Risk factors associated with treatment failure*
| . | Univariate . | Multivariate . | ||
|---|---|---|---|---|
| Factor . | HR (95% CI) . | P . | HR (95% CI) . | P . |
| Time from transplantation to initial systemic treatment (per year) | 0.73 (0.50-1.05) | .09 | ||
| Time from initial treatment to second-line treatment (per year) | 0.88 (0.75-1.02) | .09 | ||
| Patient age at second-line treatment (per decade) | 0.97 (0.90-1.04) | .40 | ||
| Female donor to male recipient | 0.87 (0.66-1.16) | .36 | ||
| Disease risk at transplantation | ||||
| Low | 1.00 (reference) | 1.00 (reference) | ||
| High | 1.47 (1.12-1.93) | .005 | 1.49 (1.13-1.96) | .004 |
| Conditioning regimen | ||||
| High intensity without TBI | 1.00 (reference) | |||
| High intensity with TBI | 1.61 (1.17-2.23) | .004 | ||
| Reduced intensity | 1.28 (0.94-1.74) | .11 | ||
| Graft source | ||||
| Bone marrow | 1.00 (reference) | |||
| Mobilized blood cells | 0.83 (0.55-1.24) | .36 | ||
| Umbilical cord blood | 1.36 (0.67-2.75) | .39 | ||
| Donor and HLA type | ||||
| HLA-matched related | 1.00 (reference) | |||
| HLA-matched unrelated | 1.11 (0.83-1.49) | .49 | ||
| HLA-mismatched | 1.31 (0.93-1.84) | .12 | ||
| Initial systemic treatment | ||||
| Prednisone + CNI | 1.00 (reference) | |||
| Prednisone + CNI + mycophenolate mofetil | 1.28 (0.90-1.81) | .17 | ||
| Prednisone alone | 0.83 (0.54-1.28) | .39 | ||
| Prednisone + others | 1.49 (0.93-2.39) | .09 | ||
| Reason for second-line treatment | ||||
| Progression | 1.00 (reference) | |||
| Lack of improvement | 0.95 (0.71-1.27) | .73 | ||
| Presence of involvement at second-line treatment | ||||
| Skin | 1.22 (0.91-1.65) | .19 | ||
| Eyes | 1.03 (0.79-1.34) | .86 | ||
| Mouth | 1.19 (0.89-1.60) | .25 | ||
| Liver | 1.27 (0.96-1.68) | .09 | ||
| Gastrointestinal tract | ||||
| No involvement | 1.00 (reference) | 1.00 (reference) | ||
| Upper only | 1.14 (0.79-1.64) | .48 | 1.15 (0.80-1.66) | .45 |
| Any lower | 1.62 (1.13-2.31) | .008 | 1.85 (1.29-2.65) | .0009 |
| Lung | 0.71 (0.46-1.09) | .12 | ||
| Joint or fascia | 1.07 (0.79-1.44) | .66 | ||
| Genital tract | 1.10 (0.71-1.69) | .67 | ||
| No. of sites involved at second-line treatment | ||||
| 1 or 2 | 1.00 (reference) | |||
| 3 | 0.98 (0.72-1.35) | .91 | ||
| >3 | 1.36 (1.00-1.86) | .05 | ||
| NIH global score at second-line treatment | ||||
| Mild/moderate | 1.00 (reference) | 1.00 (reference) | ||
| Severe | 1.44 (1.11-1.87) | .006 | 1.49 (1.15-1.95) | .003 |
| Thrombocytopenia at second-line treatment | 1.42 (1.02-1.98) | .04 | ||
| Hyperbilirubinemia at second-line treatment | 1.72 (1.10-2.70) | .02 | ||
| Prednisone-equivalent steroid dose immediately before second-line treatment | ||||
| None | 1.00 (reference) | |||
| <0.5 mg/kg per day | 0.86 (0.58-1.29) | .47 | ||
| 0.5-1.0 mg/kg per day | 0.92 (0.59-1.43) | .70 | ||
| ≥1.0 mg/kg per day | 1.61 (1.03-2.53) | .04 | ||
| . | Univariate . | Multivariate . | ||
|---|---|---|---|---|
