Clinical features and prognostic factors of primary bone marrow lymphoma

Figures & data

Table 1 Clinical features of seven patients with PBML in our center

Case	Diagnosis	Age/sex	Main symptoms	WBC count (10^9/L)	Hb (g/ dL)	Platelets (10^9/L)	LDH	B2MG	IPI	Treatment	Outcome overall	Overall survival (months)
1	PTCL, NOS	47/F	Cytopenia	6.75	94	30	N	N	1	3GDPT – PR 3CHOP – PD 4ESHAP – PD 2DICE – not been evaluated	Dead	18
2	T-cell lymphoma and HLH	38/F	B cytopenia	0.46	79	15	H	H	2	1RCHOP – not been evaluated 1 (Etoposide + dexamethasone + cyclosporine) – not been evaluated	Dead	1
3	T-cell lymphoma	62/M	B cytopenia	2.07	85	115	N	N	3	GDPT×2 – SD 3CHOP – PR 1 (Decitabine + thalidomide + etoposide + dexamethasone) – CR	Alive	12
4	DLBCL	62/M	B cytopenia	3.2	60	81	H	H	4	2REPOCH – CR 2REPOCH – CR 2RCHOP – CR	Alive	25
5	DLBCL	50/F	B cytopenia	5.3	99	286	N	H	2	6RCHOP – PR – relapse – 2 (fotemustine + temozolomide + dexamethasone) – not been evaluated	Dead	7
6	DLBCL and HLH	62/M	B cytopenia, joint pain, chest distress	3.2	71	3	H	H	3	1 (Rituximab + methylprednisolone + etoposide) – not been evaluated	Dead	1
7	DLBCL and HLH	72/M	B cytopenia, fatigue	9.9	113	77	H	H	3	2 (Etoposide + dexamethasone + cyclosporine) – CR – relapse – 2 (etoposide + dexamethasone + cyclosporine)	Dead	9

Abbreviations: B, B symptoms; B2MG, β2-microglobulin; CHOP, cyclophosphamide, epirubicin, vincristine, prednisone; CR, complete response; DICE, dexamethasone, ifosfamide, mesna, etoposide; DLBCL, diffuse large B-cell lymphoma; ESHAP, etoposide, methylprednisolone, high-dose cytarabine, and cisplatin; GDPT, gemcitabine, cisplatin, prednisone, and thalidomide; H, high; Hb, hemoglobin; HLH, hemophagocytic lymphohistiocytosis; IPI, international prognostic index; N, normal; PBML, primary bone marrow lymphoma; PD, progressive disease; PR, partial response; PTCL, NOS, peripheral T-cell lymphoma, not otherwise specified; REPOCH, rituximab, etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin; SD, stable disease; WBC, white blood cells.

Figure 1 Univariable analyses of prognostic factors for OS for our 66 patients with PBML.

Notes: (A) Kaplan meier of OS in two groups with and without B symptoms. (B) Kaplan meier of OS in two groups with serum platelet level >75×10⁹/L and with serum platelet level <75x10⁹/L; (C) Kaplan meier of OS in two groups with normal LDH and with elevated LDH; (D) Kaplan meier of OS in two groups achieving CR and not achieving CR in the initial therapy; (E) Kaplan meier of OS in two groups with hematopoietic function grade 1,2 and hematopoietic function grade 3,4.

Abbreviations: CR, complete response; OS, overall survival; PBML, primary bone marrow lymphoma.

Figure 2 Curve of cumulative survival of patients with PBML diagnosed as DLBCL with general therapy or with intensive therapy.

Notes: n1 represents the initial number of recipients of the intensive therapy; n2 represents the initial number of recipients of the general therapy.

Abbreviations: DLBCL, diffuse large B-cell lymphoma; OS, overall survival; PBML, primary bone marrow lymphoma.

