Protective Effects of Cytomegalovirus DNA Copies ≧1000/mL for AML Patients in Complete Remission After Single Cord Blood Transplantation

Figures & data

Table 1 Patients’ Characteristics for the Groups According to CMV DNA Load

Characteristic	CR+NR		P	CR		P
	High DNA Load	Low DNA Load		High DNA Load	Low DNA Load
	No. (%)	No. (%)		No. (%)	No. (%)
Number of patients	130 (52)	119 (48)	_	107 (54)	92 (46)	–
Median age, years (range)	13 (0–55)	14 (1–55)	0.259	13 (0–54)	14 (1–55)	0.196
Median weight, kg (range)	40 (10–82)	45 (9–95)	0.275	40 (10–82)	45 (9–95)	0.159
Gender			0.913			0.791
Male	73 (56)	66 (55)		59 (55)	49 (53)
Female	57 (44)	53 (45)		48 (45)	43 (37)
ABO compatibility			0.037			0.072
Match	48 (37)	50 (42)		40 (37)	43 (47)
Major mismatch	31 (24)	30 (25)		22 (21)	20 (21)
Minor mismatch	45 (34)	25 (21)		39 (36)	19 (21)
Major and minor mismatch	6 (5)	14 (12)		6 (6)	10 (11)
HLA compatibility (A, B, DR)			0.891			0.688
6/6	13 (10)	14 (12)		11 (10)	13 (14)
5/6	61 (47)	56 (47)		54 (51)	43 (47)
4/6 or 3/6	56 (43)	49 (41)		42 (39)	36 (39)
Disease stage			0.760			0.460
First remission	74 (57)	68 (57)		74 (69)	68 (74)
Second/third remission	33 (25)	24 (20)		33 (31)	24 (26)
Non-remission	23 (18)	27 (23)		—	—
Risk stratification			0.759			0.962
Poor	80 (62)	85 (71)		62 (58)	53 (58)
Intermediate	39 (38)	45 (29)		45 (42)	39 (42)
TNC (×10^Citation7/kg)	4.0 (1.0–13.1)	3.6 (0.4–11.0)	0.139	4.0 (1.0–13.1)	3.6 (0.4–11.0)	0.067
CD34 (×10^5/kg)	2.1 (0.5–10.6)	1.9 (0.2–13.8)	0.318	2.1 (0.5–10.6)	1.9 (0.2–13.8)	0.108
Conditioning regimen			0.002			0.002
BU-based	91 (70)	106 (89)		75 (70)	81 (88)
TBI-based	39 (30)	13 (11)		32 (30)	11 (12)
PES			<0.001			<0.001
With	114 (88)	79 (66)		95 (89)	59 (64)
Without	16 (12)	40 (34)		12 (11)	33 (36)
aGVHD			0.027			0.054
0 –Ⅰ	73 (56)	83 (70)		64 (60)	67 (73)
Ⅱ–Ⅳ	57 (44)	36 (30)		43 (40)	25 (27)
cGVHD			0.116			0.160
With	26 (20)	15 (13)		22 (21)	12 (13)
Without	104 (80)	104 (87)		85 (79)	80 (87)
CMV-IgG			0.001			0.036
Positive	93 (72)	104 (87)		78 (73)	79 (86)
Negative	2 (1)	3 (3)		2 (2)	2 (2)
None	35 (27)	12 (10)		27 (25)	11 (12)

Table 2 Univariate Analysis of 3-Year Outcomes for the Groups According to CMV DNA Load

Outcome	CR+NR		P	CR		P
	High DNA Load	Low DNA Load		High DNA Load	Low DNA Load
	% (95% CI)	% (95% CI)		% (95% CI)	% (95% CI)
Relapse	7.9 (4.0–13.5)	16.7 (9.2–26.0)	0.102	3.9 (1.3–9.0)	14.6 (7.8–23.4)	0.012
NRM	20.9 (14.4–28.4)	19.0 (12.4–26.8)	0.639	18.0 (11.3–25.9)	17.0 (9.9–25.7)	0.777
OS	71.8 (63.1–78.8)	68.8 (56.8–78.1)	0.858	79.0 (69.9–85.7)	74.6 (61.7–83.6)	0.781
DFS	71.2 (62.5–78.2)	65.2 (54.1–74.2)	0.664	78.2 (69.0–84.9)	69.6 (58.2–78.4)	0.277
GRFS	48.9 (40.0–57.2)	50.3 (39.4–60.3)	0.371	53.9 (43.9–62.8)	58.3 (47.0–68.0)	0.357
Grade Ⅱ–Ⅳ aGVHD	43.8 (35.2–52.2)	30.3 (20.2–38.7)	0.037	40.2 (30.8–49.3)	27.2 (18.5–36.6)	0.062
cGVHD	20.2 (13.7–27.6)	14.1 (8.1–21.8)	0.143	20.8 (13.6–29.1)	14.1 (7.6–22.5)	0.187

