Correlation Study on HLA-DR and CD117 (c-Kit) Expressions: Its Prognosis and Treatment Response in Acute Myeloid Leukemia Patients

Figures & data

Figure 1 (A) Illustrates forward scatter versus side scatter on blast area. (B) Illustrates CD45 versus side scatter on blast area. (C) Flow histogram showing HLA-DR positive HLA-DR on myeloblasts. (D) Flow histogram showing negative CD117 and negative HLA-DR on myeloblasts. (E) Flow histogram showing positive CD117 and positive HLA-DR on myeloblasts.

Table 1 Clinico-Pathological Characteristics of 100 Adult Acute Myeloid Leukemia Patients

Parameter	Finding
Age: Years*	40.5 ±14.3
	40.5 (18–70)
Gender: (n=100)
Males	48 (48%)
Females	52 (52%)
Hemoglobin: gm/dl*	7.9±1.8
	7.8 (3.1–12.3)
TLC: x10^9/L*	51.9 ±68.5
	26.1 (1–345)
Platelets: x10^9/L*	58 ±72.9
	36 (1–436)
Blast: %*
Peripheral blood	51.8 ±26.5
Bone marrow	62.6 ±20.3
Lymph node enlargement: No (%)	21/97 (21.6%)
Hepatomegaly: No (%)	42/97 (43.3%)
Splenomegaly: No (%)	36/97 (37.1%)
Morphology (FAB types):	n=100
M0	1
M1	22
M2	39
M3	8
M4	23
M5	5
M7	2
Cytogenetic analysis (n=60)	No (%)
Favorable cytogenetic:	17 (28.3%)
Intermediate cytogenetic:	21 (35%)
Poor cytogenetic:	22 (36.7%)
Unfavorable genetics: FLT3-ITD: No (%)	14/82 (17.1%)
CD34 expression: No (%)	52/97 (53.6%)
CD117 expression: No (%)	63/97 (64.9%)
HLA-DR expression: No (%)	75/97 (77.3%)
CD117. HLA-DR expressions (n=97)	No (%)
Double-positive	50 (51.5%)
Double-negative	9 (9.3%)
Single +ve	38 (39.2%)
Response at day 28 (n=93)	No (%)
CR**	47 (50.5%)
Delayed CR	10 (10.8%)
Early death	28 (30.1)
Resistant***	8 (8.6%)
Median survival time (months)***	4.11

Notes: *Mean ± SD, Median (range). **CR percentage was calculated who achieved complete response. ***Survival data were available for 93 patients.

Table 2 Cytogenetic Analysis Findings in 60 Adult Acute Myeloid Leukemia Patients

Cytogenetic Analysis	Frequency	Percent
t(15:17)	8	13.3
t(8:21)	7	11.7
t(8:21), tri 8	1	1.7
inv16	1	1.7
NK (normal karyotype)	19	31.7
tri3	1	1.7
tri8, mono22	1	1.7
mono15, 20, 22	1	1.7
mono16, 4q+	1	1.7
mono12, 21, tri19	1	1.7
mono5, 13, 17, 22	1	1.7
mono17, 21, inv1q	1	1.7
t(6:17),+17p	1	1.7
47, xy, tri19	1	1.7
t(9:22)	7	11.7
t(9:22), tri8	1	1.7
t(9:22), mono7	1	1.7
tri11	1	1.7
tri21	2	3.3
tri8, 13, 17, mono22	1	1.7
tri8, mono21	1	1.7
Tri2	1	1.7
Total	60	100.0

Table 3 Clinical and Hematological Findings of Acute Myeloid Leukemia Patients According to HLA-DR and CD117 Expression