Table 2 Clinical characteristics of 66 patients with PBML from literature (cases 1–66)

Case	Initial diagnosis	Age (years)	Sex	Initial symptoms	B2MG	LDH	WBC/Hb/PLT	G	Initial treatment	IR	OS (months)	Reference
1	HIV-negative HL	64	M	Fever, cytopenia	NA	H	2.1/85/61	2	ABVD	F	0.1	Ponzoni et al^Citation33
2	HIV-negative HL	50	M	Fever, cytopenia	NA	H	2.1/74/40	3	ABVD	F	0.7	Cacoub et al^Citation34
3	HIV-negative HL	66	F	Fever, cytopenia	NA	N	2.5/112/132	2	ABVD	CR	15.0+	Dholaria et al^Citation35
4	HIV-negative HL and HLH	68	M	Fever, cytopenia	NA	H	3.2/78/16	4	NO	NA	2.0	Yasuyoshi et al^Citation21
5	HIV-positive HL	29	M	Fever, cytopenia	NA	H	3.2/91/102	2	MOPP/ABV	CR	31.0	Gerard et al^Citation36
6	HIV-positive HL	58	M	Fever, cytopenia	NA	NA	NA	NA	ABVD	F	2.0	Ponzoni et al^Citation37
7	HIV-positive HL	36	M	Fever, cytopenia	NA	NA	NA	NA	ABVD	F	4.0	Ponzoni et al^Citation37
8	HIV-positive HL	31	M	Fever, cytopenia	NA	NA	NA	NA	ABVD	CR	18.0+	Ponzoni et al^Citation37
9	HIV-positive HL	49	M	Fever, cytopenia	NA	NA	NA	NA	ABVD	CR	114.0+	Ponzoni et al^Citation37
10	HIV-positive HL	33	M	Fever, cytopenia	NA	NA	NA	NA	EBV	NA	4.0	Ponzoni et al^Citation37
11	HIV-positive HL	34	M	Fever, cytopenia	NA	NA	NA	NA	ABVD	CR	3.0+	Ponzoni et al^Citation37
12	HIV-positive HL	55	M	Fever, chills, weight loss, cytopenia	NA	NA	NA	NA	NA	NA	NA	Salama et al^Citation38
13	HIV-positive HL	43	M	Fever, cytopenia, vomiting	NA	NA	2.1/90/115	2	ABVD	NA	1.0+	Shah et al^Citation39
14	HL	89	F	Fever, cytopenia	NA	NA	NA	3	NA	NA	NA	Suzuki et al^Citation40
15	T-cell lymphoma and HLH	38	M	Fever, cytopenia	H	H	0.46/79/15	4	RCHOP	F	1.0	Our case
16	T-cell lymphoma	62	F	Fever, cytopenia	N	N	2.07/85/115	2	GDPT	PR	12.0+	Our case
17	PTCL, NOS	34	M	Hypercalcemia	NA	H	NA	NA	ALL	F	9.6	Martinez et al^Citation1
18	PTCL, NOS	73	F	Fatigue, malaise, cytopenia	NA	NA	1.3/76/33	3	Pentostatin	F	44.4	Martinez et al^Citation1
19	PTCL, NOS	47	M	Cytopenia	N	N	6.75/94/30	3	3GDPT	PR	18.0	Our case
20	ALK-negative ALCL and HLH	60	M	Fever, jaundice, cytopenia	NA	NA	1.7/N/107	3	Cortisol + cyclosporine	F	NA	Gudgin et al^Citation41
21	ALK-negative ALCL	60	M	Fever, cytopenia	H	N	1.5/86/105	3	1CHOP	CR	NA	Szomoret al^Citation42
22	FL	76	M	NO	N	N	13.65/140/216	0	NO	NA	64.8+	Martinez et al^Citation1
23	FL	81	F	Cytopenia	H	H	19.9/73/67	3	COP	F	3.6	Martinez et al^Citation1
24	FL	61	F	Bone pain	N	N	7.1/132/236	0	RCHOP	CR	40.8+	Martinez et al^Citation1
25	FL	55	M	Cytopenia	N	H	11.4/97/300	1	RCHOP	CR	12.0+	Martinez et al^Citation1
26	FL	78	M	Hemorrhage, cytopenia	NA	N	8.6/75/1	4	THP-COP	PR	NA	Kagoya et al^Citation43
27	DLBCL and HLH	62	F	Fever, joint pain, cytopenia, chest stress	H	H	3.2/71/3	4	R+methylprednisolone + etoposide	F	1.0	Our case
28	DLBCL and HLH	72	F	Fever, fatigue, cytopenia	H	H	9.9/113/77	1	Etoposide + dexamethasone + cyclosporine	CR	9.0	Our case
29	DLBCL and HLH	57	M	Fever, weight loss, cytopenia	H	H	4.8/65/68	3	RCHOP	CR	10.0+	Kim et al^Citation24
30	DLBCL and CAD	70	F	Cytopenia, jaundice	NA	H	5.9/4.6/331	4	RCHOP	CR	22.0+	Kosugi et al^Citation44
31	DLBCL and CAD	75	F	Cytopenia	NA	NA	NA	NA	RCHOP	CR	NA	Sumi et al^Citation45
