Jin Hyuk Choi, M.D., Ph.D., Hugh Chul Kim, M.D., Sung Ran Cho, M.D.¹, Joon Seong Park, M.D.

Departments of Hematology-Oncology, Ajou University School of Medicine, Suwon, Korea

¹Department of Laboratory Medicine, Ajou University School of Medicine, Suwon, Korea

Correspondence to：Joon Seong Park, M.D., Ph.D. Department of Hematology-Oncology, Ajou University School of Medicine San 5, Wonchon-dong, Youngtong-gu, Suwon 443-721, Korea Tel: ＋82-31-219-5989, Fax: ＋82-31-210-5983 E-mail: jspark65@ajou.ac.kr

Received 22 December 2008 Revised 21 April 2009 Accepted 25 April 2009

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

Acute leukemias co-expressing myeloid and lymphoid antigens but does not meet the criteria for biphenotypic acute leukemia (BAL) is common, however its clinical significance is not fully defined.

Methods

In this study, clinical features of 68 co-expressing (myeloid and lymphoid) acute leukemias diagnosed between January 2000 and December 2006 were studied and compared with those of a control group of patients (pure AML or ALL).

Results

Age, gender, initial Lactate dehydrogenase (LDH) level and cytogenetics were not different between the co-expressing group and the control group. But, the initial bone marrow blast percent was significantly higher in the co-expressing group (70% vs. 54.5%, P=0.003). Fifty five percent (16/29) of ALL and 30% (52/172) of AML patients showed myeloid and lymphoid markers concomitantly. The lymphoid antigen positive AML (Ly+ AML) patients showed significantly shorter survival rates than pure AML patients (4 year survival rate, 17.6% vs. 45.6%, P=0.002). However hematopoietic stem cell transplantation (HST) abrogated the difference (4 year survival rate, 54.7% vs. 50.6%, P=0.894). In ALL patients, survival rate was not affected by myeloid antigen co-expression (4 year survival rate 26.1% vs. 20%, P=0.954).

Conclusion

Co-expression of lymphoid markers in AML should be regarded as a poor prognostic factor and more aggressive treatment such as HST should be considered.

Keywords: Acute leukemia, Immunophenotyping, Co-expression, Prognosis

References

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Fig. 1.

Survival of patients with co-expression against matched control. (A) Overall survival of AML patients, (B) Survival of AML patients without HST. (C) Survival of AML patients with HST. (D) Overall survival of ALL patients.

Table 1.

Panel of antibodies used

B-lymphoid	T-lympho	id Myeloid	Non-lineage Ag
CD10	CD2	CD13	CD34
CD19	CD3	CD14	HLA-DR
CD20	CD5	CD33
CD22	CD7	anti-MPO∗
CD79a	Tdt^†

Abbreviations: CD, cluster of differentiation; HLA, human leukocyte antigen; anti-MPO, anti-myeloperoxidase; Tdt, terminal deoxytransferase ∗anti-MPO was tested only when the leukemic cell looked like myeloid lineage,

^† Tdt was tested only when the leukemic cell looked like lymphoid lineage.

Table 2.

Clinical characteristics of the patients

	Historical control group	Co-expression group	P-value
Number	133 (120 AML, 13 ALL)	68 (52 Ly+ AML, 16 My+ ALL)
Median Age	44 (16∼83)	43 (20∼80)	.895
Sex	1：0.77 (75/58)	1：0.7 (40/28)	.528
LDH	516IU/ml	619IU/mL	.380
Chromosomal abnormality	52/133 (39%)	27/68 (40%)	.897
Good	12 (9%)	10 (15%)
Intermediate	81 (61%)	39 (57%)
Poor	40 (30%)	17 (25%)
Blast % in BM	54.5%	70%	.003

Abbreviations: LDH, lactate dehydrogenase; BM, bone marrow.

Table 3.

Co-expression profiles of acute leukemia

AML		ALL
Incidence of markers in AML	Ly+ AML in each FAB subtype	Incidence of markers in ALL	L My+ ALL in each FAB subtype
CD19 19 (11%)	AML M0 4/9 (44%)	CD13 12 (41%)	ALL L1 5/10 (50%)
CD7 17 (10%)	AML M1 10/26 (38%)	CD33 10 (34%)	ALL L2 10/16 (63%)
CD22 14 (8%)	AML M2 21/45 (47%)	CD14 1 (3%)	ALL L3 1/3 (33%)
CD5 14 (8%)	AML M3 3/35 (9%)
CD10 2 (1%)	AML M4 10/37 (27%)
	AML M5 3/11 (27%)
	AML M6 1/7 (14%)
	AML M7 0/2 (0%)

Abbreviations: Ly+ AML, lymphoid antigen positive AML; My+ ALL, myeloid antigen positive ALL; CD, cluster of differentiation.

Table 4.

Details of treatment in AML

	Ly? AML	Ly+ AML	P-value
Remission rate	96/120 (80%)	42/52 (81%)	.908
HST	46/120 (38%)	17/52 (33%)	.484
Auto-PBSCT	2 (4%)	2 (12%)
Allo-BMT	26 (57%)	9 (53%)
Allo-PBSCT	18 (39%)	6 (35%)
Cause of death	58	31
Disease progression	37 (64%)	19 (61%)
Infection	17 (30%)	9 (29%)
TRM	4 (7%)	3 (10%)

Abbreviations: Ly? AML, lymphoid antigen positive AML; Ly+ AML, lymphoid antigen negative AML; HST, hematopoietic stem cell transplantation; Auto-PBSCT, autologous peripheral blood stem cell transplantation; Allo-BMT, allogeneic bone marrow transplantation; Allo-PBSCT, allogeneic peripheral blood stem cell transplantation; TRM, treatment related mortality.

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