Patient characteristics at HSCT conditioning, for all evaluated children, children with and without verified FHL, and children without verified FHL aged <1 year and aged ≥1 year at the start of HLH-2004 treatment
| Characteristic . | All children (N = 187) . | Children with FHL (n = 134) . | Children without verified FHL (n = 53) . | Children without verified FHL aged <1 y at start of HLH-2004 (n = 24) . | Children without verified FHL aged ≥1 y at start of HLH-2004 (n = 29) . |
|---|---|---|---|---|---|
| No. yes/no. evaluated/% yes of evaluated/no. missing | |||||
| Male sex | 90/187/48/0 | 61/134/46/0 | 29/53/55/0 | 16/24/67/0 | 13/29/45/0 |
| Age at start of HLH-2004, y | |||||
| <1 | 124/187/66/0 | 100/134/75/0 | 24/53/45/0 | 24/24/100/0 | 0/29/0/0 |
| 1-2.99 | 34/187/18/0 | 20/134/15/0 | 14/53/26/0 | 0/24/0/0 | 14/29/48/0 |
| 3-5.99 | 12/187/6/0 | 7/134/5/0 | 5/53/9/0 | 0/24/0/0 | 5/29/17/0 |
| ≥6 | 17/187/9/0 | 7/134/5/0 | 10/53/19/0 | 0/24/0/0 | 10/29/34/0 |
| Age at HSCT, y | |||||
| <1 | 91/187/49/0 | 78/134/58/0 | 13/53/25/0 | 13/24/54/0 | 0/29/0/0 |
| 1-2.99 | 60/187/32/0 | 37/134/28/0 | 23/53/44/0 | 11/24/46/0 | 12/29/43/0 |
| 3-5.99 | 15/187/8/0 | 9/134/7/0 | 6/53/11/0 | 0/24/0/0 | 6/29/21/0 |
| ≥6 | 21/187/11/0 | 10/134/8/0 | 11/53/21/0 | 0/24/0/0 | 11/29/38/0 |
| Time to HSCT from HLH-2004 start, mo | |||||
| <6 | 120/187/64/0 | 94/134/70/0 | 26/53/49/0 | 12/24/50/0 | 14/29/48/0 |
| ≥6 | 67/87/36/0 | 40/134/30/0 | 27/53/51/0 | 12/24/50/0 | 15/29/52/0 |
| Fever | 17/149/11/38 | 13/106/12/28 | 4/43/9/10 | 1/21/5/3 | 3/22/14/7 |
| Splenomegaly | 35/145/24/42 | 23/102/23/32 | 12/43/28/10 | 8/21/38/3 | 4/22/18/7 |
| Hepatomegaly | 62/145/43/42 | 47/103/46/31 | 15/42/36/11 | 6/20/30/4 | 9/22/41/7 |
| Hemoglobin, g/L | |||||
| <90 | 49/145/34/42 | 34/105/32/29 | 15 /40/38 /13 | 9/20/45/4 | 6/20/30/9 |
| Neutrophils (ANC), ×109/L | |||||
| <1.0 | 36/134/27/53 | 27/95/28/39 | 9/39/23/14 | 6/19/32/5 | 3/20/15/9 |
| Platelets, ×109/L | |||||
| <100 | 25/145/17/42 | 14/106/13/28 | 11/39/28/14 | 4/19/21/5 | 7/20/35/9 |
| Triglycerides, mmol/L | |||||
| ≥3.0 | 45/108/42/79 | 34/73/47/61 | 11/35/31/18 | 4/16/25/8 | 7/19/37/10 |
| Fibrinogen, g/L | |||||
| ≤1.5 | 10/111/9/76 | 8/79/10/55 | 2/32/6/21 | 0/15/0/9 | 2/17/12/12 |
| Ferritin, µg/L | |||||
| ≥500 | 58/114/51/73 | 38/81/47/53 | 20/33/61/20 | 6/14/43/10 | 14/19/74/10 |
| ≥2000 | 20/114/18/73 | 14/81/17/53 | 6/33/18/20 | 1/14/7/10 | 5/19/26/10 |
| NK cell activity absent /low† | 24/36/67/151 | 17/20/85/114 | 7/16/44/37 | 2/6/33/18 | 5/10/50/19 |
| Soluble CD25, U/L† | |||||
| ≥2400 | 8/29/28/158 | 4/18/22/116 | 4/11/36/42 | 2/4/50/20 | 2/7/29/22 |
| CSF cells or CSF protein abnormal†‡ | 24/54/44/133 | 17/36/47/98 | 7/18/39/35 | 4/9/44/15 | 3/9/33/20 |
| Neurologic symptoms | 30/150/20/37 | 24/108/22/26 | 6/42/14/11 | 2/20/10/4 | 4/22/18/7 |
