HRs, 95% CIs, and P values from Cox proportional hazards models, for all evaluated children, and for children with and without verified FHL
| Reference group . | Group compared with the reference group . | All children (N = 187), HR (95% CI; P) . | Children with FHL (n = 134), HR (95% CI; P) . | Children without verified FHL (n = 53), HR (95% CI; P) . | |||
|---|---|---|---|---|---|---|---|
| OS . | EFS . | OS . | EFS . | OS . | EFS . | ||
| Sex | |||||||
| Female | Male | 1.26 (0.78-2.03; .35) | 1.22 (0.78-1.90; .38) | 1.68 (0.92-3.07; .092) | 1.59 (0.93-2.71; .092) | 0.65 (0.29-1.46; .30) | 0.64 (0.29-1.44; .28) |
| Age group at HSCT | |||||||
| Age at HSCT conditioning <1 y | Age at HSCT conditioning 1-2.99 y | 0.84 (0.49-1.49; .56) | 1.06 (0.64-1.75; .83) | 0.66 (0.31-1.40; .28) | 1.07 (0.58-1.96; .83) | 0.78 (0.28-2.14; .62) | 0.77 (0.28-2.13; .62) |
| Age at HSCT conditioning 3-5.99 y | 1.10 (0.46-2.63; .83) | 0.97 (0.42-2.37; .99) | 1.38 (0.48-3.97; .55) | 1.20 (0.42-3.43; .73) | 0.53 (0.11-2.61; .43) | 0.55 (0.11-2.76; .47) | |
| Age at HSCT conditioning ≥6 y | 1.51 (0.74-3.07; .26) | 1.34 (0.66-2.70; .42) | 1.17 (0.41-3.36; .77) | 1.03 (0.36-2.93; .96) | 1.19 (0.39-3.71: .76) | 1.19 (0.38-3.70; .76) | |
| Time to HSCT and interval | |||||||
| Time to HSCT <6 mo | Time to HSCT ≥ 6 mo | 1.22 (0.75-1.99; .42) | 1.35 (0.86-2.11; .20) | 0.89 (0.46-1.73; .73) | 1.18 (0.67-2.08; .56) | 1.63 (0.71-3.73; .25) | 1.58 (0.69-3.20; .28) |
| HSCT time interval 2004-2006 | HSCT time interval 2007-2009 | 1.60 (0.87-2.90; .12) | 1.28 (0.74-2.19; .39) | 1.55 (0.73-3.37; .25) | 1.12 (0.58-2.14; .74) | 1.76 (0.66-4.70; .26) | 1.71 (0.64-4.56; .28). |
| HSCT time interval 2010-2012 | 1.08 (0.55-2.10; .83) | 0.99 (0.55-1.80; .97) | 1.08 (0.47-2.48; .87) | 0.94 (0.47-1.90; .86) | 1.18 (0.38-3.67; .77) | 1.14 (0.37-3.54; .82) | |
| Donor and conditioning | |||||||
| Donor: MRD | Donor: MUD | 0.60 (0.32-1.15; .12) | 0.71 (0.40-1.28; .26) | 0.60 (0.27-1.33; .21) | 0.74 (0.37-1.49; .40) | 0.72 (0.24-2.15; .55) | 0.73 (0.25-2.19; .58) |
| Donor: UCB | 0.92 (0.50-1.70; .79) | 0.86 (0.47-1.55; .61) | 0.85 (0.39-1.87; .68) | 0.75 (0.37-1.57; .45) | 1.16 (0.43-3.12; .77) | 1.20 (0.45-3.22; .72) | |
| Conditioning busulfan-based | Conditioning fludarabine-based | 0.85 (0.45-1.60; .62) | 1.10 (0.63-1.91; .74) | 0.83 (0.35-1.94; .66) | 1.27 (0.64-2.52; .49) | 0.80 (0.31-2.08; .65) | 0.79 (0.31-2.05; .63) |
| Conditioning treosulfan-based | 0.47 (0.17-1.32; .15) | 0.51 (0.20-1.29; .16) | 0.67 (0.23-1.95; .46) | 0.68 (0.26-1.77; .43) | † | † | |
| Disease activity at conditioning | |||||||
