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Severity of chronic GvHD after alternative donor HCT
at least 2-fold higher in the 1-mMUD group than in the Haplo/PTCY group. Prospective trials have shown that quality of life is impaired in patients with chronic GvHD involving the eyes.23,24
Sclerotic manifestations of chronic GvHD were the sec- ond most common severe morbidity in the three donor groups, but were seen in less than 5% of the UCB and Haplo/PTCY groups as compared to nearly a quarter of the 1-mMUD HCT group. The reported overall cumula- tive incidence of sclerotic chronic GvHD after HCT is approximately 20%, with lower rates in recipients of HLA-mismatched HCT than in recipients of HLA- matched HCT.25,26 The use of growth factor-mobilized blood cells is a known risk factor for the development of sclerotic GvHD after HCT. The frequent use of mobilized blood cells could explain the 25% incidence of sclerotic manifestations in our 1-mMUD HCT group. The remark- ably low rate of sclerotic manifestations in the UCB cohort is consistent with prior reports of outcomes after UCB HCT.26,27
In order to assess protracted chronic GvHD, we evaluat- ed the duration of systemic therapy used to control the disease manifestations and the impact on functional out- comes among the three alternative donor groups. A large proportion of UCB (45%) and Haplo/PTCY (59%) HCT recipients were able to discontinue all systemic treatment for chronic GvHD by 3 years after onset of the condition, in contrast to only 15% of the 1-mMUD group. The use of mobilized blood as the stem cell graft and the involve- ment of multiple sites at initial diagnosis are risk factors for prolonged immunosuppressive treatment.28-30 The sig- nificantly lower incidence of second-line systemic immunosuppressive treatment of chronic GvHD in the UCB and Haplo/PTCY groups than in the 1-mMUD group also supports the conclusion that the severity of chronic GvHD is greater after HCT with 1-mMUD donors than with UCB or HLA-haploidentical related donors.
The presence of chronic GvHD has been consistently associated with failure to return to work or school, limited resilience and poor quality of life among HCT survivors.1- 3,31 In our study, a significantly higher proportion of the UCB group were more likely to return to work or school compared to the that of the 1-mMUD group, and a similar benefit trend was also evident for the Haplo/PTCY group, supporting the conclusion that GvHD manifestations associated with disability frequently impaired recovery of pre-transplant function in the 1-mMUD group.
Our study has several limitations. First, the three groups were heterogeneous with respect to the patients’ age, gen- der, race, underlying disease and conditioning regimen intensity. Among these factors, only the patients’ age has been associated with an increased incidence of chronic GvHD. An association of older patients’ age with higher risk of chronic GvHD has not been consistently observed after UCB HCT, and very few data addressing this issue are available for Haplo/PTCY recipients.32-37 A second lim- itation of the study is that the small numbers of patients with chronic GvHD in the UCB and Haplo/PTCY groups precluded a direct comparison of outcomes between these two groups. Third, we included both one-antigen and allele-mismatched unrelated donor peripheral blood stem cell recipients irrespective of the “direction” of mismatch- ing. However, there was no significant difference in inci- dence of chronic GvHD between these mismatched unre- lated donor groups (data not shown), consistent with the
results of a large, previous study from the Center for International Blood and Marrow Transplant Research.38 Fourth, the incidence of chronic GvHD in the 1-mMUD group in our study may not be representative of results with T-cell depleted 1-mMUD grafts.26,34,39,40 Moreover, considering that mobilized blood stem cells were the graft source used for the 1-mMUD HCT group in our study, the risk and morbidity of chronic GvHD with unrelated donor bone marrow grafting might not differ from those for
A
B
C
Figure 4. Patients in the mismatched unrelated donor group had a high cumu- lative incidence of second-line treatment, and withdrawal of immunosuppres- sive treatment and return to work or school were delayed. Cumulative incidence of (A) change of systemic therapy after first-line therapy for chronic GVHD; (B) dis- continuation of systemic immunosuppressive therapy, and (C) return to work/school after the diagnosis of chronic GVHD according to the alternative HCT group. Rx: treatment; IST: immunosuppressive therapy; URD Mism, mis- matched unrelated peripheral blood stem cell; Haplo, related haploidentical; cGVHD, chronic graft-versus-host disease.
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