| Response (ferritin <500 µg/L) | |||||
| Complete§ | 42/129/33/58 | 30/95/32/39 | 12/34/35/19 | 6/15/40/9 | 6/19/32/10 |
| Partial‖ | 87/129/67/58 | 65/95/68/39 | 22/34/65/19 | 9/15/60/9 | 13/19/68/10 |
| Response (ferritin <2000 µg/L) | |||||
| Complete¶ | 55/131/42/56 | 38/96/40/38 | 17/35/49/18 | 8/15/53/9 | 9/20/45/9 |
| Partial# | 76/131/58/56 | 58/96/60/38 | 18/35/51/18 | 7/15/47/9 | 11/20/55/9 |
| Median (mean; range; no. missing) | |||||
| Age at start of HLH-2004, d | 138 (700; 3-6412; 0) | 103 (487; 3-5729; 0) | 441 (1239; 34-6412; 0) | 120 (153; 34-363; 0) | 1360 (2138; 384-6412; 0) |
| Age at HSCT, d | 371 (925; 86-7287; 0) | 309 (701; 86-6403; 0) | 651 (1490; 87-7287; 0) | 323 (363; 87-682; 0) | 1493 (2423; 578-7287; 0) |
| Time to HSCT, d | 148 (225; 25-2105; 0) | 129 (214; 25-2105; 0) | 190 (251; 25-1295; 0)* | 178 (210; 25-489; 0) | 194 (286; 35-1295; 0) |
| Hemoglobin, g/L | 96 (95; 25-151; 42) | 97 (97; 58-151; 29) | 95 (93; 67-127; 13) | 91 (93; 70-127; 4) | 96 (92; 67-109; 9) |
| Neutrophils, ANC, ×109/L | 1.82 (2.34; 0.00-12; 53) | 1.83 (2.40; 0.00-12; 39) | 1.73 (2.14; 0.00-9.50; 14) | 1.61 (1.80; 0.00-5.30; 5) | 2.14 (2.47; 0.00-9.50; 9) |
| Platelets, ×109/L | 288 (300; 3-925; 42) | 319 (327; 3-925; 28) | 244 (227; 13-493; 14) | 249 (245; 29-493; 5) | 201 (210; 13-484; 9) |
| Triglycerides, mmol/L | 2.53 (3.45; 0.45-20.90; 79) | 2.59 (3.81; 0.66-20.90; 61) | 1.90 (2.70; 0.45-8.28; 18) | 1.77 (2.13; 0.50-4.34; 8) | 2.37 (3.19; 0.45-8.28; 10) |
| Fibrinogen, g/L | 2.80 (3.00; 0.09-8.65; 76) | 2.77 (2.94; 0.09-6.63; 55) | 2.99 (3.17; 1.08-8.65; 21) | 2.60 (2.88; 1.60-5.90; 9) | 3.60 (3.43; 1.08-8.65; 12) |
| Ferritin, µg/L | 515 (2186; 11-74651; 73) | 460 (1637; 11-38934; 53) | 657 (3529; 19-74651; 20) | 344 (1054; 19-8219; 10) | 932 (5354; 97-74651; 10) |
| Soluble CD25, U/L† | 1559 (2389; 69-16200; 158) | 1266 (2743; 252-16200; 116) | 1682 (1810; 69-3126; 42) | 2588 (2362; 1390-2880; 20) | 1559 (1495; 69-3126; 22) |
| AST, U/L | 37 (62; 7-408; 52) | 38 (63; 9-408; 39) | 36 (60; 7-387; 13) | 33 (36; 7-103; 3) | 52 (87; 23-387; 10) |
| ALT, U/L | 34 (66; 5-634; 95) | 34 (72; 5-634; 82) | 34 (58; 8-313; 13) | 26 (31; 8-65; 3) | 49 (86; 13-313; 10) |
| Characteristic . | All children (N = 187) . | Children with FHL (n = 134) . | Children without verified FHL (n = 53) . | Children without verified FHL aged <1 y at start of HLH-2004 (n = 24) . | Children without verified FHL aged ≥1 y at start of HLH-2004 (n = 29) . |
|---|---|---|---|---|---|
| No. yes/no. evaluated/% yes of evaluated/no. missing | |||||
| Male sex | 90/187/48/0 | 61/134/46/0 | 29/53/55/0 | 16/24/67/0 | 13/29/45/0 |
| Age at start of HLH-2004, y | |||||
| <1 | 124/187/66/0 | 100/134/75/0 | 24/53/45/0 | 24/24/100/0 | 0/29/0/0 |
| 1-2.99 | 34/187/18/0 | 20/134/15/0 | 14/53/26/0 | 0/24/0/0 | 14/29/48/0 |