| Factor . | HR (95% CI) . | P . | HR (95% CI) . | P . |
| Time from transplantation to initial systemic treatment (per year) | 0.73 (0.50-1.05) | .09 | ||
| Time from initial treatment to second-line treatment (per year) | 0.88 (0.75-1.02) | .09 | ||
| Patient age at second-line treatment (per decade) | 0.97 (0.90-1.04) | .40 | ||
| Female donor to male recipient | 0.87 (0.66-1.16) | .36 | ||
| Disease risk at transplantation | ||||
| Low | 1.00 (reference) | 1.00 (reference) | ||
| High | 1.47 (1.12-1.93) | .005 | 1.49 (1.13-1.96) | .004 |
| Conditioning regimen | ||||
| High intensity without TBI | 1.00 (reference) | |||
| High intensity with TBI | 1.61 (1.17-2.23) | .004 | ||
| Reduced intensity | 1.28 (0.94-1.74) | .11 | ||
| Graft source | ||||
| Bone marrow | 1.00 (reference) | |||
| Mobilized blood cells | 0.83 (0.55-1.24) | .36 | ||
| Umbilical cord blood | 1.36 (0.67-2.75) | .39 | ||
| Donor and HLA type | ||||
| HLA-matched related | 1.00 (reference) | |||
| HLA-matched unrelated | 1.11 (0.83-1.49) | .49 | ||
| HLA-mismatched | 1.31 (0.93-1.84) | .12 | ||
| Initial systemic treatment | ||||
| Prednisone + CNI | 1.00 (reference) | |||
| Prednisone + CNI + mycophenolate mofetil | 1.28 (0.90-1.81) | .17 | ||
| Prednisone alone | 0.83 (0.54-1.28) | .39 | ||
| Prednisone + others | 1.49 (0.93-2.39) | .09 | ||
| Reason for second-line treatment | ||||
| Progression | 1.00 (reference) | |||
| Lack of improvement | 0.95 (0.71-1.27) | .73 | ||
| Presence of involvement at second-line treatment | ||||
| Skin | 1.22 (0.91-1.65) | .19 | ||
| Eyes | 1.03 (0.79-1.34) | .86 | ||
| Mouth | 1.19 (0.89-1.60) | .25 | ||
| Liver | 1.27 (0.96-1.68) | .09 | ||
| Gastrointestinal tract | ||||
| No involvement | 1.00 (reference) | 1.00 (reference) | ||
| Upper only | 1.14 (0.79-1.64) | .48 | 1.15 (0.80-1.66) | .45 |
| Any lower | 1.62 (1.13-2.31) | .008 | 1.85 (1.29-2.65) | .0009 |
| Lung | 0.71 (0.46-1.09) | .12 | ||
| Joint or fascia | 1.07 (0.79-1.44) | .66 | ||
| Genital tract | 1.10 (0.71-1.69) | .67 | ||
| No. of sites involved at second-line treatment | ||||
| 1 or 2 | 1.00 (reference) | |||
| 3 | 0.98 (0.72-1.35) | .91 | ||
| >3 | 1.36 (1.00-1.86) | .05 | ||
| NIH global score at second-line treatment | ||||
| Mild/moderate | 1.00 (reference) | 1.00 (reference) | ||
| Severe | 1.44 (1.11-1.87) | .006 | 1.49 (1.15-1.95) | .003 |
| Thrombocytopenia at second-line treatment | 1.42 (1.02-1.98) | .04 | ||
| Hyperbilirubinemia at second-line treatment | 1.72 (1.10-2.70) | .02 | ||
| Prednisone-equivalent steroid dose immediately before second-line treatment | ||||
| None | 1.00 (reference) | |||
| <0.5 mg/kg per day | 0.86 (0.58-1.29) | .47 | ||
| 0.5-1.0 mg/kg per day | 0.92 (0.59-1.43) | .70 | ||
| ≥1.0 mg/kg per day | 1.61 (1.03-2.53) | .04 | ||
CNI, calcineurin inhibitor; TBI, total-body irradiation.
Treatment failure was defined by the onset of third-line systemic treatment, nonrelapse mortality, or recurrent malignancy during second-line treatment.