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Severity of chronic GvHD after alternative donor HCT
Table 3. Outcomes analyzed according to alternative hematopoietic cell transplant donor group.
Alternative donor group Cumulative incidence at 3 years
Unrelated Umbilical Related mismatched cord blood haploidentical
(N=79) (N=29) (N=21)
15% 45% 50%
35% 68% 62% 39% 17% 25% 72% 82% 90% 22% 11% 6% 17% 18% 29%
58% 17% 23%
39% 10% 15%
Cord blood
vs. unrelated mismatched
Haploidentical
vs. unrelated mismatched
Hazard ratio P (95% CI)
Outcome
Off systemic therapy*
Return to work1 Change of therapy Overall survival Non-relapse mortality Relapse/ progression
Manifestation of GvHD associated with disability3
Any
Kerato conjunctivitis sicca (eyes) Sclerotic features
Bronchiolitis obliterans (lung) Joint/fasciae
Esophageal stricture
Hazard ratio (95% CI)
3.96 (1.9-8.4)
2.54 (1.1-5.7) 0.30 (0.1-0.8) 0.59 (0.3-1.4) 0.32 (0.1-1.4) 0.95 (0.3-2.7)
0.16 (0.1-0.4)
0.17 (0.1-0.5) 0.1 (0.0-0.7) 0.15 (0.0-1.1)
P
0.0003
0.02 0.01 0.21 0.13 0.93
0.0001
0.003 0.02 0.16
4.93 (2.2-11.1)
0.0001
2.38 (1.0-5.9) 0.06 0.53 (0.2-1.4) 0.19 0.49 (0.2-1.4) 0.18 0.20 (0.0-1.5) 0.12 1.43 (0.5-4.1) 0.50
24% 18% 5%
1%
3% 0 3% 5%
0.35 (0.1-1.0) 0.05 0.14 (0.0-1.0) 0.05 0.23 (0.0-1.8) 0.16
0.32 (0.1-0.7)
0.009
Change in Karnofsky Performance Status2
Median (range) 0 (-81 – 46)
0 0 0.0 0.08 0.0 0.13 (undefined) (undefined)
00
5 (-12 – 44) 11 (-14 – 64) NA 0.05 NA 0.06
*Discontinuation of systemic treatment after resolution of chronic GvHD. 1Among 35, 19, and 13 patients who were working or in school prior to HCT, and had not returned to work or school prior to the onset of chronic GvHD. 2Among 54, 20, and 11 patients who had a value at onset and a value after 6 months. Change is annualized change between onset and last value through 3.5 years. 3Patients could have more than one chronic GvHD manifestation associated with disability defined as .grade 2 or 3 keratoconjunctivitis sicca, scleroderma features, bronchiolitis obliterans, grade 2 or 3 joint/fasciae involvement, or esophageal stricture requiring dilation. KPS: Karnofsky Performance Status; NA: not applicable; GvHD: graft-versus-host disease.
mmUD, 43% of Haplo/PTCY, and 24% of UCB HCT recipients). On the other hand, gastrointestinal tract involvement at any time developed in 72% of the UCB patients, but in 58% of the 1-mmUD and 52% of the Haplo/PTCY HCT recipients.
Results of major outcomes according to the alternative donor HCT groups are shown in Table 3.
Chronic graft-versus-host disease manifestations of high morbidity
The cumulative incidence of any manifestation of high morbidity at 3 years after the diagnosis of chronic GvHD is shown in Figure 3A and was significantly lower in the UCB (17%) and Haplo/PTCY (23%) groups than in the 1- mMUD group (58%) [HR 0.16 (95% CI: 0.1-0.4); P=0.0001, and HR 0.32 (95% CI: 0.1-0.7), P=0.009, respec- tively], (Figure 3A). Table 3 shows the distribution of chronic GvHD manifestations of high morbidity accord- ing to the three HCT donor groups. The most frequent high morbidity was keratoconjunctivitis sicca followed by sclerosis and bronchiolitis obliterans (lungs). Moderate or severe joint/fasciae involvement and esophageal stricture requiring dilation were less frequent high morbidity man- ifestations. The cumulative incidence of keratoconjunc- tivitis sicca was significantly lower in the UCB group than in the 1-mMUD group (10% versus 39%, P=0.003) and was also lower in the Haplo/PTCY group (10%, P=0.05). The 3-year cumulative incidence of any high morbidity
and the three most frequent high morbidity chronic GvHD manifestations according to the alternative donor groups are displayed in Figure 3.
Duration of immunosuppressive therapy and change in systemic therapy
The proportion of patients in each group requiring changes in systemic therapy for control of chronic GvHD at 3 years after first-line treatment was 17% for the UCB group, 25% for the Haplo/PTCY groups and 39% for the 1-mMUD group, and was significantly lower for the UCB group than for the 1-mMUD group [HR 0.30 (95% CI: 0.1- 0.8), P=0.01] (Figure 4A and Table 3).
The cumulative incidence of discontinued systemic immunosuppression at 3 years was significantly lower in the 1-mMUD (15%) group than in the UCB (45%) and Haplo/PTC (50%) groups [HR 3.96 (95% CI: 1.9–8.4), P=0.0003, and HR 4.93 (95% CI: 2.2–11.1), P=0.0001, respectively] (Figure 4B).
Functional endpoints
A higher proportion of UCB patients than 1-mMUD HCT recipients (68% versus 35%) returned to work or school within 3 years after the onset of chronic GvHD [HR 2.54 (95% CI: 1.1-5.7), P=0.02], and a similar trend was observed in the Haplo/PTCY group [62% versus 35%, HR 2.38 (95% CI: 1.0-5.9), P=0.06] (Figure 4C). Eighteen patients had returned to work or school before the onset
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