| 3-5.99 | 12/187/6/0 | 7/134/5/0 | 5/53/9/0 | 0/24/0/0 | 5/29/17/0 |
| ≥6 | 17/187/9/0 | 7/134/5/0 | 10/53/19/0 | 0/24/0/0 | 10/29/34/0 |
| Age at HSCT, y | |||||
| <1 | 91/187/49/0 | 78/134/58/0 | 13/53/25/0 | 13/24/54/0 | 0/29/0/0 |
| 1-2.99 | 60/187/32/0 | 37/134/28/0 | 23/53/44/0 | 11/24/46/0 | 12/29/43/0 |
| 3-5.99 | 15/187/8/0 | 9/134/7/0 | 6/53/11/0 | 0/24/0/0 | 6/29/21/0 |
| ≥6 | 21/187/11/0 | 10/134/8/0 | 11/53/21/0 | 0/24/0/0 | 11/29/38/0 |
| Time to HSCT from HLH-2004 start, mo | |||||
| <6 | 120/187/64/0 | 94/134/70/0 | 26/53/49/0 | 12/24/50/0 | 14/29/48/0 |
| ≥6 | 67/87/36/0 | 40/134/30/0 | 27/53/51/0 | 12/24/50/0 | 15/29/52/0 |
| Fever | 17/149/11/38 | 13/106/12/28 | 4/43/9/10 | 1/21/5/3 | 3/22/14/7 |
| Splenomegaly | 35/145/24/42 | 23/102/23/32 | 12/43/28/10 | 8/21/38/3 | 4/22/18/7 |
| Hepatomegaly | 62/145/43/42 | 47/103/46/31 | 15/42/36/11 | 6/20/30/4 | 9/22/41/7 |
| Hemoglobin, g/L | |||||
| <90 | 49/145/34/42 | 34/105/32/29 | 15 /40/38 /13 | 9/20/45/4 | 6/20/30/9 |
| Neutrophils (ANC), ×109/L | |||||
| <1.0 | 36/134/27/53 | 27/95/28/39 | 9/39/23/14 | 6/19/32/5 | 3/20/15/9 |
| Platelets, ×109/L | |||||
| <100 | 25/145/17/42 | 14/106/13/28 | 11/39/28/14 | 4/19/21/5 | 7/20/35/9 |
| Triglycerides, mmol/L | |||||
| ≥3.0 | 45/108/42/79 | 34/73/47/61 | 11/35/31/18 | 4/16/25/8 | 7/19/37/10 |
| Fibrinogen, g/L | |||||
| ≤1.5 | 10/111/9/76 | 8/79/10/55 | 2/32/6/21 | 0/15/0/9 | 2/17/12/12 |
| Ferritin, µg/L | |||||
| ≥500 | 58/114/51/73 | 38/81/47/53 | 20/33/61/20 | 6/14/43/10 | 14/19/74/10 |
| ≥2000 | 20/114/18/73 | 14/81/17/53 | 6/33/18/20 | 1/14/7/10 | 5/19/26/10 |
| NK cell activity absent /low† | 24/36/67/151 | 17/20/85/114 | 7/16/44/37 | 2/6/33/18 | 5/10/50/19 |
| Soluble CD25, U/L† | |||||
| ≥2400 | 8/29/28/158 | 4/18/22/116 | 4/11/36/42 | 2/4/50/20 | 2/7/29/22 |
| CSF cells or CSF protein abnormal†‡ | 24/54/44/133 | 17/36/47/98 | 7/18/39/35 | 4/9/44/15 | 3/9/33/20 |
| Neurologic symptoms | 30/150/20/37 | 24/108/22/26 | 6/42/14/11 | 2/20/10/4 | 4/22/18/7 |
| Response (ferritin <500 µg/L) | |||||
| Complete§ | 42/129/33/58 | 30/95/32/39 | 12/34/35/19 | 6/15/40/9 | 6/19/32/10 |
| Partial‖ | 87/129/67/58 | 65/95/68/39 | 22/34/65/19 | 9/15/60/9 | 13/19/68/10 |
| Response (ferritin <2000 µg/L) | |||||
| Complete¶ | 55/131/42/56 | 38/96/40/38 | 17/35/49/18 | 8/15/53/9 | 9/20/45/9 |
| Partial# | 76/131/58/56 | 58/96/60/38 | 18/35/51/18 | 7/15/47/9 | 11/20/55/9 |
| Median (mean; range; no. missing) | |||||
| Age at start of HLH-2004, d | 138 (700; 3-6412; 0) | 103 (487; 3-5729; 0) | 441 (1239; 34-6412; 0) | 120 (153; 34-363; 0) | 1360 (2138; 384-6412; 0) |
| Age at HSCT, d | 371 (925; 86-7287; 0) | 309 (701; 86-6403; 0) | 651 (1490; 87-7287; 0) | 323 (363; 87-682; 0) | 1493 (2423; 578-7287; 0) |
