Pretransplant T-cell immune imbalance predicts slow engraftment after autologous hematopoietic stem cell transplantation in lymphoma

Table 1 Baseline clinical and laboratory characteristics of patients stratified by early vs slow engraftment group after autologous hematopoietic stem cell transplantation, n (%)

Variable	Early engraftment group	Slow engraftment group	P value
Baseline characteristics
Age (years), median (IQR, Q1-Q3)	50 (38-56)	55 (47.5-61.5)	0.0011,a
Sex			0.3922
Male	43 (62.3)	54 (55.7)
Female	26 (37.7)	43 (44.3)
BM involvement at diagnosis			0.7742
Yes	11 (16.4)	16 (18.2)
No	56 (83.6)	72 (81.8)
Ann Arbor stage			0.1332
IV	33 (55.9)	58 (70.7)
Non-IV	26 (44.1)	24 (29.3)
Risk stratification			0.3842
High risk	15 (30.0)	26 (37.7)
Non-high risk	35 (70.0)	43 (62.3)
LDH at diagnosis (U/L), median (IQR, Q1-Q3)	228 (175.5-393.3)	292 (204-546)	0.0391,a
β2-MG at diagnosis (mg/L), median (IQR, Q1-Q3)	2.58 (1.9-4.2)	3.215 (2.3-4.4725)	0.1141
HB at diagnosis (g/L), median (IQR, Q1-Q3)	129 (111.5-136)	119 (102-133.75)	0.0431,a
WBC at diagnosis (× 109/L), median (IQR, Q1-Q3)	6.29 (4.83-8.03)	6.24 (4.72-7.8875)	0.5971
PLT at diagnosis (× 109/L), median (IQR, Q1-Q3)	228 (172.5-293)	239.5 (155-307.75)	0.8311
Transplant-related indicators
CD34+ cells (× 106/kg), median (IQR, Q1-Q3)	5.27 (3.93-8.645)	3.59 (2.64-5.54)	< 0.0011,a
Mononuclear cells (× 108/kg), median (IQR, Q1-Q3)	5.15 (3.44-7.055)	5.01 (3.7-7.64)	0.7291
Stem cell storage time (days), median (IQR, Q1-Q3)	46 (33-70)	50 (30-72.5)	0.9261
Pretransplant indicators
Pretransplant remission status			0.1742
CR	47 (68.1)	56 (57.7)
NR	22 (31.9)	41 (42.3)
Change in BMI (kg/m2), median (IQR, Q1-Q3)	0 (-0.535 to 0.335)	-0.35 (-1.7525 to 0.065)	0.0251,a
Pretransplant nutritional score, median (IQR, Q1-Q3)	2 (2-2)	2 (2-2)	0.1351
Pretransplant albumin (g/L), mean ± SD	27.08 ± 5.38	26.10 ± 5.55	0.2573
Pretransplant prealbumin (mg/L), median (IQR, Q1-Q3)	236 (203-265.32)	236 (214-267)	0.661
Pretransplant globulin (g/L), median (IQR, Q1-Q3)	39.8 (37.6-44.2)	40.92 (37-44.2)	0.7321
Pretransplant LDH (U/L), median (IQR, Q1-Q3)	203.5 (182-269.25)	221 (181-282.5)	0.5241
Pretransplant β2-MG (mg/L), median (IQR, Q1-Q3)	2.465 (1.9-3)	2.715 (2.2125-3.3375)	0.0161,a
Pretransplant HB (g/L), mean ± SD	105.9 ± 18.7	102.5 ± 17.5	0.2323
Pretransplant WBC (× 109/L), median (IQR, Q1-Q3)	3.96 (2.9-5.795)	3.83 (2.855-5.9275)	0.8841
Pretransplant PLT (× 109/L), median (IQR, Q1-Q3)	199 (148-253)	183 (131-215.75)	0.0721

¹Mann-Whitney U test.

²χ² test.

³Student’s t-test.

^aP < 0.05.

All lymphocyte subsets and inflammatory factors were measured at pretransplant baseline. Pretransplant nutritional score was assessed using the Nutritional Risk Screening 2002 criteria. Change in body mass index (BMI) =BMI at pretransplantation - BMI at diagnosis. IQR: Interquartile range; BM: Bone marrow; LDH: Lactate dehydrogenase; β2-MG: Beta 2-microglobulin; HB: Hemoglobin; WBC: White blood cell; PLT: Platelet; CR: Complete remission; NR: Non-complete remission; BMI: Body mass index.

