Five RCTs were included (652 patients, of whom 314 received TBI and 338 BUCY).
Statistically significant heterogeneity was present only for disease-free interval (Q = 9.99, P = 0.04). Non-statistically significant heterogeneity was present for survival (Q = 6.1; P = 0.19), and VOD (Q = 3.1; P = 0.38).
TBI-based regimes were superior but not statistically significantly superior for survival and disease-free survival. OR for overall survival = 1.4 (95% CI: 0.9, 2.0; P = 0.09). OR for disease-free survival = 1.2 (95% CI: 0.7, 2.1; P = 0.44).
Toxicity outcomes: VOD was significantly less common among TBI-treated patients but other toxicities did not differ between TBI and BUCY regimes. The overall incidence of toxicities were as follows: VOD in 9% with BUCY and 3% with TBI; interstitial pneumonitis in 12% with BUCY and 14% with TBI. OR for VOD (4 RCTs)= 2.5 (95% CI: 1.2, 5.0; P = 0.02). OR for acute GVHD (5 RCTs) = 0.9 (95% CI: 0.6, 1.2; P = 0.44). OR for chronic GVHD (4 RCTs) = 1.1 (95% CI: 0.8, 1.6; P = 0.58). OR for interstitial pneumonitis (3 RCTs) = 0.9 (95% CI: 0.5, 1.6; P = 0.66).
No study was a statistical outlier for any outcome.
Sensitivity analysis: Dropping one study led to a significant survival advantage for TBI with OR = 1.6 (95% CI: 1.1, 3.5; P = 0.03). Dropping any one of three studies eliminated the statistical significance of the VOD difference. Stratifying for stage of disease was not statistically significant for any outcome. Including the one study reporting fatal VOD and not overall VOD and estimating the pooled fatal VOD outcome, did not change the VOD results. Power analysis indicated that BUCY was unlikely to have a clinically relevant advantage over TBI for survival, disease-free interval, VOD or chronic GVHD. An advantage for acute GVHD or interstitial pneumonits could not be ruled out. TBI-based regimes are unlikely to have a clinically relevant advantage over BUCY for acute GVHD but such an advantage could not be ruled out for other outcomes.
Probability that TBI has a 25% OR advantage; probability that BUCY has a 25% OR advantage:
Survival: TBI 64%; BUCY 0.1%. Disease-free survival: TBI 38%; BUCY 3%. VOD: TBI 95%; BUCY 0.08%.
Acute GVHD: TBI 0.7%; BUCY 19%.
Chronic GVHD: TBI 16%; BUCY 2%. Interstitial pneumonitis: TBI 8%; BUCY 31%.