Serum ferritin is a good indicator for predicting the efficacy of adult HLH induction therapy

Figures & data

Figure 1. HLH-2004 diagnostic criteria.

Figure 2. Diagram of enrolled patients.

Table 1. General information and laboratory indicators of the included patients.

	Remission	Non-remission	p
Median age (years)	36 (26–55)	44 (29–53)	.406
Race
(All Chinese)	53	49
Gender	53	49	.314
(Male/female)	25/28	28/21
Aetiology	53	49	.025
Infectious diseases	20/53	26/49
Malignancies	11/53	17/49
Autoimmune disorders	7/53	2/49
Primary HLH	3/53	3/53
No identified	12/53	12/53
Fever (all patients)	53	49
Splenomegaly	53	49	.363
(N/Y)	15/38	18/31
Haemophagocytosis	53	49	.254
(N/Y)	11/42	15/34
TG (mmol/L)	2.32 (1.6–3)	2.4 (1.8–3.6)	.606
FIB (g/L)	2.04 (1.4–3.8)	1.57 (1.08–2.36)	.074
NK % activity	15.13% (13%–16.56%)	14% (12.84%–17.78%)	.616
sCD25 (pg/ml)	13682 (4775–33881)	25982 (14414–39578)	.035
Admission ferritin (μg/L)	1608 (881–7256)	2256 (1156–12481)	.24
WBC (×10^9/L)	3.60 (1.94–6.75)	3.37 (1.26–5.28)	.095
NEUT (×10^9/L)	1.79 (1.11–4.67)	1.69 (0.72–3.33)	.134
HB (g/L)	85 (72.5–106.5)	84 (68–108)	.112
PLT (×10^9/L)	105 (62–222)	61 (22.5–98.5)	.003
ALT (U/L)	76 (27.5–154.5)	52 (38.5–106.3)	.684
AST (U/L)	57 (22–101)	73.5 (30.8–162)	.327
LDH (U/L)	428 (322.5–629.5)	418.5 (277.8–873.8)	.714
DBIL (µmol/L)	4.82 (2.54–9.28)	7.24 (3.78–21.65)	.034
HDL (mmol/L)	0.66 (0.47–1.1)	0.68 (0.35–1.06)	.342
LDL (mmol/L)	2.27 (1.71–2.91)	1.94 (1.34–2.89)	.198
ALB (g/L)	30.76 ± 5.7	29.23 ± 5.11	.49
Urea (mmol/L)	4.24 (3.18–6.65)	5.72 (4.38–6.74)	.03
ALP (U/L)	136 (81–271.5)	134.5 (87–446.5)	.522
UA (µmol/L)	220 ± 97	235 ± 85	.464
Ca2+ (mmol/L)	2.07 ± 0.169	2.02 ± 0.171	.323
Induction treatment (all received HLH-94 regimen)	53	49
Treatment response at eight weeks	53	49

TG: triglyceride; FIB: fibrinogen; WBC: white blood cell; NEUT: neutrophile granulocyte; HB: haemoglobin; PLT: platelets; ALT: alanine aminotransferase; AST: aspartate aminotransferase; LDH: lactate dehydrogenase; DBIL: direct bilirubin; HDL: high-density lipoprotein; LDL: low density lipoprotein; ALB: albumin; ALP: alkaline phosphatase; UA: uric acid; Ca2+: calcium.

Table 2. Multivariate analyses of factors which affect the response of induction therapy.

Variables	Multivariate analysis
	OR	95%CI	p
PLT (×10^9/L)	1.004	0.997–1.010	.250
DBIL (µmol/L)	0.983	0.964–1.004	.108
Urea (mmol/L)	0.869	0.701–1.077	.200
sCD25 (pg/ml)	1.000	1.0–1.0	.993
Aetiology	0.776	0.060–10.096	.847

PLT: platelets; DBIL: direct bilirubin.

Table 3. Ferritin and response to induction therapy.

	Remission	Non-remission	p
Before treatment (μg/L)	3652 (976–8362)	2722 (1218–15007)	.526
One week after treatment (μg/L)	1554 (850–3801)	2789 (1416–11442)	.013
Two weeks after treatment (μg/L)	903 (498–1947)	1720 (1464–3564)	.004
Three weeks after treatment (μg/L)	755 (549–1734)	1883 (1385–3717)	.005
Four weeks after treatment (μg/L)	631 (273–1493)	2205 (919–3749)	.002

Figure 3. Comparison of AUC of ferritin in predicting induction response.

Table 4. Ferritin for predicting induction response.

	AUC	p	Sensitivity	Specificity	Cut-off value (μg/L)
Ferritin one week after treatment	0.653 (0.540–0.766)	.013	0.578	0.689	2602.0
Ferritin two weeks after treatment	0.731 (0.589–0.873)	.004	0.885	0.63	1188.5
Ferritin three weeks after treatment	0.732 (0.594–0.880)	.005	0.857	0.591	1149.0
Ferritin four weeks after treatment	0.735 (0.603–0.868)	.002	0.846	0.645	846.5

Table 5. Ferritin for predicting survival.

	AUC	p	95% CI	Cut-off value (μg/L）	Sensitivity	Specificity
One week	0.545	.508	0.420–0.670
Two weeks	0.584	.348	0.404–0.764
Three weeks	0.743	.009	0.590–0.896	1442.5	0.684	0.769
Four weeks	0.701	.017	0.537–0.866	803.0	0.744	0.706

Figure 4. Response stratified by ferritin cut-off post-therapy initiation at: (A) one week (p = 0.552, HR = 1.194, 95%CI 0.665–2.143); (B) two weeks (p = 0.003, HR = 0.156, 95%CI 0.047–0.521); (C) three weeks (p = 0.008, HR = 0.238, 95%CI 0.082–0.686); (D) four weeks (p = 0.003, HR = 0.193, 95%CI 0.066–0.563).

Figure 5. Comparison of AUC of ferritin in predicting survival.

Figure 6. The survival curve for ferritin. (A) The survival curve for ferritin at 3 weeks after treatment (p = 0.020, HR = 0.443, 95%CI 0.223–0.881). (B) The survival curve for ferritin at 4 weeks after treatment (p = 0.005, HR = 0.351, 95%CI 0.170–0.726).

Data availability statement

The datasets used during the current study are available from the corresponding author on request.