Lymphocyte recovery is an independent predictor of relapse in allogeneic hematopoietic cell transplantation recipients for acute leukemia

Table 1 Baseline characteristics of patients stratified by lymphocyte recovery n (%)

Variable	ALC > 0.3 (n = 24)	ALC ≤ 0.3 (n = 48)	P value
Patient age in years, median (range)	28 (16-57)	23 (14-63)	0.57
Recipient gender, male	13 (54)	28 (58)	0.74
Diagnosis			0.54
AML	13 (54)	22 (45)
ALL	11 (46)	26 (54)
ECOG	1 (0-2)	0 (0-3)	0.86
Cytogenetics (AML)			0.5
Favorable	3 (25)	2 (10)
Intermediate	7 (58)	15 (71)
High risk	2 (17)	4 (67)
Cytogenetics (ALL)			0.78
Standard	5 (56)	11 (50)
High risk	4 (44)	11 (50)
Female donor/male recipient	4 (17)	11 (23)	0.53
Related donor	21 (88)	42 (88)	1
Status at HCT			0.33
CR1	13 (54)	31 (66)
≥ CR2	11 (46)	16 (34)
ABO Matching			0.89
Match	16 (67)	31 (64)
Major/bidirectional	3 (12)	8 (17)
Minor	5 (21)	9 (19)
TBI containing regimen	8 (33)	30 (63)	0.019
Conditioning intensity			0.19
MAC	18 (75)	42 (88)
RIC	6 (25)	6 (12)

HCT: Hematopoietic stem cell transplant; AML: Acute myeloid leukemia; ALL: Acute lymphoblastic leukemia; ALC: Absolute lymphocyte count; ECOG: Eastern cooperative oncology group; TBI: Total body irradiation; CR: Complete remission; MAC: Myeloablative conditioning; RIC: Reduced intensity conditioning.

Table 2 Graft characteristics as predictors of lymphocyte recovery n (%)

Graft characteristic	ALC > 0.3 (n = 24)	ALC ≤ 0.3 (n = 48)	P value
CD 34 × 106/kg < 6	17 (71)	20 (42)	0.018
TNC > 7 × 107/kg	5 (21)	10 (21)	1
CD 3 > 24 × 107/kg	4 (19)	1 (2)	0.017
CD 34 < 6 × 106/kg, CD 3 > 24 × 107/kg	3 (100)	0 (0)	0.0088
MNC > 2.7 × 108/kg	20 (83)	33 (69)	0.17
ALC > 1.3 × 108/kg	23 (96)	35 (74)	0.015
AMC > 1.75 × 108/kg	3 (13)	14 (30)	0.093
ALC > 1.3 × 108/kg, CD34 < 6 × 108/kg	16 (67)	13 (27)	0.0012
LMR > 4	8 (33)	5 (11)	0.022

ALC: Absolute lymphocyte count; TNC: Total nuclear count; MNC: Mono-nuclear count; AMC: Absolute monocyte count; LMR: Lymphocyte-monocyte ratio.

Table 3 Transplant related outcomes

Variables	ALC > 0.3 (n = 24)	ALC ≤ 0.3 (n = 48)	P value
CIR (2-yr)	16.90%	46.90%	0.025
NRM (2-yr)	23.20%	14.20%	0.51
PFS (2-yr)	61.90%	40.10%	0.09
OS (2-yr)	70.10%	53.90%	0.12
Plt engraftment (median, d)	24 (21-37)	24 (7-42)	0.98
ANC engraftment (median, d)	17 (12-29)	17 (12-25)	0.76
aGVHD	5 (22)	15 (31)	0.4
cGVHD	16 (70)	13 (27)	0.0006

ALC: Absolute lymphocyte count; CIR: Cumulative incidence of relapse; NRM: Non-relapse mortality; PFS: Progression free survival; OS: Overall survival; Plt: Platelet; ANC: Absolute neutrophil count; aGVHD: Acute or chronic graft vs host disease; cGVHD: Chronic graft vs host disease.

Table 4 Univariable and multivariable risk factors influencing incidence of relapse

IR	Univariable HR (95%CI, P value)	Multivariable HR (95%CI, P value)
Age at HCT	0.97 (0.94-1.01, P = 0.1)	0.13 (0.0096-1.38, P = 0.093)
Single Marital status	2.59 (1.13-6.65, P = 0.023)	0.82 (0.21-3.27, P = 0.77)
AML vs ALL	0.82 (0.36-1.8, P = 0.62)
Female D vs Male R	2.15 (0.91-4.7, P = 0.079)	2.24 (0.88-5.31, P = 0.086)
Match vs Mismatch	1.9 (0.3-6.7, P = 0.42)
MRD vs Other	1.6 (0.47-10, P = 0.49)
D14 ALC > 0.3	0.31 (0.09-0.8, P = 0.014)	0.27 (0.05-0.94, P = 0.038)
MAC vs RIC	1.38 (0.46-3.4, P = 0.53)
CR1 vs other	0.52 (0.23-1.15, P = 0.1)	0.36 (0.15-0.87, P = 0.024)
aGVHD	0.54 (0.16-1.43, P = 0.23)
cGVHD	0.24 (0.079-0.59, P = 0.0013)	0.33 (0.1-0.92, P = 0.035)

ALC: Absolute lymphocyte count; HR: Hazard ratio; CR1: First complete remission; R: Recipient; D: Donor; AML: Acute myeloid leukemia; ALL: Acute lymphoblastic leukemia; cGVHD: Chronic graft vs host disease; MAC: Myeloablative conditioning; RIC: Reduced intensity conditioning; MRD: Matched related donor.

Table 5 Causes of mortality stratified by absolute lymphocyte count recovery

Variables	ALC > 0.3 (n = 8)	ALC ≤ 0.3 (n = 24)
Primary disease	3	18
Infection	1	N/A
Organ failure	N/A	1
aGVHD	1	2
cGVHD	3	3

ALC: Absolute lymphocyte count; aGVHD: Acute or chronic graft vs host disease; cGVHD: Chronic graft vs host disease; N/A: Not available.