乌鸦传媒

Skin-involved chronic graft-versus-host disease (cGVHD) had a significant association with long-term impairment of patient-reported outcomes (PROs), which also had a prognostic association with mortality, a multicenter prospective study showed.

Patients with sclerotic cGVHD had significantly worse scores on a validated quality-of-life (QOL) instrument compared with those who had epidermal-type cGVHD. Patients with combination GVHD subtypes had significantly worse skin symptoms versus the epidermal-type subgroup.

Clinically meaningful worsening of QOL or symptom scores were associated with significantly higher nonrelapse mortality (NRM), suggesting PROs could help inform risk stratification and treatment selection, reported Emily Baumrin, MD, of the University of Pennsylvania in Philadelphia, and co-authors in .

"The results of this cohort study demonstrated that skin chronic GVHD was associated with clinically meaningful impairment in QOL and symptom burden," the authors concluded. "The degree of impairment in PROs at skin chronic GVHD diagnosis was shown to be a prognostic marker for overall survival [OS] and non-relapse mortality independent of clinical severity. Future studies should focus on psychometric validation of PROs so that they can be incorporated as a prognostic and response marker in clinical practice and clinical trials."

Despite several noteworthy limitations, the study suggests that PROs may hone the precision of clinical assessment of cGVHD and mitigate inherent measurement error in clinical measurement of therapeutic response, said the authors of an . PROs provide additional distinct and complementary information to objective disease measures.

"This granularity of information can better inform decisions to augment or decrease the intensity of cGVHD-directed therapy," wrote Sandra Mitchell, PhD, of the Division of Cancer Control and Population Sciences, National Cancer Institute in Rockville, Maryland, and Edward Cowen, MD, of the Dermatology Branch of the National Institute of Arthritis and Musculoskeletal and Skin Diseases in Bethesda, Maryland. "Including PROs may be particularly important in evaluating patients with skin sclerosis, since identifying active disease can be challenging for this condition."

"The observed association between sclerotic cGVHD and mortality seen in the study ... may have important potential implications for care delivery, underscoring the need for close monitoring of survivors of allogeneic hematopoietic stem cell transplantation to support earliest recognition of the onset of sclerotic cGVHD and timely implementation of supportive care," they added. "Future studies are needed to determine if sclerotic cGVHD is directly and causally related to mortality or whether [other factors] represent more direct contributors to inferior survival outcomes."

As many as 80% of patients with cGVHD have , broadly characterized as epidermal or sclerotic-type disease, Baumrin and colleagues noted in their introduction. Skin involvement is a crucial prognostic factor, as each of epidermal cGVHD increases the mortality hazard by 33%.

Previous studies suggested that impaired PROs with skin cGVHD have a possible association with mortality, the authors continued. However, the comparative association of mortality with epidermal and sclerotic disease remained unexplored, as did associations with changes in QOL and symptoms in different skin subtypes.

To address the uncertainty, the investigators analyzed data for patients from the Chronic GVHD Consortium, enrolled from August 2007 to April 2012 at nine U.S. centers. The study included adults with cGVHD requiring systemic immunosuppression and with skin involvement.

QOL was assessed by means of the Functional Assessment of Cancer Therapy-Bone Marrow Transplantation (FACT-BMT) instrument (lower scores equal worse outcomes) and symptom burden with the Lee Symptom Scale (LSS), whereby higher scores reflect worse outcomes. Investigators examined associations between NRM and OS with PROs measured at diagnosis.

Data analysis included 436 patients who had a median age of 51 at transplant. The study population comprised 229 patients with epidermal-type cGVHD, 131 with sclerotic cGVHD, and 76 with combined disease.

After adjustment, the data showed that patients with sclerotic cGVHD had mean FACT-BMT scores 6.1 points worse than those with epidermal-type disease (95% CI 11.7-0.4, P=0.04). Patients with combination disease had mean LSS scores that were 9.0 points worse than the patients with epidermal disease (95% CI 4.2-13.8, P<0.001).

For the analyses of baseline PROs and mortality, a 7-point worsening of the FACT-BMT and an 11-point worsening of the LSS were considered clinically meaningful. Each 7-point worsening of baseline FACT-BMT was associated with a 9.1% increase in the odds of death from any cause (P=0.002) and 9.1% increase in the odds of NRM (P=0.01). The association between PROs and death was strongest among patients in the highest tertile of QOL impairment.

For every 11-point worsening of baseline LSS, the odds of death from any cause increased by 10.0% (P=0.02) and the odds of NRM by 16.4% (P=0.003). Patients with the highest tertile of skin symptom burden had the highest odds of NRM, but the association with OS did not achieve statistical significance.

In their review of the study, Mitchell and Cowen noted that almost 90% of patients had at least one site of extracutaneous involvement, which statistical modeling could not completely account for. The analysis also could not account for changes in immunosuppression.

Causes of death were not reported, Mitchell and Cowen continued. Additionally, sclerotic disease tends to be more treatment refractory, so the excess mortality associated with sclerotic disease might be, at least in part, attributable to adverse effects of prolonged use of immunosuppression.

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