Table 1 -.

Studies published to date assessing the association of post-transplantation absolute lymphocyte counts (ALC) with clinical outcomes

Study (year)	Patient characteristics	ALC timepoint and cutoffs assessed and rationale for their selection	OS	RFS	NRM	RI	aGVHD	cGVHD
Rigoni L, 201515	100 chemo-responsive AML/ALL/MDS pts. All sources and donors. 78% MA, 22% RIC	Timepoints and cutoff arbitrarily chosen	OS longer in high ALC group. HR:		HR:
		300@d21 (30%)	1.3 (0.7–2.6)		1.2(0.6–2.6)	25% vs. 26% (NS)	76% vs. 52% (NS)	33% vs. 36% (NS)
		300@d30 (18%)	2.2 (1.0–4.7)		2.0 (0.9–4.4)	12% vs. 29% (NS)	94% vs. 50% (0.003)	46% vs. 34% (NS)
Kim HT, 201513	1109 pts. All diseases. UCB and haplo excluded. 48% MA, 52% RIC	Timepoints arbitrarily, cutoff b/o RFS curves	At 5 yr:	At 5 yr:	At 5 yr:	pts with <200 at any time point (14% of all pts) vs. >200 at m1, m2 and m3: 40% vs. 43% (NS)
		200@m1 (8%)	30% vs. 45% (<0.001)	19% vs. 38% (<0.001)	33% vs. 20% (0.002)
		200@m2 (6%)	28% vs. 49% (<0.001)	25% vs. 41% (<0.001)	44% vs. 19% (<0.001)
		200@m3 (6%)	27% vs. 53% (<0.001)	22% vs. 45% (<0.001)	41% vs. 18% (<0.001)
Yamamo to, 201416	206 AML/ALL/MDS pts. MA and RIC. All sources and donors	Timepoint d100 selected to exclude aGVHD effect. Cutoff b/o OS curves	OS longer in high ALC group. HR:		NRM lower in high ALC group. HR:
		500@d100 (18%)	2.4 (1.3–4.5)		2.8 (1.1–6.8)	1.4 (0.7–3.0)
Michelis FV, 201417	191 AML pts in CR. MRD or MUD. PB only. MA and RIC	Cutoff arbitrarily chosen. Timepoint b/o the median # of days to achieve ALC500				RI lower in high ALC group
		500@d28 (42%)	NS in MVA		NS in MVA	0.49 (0.26–0.92)
Han DK, 201318	69 children with heme malignancies. 64 MA, 5 RIC. All sources and donors	Cutoff b/o prelim analyses between ALC200, 300, 400, 500	At 5 yr:		At 5 yr	At 5 yr:	GII-IV incidence:	Extensive
		500@d21 (41%)	62% vs. 67% (NS)		19% vs. 16% (NS)	20% vs. 22% (NS)		14% vs. 15% (NS)
		500@d30 (28%)	53% vs. 71% (0.043) (NS on MVA)		34% vs. 11% (0.019	20% vs. 22% (NS)	29% vs. 17% (NS)	11% vs. 16% (NS)
DeCook LJ, 201219	118 pts with heme malignancies. RIC with Flu/Mel. PB and BM. All donors	Rationale not provided	UVar OS analyses: On MVar only d100 was sig (0.049)
		300@d15 (57%)	0.25
		300@d30 (6%)	<0.001
		300@d60 (11%)	<0.001
		300@d100 (18%)	<0.001
Le Blanc K, 200920	102 pts AML-CML-MDS only, MA only, MUD only, PB and BM	MVarA performed with ALC on day 30 as a continuous variable. d30 chosen b/o previous studies	NS on MVarA	sig increases with ALC (0.04)	sig decreases with ALC (<0.05)
Afzal S, 200921	71 children with AML in CR. All sources.	Rationale not provided			At 3 yr:	At 3 yr:	G III-IV:	Extensive:
		300@d21			14% vs. 27% (NS)	25% vs. 20% (NS)	16% vs. 12% (NS)	18% vs. 13% (NS)
		300@d30			21% vs. 13% (NS)	21% vs. 26% (NS)	18% vs. 16% (NS)	21% vs. 11% (NS)
Ishaqi MK, 200822	132 children with ALL in CR. All sources. MA only	Rationale not provided		At 3 yr:	At 3 yr:	At 3 yr:	G III-IV:	Extensive:
