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The baseline characteristics of the study population are presented in Table 1. A total of 8764 patients were included, from which 7725 (88%) received rATG, and 1039 (12%) received PTCy as GVHD prophylaxis.
Table 1 Baseline patient-, donor- and transplant-related characteristics by graft-versus-host disease prevention strategy.Overall, the majority of patients were transplanted for acute leukemia (58%), myelodysplastic syndrome (MDS) (19.7%), myeloproliferative neoplasm (MPN) (9.7%) or lymphoma (9%). A high proportion of patients had a low/intermediate Disease Risk Index (DRI, 72.1%), and myeloablative conditioning (MAC) was more frequently performed (53.3%) than reduced intensity conditioning (RIC).
Patients in the rATG group were older, with a median age of 58.6 years (IQR (48.1, 65.4)) vs. 53 years in the PTCy group (IQR 38.6, 62.3) (p < 0.01), with a similar proportion of males (57.3% in rATG vs. 58.9% in PTCy, p = 0.33), along with a significantly lower use of TBI (14.5% vs. 24.7%, p < 0.01) and lower use of MAC (52% vs. 62.3%, p < 0.01). Also, the disease relapse index was lower and the year of transplant was more recent in the PTCy group (Table 1). The remaining parameters were balanced between the two groups. Median follow up was 2.1 years in both arms. More detailed information is given in Table 1.
Survival, RI and NRMUnivariate outcomes are shown in Figs. 1, 2 and Table 2. The results of the multivariate analyses are summarized in Table 3. The P-values and hazard ratios (HR) presented in the following results section are derived from the multivariate analysis.
Fig. 1: Survival outcome parameters and relapse.
A NRM; B Overall survival, C Relapse incidence, D Progression-free survival and E GVHD-free relapse-free survival. Cumulative incidences are shown.
Table 2 Incidence of univariate outcomes. Percentages (%) are given. All outcomes except acute GVHD are given at two years. Acute GVHD is given at day +100 after alloSCT.Table 3 Multivariate analysis. Hazard ratios (HR) are given for PTCy with rATG being the comparator. All known potential risk factors, and variables differing significantly across the groups were included in the multivariate models: patient age at transplant, year of transplant, patient and donor gender, donor to patient CMV combination, Disease Risk Index (DRI), Karnofsky Performance Status (KPS), any level of total body irradiation (TBI), conditioning intensity (RIC vs. MAC). Center effect was taken into account by introducing a random effect or ‘frailty’ into all models.Fig. 2: GVHD outcome parameters.
A Acute GVHD grades II–IV; B Acute GVHD grades III–IV, C Chronic GVHD all grades and D Extensive chronic GVHD - Cumulative incidences are shown.
Patients receiving PTCy had a significantly lower NRM as compared to patients receiving rATG (2 y incidence: 12.4% vs. 16.1%; HR: 0.72 [95% CI 0.55–0.94], p = 0.016). Similarly, OS and PFS showed a statistically significant and clinically meaningful benefit for PTCy arm, with a higher OS (2 y incidence: 73.9% vs. 65.1%; HR: 0.82 [95% CI 0.72–0.92], p = 0.001), and a higher PFS (2 y incidence: 64.9% vs. 57.2%; HR: 0.83 [95% CI 0.74–0.93], p < 0.001). RI was lower in the PTCy arm (2 y incidence: 22.8% vs. 26.6%; HR: 0.87 [95% CI 0.75–1.00], p = 0.046).
The causes of death are given in Table 4. No major differences between the two groups were apparent. Relapse of the underlying malignancy was the most frequent cause of death, accounting for ~50% of total deaths in both arms, followed by NRM causes: infections ~18%, GVHD ~ 16% and other alloSCT-related causes ~8% of total deaths. Secondary malignancies contributed to approximately 1% of total deaths.
Table 4 Causes of death in both cohorts. Absolute numbers and percentages are given.Incidence of acute and chronic GVHD, and GRFSOverall chronic GVHD was lower in the PTCy group (2 y incidence: PTCy 28.4% vs. rATG 31.4%; HR: 0.77 [95% CI 0.63–0.95], p = 0.012). Extensive chronic GVHD was also reduced in patients receiving PTCy vs. rATG: (2 y incidence: 11.9% vs. 13.5%; HR: 0.75 [95% CI 0.62–0.91], p = 0.004).
The incidence of acute GVHD grades II-IV in patients receiving PTCy, compared to those receiving ATG was not statistically significant: (100d incidence: 24.1% vs. 26.5%; HR: 0.85 [95% CI 0.69–1.04], p = 0.11). Similarly, for severe acute GVHD grades III–IV (100d incidence: 8.7% vs. 9.7%; HR: 0.76 [95% CI 0.55–1.05], p = 0.091).
GRFS was significantly higher in the PTCy arm compared to the rATG arm (2 y incidence: 51% vs. 45%; HR: 0.86 [95% CI 0.75–0.99], p = 0.035).
Incidence of neutrophil recovery and second alloSCTThe EBMT Database does not contain data on graft failure/rejection. To get insight into the initial graft’s success and any subsequent requirement for additional transplantation procedures, we investigated neutrophil recovery after the first alloSCT as well as the incidence of a second alloSCT. The median incidence of neutrophil recovery at days +30 and +60 in the ATG vs. PTCy groups was: d + 30 ATG 96% (IC95% 95.5–96.4) vs. PTCy 91% (89–92.7) and d + 60 ATG 97.9% (97.6–98.2) vs. PTCy 97.4% (96.2–98.3). The median incidence of a second alloSCT at 2 years was 4.3% (3.8–4.8) in the ATG group and 3.2% (2.2–4.6) in the PTCy group.
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