32	DLBCL and CAD	76	M	Fever, cytopenia, jaundice	NA	H	5.3/74/NA	NA	RCHOP	CR	19.0	Yamashita et al^Citation3
33	DLBCL and CAD	69	M	Fatigue, somnolence, cytopenia	NA	H	NA/80/NA	NA	RCHOP	CR	NA	Níáinle et al^Citation46
34	DLBCL	62	F	Cytopenia	H	H	3.2/70/81	4	REPOCH	CR	25.0+	Our case
35	DLBCL	50	M	Fever, cytopenia	N	H	5.3/99/286	1	RCHOP	PR	7.0	Our case
36	DLBCL	70	F	Fatigue, cytopenia	NA	NA	5.4/81/67	2	NA	F	NA	Huimin et al^Citation47
37	DLBCL	60	F	Fever, cytopenia	NA	NA	0.58/71/176	4	RCHOP	CR	NA	Huimin et al^Citation47
38	DLBCL	56	M	Fatigue, cytopenia	NA	NA	2.84/73/33	3	RCHOP	4CR	NA	Huimin et al^Citation47
39	DLBCL	58	M	Fever, fatigue, cytopenia	NA	H	52.8/106/21	4	RCHOP	CR	19.0	Wang et al^Citation48
40	DLBCL	41	M	Fever, joint pain, weight loss, cytopenia	NA	H	2.75/100/NA	NA	CHOEP	PR	10.0	Ren et al^Citation49
41	DLBCL	56	M	Cytopenia, jaundice	H	N	1.9/41/62	4	RCHOP	NA	40.0+	Hu et al^Citation50
42	DLBCL	52	F	Cytopenia	NA	NA	8.1/60/386	4	RCHOP	NA	NA	Bhagat et al^Citation2
43	DLBCL	52	F	Cytopenia	NA	NA	2.3/77/48	3	RCHOP	F	NA	Bhagat et al^Citation2
44	DLBCL	64	M	Cytopenia	NA	NA	4.8/60/27	4	Chlorambucil + prednisolone	NA	NA	Bhagat et al^Citation2
45	DLBCL	51	F	Cytopenia	NA	NA	1.9/81/24	4	RCHOP	CR	NA	Bhagat et al^Citation2
46	DLBCL	76	F	Dyspnea, cytopenia	NA	H	NA	NA	RCHOP	CR	27.0+	Niscola et al^Citation51
47	DLBCL	52	F	Cytopenia	NA	N	8.1/60/286	4	NA		NA	Sharma et al^Citation52
48a	DLBCL	39	F	Fever, cytopenia	NA	N	2.95/65/NA	NA	RCHOP	CR	NA	Kazama et al^Citation32
49	DLBCL	44	M	Fever, cytopenia	N	H	NA	NA	CHOP	NA	8.0	Chang et al^Citation53
50	DLBCL	65	M	B, cytopenia	H	N	3.5/102/56	2	RCHOP	CR	20.4+	Martinez et al^Citation1
51	DLBCL	63	F	Fatigue, cytopenia	H	H	2.8/97/121	2	HD-CHOP	PR	54.0	Martinez et al^Citation1
52	DLBCL	29	M	Malaise, cytopenia	H	H	1.7/82/66	3	CHOP	F	7.2	Martinez et al^Citation1
53	DLBCL	63	F	Bone pain, fatigue, cytopenia, malaise	N	H	5.1/89/207	2	COP	PR	21.6	Martinez et al^Citation1
54	DLBCL	71	F	Fatigue	H	H	NA	NA	RCHOP	CR	18.0	Martinez et al^Citation1
55	DLBCL	45	M	Bone pain	NA	NA	NA	NA	RCHOP	F	7.2	Martinez et al^Citation1
56	DLBCL	72	M	Fatigue, cytopenia	NA	H	5.2/52/221	4	RCHOP	F	4.8+	Martinez et al^Citation1
57	DLBCL	67	M	Infections, cytopenia	NA	H	2.6/108/61	2	ALL	F	28.8	Martinez et al^Citation1
58	DLBCL	32	M	Bone pain, fatigue, malaise, cytopenia	NA	H	3.7/106/162	1	VACOPB	CR	105.6+	Martinez et al^Citation1
59	DLBCL	78	F	B, cytopenia	NA	H	22.5/120/67	3	RCHOP	CR	4.0	Alvares et al^Citation54
60	DLBCL	73	F	B, cytopenia	H	H	7.7/110/46	3	CHOP	F	NA	Alvares et al^Citation54
61	DLBCL	42	M	B, fatigue, cytopenia	NA	H	2.3/105/50	2	RCHOP	F	NA	Alvares et al^Citation54
62	DLBCL	51	M	Bone pain, fatigue, malaise, cytopenia	NA	H	3.7/117/273	1	CHOP	F	12.0	Martinez et al^Citation1
63	DLBCL	79	M	Bone pain, fatigue, malaise, cytopenia	NA	H	4.5/87/500	2	RCHOP	CR	18.0+	Martinez et al^Citation1
64	DLBCL	70	M	B, bone pain, cytopenia	N	N	2.8/63/173	4	CHOEP	PR	9.0	Martinez et al^Citation1
65	DLBCL	67	M	Fever, cytopenia	NA	NA	N/71/N	NA	NA	NA	NA	Nagasaki et al^Citation55
66	DLBCL	40	M	Fatigue, dyspnea, cytopenia	NA	H	NA/43/NA	NA	HYPERCAVD	CR	33.0+	Matthieset al^Citation5