| Time to HSCT, d | 148 (225; 25-2105; 0) | 129 (214; 25-2105; 0) | 190 (251; 25-1295; 0)* | 178 (210; 25-489; 0) | 194 (286; 35-1295; 0) |
| Hemoglobin, g/L | 96 (95; 25-151; 42) | 97 (97; 58-151; 29) | 95 (93; 67-127; 13) | 91 (93; 70-127; 4) | 96 (92; 67-109; 9) |
| Neutrophils, ANC, ×109/L | 1.82 (2.34; 0.00-12; 53) | 1.83 (2.40; 0.00-12; 39) | 1.73 (2.14; 0.00-9.50; 14) | 1.61 (1.80; 0.00-5.30; 5) | 2.14 (2.47; 0.00-9.50; 9) |
| Platelets, ×109/L | 288 (300; 3-925; 42) | 319 (327; 3-925; 28) | 244 (227; 13-493; 14) | 249 (245; 29-493; 5) | 201 (210; 13-484; 9) |
| Triglycerides, mmol/L | 2.53 (3.45; 0.45-20.90; 79) | 2.59 (3.81; 0.66-20.90; 61) | 1.90 (2.70; 0.45-8.28; 18) | 1.77 (2.13; 0.50-4.34; 8) | 2.37 (3.19; 0.45-8.28; 10) |
| Fibrinogen, g/L | 2.80 (3.00; 0.09-8.65; 76) | 2.77 (2.94; 0.09-6.63; 55) | 2.99 (3.17; 1.08-8.65; 21) | 2.60 (2.88; 1.60-5.90; 9) | 3.60 (3.43; 1.08-8.65; 12) |
| Ferritin, µg/L | 515 (2186; 11-74651; 73) | 460 (1637; 11-38934; 53) | 657 (3529; 19-74651; 20) | 344 (1054; 19-8219; 10) | 932 (5354; 97-74651; 10) |
| Soluble CD25, U/L† | 1559 (2389; 69-16200; 158) | 1266 (2743; 252-16200; 116) | 1682 (1810; 69-3126; 42) | 2588 (2362; 1390-2880; 20) | 1559 (1495; 69-3126; 22) |
| AST, U/L | 37 (62; 7-408; 52) | 38 (63; 9-408; 39) | 36 (60; 7-387; 13) | 33 (36; 7-103; 3) | 52 (87; 23-387; 10) |
| ALT, U/L | 34 (66; 5-634; 95) | 34 (72; 5-634; 82) | 34 (58; 8-313; 13) | 26 (31; 8-65; 3) | 49 (86; 13-313; 10) |
All clinical parameters and laboratory values were analyzed at the time of HSCT conditioning.
ALT, alanine aminotransferase; AST, aspartate aminotransferase; CSF, cerebral spinal fluid.
Information on NK cell activity, soluble CD25, and CSF was reported as not analyzed in 95, 102, and 97 children, respectively.
Pathologic levels by age at HSCT conditioning.
Complete response was defined as no fever, no splenomegaly, ANC >1.0 × 109/L, platelets >100 × 109/L, fibrinogen >1.5 g/L, ferritin <500 µg/L; 6 of 6 or 5 of 5 (allowing missing information on 1 variable).
Partial response was defined as 3 to 5 of 6 normal parameters (fever, splenomegaly, ANC >1.0 × 109/L, platelets >100 × 109/L, fibrinogen >1.5 g/L, ferritin <500 µg/L), and the rest of the parameters abnormal.
Complete response was defined as no fever, no splenomegaly, ANC >1.0 × 109/L, platelets >100 × 109/L, fibrinogen >1.5 g/L, ferritin <2000 µg/L; 6 of 6 or 5 of 5 (allowing missing information on 1 variable).
Partial response was defined as 3 to 5 of 6 normal parameters (fever, splenomegaly, ANC >1.0 × 109/L, platelets >100 × 109/L, fibrinogen >1.5 g/L, ferritin <2000 µg/L), and the rest of the parameters abnormal.
P = .011 for time to HSCT; FHL children vs not verified FHL children. ***P < .001 for age at start HLH-2004 for FHL children vs not verified FHL children, and for age at HSCT conditioning for FHL children vs not verified FHL children.