Role of serum high mobility group box 1 in hematological malignancies complicated with systemic inflammatory response syndrome and effect of recombinant thrombomodulin

Figures & data

Table I. Patient characteristics.

	Patients in remission (group 1)	Patients in non-remission (group 2)	Patients with SIRS (group 3)
Number	13	16	25
Male	5	10	17
Female	8	6	8
Age (median)	60	57	63
Disease
Acute myeloid leukemia	4	5	9
Acute lymphoblastic leukemia	4	1
Non-Hodgkin lymphoma
Diffuse large B-cell lymphoma	2	1	4
Follicular lymphoma	1	3	1
Angioimmunoblastic T cell lymphoma			1
Myelodysplastic syndrome
Refractory cytopenia			2
Refractory anemia with excess blasts	2	4
Multiple myeloma		2	3
Adult T cell leukemia			1
iTAM post-allo-HSCT			2
aGVHD post-allo-HSCT			2
Serum HMGB1 level (ng/mL) mean [95% CI mini-max]	0.9 [0.5–1.9]	3.1 [2.3–4.8]	10.7 [7.7–17.4]

SIRS, systemic inflammatory response syndrome; iTAM, intestinal transplant-associated microangiopathy; allo-HSCT, allogeneic hematopoietic stem cell transplant; aGVHD, acute graft-versus-host disease; HMGB1, high mobility group box 1; CI, confidence interval.

Figure 1. Serum HMGB1 levels did not differ between groups 1 and 2, but were significantly elevated in group 3 compared with groups 1 and 2.

Figure 2. Seventeen patients with both SIRS and DIC in group 3 were treated with rhTM. Serum HMGB1 concentrations, before and after rhTM administration, could be analyzed in 16 patients. Therapy improved the condition in 13 patients and significantly ameliorated their serum HMGB1 concentrations.

Figure 3. Pretreatment levels of serum HMGB1 between survival patients and non-survival patients in group 3.

Figure 4. Receiver operator characteristic (ROC) curve generated with serum HMGBI levels in group 3.

Table II. Treatment outcome of 17 patients complicated by SIRS and DIC in group 3 using rhTM.

No.	Age	Sex	Disease	Complications	DIC score pre rhTM	DIC score post rhTM	HMGB1 pre rhTM (ng/mL)	HMGB1 post rhTM (ng/mL)	CRP pre rhTM	CRP post rhTM	ELAM-1 pre rhTM (ng/mL)	ELAM-1 post rhTM (ng/mL)	Dose of rhTM (U/kg)	Term of rhTM (days)	Concomitant drug for DIC	Improvement of SIRS	Survival of 28 days
1	75	F	FL, PR	Sepsis (P. aeruginosa)	6	2	4.4	3.5	15.4	2.52	47.3	53.4	380	6		Yes	s
2	77	M	DLBCL, PR	Tumor lysis syndrome	3	2	19.1	10.8	16.51	9.62	62.3	57.1	130	3	AT3	Yes	s
3	77	M	AML, CR	Sepsis (E. cloacae)	4	4	1.5	3.5	21.8	15.7	36.1	12.7	380	6	AT3	Yes	s
4	49	M	Allo-HSCT, iTAM	aGVHD	4	3	10.7	6.4	5.24	0.88	70.3	53.9	380	6	LMWH	Yes	s
5	60	F	ATL, PD		3	3	1.7	1.7	8.59	1.51	29	86.2	380	9		Yes	s
6	63	M	MM	FN	4	2	6.8	3.1	10.8	3.7	151	32.8	130	6	AT3	Yes	s
7	77	M	MDS	Sepsis suspected	6	2	29.6	16.4	9.26	1.04	45.2	26	380	6		Yes	s
8	61	M	AML, non-CR	ARDS	8	4	6.1	4.3	7.72	0.72	37.1	12.4	380	6		Yes	s
9	59	M	AML, non-CR	FN	6	5	4.6	0.6	10.15	6.53	29.3	15	380	6		Yes	s
10	76	F	MM	Tumor lysis syndrome	5	5	1.8	1.1	0.96	0.14	15.9	15.3	380	6		Yes	s
11	36	M	Allo-HSCT	aGVHD	6	3	13.7	4.8	3.37	1.15	26.1	31.8	380	24		Yes	s
12	73	F	DLBCL, PD, LC	FN	2	3	19.4	30	13.22	10.98	292	195	380	6	AT3	No	d
13	73	M	AML, PD		8	NT	42.8	NT	18.88	NT	NT	NT	380	3	AT3	No	d
14	46	F	AITL, PD	FN	3	3	12.8	2.1	22.09	2.53	45.2	35.3	380	8		Yes	d
15	54	M	DLBCL, PD	Tumor lysis syndrome	3	5	17.5	25.7	11.5	1.33	22.2	30.7	380	6		No	d
16	73	M	AML, PD		7	2	46.2	5.5	10.29	1.97	66.8	48.5	380	4		Yes	d
17	75	M	DLBCL, PD	MOF	8	8	12.9	8.5	5.13	10.22	26.1	26.7	380	4		No	d

SIRS, systemic inflammatory response syndrome; DIC, disseminated intravascular coagulation; HMGB1, high mobility group box 1; CRP, C-reactive protein; ELAM-1, serum endothelial leukocyte adhesion molecule-1; rhTM, recombinant human soluble thrombomodulin; F, female; M, male; FL, follicular lymphoma; PR, partial remission; DLBCL, diffuse large B-cell lymphoma; AML, acute myeloid leukemia; CR, complete remission; allo-HSCT, allogeneic hematopoietic stem cell transplant; iTAM, intestinal transplant-associated microangiopathy; ATL, adult T cell leukemia; PD, progression of disease; AITL, angioimmunoblastic T cell lymphoma; P. aeruginosa, Pseudomonas aeruginosa; E. cloacae, Enterobacter cloacae; ARDS, acute respiratory distress syndrome; aGVHD, acute graft-versus-host disease; FN, febrile neutropenia; MOF, multiple organ failure; NT, not tested; AT3, antithrombin 3; LMWH, low molecular weight heparin; s, survival; d, death.

Table III. Cut-off values (ng/mL) of serum HMGB1 levels in group 3.

Cut-off value	HMGB1 (ng/mL)
	11.45	12.35	12.65	12.85
Sensitivity (%)	85.7	85.7	85.7	71.4
Specificity (%)	72.2	77.8	83.3	83.3
	AUC = 0.810 ± 0.113 (p = 0.018)

HMGB1, high mobility group box 1; AUC, area under the curve.