Univariate and multivariate analysis of IFI risk in patients with severe GVHD
Characteristic . | No. . | IFI (%) . | Days after GVHD* . | IR†(95% CI) . | IRR (95% CI) . | Unadjusted HR‡ . | P . | Adjusted HR§ . | P . |
|---|---|---|---|---|---|---|---|---|---|
| Severe GVHD | 53 | 10 (18.9) | 10 115 | 0.99 (0.48-1.82) | — | — | — | — | — |
| Sex | |||||||||
| Female | 21 | 4 (19.1) | 5255 | 0.76 (0.21-1.95) | — | — | — | — | — |
| Male | 32 | 6 (18.8) | 4900 | 1.22 (0.45-2.67) | 1.61 (0.45-5.70) | 1.29 | .69 | — | — |
| Age, y | |||||||||
| 18-44 | 23 | 3 (13.0) | 4240 | 0.71 (0.15-2.07) | — | — | — | — | — |
| 45-66 | 30 | 7 (23.3) | 5915 | 1.18 (0.48-2.44) | 1.67 (0.43-6.47) | 1.58 | .51 | — | — |
| Transplant type | |||||||||
| Myeloablative | 36 | 2 (5.6) | 7227 | 0.28 (0.03-0.99) | — | — | — | — | — |
| Nonmyeloablative | 17 | 8 (47.1) | 2928 | 2.73 (1.18-5.38) | 9.87 (2.10-46.5) | 8.54 | .007 | 8.05 (1.56-41.4) | .013 |
| Relationship to donor | |||||||||
| Related | 18 | 2 (11.1) | 4394 | 0.46 (0.06-1.64) | — | — | — | — | — |
| Unrelated | 35 | 8 (22.9) | 5761 | 1.39 (0.60-2.74) | 3.05 (0.65-14.4) | 2.87 | .18 | — | — |
| Stem cell source | |||||||||
| Bone marrow | 33 | 3 (9.1) | 6647 | 0.45 (0.09-1.32) | — | — | — | — | — |
| Peripheral blood | 20 | 7 (35) | 3508 | 2.00 (0.80-4.11) | 4.42 (1.14-17.1) | 3.52 | .07 | — | — |
| Risk group | |||||||||
| Low risk | 15 | 1 (6.7) | 3540 | 0.28 (0.01-1.57) | — | — | — | — | — |
| High risk | 38 | 9 (23.7) | 6615 | 1.36 (0.62-2.59) | 4.82 (0.61-38.0) | 3.93 | .20 | — | — |
| CMV serology of donor/recipient | |||||||||
| Any seropositive | 28 | 5 (17.9) | 6526 | 0.77 (0.25-1.79) | 0.63 (0.17-2.36) | 0.77 | .7 | — | — |
| D-/R- | 24 | 4 (16.7) | 3313 | 1.21 (0.33-3.09) | — | — | — | — | — |
| GVHD treatments | |||||||||
| Cumulative prednisone-equivalents | |||||||||
| 1-100 mg/kg | 21 | 1 (4.8) | 2359 | 0.42 (0.01-2.36) | — | — | — | — | — |
| 101-200 mg/kg | 26 | 7 (26.9) | 5350 | 1.31 (0.53-2.70) | — | — | — | — | — |
| 201-300 mg/kg | 4 | 2 (50) | 1088 | 1.84 (0.22-6.64) | — | — | — | — | — |
| 301-400 mg/kg | 2 | 0 (0) | 1358 | — | — | — | — | — | — |
| Cyclosporine | 29 | 8 (27.6) | 6939 | 1.15 (0.50-2.27) | 3.35 (0.71-15.8) | 3.56 | 0.11 | — | — |
| No cyclosporine | 24 | 2 (8.3) | 5809 | 0.34 (0.04-1.24) | — | — | — | — | — |
| Tacrolimus | 34 | 3 (8.8) | 7030 | 0.43 (0.09-1.25) | 0.19 (0.05-0.74) | 0.21 | 0.02 | — | — |
| No tacrolimus | 19 | 7 (36.8) | 3125 | 2.24 (0.90-4.61) | — | — | — | — | — |
| Sirolimus | 11 | 2 (18.2) | 1493 | 1.34 (0.16-4.84) | 1.45 (0.31-6.83) | 1.25 | 0.78 | — | — |
| No sirolimus | 42 | 8 (19.1) | 8662 | 0.92 (0.40-1.82) | — | — | — | — | — |
| MMF | 28 | 8 (28.6) | 5056 | 1.58 (0.68-3.12) | 4.03 (0.86-19.0) | 3.36 | 0.13 | — | — |
| No MMF | 25 | 2 (8) | 5099 | 0.39 (0.05-1.42) | — | — | — | — | — |
| Daclizumab | 29 | 4 (13.8) | 4720 | 0.85 (0.23-2.17) | 0.77 (0.22-2.72) | 0.74 | 0.64 | — | — |