		300@d21		42% vs. 66% (0.02)	17% vs. 19% (NS)	40% vs. 10% (0.002)	32%−24% (NS)	13% vs. 12% (NS)
		300@d30		30% vs. 57% (<0.001)	25% vs. 14% (NS)	46% vs. 26% (0.01)	31% vs. 29%	19% vs. 9% (NS)
Savani BN, 200723	160 pts with leukemia after TCD from MRD with MA. BM and PB grafts	d30 chosen as a marker for NK cells.Cutoff b/o median ALC on d30	OS longer in high ALC group		NRM lower in high ALC group	Worsening effect of low ALC seen only in AML/MDS but not in ALL pts	Low ALC a/w more aGVHD.G II-IV:	High ALC a/w more cGVHD
		450@d30	2.7 (1.03–5.1)		3.6 (1.2–10.6)	3(1.5–6)	1.8 (1.1–2.9)	0.55 (0.34–0.87)
Kim DH, 200414	82 pts with heme malignancies. MA and RIC. BM and PB grafts. All donors	d21 chosen because it was an early timemark. Rationale for ALC cutoff not provided	OS longer in high ALC group	RFS longer in high ALC group	At 1 yr:	RI lower in high ALC group
		350@d21	2.7 (1.2–6.0)	2.8 (1.4–5.8)	52% vs. 31% (NS)	2.5 (1.1–6.2)
Kumar S, 200324	43 pts with ALL; MA only; BM only	Assessed measures: ALC@d21 => 150, 175, 200, 225 ALC@d30 => 150, 175, 200, 225		RFS longer in high ALC group		RI lower in high ALC group
		175@d21		p = 0.0028		4.5 (1.2–16.6)	NS	NS
Chakrabarti S, 200325	29 pts with heme malignancies. TCD BM or PB followed by TCAB. UCB and haplo excluded	Timepoint chosen arbitrarily. Cutoff b/o median ALC on d30	OS longer in high ALC group
		350@d30	18.5 (1.3–256)		NS
Kumar S, 200126	87 AML pts. BM only. Syngeneics and haplos excluded	Assessed measures: ALC@d21: 100, 150, 200 ALC@d30: 125, 150, 175, 200, 225	OS longer in high ALC group	RFS longer in high ALC group		RI lower in high ALC group
		150@d30 with highest sig in RI	0.0047 UVar	0.0079 UVar		8.2 (2.2–30.1)
Powles R, 199827	201 AML pts. BM only. MA only. MRD only	d27,28,29,30 timepoints and ALC 100, 200, 300 cutoffs assessed	At 1 yr:
		200@d29	25% vs. 65% (0.003)			2.9 (0.9–9.1)

^*:Where percentages are given for OS, RFS, NRM, RI, and GVHD incidences, the first and second percentages indicate the survival/incidence in low and high absolute lymphocyte count groups, respectively

aGVHD: acute graft-versus-host disease, ALC: Absolute lymphocyte count, ALL: Acute lymphoid leukemia, AML: Acute myeloid leukemia, ATG: Anti-thymocyte globulin, BM: Bone marrow, b/o: based on, cGVHD: chronic graft-versus-host disease, CR: Complete remission, d: day, haplo: Haploidentical donor, HR: Hazard ratio, m: month, MA: Myeloablative, MDS: Myelodysplastic syndrome, MRD: Matched-related donor, MUD: Matched unrelated donor, NRM: Non-relapse mortality, NS: Not significant, OS: Overall survival PB: Peripheral blood, pts: patients, RFS: Relapse-free survival, RI: Relapse incidence, RIC: Reduced intensity conditioning, sig: significant, TBI: Total body irradiation, TCAB: T cell add-back, TCD: T cell depleted, UCB: Umbilical cord blood, UV: Univariate, yr: year