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Table 1 Characteristics of studies included in the meta-analysis

From: Meta-analysis of the prognostic and clinical value of tumor-associated macrophages in adult classical Hodgkin lymphoma

Study, Year Country Number of subjects Stage Treatment, n (%) WHO subtypes, n (%) Hodgkin-Reed-Sternberg EBV status, n (%) Antibodies (clone) Scoring Threshold(s) Follow-up median (range) & mean (range) (in years) Outcome correlation
Steidl et al., 2010 [10] Canada 166 Limited/advanced ABVD ± RT 165 (99), RT alone 1 (1) NS 140 (84), MC 11 (7), Others 5 (3), NOS 10 (6) Neg 137 (84), Pos 27 (16) CD68 (KP1) Visual estimation 5 %, 25 % 4.0 (0.5–20.8) CD68, adverse (PFS, DSS)
Tzankov et al., 2010 [11] Switzerland 105 Limited/advanced ABVD ± RT 30 (28), COPP ± RT 48 (46), RT alone 27 (26) NS 60 (57), MC 32 (30), Others 5 (5), NOS 8 (8) Neg 85 (81), Pos 20 (19) CD68 (PGM1) Visual, cell counting 0.82 % 11.8 (1.0–27.6) CD68, adverse (OS)
Kamper et al., 2011 [12] Denmark 288 Limited/advanced ABVD/COPP ± RT, ABVD ± RT, RT alone NS 237 (82), MC 47 (16), NOS 4 (1) Neg 193 (67), Pos 95 (33) CD68 (KP1), CD163 (10D6) Computer-assisted point counting 7.8 % (CD68), 21.1 % (CD163) 7.0 (0.2–18.6) CD68, adverse (EFS, OS); CD163, adverse (EFS, OS)
Hohaus et al., 2011 [13] Italy 93 Limited/advanced ABVD ± RT 55 (59), BEACOPP ± RT 32 (34), MOPP/Other ± RT 6 (7) NS 64 (69), MC 4 (4), Other 6 (8), NOS 19 (20) Neg 37 (69), Pos 17 (31) CD68 (PGM1) Visual estimation 5 % 1.1 (0.1–6.8) CD68, adverse (PFS)
Zaki et al., 2011 [23] Japan 82 Limited/advanced ABVD ± RT, RT alone NS 20 (24), MC 52 (63), Other 10 (12) NR CD68 (PGM1), CD163 (10D6) Visual, cell counting in 0.146 mm2 Median (CD68), Median (CD163) Mean: 4.0 (0.8–9.6) CD68, NSS (OS); CD163, adverse (OS)
Azambuja et al., 2012 [24] USA 265 Limited/advanced ABVD ± RT 265 (100) NS 180 (68), MC 52 (20), Others 18 (6), NOS 15 (6) Neg 122 (58), Pos 87 (42) CD68 (KP1), CD163 (10D6) Visual estimation 5 %, 25 % (CD68), 5 %, 25 % (CD163) 6 (1.5–11.7) CD68, NSS (PFS, DSS); CD163, NSS (PFS, DSS)
Yoon et al., 2012 [14] South Korea 144 Limited/advanced ABVD 113 (79), C-MOPP 10 (7), ABVD/C-MOPP hybrid 15 (10), BEACOPP 6 (4) NS 90 (63), MC 34 (24), Others 11 (7), NOS 9(6) Neg 66 (46), Pos 78 (54) CD68 (KP1), CD163 (10D6) Visual estimation 20 % (CD68), 20 % (CD163) 5.4 (0.7–19.0) CD68, adverse (EFS, OS); CD163, adverse (EFS, OS)
Tan et al., 2012 [15] Canada 287 Advanced ABVD ± RT 144 (50), Stanford V ± RT 143 (50) NS 223 (78), MC 38 (13), Others 9 (3), NOS 17(6) Neg 238 (83), Pos 49 (17) CD68 (KP1), CD163 (10D6) Computer-assisted image analysis 12.7 % (CD68), 16.8 % (CD163) 5.5 CD63, adverse (FFS, OS); CD163, adverse (FFS, OS)
Sanchez-Espiridion et al., 2012 [31] USA 103 Advanced NR NS 74 (73), MC 22 (22), Others 6 (6) NR CD68 (KP1 and PGM1), CD163 (10D6) Computer-assisted point counting 5 %, 25 %, median (CD68), 5 %, 25 %, median (CD163) NR CD68, NSS (FFS, OS); CD163, NSS (FFS, OS)
Abdou et al., 2013 [16] Egypt 61 Limited/advanced Chemotherapy NS 33 (54), MC 20 (33), Others 8 (13) NR CD68 (KP1) Visual, cell counting 40 % (CD68) Mean: 1.2 ± 1.7 CD68, adverse (OS)
Greaves et al., 2013 [17] United Kingdom 122 Limited/advanced Anthracycline-based ± RT 56 (46), Alkalator-based ± RT 52 (43), RT alone 14 (11) NS 93 (78), MC 25 (20), Others 2 (2) Neg 84 (69), Pos 38 (31) CD68 (KP1) Computer-assisted image analysis 5 %, 15 % 16.5 (2–40) CD68, adverse (FFTF, OS) across the 3 defined groups