| No daclizumab | 24 | 6 (25) | 5435 | 1.10 (0.41-2.41) | — | — | — | — | — |
| Infliximab | 11 | 5 (45.5) | 737 | 6.78 (2.20-15.8) | 12.8 (3.70-44.1) | 30.4 | 0.002 | 13.6 (2.29-80.2) | .004 |
| No infliximab | 42 | 5 (11.9) | 9418 | 0.53 (0.17-1.24) | — | — | — | — | — |
| Empiric amphotericin B | 37 | 7 (18.9) | 5309 | 1.32 (0.53-2.72) | 2.13 (0.55-8.24) | 1.93 | 0.34 | — | — |
| No empiric amphotericin B | 16 | 3 (18.8) | 4846 | 0.62 (0.13-1.81) | — | — | — | — | — |
| Empiric fluconazole | 32 | 8 (25) | 5938 | 1.35 (0.58-2.65) | 2.84 (0.60-13.4) | 2.16 | 0.34 | — | — |
| No empiric fluconazole | 21 | 2 (9.5) | 4217 | 0.47 (0.06-1.71) | — | — | — | — | — |
| Organ-specific GVHD | |||||||||
| Gastrointestinal 3 or 4 | 19 | 6 (31.6) | 1950 | 3.08 (1.13-6.71) | 6.31 (1.78-22.4) | 4.56 | 0.02 | 3.46 (0.67-17.9) | .14 |
| No gastrointestinal 3 or 4 | 34 | 4 (11.8) | 8205 | 0.49 (0.13-1.25) | — | — | — | — | — |
| Hepatic 3 or 4 | 21 | 2 (9.5) | 3233 | 0.62 (0.08-2.23) | 0.54 (0.11-2.52) | 0.50 | 0.38 | — | — |
| No hepatic 3 or 4 | 32 | 8 (25) | 6922 | 1.16 (0.50-2.27) | — | — | — | — | — |
| Cutaneous 3 or 4 | 23 | 5 (21.7) | 4141 | 1.21 (0.39-2.81) | 1.45 (0.42-5.02) | 1.47 | 0.55 | — | — |
| No cutaneous 3 or 4 | 30 | 5 (16.7) | 6014 | 0.83 (0.27-1.94) | — | — | — | — | — |
Characteristic . | No. . | IFI (%) . | Days after GVHD* . | IR†(95% CI) . | IRR (95% CI) . | Unadjusted HR‡ . | P . | Adjusted HR§ . | P . |
|---|---|---|---|---|---|---|---|---|---|
| Severe GVHD | 53 | 10 (18.9) | 10 115 | 0.99 (0.48-1.82) | — | — | — | — | — |
| Sex | |||||||||
| Female | 21 | 4 (19.1) | 5255 | 0.76 (0.21-1.95) | — | — | — | — | — |
| Male | 32 | 6 (18.8) | 4900 | 1.22 (0.45-2.67) | 1.61 (0.45-5.70) | 1.29 | .69 | — | — |
| Age, y | |||||||||
| 18-44 | 23 | 3 (13.0) | 4240 | 0.71 (0.15-2.07) | — | — | — | — | — |
| 45-66 | 30 | 7 (23.3) | 5915 | 1.18 (0.48-2.44) | 1.67 (0.43-6.47) | 1.58 | .51 | — | — |
| Transplant type | |||||||||
| Myeloablative | 36 | 2 (5.6) | 7227 | 0.28 (0.03-0.99) | — | — | — | — | — |
| Nonmyeloablative | 17 | 8 (47.1) | 2928 | 2.73 (1.18-5.38) | 9.87 (2.10-46.5) | 8.54 | .007 | 8.05 (1.56-41.4) | .013 |
| Relationship to donor | |||||||||
| Related | 18 | 2 (11.1) | 4394 | 0.46 (0.06-1.64) | — | — | — | — | — |
| Unrelated | 35 | 8 (22.9) | 5761 | 1.39 (0.60-2.74) | 3.05 (0.65-14.4) | 2.87 | .18 | — | — |
| Stem cell source | |||||||||
| Bone marrow | 33 | 3 (9.1) | 6647 | 0.45 (0.09-1.32) | — | — | — | — | — |
| Peripheral blood | 20 | 7 (35) | 3508 | 2.00 (0.80-4.11) | 4.42 (1.14-17.1) | 3.52 | .07 | — | — |
| Risk group | |||||||||
| Low risk | 15 | 1 (6.7) | 3540 | 0.28 (0.01-1.57) | — | — | — | — | — |
| High risk | 38 | 9 (23.7) | 6615 | 1.36 (0.62-2.59) | 4.82 (0.61-38.0) | 3.93 | .20 | — | — |
| CMV serology of donor/recipient | |||||||||
| Any seropositive | 28 | 5 (17.9) | 6526 | 0.77 (0.25-1.79) | 0.63 (0.17-2.36) | 0.77 | .7 | — | — |
| D-/R- | 24 | 4 (16.7) | 3313 | 1.21 (0.33-3.09) | — | — | — | — | — |
| GVHD treatments | |||||||||
