Risk factors for early cardiac toxicity
| Univariate analysis . | Cardiac toxicity first the 180 d HR (95% CI) . | P value . |
|---|---|---|
| PTCY-based prophylaxis (vs others) | 3.08 (1.28-7.42) | 0.012 |
| TBI (overall) | ||
| Yes (any dose) (vs no) | 2.96 (1.53-5.78) | 0.001 |
| TBI according to dose | ||
| 2 Gy (vs no) | 3.17 (1.43-7.01) | 0.004 |
| ≥8 Gy (vs no) | 2.78 (1.25-6.20) | 0.012 |
| Age at allo-HCT | ||
| Continuous | 1.01 (0.98-1.04) | 0.21 |
| Age ≥55 y (vs younger) | 1.53 (0.79-2.98) | 0.20 |
| Female (vs male) | 1.18 (0.60-2.33) | 0.62 |
| History of HTN (vs no) | 1.94 (0.94-4.03) | 0.073 |
| History of diabetes (vs no) | 1.79 (0.62-5.14) | 0.27 |
| History of hyperlipidemia (vs no) | 0.62 (0.18-2.06) | 0.44 |
| History of cardiac disease (vs no) | 5.56 (2.81-11.0) | <0.001 |
| LVEF <50% without pre-existing cardiac morbidity (vs others)‡ | 4.02 (0.96-16.77) | 0.056 |
| Prior treatment with anthracycline (vs no) | 0.76 (0.38-1.50) | 0.44 |
| Prior treatment with CY (vs no) | 2.20 (1.07-4.50) | 0.031 |
| High-dose CY-containing conditioning regimen (vs others) | 0.68 (0.20-2.24) | 0.53 |
| HCT-CI >3 (vs 0-3)† | 1.85 (0.92-3.71) | 0.084 |
| KPS ≤80% (vs 90%-100%) | 0.90 (0.41-0.98) | 0.80 |
| RIC (vs MAC) | 1.06 (0.55-2.07) | 0.81 |
| BM (vs PB) | 0.90 (0.21-3.72) | 0.88 |
| Univariate analysis . | Cardiac toxicity first the 180 d HR (95% CI) . | P value . |
|---|---|---|
| PTCY-based prophylaxis (vs others) | 3.08 (1.28-7.42) | 0.012 |
| TBI (overall) | ||
| Yes (any dose) (vs no) | 2.96 (1.53-5.78) | 0.001 |
| TBI according to dose | ||
| 2 Gy (vs no) | 3.17 (1.43-7.01) | 0.004 |
| ≥8 Gy (vs no) | 2.78 (1.25-6.20) | 0.012 |
| Age at allo-HCT | ||
| Continuous | 1.01 (0.98-1.04) | 0.21 |
| Age ≥55 y (vs younger) | 1.53 (0.79-2.98) | 0.20 |
| Female (vs male) | 1.18 (0.60-2.33) | 0.62 |
| History of HTN (vs no) | 1.94 (0.94-4.03) | 0.073 |
| History of diabetes (vs no) | 1.79 (0.62-5.14) | 0.27 |
| History of hyperlipidemia (vs no) | 0.62 (0.18-2.06) | 0.44 |
| History of cardiac disease (vs no) | 5.56 (2.81-11.0) | <0.001 |
| LVEF <50% without pre-existing cardiac morbidity (vs others)‡ | 4.02 (0.96-16.77) | 0.056 |
| Prior treatment with anthracycline (vs no) | 0.76 (0.38-1.50) | 0.44 |
| Prior treatment with CY (vs no) | 2.20 (1.07-4.50) | 0.031 |
| High-dose CY-containing conditioning regimen (vs others) | 0.68 (0.20-2.24) | 0.53 |
| HCT-CI >3 (vs 0-3)† | 1.85 (0.92-3.71) | 0.084 |
| KPS ≤80% (vs 90%-100%) | 0.90 (0.41-0.98) | 0.80 |
| RIC (vs MAC) | 1.06 (0.55-2.07) | 0.81 |
| BM (vs PB) | 0.90 (0.21-3.72) | 0.88 |
| Univariate analysis . | HR (95% CI) . | P value . |
|---|---|---|
| Effect of PTCY and TBI on early cardiac toxicity‡ | ||
| PTCY without TBI (vs no PTCY, no TBI) | 3.84 (1.08-13.61) | .037 |
| TBI (any dose) without PTCY (vs no TBI, no TBI) | 6.56 (1.32-32.50) | .021 |
| PTCY with TBI (vs no PTCY, no TBI) | 7.41 (2.17-25.27) | .001 |
| Univariate analysis . | HR (95% CI) . | P value . |
|---|---|---|
| Effect of PTCY and TBI on early cardiac toxicity‡ | ||
| PTCY without TBI (vs no PTCY, no TBI) | 3.84 (1.08-13.61) | .037 |
| TBI (any dose) without PTCY (vs no TBI, no TBI) | 6.56 (1.32-32.50) | .021 |
| PTCY with TBI (vs no PTCY, no TBI) | 7.41 (2.17-25.27) | .001 |
| Multivariate analysis . | HR (95% CI) . | P value . |
|---|---|---|
| Effect of PTCY and TBI on early cardiac toxicity‡ | ||
| PTCY without TBI (vs no PTCY, no TBI) | 3.79 (1.05-13.60) | .041 |
| TBI (any dose) without PTCY (vs no TBI, no TBI) | 6.0 (1.24-34.07) | .027 |
| PTCY with TBI (vs no PTCY, no TBI) | 6.98 (2.01-24.24) | .002 |
| Prior history of cardiac disease (vs no) | 5.28 (2.63-10.60) | <.001 |
| Prior treatment with CY (vs no) | 1.66 (0.78-3.52) | .190 |
| Multivariate analysis . | HR (95% CI) . | P value . |
|---|---|---|
| Effect of PTCY and TBI on early cardiac toxicity‡ | ||
| PTCY without TBI (vs no PTCY, no TBI) | 3.79 (1.05-13.60) | .041 |
| TBI (any dose) without PTCY (vs no TBI, no TBI) | 6.0 (1.24-34.07) | .027 |
| PTCY with TBI (vs no PTCY, no TBI) | 6.98 (2.01-24.24) | .002 |
| Prior history of cardiac disease (vs no) | 5.28 (2.63-10.60) | <.001 |
| Prior treatment with CY (vs no) | 1.66 (0.78-3.52) | .190 |
BM, bone marrow; HTN, hypertension; HCT-CI, HCT comorbidity index; KPS, Karnofsky Performance Status; MAC, myeloablative conditioning; PB, peripheral blood, RIC, reduced-intensity conditioning.
The administration of TBI and PTCY were found to be independent predictors of cardiac toxicity. Considering that 111 patients included in the study received TBI and PTCY, 4 explanatory variables were defined to be included in the univariate and multivariate model: not receiving neither PTCY nor TBI (n = 147); receiving PTCY but not TBI (n = 136); receiving TBI but not PTCY (n = 111); and receiving both, PTCY and TBI (n = 22) to independently explore the effect of TBI, PTCY, and TBI combined with PTCY.
Considering that pre-existing cardiac morbidity is one of the variables accounted in the HCT-CI score, the variable HCT-CI was not included in the multivariate model reported in Table 4.