Lymphoma-associated hemophagocytic syndrome: a retrospective study from a single center

Figures & data

Table 1. Characteristics of patients with LAHS.

Characteristics	No. of patients (%)
Age(years), median(range)	44(13–72)
Gender
Female	32 (27.4)
Male	85(72.6)
Lineage
B cell lineage	22(18.8)
T/NK cell lineage	95(81.2)
Histopathology
B-LAHS
DLBCL	11(9.4)
IVL	3(2.6)
Other type	8(6.8)
T/NK-LAHS
ENKTL	83(70.9)
ALCL	3(2.6)
PTCL-NOS	4(3.4)
AITL	2(1.7)
Other type	3(2.6)
Ann Arbor stage (III-IV)	105(89.7)
Fever	117(100)
Hepatosplenomegaly	85(72.6)
Hemophagocytosis in BM*	56(53.3)
BM involvement**	72(63.2)
LAHS status
At lymphoma diagnosis	82(70.1)
At lymphoma relapse	35 (29.9)
PLT (×10^9/L), median(range)	50(2-237)
HB (g/L), median(range)	86(44-135)
Net (×10^9/L), median(range)	1.17(0.01-6.85)
LDH concentration (IU/L), median(range)	732(207-4379)
TB (umol/l), median (range)	16.2(4.7-199.9)
ALT (IU/L), median(range)	72(7-597)
AST (IU/L), median(range)	108 (5-661)
Albumin(g/L), median (range)	29.5 (16.6-51.9)
Creatinine (umol/l), median (range)	57 (5.9-203)
Ferritin≥500 ng/mL	117 (100)
soluble CD25 ≥ 2400U/mL***	73(96)
Triglyceride (mmol/L), median (range)	2.42 (0.69-13.59)
Fibrinogen (g/l), median (range)	1.4 (0.5-6.34)

LAHS lymphoma-associated hemophagocytic syndrome, DLBCL diffuse large B cell lymphoma, IVL intravascular large B cell lymphoma, ENKTL nasal type, extranodal nature killer/T cell lymphoma, ALCL, anaplastic large cell lymphoma, PTCL-NOS peripheral T cell lymphoma not specified, AITL angioimmunoblastic T-cell lymphoma, LAHS lymphoma-associated hemophagocytic syndrome, BM bone marrow, PLT platelet, HB hemoglobin, Net neutrophil, LDH lactate dehydrogenase, TB Total bilirubin, ALT alanine transaminase, AST aspartate transaminase.

*Bone marrow biopsies were available for 105 patients during hospitalization at diagnosis of hemophagocytic syndrome.

**Bone marrow biopsies were available for 114 patients during hospitalization at diagnosis of lymphoma or hemophagocytic syndrome.

*** soluble CD25 test were available for 76 patients during hospitalization at diagnosis of lymphoma or hemophagocytic syndrome

Table 2. Comparisons between patients with B-LAHS and T/NK-LAHS.

Characteristics	B-LAHS(n = 22)	T/NK-LAHS(n = 95)	P value
Age (years) median (range)	52(31-72)	41(13-71)	0.032
Gender
Female	8 (36.4)	24(25.3)	0.293
Male	14 (63.6)	71 (74.7)
ECOG PS
0–1	2(9.1)	12(12.6)	0.645
≥2	20 (90.9)	83 (87.4)
Hepatosplenomegaly			0.129
Positive	19(86.4)	67(70.5)
Negative	3(15.6)	28(29.5)
Ann Arbor stage
I-II	0(0)	12(12.6)	0.078
III-IV	22(100)	83(87.4)
Hemophagocytosis in BM*
Positive	10(47.6)	46((54.8)	0.557
Negative	11(52.4)	38(45.2)
BM involvement**
Positive	16(76.2)	55 (59.8)	0.16
Negative	5 (23.8)	37 (40.2)
LAHS status
At lymphoma onset	20 (90.9)	62(65.3)	0.018
At lymphoma relapse	2(9.1)	33(34.7)
IPI score			0.492
0–1	0(0)	2 (2.1)
2–4	22(100)	93 (97.9)
Extranodal sites
<2	8(36.4)	33(34.7)	0.885
≥2	14(63.6)	62(65.3)
EBV-DNA (copies/mL)***
>4450	3(20.0)	51(75.0)	<0.001
≤4450	12(80.0)	17(25.0)
Concurrent infection	16(72.7)	68(71.6)	0.914
PLT (×10^9/L), median(range)	48(9-147)	50(2-237)	0.74
HB (g/L), median(range)	80(48-125)	89(44-135)	0.027
Net (×10^9/L), median(range)	1.59(0.05-27.45)	1.12(0.01-6.85)	0.045
TB (umol/L), median (range)	14.2(7.9-58.9)	16.8(4.7-199.9)	0.503
LDH (IU/L), median(range)	536(207-2255)	752(229-4379)	0.046
ALT (IU/L), median(range)	44(7-114)	86(9-597)	<0.001
AST (IU/L), median(range)	53(21-661)	118(5-466)	0.002
Albumin(g/L), median (range)	29.2(18.3-35.8)	29.9(16.6-51.9)	0.66
Creatinine (umol/L), median (range)	60(32-203)	57.4(21-203)	0.348
Triglyceride (mmol/L), median (range)	2.52(1.3-5.75)	2.42(0.69-13.59)	0.27
Fibrinogen(g/L), median (range)	2.50(1.09-6.34)	1.24(0.5-3.76)	<0.001