| Cumulative prednisone-equivalents | |||||||||
| 1-100 mg/kg | 21 | 1 (4.8) | 2359 | 0.42 (0.01-2.36) | — | — | — | — | — |
| 101-200 mg/kg | 26 | 7 (26.9) | 5350 | 1.31 (0.53-2.70) | — | — | — | — | — |
| 201-300 mg/kg | 4 | 2 (50) | 1088 | 1.84 (0.22-6.64) | — | — | — | — | — |
| 301-400 mg/kg | 2 | 0 (0) | 1358 | — | — | — | — | — | — |
| Cyclosporine | 29 | 8 (27.6) | 6939 | 1.15 (0.50-2.27) | 3.35 (0.71-15.8) | 3.56 | 0.11 | — | — |
| No cyclosporine | 24 | 2 (8.3) | 5809 | 0.34 (0.04-1.24) | — | — | — | — | — |
| Tacrolimus | 34 | 3 (8.8) | 7030 | 0.43 (0.09-1.25) | 0.19 (0.05-0.74) | 0.21 | 0.02 | — | — |
| No tacrolimus | 19 | 7 (36.8) | 3125 | 2.24 (0.90-4.61) | — | — | — | — | — |
| Sirolimus | 11 | 2 (18.2) | 1493 | 1.34 (0.16-4.84) | 1.45 (0.31-6.83) | 1.25 | 0.78 | — | — |
| No sirolimus | 42 | 8 (19.1) | 8662 | 0.92 (0.40-1.82) | — | — | — | — | — |
| MMF | 28 | 8 (28.6) | 5056 | 1.58 (0.68-3.12) | 4.03 (0.86-19.0) | 3.36 | 0.13 | — | — |
| No MMF | 25 | 2 (8) | 5099 | 0.39 (0.05-1.42) | — | — | — | — | — |
| Daclizumab | 29 | 4 (13.8) | 4720 | 0.85 (0.23-2.17) | 0.77 (0.22-2.72) | 0.74 | 0.64 | — | — |
| No daclizumab | 24 | 6 (25) | 5435 | 1.10 (0.41-2.41) | — | — | — | — | — |
| Infliximab | 11 | 5 (45.5) | 737 | 6.78 (2.20-15.8) | 12.8 (3.70-44.1) | 30.4 | 0.002 | 13.6 (2.29-80.2) | .004 |
| No infliximab | 42 | 5 (11.9) | 9418 | 0.53 (0.17-1.24) | — | — | — | — | — |
| Empiric amphotericin B | 37 | 7 (18.9) | 5309 | 1.32 (0.53-2.72) | 2.13 (0.55-8.24) | 1.93 | 0.34 | — | — |
| No empiric amphotericin B | 16 | 3 (18.8) | 4846 | 0.62 (0.13-1.81) | — | — | — | — | — |
| Empiric fluconazole | 32 | 8 (25) | 5938 | 1.35 (0.58-2.65) | 2.84 (0.60-13.4) | 2.16 | 0.34 | — | — |
| No empiric fluconazole | 21 | 2 (9.5) | 4217 | 0.47 (0.06-1.71) | — | — | — | — | — |
| Organ-specific GVHD | |||||||||
| Gastrointestinal 3 or 4 | 19 | 6 (31.6) | 1950 | 3.08 (1.13-6.71) | 6.31 (1.78-22.4) | 4.56 | 0.02 | 3.46 (0.67-17.9) | .14 |
| No gastrointestinal 3 or 4 | 34 | 4 (11.8) | 8205 | 0.49 (0.13-1.25) | — | — | — | — | — |
| Hepatic 3 or 4 | 21 | 2 (9.5) | 3233 | 0.62 (0.08-2.23) | 0.54 (0.11-2.52) | 0.50 | 0.38 | — | — |
| No hepatic 3 or 4 | 32 | 8 (25) | 6922 | 1.16 (0.50-2.27) | — | — | — | — | — |
| Cutaneous 3 or 4 | 23 | 5 (21.7) | 4141 | 1.21 (0.39-2.81) | 1.45 (0.42-5.02) | 1.47 | 0.55 | — | — |
| No cutaneous 3 or 4 | 30 | 5 (16.7) | 6014 | 0.83 (0.27-1.94) | — | — | — | — | — |
Abbreviations and variables are explained in Tables 1, 2, 3.
Days of follow-up after onset of GVHD, censored for IFI, death, or end of follow-up period.
Cases/1000 GVHD patient-days of observation from onset of GVHD. Confidence intervals were calculated using the Haenszel method.
Unadjusted hazard ratio (HR) obtained from univariate time-dependent Cox model.
Adjusted HR from multivariate time-dependent Cox model, with 95% CI shown in parentheses. Values shown are from covariates retained in final model. See text for details.