Notes:

a Recieved autologous stem cell transplantation. + Alive.

Abbreviations: ALL, prednisone, vincristine, daunorubicin, L-asparaginase, cyclophosphamide, cytarabine, bleomycin, 6-mercaptopurine; ALK-negative ALCL, ALK-negative anaplastic large cell lymphoma; B, B symptoms; B2MG, β2-microglobulin; CAD, cold agglutinin disease; CHOEP, cyclophosphamide, doxorubicin, vincristine, prednisolone, etoposide; CHOP, cyclophosphamide, epirubicin, vincristine, prednisone; COP, cyclophosphamide, vincristine, prednisone; CR, complete response; DLBCL, diffuse large B-cell lymphoma; EBV, epiadriamicin, bleomicin, vinblastin; F, failure; FL, follicular lymphoma; G, hematopoietic function grade; GDPT, gemcitabine, cisplatin, prednisone, and thalidomide; H, high; Hb, hemoglobin; HD, high dose; HL, Hodgkin’s lymphoma; HLH, hemophagocytic lymphohistiocytosis; HYPERCAVD, cyclophosphamide, vincristine, dexamethasone, adriamycin/methotrexate, cytarabine; IR, initial response; MOPP/ABV, metchlorethamine, vincristine, cyclophosphamide, prednisone/adriamycin, bleomycin, vinblastin; N, normal; NA, not available; OS, overall survival; PLT, platelets; PR, partial response; PTCL, NOS, peripheral T-cell lymphoma, not otherwise specified; RCHOP, rituximab,cyclophosphamide, epirubicin, vincristine, prednisone; REPOCH, rituximab, etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin; THP-COP, pirarubicin, cyclophosphamide, vincristine, prednisolone; VACOPB, etoposide, doxorubicin, cyclophosphamide, vincristine, prednisone, bleomycin; WBC, white blood cells.