| Complete response (ferritin <500 µg/L)‡ | Partial response (ferritin <500 µg/L)§ | 2.12 (1.06-4.27; .035)* | 1.30 (0.74-2.30; .36) | 1.89 (0.82-4.37; .14) | 0.99 (0.52-1.88; .96) | 2.96 (0.83-10.51; .094) | 3.01 (0.85-10.69; .089) |
| Complete response (ferritin <2000 µg/L)‖ | Partial response (ferritin <2000 µg/L)¶ | 1.74 (0.94-3.22; .080) | 1.16 (0.68-1.98; .58) | 1.88 (0.86-4.09; .11) | 1.01 (0.54-1.89; .97) | 1.68 (0.60-4.73; .32) | 1.71 (0.61-4.82; .31) |
| No neurologic symptoms | Neurologic symptoms | 1.34 (0.72-2.52; .36) | 1.26 (0.70-2.25; .45) | 1.49 (0.71-3.13; .30) | 1.30 (0.67-2.53; .45) | 1.24 (0.36-4.19; .74) | 1.24 (0.36-4.30; .73) |
| CSF cells or protein normal# | CSF cells or protein abnormal# | 1.32 (0.57-3.04; .52) | 1.64 (0.76-3.55; .21) | 1.44 (0.48-4.29; .52) | 1.93 (0.73-5.09; .19) | 1.27 (0.34-4.75; .72) | 1.22 (0.33-4.55; .77) |
| Ferritin, 1-unit increase in ln | 1.23 (1.03-1.48; .023)* | 1.08 (0.90-1.28; .42) | 1.29 (1.01-1.66; .040)* | 1.03 (0.82-1.28; .82) | 1.13 (0.86-1.50; .37) | 1.14 (0.87-1.51; .35) | |
| Reference group . | Group compared with the reference group . | All children (N = 187), HR (95% CI; P) . | Children with FHL (n = 134), HR (95% CI; P) . | Children without verified FHL (n = 53), HR (95% CI; P) . | |||
|---|---|---|---|---|---|---|---|
| OS . | EFS . | OS . | EFS . | OS . | EFS . | ||
| Sex | |||||||
| Female | Male | 1.26 (0.78-2.03; .35) | 1.22 (0.78-1.90; .38) | 1.68 (0.92-3.07; .092) | 1.59 (0.93-2.71; .092) | 0.65 (0.29-1.46; .30) | 0.64 (0.29-1.44; .28) |
| Age group at HSCT | |||||||
| Age at HSCT conditioning <1 y | Age at HSCT conditioning 1-2.99 y | 0.84 (0.49-1.49; .56) | 1.06 (0.64-1.75; .83) | 0.66 (0.31-1.40; .28) | 1.07 (0.58-1.96; .83) | 0.78 (0.28-2.14; .62) | 0.77 (0.28-2.13; .62) |
| Age at HSCT conditioning 3-5.99 y | 1.10 (0.46-2.63; .83) | 0.97 (0.42-2.37; .99) | 1.38 (0.48-3.97; .55) | 1.20 (0.42-3.43; .73) | 0.53 (0.11-2.61; .43) | 0.55 (0.11-2.76; .47) | |
| Age at HSCT conditioning ≥6 y | 1.51 (0.74-3.07; .26) | 1.34 (0.66-2.70; .42) | 1.17 (0.41-3.36; .77) | 1.03 (0.36-2.93; .96) | 1.19 (0.39-3.71: .76) | 1.19 (0.38-3.70; .76) | |
| Time to HSCT and interval | |||||||
| Time to HSCT <6 mo | Time to HSCT ≥ 6 mo | 1.22 (0.75-1.99; .42) | 1.35 (0.86-2.11; .20) | 0.89 (0.46-1.73; .73) | 1.18 (0.67-2.08; .56) | 1.63 (0.71-3.73; .25) | 1.58 (0.69-3.20; .28) |
| HSCT time interval 2004-2006 | HSCT time interval 2007-2009 | 1.60 (0.87-2.90; .12) | 1.28 (0.74-2.19; .39) | 1.55 (0.73-3.37; .25) | 1.12 (0.58-2.14; .74) | 1.76 (0.66-4.70; .26) | 1.71 (0.64-4.56; .28). |