Table 3 Multivariate Analysis of 3-Year Outcomes in CR Patients

Characteristic	Hazard Ratio	95% CI	P
RELAPSE
Gender (male vs female)	4.39 vs 1	1.24–15.54	0.022
Risk stratification (intermediate vs poor)	0.33 vs 1	0.11–1.04	0.058
CMV DNA load (high vs low)	0.23 vs 1	0.07–0.73	0.012
Grade Ⅱ–Ⅳ aGVHD (without vs with)	0.99 vs 1	0.90–1.12	0.929
cGVHD (with vs without)	0.30 vs 1	0.04–2.33	0.250
NRM
Age (years), (≥17 vs <17)	1.21 vs 1	0.56–2.63	0.630
Risk stratification (intermediate vs poor)	0.61 vs 1	0.23–1.60	0.310
Disease stage (second/third vs first remission)	1.52 vs 1	0.63–3.65	0.360
Conditioning regimen (TBI vs BU)	2.45 vs 1	0.99–6.04	0.052
CMV DNA load (low vs high)	0.66 vs 1	0.31–1.38	0.270
PES (with vs without)	1.58 vs 1	0.51–4.96	0.430
Grade Ⅱ–Ⅳ aGVHD (with vs without)	6.79 vs 1	3.13–14.72	<0.001
DFS
Age (years), (≥17 vs <17)	1.38 vs 1	0.67–2.84	0.385
Gender (male vs female)	2.21 vs 1	1.15–3.87	0.016
Risk stratification (intermediate vs poor)	0.51 vs 1	0.24–1.06	0.073
Disease stage (second/third vs first remission)	1.51 vs 1	0.78–2.90	0.226
Conditioning regimen (TBI vs BU)	2.00 vs 1	0.90–4.43	0.087
CMV DNA load (high vs low)	0.51 vs 1	0.27–0.91	0.024
Grade Ⅱ–Ⅳ aGVHD (with vs without)	4.87 vs 1	2.70–8.79	<0.001
OS
Gender (male vs female)	1.94 vs 1	1.01–3.71	0.046
Risk stratification (intermediate vs poor)	0.36 vs 1	0.17–0.76	0.007
Conditioning regimen (TBI vs BU)	2.79 vs 1	1.43–5.43	0.003
CMV DNA load (high vs low)	0.60 vs 1	0.32–1.13	0.115
Grade Ⅱ–Ⅳ aGVHD (with vs without)	5.45 vs 1	2.85–10.42	<0.001
GRFS
CD34 (×10^5/kg), (≥2.0 vs <2.0)	1.40 vs 1	0.91–2.17	0.126
CMV DNA load (high vs low)	1.01 vs 1	0.65–1.60	0.934
PES (with vs without)	1.63 vs 1	0.89–2.97	0.111
aGVHD
Recipient weight (kg), (≥40 vs <40)	0.62 vs 1	0.32–1.22	0.170
TNC (×10^7/kg), (≥3.7 vs <3.7)	0.97 vs 1	0.48–1.96	0.920
CD34 (×10^5/kg), (≥2.0 vs <2.0)	1.20 vs 1	0.70–2.04	0.520
CMV DNA load (high vs low)	1.27 vs 1	0.74–2.17	0.390
PES (with vs without)	2.20 vs 1	0.96–4.94	0.058
cGVHD
Gender (male vs female)	0.52 vs 1	0.26–1.04	0.063
CMV DNA load (high vs low)	1.47 vs 1	0.72–3.00	0.290
Grade Ⅱ–Ⅳ aGVHD (with vs without)	2.45 vs 1	1.25–4.82	0.009

Figure 1 Cumulative incidence of relapse and NRM according to CMV DNA load in CR patients. (A) Relapse; (B) Non-relapse mortality.

Figure 2 Probability of survival according to CMV DNA load in CR patients. (A) Disease-free survival; (B) Overall survival; (C) GVHD-free, relapse-free survival.

Figure 3 Lymphocytes reconstitution according to CMV DNA load in CR patients. (A) Absolute number of T cells; (B) Absolute number of NK cells; Notes: All of the statistical graphs show median±interquartile range. *P ≦ 0.05.

Figure 4 T cell subsets reconstitution according to CMV DNA load in CR patients. (A) Absolute number of CD8⁺ T cells; (B) Absolute number of CD4⁺ T cells; (C) Absolute number of Treg cells.

Notes: All of the statistical graphs show median±interquartile range. *P ≦ 0.05.

Broers AEC, Holt R, Esser J, et al. Increased transplant-related morbidity and mortality in CMV-seropositive patients despite highly effective prevention of CMV disease after allogeneic T-cell–depleted stem cell transplantation. Blood. 2000;95(7):2240–2245. doi:10.1182/blood.V95.7.224010733491

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