High Rates of Severe aGVHD with Tacrolimus and Mycophenolate Mofetil in a Large Cohort of Related and Unrelated Allogeneic Transplant Patients

We retrospectively evaluated clinical outcomes in a cohort of 414 consecutive pts who underwent related or unrelated allo-HCT with Tac-MMF for GVHD prophylaxis. Consecutive pts were transplanted with myeloablative or low intensity preparative regimens between January 2005 and June 2011 at Karmanos Cancer Center. Study end points were: Overall survival (OS), progression free survival (PFS) (Kaplan Meir), cumulative incidence (CI) of acute and chronic GVHD, relapse, CMV infection and non-relapse mortality (NRM).

Pt characteristics are summarized in Table 1. There were 211 pts who underwent allo-HCT from a related donor (RD) and 203 patients who had allo-HCT from an unrelated donor (UD). Sixty three pts (31%) of the UD were 7/8 HLA matched. Median follow up of all patients was 60 months with 95% confidence interval (95%CI) 54.4 – 64.7 months.

The CI of aGVHD for grades II-IV was 47.4% (95%CI 40.5–54.0), 55.2% (95%CI 48.0–61.7) in RD and UD groups respectively. The CI of aGVHD grades III-IV was 22.3% (95%CI 16.9–28.1), 36.5% (95%CI 29.9–43.1) in RD and UD groups respectively (Gray's test p-value 0.0007). The CI of cGVHD at 60 months was 56.2% (95%CI 48.7–63.1), 66.3% (95%CI 58.8–72.7) in RD and UD groups respectively (Gray's test p-value 0.015). The CI of severe cGVHD (NIH grade3) at 60 months was 28.1% (95%CI 22.2–34.3), 26.1% (95%CI 20.3–32.3) in RD and UD groups respectively. The CI of bronchiolitis obliterans at 60 months was 14.0% (95%CI 9.7 –19.1), 11.6% (95%CI 7.6–16.6) in RD and UD groups respectively (NS). The CI of CMV reactivation at 60 months was 27.2% (95%CI 21.3–33.4), 23.2% (95%CI 17.6–29.2) in RD and UD groups respectively (NS). NRM at 60 months was 32.5% (95%CI 25.9–39.2), 46.5% (95%CI 39.3–53.4) in RD and UD groups respectively (Gray's test p-value 0.001). The CI of relapse was 22.4% (95%CI 16.7–28.5) for UD and 28.8% (95%CI 22.6–35.2) for RD. One year survival was 61% (95%CI 55–68), 55% (95%CI 48–62) in RD and UD groups respectively. One year PFS was 55% (95%CI 48–62), 48% (95%CI 41–55) in RD and UD groups respectively. Five year OS was 43% (95%CI 35–51), 34% (95% CI 27–41) in RD and UD groups respectively. Causes of death for the RD group (n=115) were as follows: GVHD 49%, relapse 42%, sepsis 3%, multi-organ failure (MOF) 3%, Diffuse alveolar hemorrhage 2%, and secondary malignancy 3%. As for the UD group (n=133) causes of death were: GVHD 57%, relapse 29%, sepsis 7%, MOF 4%, graft failure 2%, and secondary malignancy 1%. Uni-variate and multi-variate analysis is being performed to evaluate disease risk, donor status, and regimen intensity as predictors of GVHD and survival.

The use of Tac-MMF for GVHD prophylaxis was associated with higher than previously reported incidence of severe aGVHD both in RD and UD allo-HCT. Furthermore, we observed a higher incidence of severe aGVHD, cGVHD and NRM in the UD group compared to RD. GVHD was the leading cause of mortality in both groups.

No relevant conflicts of interest to declare.