Parameter	HLA-DR –ve (n=22)	HLA-DR +ve (n=75)	p-value	CD117 – ve (n=34)	CD117 +ve (n=63)	p-value
Age: Years*	42.9±14.7	39.2±13.8	NS	41.6±13.2	39.2 ±14.5	NS
Gender: Males: Female	12:10 (1.2:1)	35:40 (0.9–1)	NS	16:18 (0.9:1)	31:32 (0.96:1)	NS
Hemoglobin (gm/dl) *	7.2±1.4	8.1±1.9	0.04	7.9±1.8	7.9±1.8	NS
TLC: x 10^9/L *	35±54.6	56.7±72.1	0.08	63.3±86.6	45.5±56.9	NS
TLC >11 x10^9/L No (%)	10/22 (45.5%)	54/75 (72%)	0.02	23/34 (67.6%)	41/63 (65.1%)	NS
Platelets: x10^9/L *	30.1±32.4	66.1±79.3	0.012	66.1±63.2	53.6±77.7	0.02
Blasts: %*:						NS
Peripheral blood	54.2±22.6	50.8±27.8	NS	47.1±25.1	54±27.4
Bone marrow	67.4±21.1	61±20	NS	62.1±19.3	62.7±21
Lymph node enlargement, No (%)	5/22 (22.7%)	16/75 (21.3%)	NS	1/34 (2.9%)	20/63 (31.7%)	0.001
Hepatomegaly: No (%)	8/22 (36.4%)	34/75 (45.3%)	NS	13/34 (38.2%)	29/63 (46%)	NS
Splenomegaly No (%)	6/22 (27.3%)	30/75 (40%)	NS	13/34 (38.2%)	23/63 (36.5%)	NS
FAB subtypes:			<0.001	17/34 (50%)	43/63 (68.2%)	NS
M0, M1, M2	12/22 (54.6%)	48/75 (64%)
M3	7/22 (31.8%)	1/75 (1.3%)		3/34 (8.8%)	5/63 (8%)
M4, M5, M7	3/22 (13.6%)	23/75 (30.7%)		14/34 (41.2%)	15/63 (23.8%)
CD34 expression: No (%)	6/22 (27.3%)	46/75 (61.3%)	0.005	14/34 (41.2%)	38/63 (60.3%)	0.07
CD117 expression: No (%)	13/22 (59.1%)	50/75 (66.7%)	NS	—	—	—
HLA-DR expression: No (%)	—	—	—	25/34 (73.5%)	50/63 (79.4%)	NS
Cytogenetic analysis:			0.017	5/23 (21.8%)	12/36 (33.3%)	NS
Favorable cytogenetics	9/16 (56.2%)	8/43 (18.6%)
Intermediate cytogenetics	3/16 (18.8%)	18/43 (41.9%)		7/23 (30.4%)	14/36 (39%)
Poor cytogenetics	4/16 (25%)	17/43 (39.5%)		11/23 (47.8%)	10/36 (27.7%)
FLT3-ITD	5/17 (29.4%)	9/65 (13.8%)	NS	3/30 (10%)	11/52 (21.1%)	NS
Response to treatment at D28 (n= 93):	N= 21	N= 72	NS	N= 33	N= 60	0.088
CR (n=47) **	11 (52.7%)	36 (50%)		13 (39.4%)	34 (56.7%)
Delayed CR (n=10)	1 (4.6%)	9 (12.5%)		5 (15.2%)	5 (8.3%)
Resistant (n=8)	1 (4.6%)	7 (9.6%)		1 (3%)	7 (11.7%)
Early death (n=28)	8 (38.1%)	20 (27.7%)		14 (42.4%)	14 (23.3%)
Median survival time/DFS (months) (n= 57)	12.8	11.1	NS	***	12.1	NS
Median survival time/OS (months) (n= 93)	2.9	5.4	NS	4.4	5.1	NS

Notes: *Mean ±SD. **CR percentage was calculated who achieved a complete response. ***No median because more than half of the patients were free till the end of the study.

Figure 2 (A, C, E, G) Kaplan–Meier curves with log-rank statistics describe disease-free survival according to CD 117, HLA-DR, Combined CD 117 and HLA-DR, and Flt3 expression level. (B, D, F, H) Kaplan–Meier curves with log-rank statistics describe overall survival according to CD117, HLA-DR, Combined CD117 and HLA-DR, and Flt3 expression level.

Table 4 Clinical and Hematological Findings of Acute Myeloid Leukemia Patients According to Combined HLA-DR and CD117 Expression

