TABLE 1.

Clinical and laboratory characteristics of 10 EBV‐triggered late‐onset primary HLH cases

	Case 1	Case 2	Case 3	Case 4	Case 5	Case 6	Case 7	Case 8	Case 9	Case 10	Median (range)
Gender	Female	Female	Female	Female	Female	Male	Male	Female	Male	Female	–
Age at onset (y), HLH	14	18	25	45	12	25	21	18	32	13	22.3 (12–45)
Fever (℃)	40.0	41.0	39.2	39.8	39.0	39.5	39.6	39.2	39.4	38.6	39.5 (39–41)
Neutrophils, 10⁹/L	0.3	0.2	0.8	0.1	0.6	0.1	0.7	0.9	0.6	0.8	0.5 (0.1–0.9)
Hemoglobin, g/L	64.0	88.0	88	122.0	96.0	98.0	99.0	86.0	64.0	76.0	88.1 (64–122)
Platelets, 10⁹/L	35.0	14.0	32	29.0	90.0	25.0	44.0	64.0	9.0	218.0	56.0 (14–90)
ALT index ^*	6.8	11.5	5.1	1.2	1.6	2.2	2.3	5.5	3.2	10.0	5.0 (1.2–11.5)
AST index ^**	28.0	24.0	6.2	4.2	1.5	2.2	1.2	1.8	0.9	9.3	7.7 (0.9–28)
LDH index ^#	21.6	16.7	6.0	8.3	0.7	6.8	1.4	1.3	2.1	4.0	6.9 (0.7–21.6)
Triglycerides, mM	4.5	3.6	4.1	13.4	2.7	2.3	2.3	3.5	2.6	2.6	4.2 (2.3–13.4)
Fibrinogen, g/L	0.8	0.5	1.0	0.6	1.5	1.2	1.4	0.9	0.6	1.4	1.0 (0.5–1.5)
Ferritin, μg/L	8000	50000	3481	8000	1500	8000	5052	1228	18403	923	8787 (1228–50000)
sCD25 index ^&	6.1	6.6	2.1	7.6	4.8	2.9	8.3	3.6	5.2	4.8	5.2 (2.1–8.
Lymphadenopathy	Yes	No	Yes	Yes	No	Yes	Yes	Yes	Yes	Yes	–
Splenomegaly (thickness, cm)	5.9	4.2	5.1	6.8	2.8	3	6.7	4.3	6.4	6.5	5.2 (2.8–6.8)
Hemophagocytosis	BM	No	BM, spleen	No	BM	BM	BM	No	BM	No	–
NK‐cell activity (%)	5.6 $\pm$ 0.6	8.9 $\pm$ 0.7	1.2 $\pm$ 0.3	7.5 $\pm$ 1.3	4.0 $\pm$ 0.5	16.8 $\pm$ 2.6	16.0 $\pm$ 3.1	4.6 $\pm$ 0.8	15.8 $\pm$ 3.2	4.3 $\pm$ 0.7	–
Perforin (%)	61.2 $\pm$ 4.7	50.8 $\pm$ 3.8	0.9 $\pm$ 0.2	27.2 $\pm$ 2.6	31.2 $\pm$ 2.4	76.6 $\pm$ 5.4	11.9 $\pm$ 1.2	52.3 $\pm$ 5.0	17.6 $\pm$ 1.8	26.6 $\pm$ 3.8	–
Degranulation of resting NK cells (%)	1.1 $\pm$ 0.2	6.7 $\pm$ 0.8	12.6 $\pm$ 1.8	2.3 $\pm$ 0.6	13.2 $\pm$ 1.6	1.3 $\pm$ 0.3	14.5 $\pm$ 3.0	27.7 $\pm$ 4.7	17.2 $\pm$ 1.7	0.4 $\pm$ 0.1	–
Degranulation of IL‐2 stimulated NK cells (%)	1.4 $\pm$ 0.1	42.8 $\pm$ 2.7	42.1 $\pm$ 3.6	3.1 $\pm$ 0.2	67.9 $\pm$ 5.7	2.8 $\pm$ 0.3	72.4 $\pm$ 6.6	49.3 $\pm$ 3.9	56.9 $\pm$ 4.6	73.1 $\pm$ 6.3	–
Sorting‐PCR	NK	NK	NK	NK	NK and T	NK	NK	NK	NK	NK	–
Sorting‐FISH	ND	ND	ND	ND	ND	ND	ND	NK	ND	NK	–
Treatment	HLH‐2004	HLH‐2004	HLH‐2004	HLH‐2004; MDL	HLH‐2004; BR	HLH‐2004; P‐Gemox; Allo‐HSCT	RCHOP; HLH‐2004; P‐Gemox	HLH‐2004; Mp; Allo‐HSCT	HLH‐2004	HLH‐2004 Allo‐HSCT	–
Disease reactivation	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	–
Outcome	Death	Death	Death	Death	Death	Alive	Death	Alive	Death	Alive	–
Cause of death	ICH	PD	PD	PD	Respiratory failure	–	PD	–	PD	–	–
Survival time (days)	35	27	112	95	199	906	180	907	66	575	–

Abbreviations: Allo‐HSCT, allogeneic hematopoietic stem cell transplantation; BM, bone marrow; BR, brentuximab vedotin and rituximab; EBV, Epstein‐Barr virus; HLH, hemophagocytic lymphohistiocytosis; MDL, methotrexate, dexamethasone, and L‐asparaginase; ICH, intracerebral hemorrhage; Mp, methylprednisolone; ND, not done; PD, progressive disease; P‐Gemox, pegaspargase, gemcitabine, and oxaliplatin; RCHOP, rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone; sCD25: soluble CD25; sorting‐FISH: immunobead sorting followed by fluorescence in situ hybridization; sorting‐PCR, immunobead sorting followed by quantitative PCR; y: year.

ALT index, patient's ALT/upper normal limit of ALT;

^**

AST index, patient's AST/upper normal limit of AST;

^{^#}

LDH, patient's LDH/upper normal limit of LDH;

^{^&}

sCD25 index, patient's sCD25/upper normal limit of sCD25.