ECOG PS Eastern Cooperative Oncology Group performance status, LAHS lymphoma-associated hemophagocytic syndrome, BM bone marrow, IPI International Prognostic Index, PLT platelet, HB hemoglobin, Net neutrophil, TB Total bilirubin, LDH lactate dehydrogenase, ALT alanine transaminase, AST aspartate transaminase

*Bone marrow biopsies were available for 105 patients during hospitalization at diagnosis of hemophagocytic syndrome.

**Bone marrow biopsies were available for 114 patients during hospitalization at diagnosis of lymphoma or hemophagocytic syndrome.

***Precise EBV-DNA data were available for 83 patients.

Figure 1. Survival curves of 117 patients with lymphoma-associated hemophagocytic syndrome.

Figure 2. Overall survival curves for patients with B cell lymphoma-associated hemophagocytic syndrome and T/natural killer cell lymphoma-associated hemophagocytic syndrome.

Table 3. Univariate analysis of the prognostic factors of LAHS.

Characteristics	p value
Age (years)	0.746
Gender	0.543
ECOG PS (≥2)	0.412
Ann Arbor stage (III-IV)	0.553
Hepatosplenomegaly	0.265
BM involvement*	0.265
HPS onset at relapse	0.001
Extranodal sites (≥2)	0.88
Concomitant infection	0.41
Etoposide treatment	0.246
Histopathology (T/NK-cell lineage)	<0.001
LDH (>1000 IU/L)	0.004
Ferritin > 1000 ng/mL	0.356
Soluble CD25 ≥ 3900 U/mL**	0.425

ECOG PS Eastern Cooperative Oncology Group performance status, BM bone marrow, HPS hemophagocytic syndrome, LDH lactate dehydrogenase

*113 patients included in this study received bone marrow biopsy.

**soluble CD25 test were available for 76 patients during hospitalization at diagnosis of lymphoma or hemophagocytic syndrome

Table 4. Univariate analysis of the prognostic factors of T/NK-LAHS.

Characteristics	p value
Age (years)	0.523
Gender	0.285
ECOG PS (≥2)	0.511
Ann Arbor stage (III-IV)	0.973
Hepatosplenomegaly	0.055
BM involvement*	0.102
HPS onset at relapse	0.037
Extranodal sites (≥2)	0.479
Concomitant infection	0.459
Etoposide treatment	0.547
LDH (>1000 IU/L)	0.042
EBV-DNA (>4450 copies/mL)**	0.016
Ferritin > 1000 ng/mL	0.197
Soluble CD25 ≥ 3900 U/mL***	0.162

ECOG PS Eastern Cooperative Oncology Group performance status, BM bone marrow, HPS hemophagocytic syndrome, LDH lactate dehydrogenase, EBV-DNA Epstein-Barr virus DNA, PINK prognostic index of natural killer lymphoma

*80 patients with ENKTL included in this study received bone marrow biopsy.

** Precise EBV-DNA data were available for 60 patients with ENKTL.

***soluble CD25 test were available for 76 patients during hospitalization at diagnosis of lymphoma or hemophagocytic syndrome