| HSCT time interval 2010-2012 | 1.08 (0.55-2.10; .83) | 0.99 (0.55-1.80; .97) | 1.08 (0.47-2.48; .87) | 0.94 (0.47-1.90; .86) | 1.18 (0.38-3.67; .77) | 1.14 (0.37-3.54; .82) | |
| Donor and conditioning | |||||||
| Donor: MRD | Donor: MUD | 0.60 (0.32-1.15; .12) | 0.71 (0.40-1.28; .26) | 0.60 (0.27-1.33; .21) | 0.74 (0.37-1.49; .40) | 0.72 (0.24-2.15; .55) | 0.73 (0.25-2.19; .58) |
| Donor: UCB | 0.92 (0.50-1.70; .79) | 0.86 (0.47-1.55; .61) | 0.85 (0.39-1.87; .68) | 0.75 (0.37-1.57; .45) | 1.16 (0.43-3.12; .77) | 1.20 (0.45-3.22; .72) | |
| Conditioning busulfan-based | Conditioning fludarabine-based | 0.85 (0.45-1.60; .62) | 1.10 (0.63-1.91; .74) | 0.83 (0.35-1.94; .66) | 1.27 (0.64-2.52; .49) | 0.80 (0.31-2.08; .65) | 0.79 (0.31-2.05; .63) |
| Conditioning treosulfan-based | 0.47 (0.17-1.32; .15) | 0.51 (0.20-1.29; .16) | 0.67 (0.23-1.95; .46) | 0.68 (0.26-1.77; .43) | † | † | |
| Disease activity at conditioning | |||||||
| Complete response (ferritin <500 µg/L)‡ | Partial response (ferritin <500 µg/L)§ | 2.12 (1.06-4.27; .035)* | 1.30 (0.74-2.30; .36) | 1.89 (0.82-4.37; .14) | 0.99 (0.52-1.88; .96) | 2.96 (0.83-10.51; .094) | 3.01 (0.85-10.69; .089) |
| Complete response (ferritin <2000 µg/L)‖ | Partial response (ferritin <2000 µg/L)¶ | 1.74 (0.94-3.22; .080) | 1.16 (0.68-1.98; .58) | 1.88 (0.86-4.09; .11) | 1.01 (0.54-1.89; .97) | 1.68 (0.60-4.73; .32) | 1.71 (0.61-4.82; .31) |
| No neurologic symptoms | Neurologic symptoms | 1.34 (0.72-2.52; .36) | 1.26 (0.70-2.25; .45) | 1.49 (0.71-3.13; .30) | 1.30 (0.67-2.53; .45) | 1.24 (0.36-4.19; .74) | 1.24 (0.36-4.30; .73) |
| CSF cells or protein normal# | CSF cells or protein abnormal# | 1.32 (0.57-3.04; .52) | 1.64 (0.76-3.55; .21) | 1.44 (0.48-4.29; .52) | 1.93 (0.73-5.09; .19) | 1.27 (0.34-4.75; .72) | 1.22 (0.33-4.55; .77) |
| Ferritin, 1-unit increase in ln | 1.23 (1.03-1.48; .023)* | 1.08 (0.90-1.28; .42) | 1.29 (1.01-1.66; .040)* | 1.03 (0.82-1.28; .82) | 1.13 (0.86-1.50; .37) | 1.14 (0.87-1.51; .35) | |
All clinical parameters and laboratory values were analyzed at the time of HSCT conditioning. For OS and EFS, death, and death or second HSCT, were defined as events, respectively. Cox proportional HRs compared with given reference group. Two-sided 95% CIs are presented.
CSF, cerebrospinal fluid.
P < .05 was considered significant.
Too few patients (n = 2) to evaluate, both alive.
Complete response was defined as no fever, no splenomegaly, ANC >1.0 × 109/L, platelets >100 × 109/L, fibrinogen >1.5, ferritin <500 µg/L; 6 of 6 or 5 of 5 (allowing missing information on one 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.
Pathologic levels by age at HSCT conditioning.