Table 3 Pathological, phenotypic, and molecular features of DLBCL cases (n=34)

Case	CD20	CD10	CD5	BCL-2	BCL-6	Involvement (%)
27	+	NA	NA	NA	NA	NA
28	+	NA	NA	NA	NA	NA
29	+	−	+	−	+	65.4
30	+	−	−	+	NA	NA
31	+	−	−	+	NA	NA
32	+	−	−	+	+	NA
33	+	−	−	NA	NA	NA
34	NA	NA	NA	NA	NA	NA
35	+	NA	NA	NA	NA	NA
36	+	−	NA	+	−	36.7
37	+	−	+	+	−	9.78
38	+	+	−	NA	+	18.4
39	+	−	−	+	−	39
40	+	+	−	NA	NA	NA
41	+	−	−	NA	NA	4.5
42	+	−	NA	NA	NA	35
43	+	−	NA	NA	NA	42
44	+	−	NA	NA	NA	50
45	+	−	NA	NA	NA	50
46	+	NA	NA	+	NA	NA
47	+	NA	NA	−	+	NA
48	+	NA	−	−	NA	NA
49	+	NA	+	NA	NA	23.5
50	+	−	−	−	−	70
51	+	−	−	+	NA	90
52	+	−	−	+	−	20
53	+	−	−	+	−	15
54	+	+	−	+	+	80
55	+	−	−	+	−	70
56	+	−	−	+	−	80
57	+	−	−	+	−	70
58	+	NA	−	NA	NA	100
59	+	NA	−	NA	NA	80
60	+	−	−	NA	NA	70
61	+	−	−	NA	NA	70
62	+	+	−	+	NA	80
63	+	−	−	+	+	90
64	+	NA	−	NA	NA	100
65	+	−	+	NA	NA	35
66	−	NA	NA	NA	NA	25–75

Abbreviations: DLBCL, diffuse large B-cell lymphoma; NA, not applicable.

Table 4 Clinical characteristics of 47 patients with PBML

Variable	Total, n	Percentage (%)
Age (years)
≤60	24	51.1
>60	23	48.9
Sex
Male	33	70.2
Female	14	29.8
Degree of cytopenia
Grades 1and 2	18	52.9
Grades 3 and 4	16	47.1
Serum hemoglobin level (g/L)
≤75	11	30.6
>75	25	69.4
Serum leukocyte level (10^9/L)
≤4.0	22	62.9
>4.0	13	37.1
Serum platelet level (10^9/L)
≤75	15	45.5
>75	18	54.5
Serum LDH level
Normal	8	21.1
High	30	78.9
Serum β2-microglobulin level
Normal	9	45
High	11	55
B symptoms
Yes	26	55.3
No	21	44.7
Response to initial treatment
CR	20	48.8
Not CR	21	51.2

Abbreviations: CR, complete remission; PBML, primary bone marrow lymphoma.

Table 5 Univariate and multivariate analyses for overall survival

Variable	Univariate analysis	Multivariate analysis	P-value
	HR (P-value)	HR (95% CI)
Age (years)	0.549
≤60
>60
Sex	0.584
Male
Female
Degree of cytopenia	0.041
Grades 1 and 2
Grades 3 and 4
Serum hemoglobin level (g/L)	0.93
≤75
>75
Serum leukocyte level (10^9/L)	0.823
≤4.0
>4.0
Serum platelet level (10^9/L)	0.06
≤75		4.553 (1.371–15.125)	0.013
>75
Serum LDH level	0.048
High
Normal
Serum β2- microglobulin level	0.615
High
Normal
B symptoms	0.037
Yes		1.4229 (2.891–70.031)	0.001
No
Response to initial treatment	<0.001
Not CR		12.429 (2.871–53.802)	0.001
CR

Abbreviation: CR, complete remission.

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