Deau et al., 2013 [25] France 59 Limited/advanced ABVD 47 (80), EBVP 8 (14), BEACOPP 3 (5) NS 54 (92), Non-NS 5 (8) NR CD68 (KP1) Visual estimation 25 % NR CD68, adverse (PFS); CD68, NSS (OS)
Panico et al., 2015 [26] Italy 121 Limited/advanced ABVD ± RT 101 (83), ABVD-like ± RT 20 (17) NS 73 (60), MC 40 (33), Others 8 (7) NR CD68 (KP1) Visual, cell counting 30 per 0.023 mm2 Mean: 3.5 (0.1–9.3) CD68, adverse (OS); CD68, NSS(PFS)
Casulo et al., 2013 [18] USA 81 Limited/advanced ABVD 38 (47), Stanford V 11(13), ABVD/MOPP 16 (20), others 16 (20) NR NR CD68 (KP1) Computer-assisted image analysis 30 % 8.8 CD68, adverse (OS)
Koh et al., 2014 [19] South Korea 116 Limited/advanced ABVD ± RT 116 (100) NS 78 (67), MC 22 (19), Others 8 (7), NOS 8 (7) Neg 73 (63), Pos 43 (37) CD68 (KP1), CD163 (10D6) Visual estimation 20 % (CD68), 20 % (CD163) 6.2 (3.8–10.3) CD68, adverse (EFS, DSS, OS); CD163, adverse (EFS, DSS, OS)
Ping et al., 2014 [27] China 72 Limited/advanced ABVD 49(68), BEACOPP 13(18), others 10 (14) NS 41(57), MC 23 (32), Others 8 (11) NR CD68 (KP1) Visual estimation 250/HPF 3.9 (0.7–15) CD68, NSS (OS);
Klein et al., 2014 [28] USA 88 Limited/advanced ABVD ± RT 88 (100) NS 55 (63), MC 6 (7), Others 1 (1), NOS 19 (22) NR CD68 (KP1), CD163 (10D6) Visual estimation 5 %, 25 % (CD68), 5 %, 25 % (CD163) NR CD68, NSS (OS); CD163, adverse (OS) 25 % threshold
Touati et al., 2014 [20] France 158 Limited/advanced ABVD 102(65), ABVD/MOPP 26 (17), BEACOPP 11 (7), ABVD-like 9 (5), others 10 (6) NS 130 (82), MC 21 (13), Others 7 (5) Neg 106 (67), Pos 40 (25), Not done 12 (8) CD68 (PGM1) Visual estimation 25 % 5.5 (0.2–16.2) CD68, adverse (PFS, OS)
Kayal et al., 2014 [30] India 100 Limited/advanced ABVD ± RT 88 (88), EVAP RT 11 (11), Other 1 (1) NS 51 (51), MC 47 (47), Others 2 (2) NR CD68 (CD68/G2) Visual, cell counting 12.9 %, 18.2 %, 25 % (the quartiles) 5.7 CD68, NSS (PFS, DSS)
Agur et al., 2015 [29] Israel 98 Limited/advanced ABVD 60(60), BEACOPP 29(29), others 9 (1) NS 33 (34), MC 7 (7), Others 58 (59) NR CD68 (PGM1) Visual, cell counting 25 % Mean: 3.8 (0.9–7.8) CD68, NSS (PFS)
Moreno et al., 2015 [21] Spain 249 Advanced NR NS 162 (65), MC 68 (27), Others 19 (8) NR CD68 (PGM1), CD163 (10D6) Computer-assisted point counting 30 % NR CD68, adverse (OS)
Jakovic et al., 2016 [22] Serbia 101 Advanced ABVD ± RT 101 (100) NS 80 (79), MC 13 (13), Others 8 (8) NR CD68 (PGM1) Visual estimation 25 % 8.6 (0.2–16) CD68, adverse (EFS, OS)
  1. ABVD doxorubicin, bleomycin, vinblastine, and dacarbazine, BEACOPP bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone, COPP cyclophosphamide, vincristine, procarbazine, and prednisone, C-MOPP cyclophosphamide, vincristine, procarbazine, prednisone, EVAP etoposide, vinblastine, adriamycin and prednisolone, EBVP epirubicin, bleomycin, vinblastine and prednisone, MOPP mustargen, oncovin, procarbazine, and prednisone, RT radiotherapy, Stanford V vinblastine, doxorubicin, vincristine, bleomycin, mustard, etoposide, and prednisone, NS nodular sclerosis, MC mixed cellularity, Neg negative, Pos positive, RT radiotherapy, NOS not otherwise specified, PFS progression-free survival, DSS disease-specific survival, EFS event-free survival, OS overall survival, FFS failure-free survival, FFTF freedom from treatment failure, NR not reported, NSS not statistically significant, HPF high power field