Table 2 Comparison of core immune and inflammatory indicators, peritransplant clinical events between early and slow engraftment groups in lymphoma patients undergoing autologous stem cell transplantation

Variable	Early engraftment group	Slow engraftment group	P value
CD8+ T cell (%), median (IQR, Q1-Q3)	41.68 (29.73-51.58)	47.47 (37.79-57.02)	0.0171,a
CD4+ T cell count (cells/μL), median (IQR, Q1-Q3)	315 (187-426.5)	234.37 (141.76-330.5)	0.0411,a
CD4/CD8 ratio, median (IQR, Q1-Q3)	0.95 (0.57-1.6)	0.79 (0.48-1.27)	0.0481,a
IL-2 (pg/mL), median (IQR, Q1-Q3)	0.74 (0.655-1.0275)	1.335 (0.8-1.75)	0.0031,a
IFN-γ (pg/mL), median (IQR, Q1-Q3)	1.275 (0.88-2.01)	2.715 (1.73-5.52)	0.0051,a
Days with fever during transplantation (days), median (IQR, Q1-Q3)	4 (2-8)	6 (3-11)	0.0061,a
Onset of neutropenia (days), median (IQR, Q1-Q3)	3 (2-4)	2 (1-4)	0.0331,a

¹Mann-Whitney U test.

^aP < 0.05.

All lymphocyte subsets and inflammatory factors were measured at pretransplant baseline. IQR: Interquartile range; IL-2: Interleukin-2; IFN-γ: Interferon-γ.

Table 3 Association between CD34+ count and hematopoietic engraftment time

	Total (n = 166)	< 3.5 × 106/kg (n = 57)	≥ 3.5 × 106/kg (n = 109)	P value
Neutrophil engraftment time (days), median (range)	10 (8-25)	11 (8-25)	10 (8-20)	0.0021,a
Platelet engraftment time (days), median (range)	12 (5-51)	12 (5-51)	11 (6-36)	0.0161,a

¹Mann-Whitney U test.

^aP < 0.05.

Table 4 Univariate and multivariate logistic regression analyses of risk factors for slow hematopoietic engraftment after autologous hematopoietic stem cell transplantation

Variable	Univariate analysis			Multivariate analysis
	OR	95%CI	P value	OR	95%CI	P value
Age (years)	1.044	1.016-1.073	0.002	1.044	1.009-1.081	0.015a
HB at diagnosis (g/L)	0.986	0.971-1.001	0.062	-	-	-
CD34+ cells (× 106/kg) (< 3.5 × 106/kg vs ≥ 3.5 × 106/kg)	3.128	1.537-6.366	0.002	2.633	1.119-6.196	0.027a
Change in BMI (kg/m2)	0.825	0.682-0.998	0.048	-	-	-
Pretransplant β2-MG (mg/L)	1.663	1.066-2.595	0.025	-	-	-
Pretransplant PLT (× 109/L)	0.997	0.993-1	0.066	-	-	-
CD8+ T cell (%)	1.027	1.007-1.048	0.008	1.039	1.010-1.070	0.009a
CD4+ T cell (%)	0.979	0.957-1.002	0.077	-	-	-
CD4/CD8 ratio	0.699	0.477-1.025	0.066	-	-	-
CD4+ T cell count (cells/μL)	0.999	0.997-1	0.136	0.997	0.995-1.000	0.038a
Days with fever during transplantation (days)	1.117	1.038-1.202	0.003	1.119	1.023-1.224	0.014a
Onset of neutropenia (days)	0.825	0.690-0.986	0.034	-	-	-

^aP < 0.05.

Change in body mass index (BMI) =BMI at pretransplantation - BMI at diagnosis. All lymphocyte subsets and inflammatory factors were measured at pretransplant baseline. Multivariate model inclusion criteria: Standard baseline covariates with univariate P < 0.1; for lymphocyte subset variables (core exposure of interest), univariate P < 0.2 was used for entry. OR: Odds ratio; CI: Confidence interval; HB: Hemoglobin; BMI: Body mass index; β2-MG: Beta 2-microglobulin; PLT: Platelet.