Parameter	CD117/ HLA-DR
	Double +ve (n=50)	Double –ve (n=9)	Single +ve (n=38)
Age: Years*	38.2±14.2	42.4±14.3	41.9±13.8	NS
Gender: Male: Female	22:28 (0.8:1)	3:6 (1:2)	22:16 (1.4:1)	NS
Hemoglobin (gm/dl) *	8.1±1.9	7.1±1.3	7.9±1.8	NS
TLC: x 10^9/L *	54.2±54.7	18.2±23.2	68.3±87.2	NS
TLC >11 x10^9/L No (%)	35/50 (70%)	4/9 (44.4%)	25/38 (65.8%)	NS
Platelets: x10^9/L *	59.8±83.9	31.2±16.1	61.8±64.9	NS
Blasts: %*
Peripheral blood	53.7±28	53±18.4	48.4±26.8	NS
Bone marrow	62.3±20.2	71.8±15.5	60.6±21.2	NS
Lymph node enlargement, No (%)	15/50 (30%)	0/9 (0%)	6/38 (15.8%)	0.07
Hepatomegaly: No (%)	24/50 (36.4%)	3/9 (30%)	15/38 (39.5%)	NS
Splenomegaly No (%)	19/50 (38%)	2/9 (22.2%)	15/38 (39.5%)	NS
FAB subtypes:				0.037
M0, M1, M2	34/50 (68%)	3/9 (30%)	23/38 (64%)
M3	1/50 (2%)	3/9 (30%)	4/38 (1.3%)
M4, M5, M7	15/50 (30%)	3/9 (30%)	11/38 (30.7%)
CD34 expression: No (%)	34/50 (68%)	2/9 (22.2%)	16/38 (42.1%)	0.008
Cytogenetic analysis:				0.04
Favorable cytogenetics	6/27 (22.2%)	3/7 (42.9%)	8/25 (32%)
Intermediate cytogenetics	14/27 (51.9%)	3/7 (42.9%)	4/25 (16%)
Poor cytogenetics	7/27 (25.9%)	1/7 (14.2%)	13/25 (52%)
FLT3-ITD	7/42 (16.7%)	1/7 (14.3%)	6/33 (18.2%)	NS
Response to treatment at D28 (n=93):				NS
CR (n=47) **	27/48 (56.3%)	4/9 (44.4%)	16/36 (44.4%)
Delayed CR (n= 10)	4 /48 (8.3%)	0/9 (0%)	6/36 (16.7%)
Resistant (n= 28)	11/48 (22.9%)	5/9 (55.6%)	12/36 (33.3%)
Early death (n= 8)	6 /48 (12.5%)	0/9 (0%)	2/36 (5.6%)
Median survival time/DFS (months) (n= 57)	11.1	***	12.8	NS
Median survival time/OS (months) (n= 93)	5.1	1.2	5.4	NS

Notes: *Mean ± SD. **CR percentage was calculated who achieved a complete response. ***No median because more than half of the patients were free till the end of the study.

Table 5 Disease-Free Survival and Overall Survival and Its Relation to Prognostic Factors in AML Patients

	Disease-Free Survival					Overall Survival
	No	No of Events	DFS Rate (%) at 9 Months	Median Survival (Months)	p-value	No	No of Events	OS Rate (%) at 6 Months	Median Survival (Months)	p-value
AML	57	29	91.1	12.1		93	61	93.5	5.1
CD117
–ve	18	8	55	12.1	NS	33	20	87.9	4.4	NS
+ve	39	21	86.8	12.1		60	41	90	5.1
HLA-DR
-ve	12	5	65.6	12.8	NS	21	14	71.4	2.9	NS
+ve	45	24	81.8	11.1		72	47	93.1	4.5
CD117/HLA-DR
Double +ve	31	17	73.3	11.1	NS	50	33	87.5	5.1	NS
Double -ve	4	1	75	*		9	6	33.3	1.2
Single +ve	22	11	63.6	12.8		38	22	91.7	5.4
FAB subtypes:
M0, M1, M2	35	22	76.5	7.6	–	56	39	91.1	5.1	NS
M3	4	1	75	*		8	5	37.5	1.2
M4, M5, M7	18	6	66.7	*		29	17	79.3	5.4
Sex
Males	29	16	69	12.1	NS	44	29	90.9	6.9	NS
Female	28	13	70.4	23.9		49	32	87.8	3.6
Age
≤ 40 years	36	16	75	23.9	0.02	48	27	89.6	13.8	0.002
> 40 years	21	13	60	5.3		45	34	86.7	1.3
TLC
≤11 x10^9/L	22	11	63.6	12.8	NS	31	17	80.5	14.5	NS
>11 x10^9/L	35	18	76.5	8.8		62	44	90.3	2.7
PB blast: 50%
< 50%	28	15	67.9	11.1	NS	40	25	85	7.1	NS
≥ 50	29	14	71.4	12.8		53	36	88.7	2.5
BM blast: 50%
< 50%	17	9	52.9	11.1	NS	23	15	73.9	8	NS
≥ 50	40	20	79.5	12.8		70	46	91.4	2.9
Cytogenetic analysis:
Favorable cytogenetics	12	7	48.6	11.1	NS	17	12	64.7	8.4	NS
Intermediate cytogenetics	13	4	69.2	*		20	11	70	6.9
Poor cytogenetics	9	6	33.3	5.3		18	14	66.7	1.02
Flt3
Wild	49	24	81.6	12.8	NS	66	37	90.9	9.3	0.007
Mutant (ITD)	4	3	40	8.8		14	12	57.1	1.2
Bone marrow transplant
No	48	29	83	7.5	0.003	84	61	92.9	3.4	0.001
Yes	9	0	0	0		9	0	0	0

Note: *No median because more than half of the patients were free till the end of the study.