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G. Fatobene et al.
of chronic GvHD (14 in the 1-mMUD and 4 in the Haplo/PTCY HCT groups). We also found trends suggest- ing improved annualized Karnovsky Performance Status change from the onset of chronic GvHD to 3.5 years after- wards in the UCB [+5 (range, -12 to +44)] and Haplo/PTCY [+11 (range, -14 to +64)] groups compared to the 1-mMUD group [0 (range, -81 to +46)] (P=0.05 and P=0.06, respectively). We found no difference in avascular necrosis at 3 years among the three alternative donor groups (12% in the 1-mMUD, 12% in the UCB, and 5% in the Haplo/PTCY HCT recipients).
Survival endpoints
The cumulative incidence of non-relapse mortality at 3 years among patients with chronic GvHD was 22% in 1- mMUD recipients, 11% in UCB recipients, and 6% in the Haplo/PTCY recipients, with no statistically significant differences between the three groups [1-mMUD versus UCB, HR 0.32 (95% CI: 0.1-1.4), P=0.13; 1-mMUD versus Haplo/PTCY, HR 0.20 (95% CI: 0.0-1.5), P=0.12] (Table 3). The cumulative incidence of overall survival at 3 years among patients with chronic GvHD was 72% in 1- mMUD recipients, 82% in UCB recipients, and 90% in Haplo/PTCY recipients, with no statistically significant differences between the three groups [1-mMUD versus UCB, HR 0.59 (95% CI: 0.3-1.4), P=0.21; 1-mMUD versus Haplo/PTCY, HR 0.49 (95% CI: 0.2-1.4), P=0.18] (Table 3).
Progression-free survival after HCT did not differ between the three groups (Figure 1B).
Discussion
In parallel with the lower rates of overall chronic GvHD, we demonstrated that the cumulative incidence of chronic GvHD manifestations associated with disability was sig- nificantly lower after UCB and Haplo/PTCY HCT than that after 1-mMUD HCT.
The overall incidence of chronic GvHD in our study was lower in the UCB and Haplo/PTCY HCT cohorts than in the 1-mMUD HCT cohort, similar to results of previous studies.9-17 The overall incidence of chronic GvHD after 1-mMUD HCT was higher in our study than in previous reports.9,11,13,17-21 This difference may be explained by the higher proportion of bone marrow grafts and more frequent use of T-cell depletion in the previous studies.9,11,13,17,18,22 Older age could also be a contributor to the higher rates of chronic GvHD in the 1-mMUD group compared to the UCB and Haplo/PTCY groups.
Keratoconjunctivitis sicca was the most common chron- ic GvHD manifestation of high morbidity. Of note, the incidence of severe keratoconjunctivitis sicca at any time after the diagnosis of chronic GvHD was at least 4-fold higher in the 1-mMUD group than in the UCB group and
AB
CD
Figure 3. Patients in the group grafted from a mismatched unrelated donor had a high cumulative incidence of disability caused by morbidity involving the skin, eyes and lungs. Cumulative incidence of: (A) any manifestations of chronic GVHD associated with disability; (B) moderate or severe keratoconjunctivitis sicca, (C) skin sclerosis and (D) bronchiolitis obliterans according to alternative donor HCT group. URD Mism: mismatched unrelated donor; Cord: umbilical cord blood; Haplo: hap- lorelated bone marrow or peripheral blood; GVHD: graft-versus-host disease.
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haematologica | 2019; 104(4)