Steroid-refractory chronic graft-versus-host disease (cGvHD) is a therapeutic challenge. Sclerotic skin manifestations are especially difficult to treat. We conducted a randomized phase-2 clinical trial to determine safety, efficacy, and preferred dose of pomalidomide in persons with moderate to severe cGvHD unresponsive to corticosteroids and/or subsequent lines of therapy. Thirty-four subjects were randomized to receive pomalidomide, 0.5 mg/d; LD) orally (n=17) or 2 mg/d at a starting dose of 0.5 mg/d increasing to 2 mg/d over 6 weeks (n=17, HD). Primary endpoint was overall response rate (ORR) at 6 months according to the 2005 NIH cGvHD Response Criteria. Thirty-two had severe sclerotic skin and received a median of 5 (range, 2-10) prior systemic therapies. ORR was 47% (95% confidence interval [95% CI], 30, 65%) in intent-to-treat analyses. All were partial responses with no difference in ORR between the cohorts. ORR was 67% (45-84%) in the 24 evaluable subjects at 6 months. Nine had improvement in NIH joint/fascia scores (p=0.018). Median change from the baseline in body surface area (BSA) of involved skin cGvHD was -7.5% (-10 to +35; p=0.002). The most frequent adverse events (AEs) were lymphopenia, infection, and fatigue. Eight subjects in the HD cohort had dose decreases because of AEs. There was one death in the LD cohort from bacterial pneumonia. Our data indicate anti-fibrotic effects of pomalidomide and possible association with increases in concentrations of blood regulatory T-cell and IL-2. Pomalidomide, 0.5 mg/d, is a safe and effective therapy of advanced corticosteroid-refractory cGvHD.

© F e r r a t a S t o r t i F o u n d a t i o nOcular cGvHD predictive models haematologica | 2015; 100(9) 1229 cGvHD manifestations, a diagnosis of ocular cGvHD can be made. This diagnostic scoring system has not yet been prospectively validated, and exact ophthalmology criteria for cGvHD diagnosis remain to be defined. The National Institutes of Health (NIH) cGvHD Consensus Project in 2005 proposed guidelines for transplant clinicians to assess ocular cGvHD severity; specified measures were the NIH eye score, Schirmer's tear test, Lee cGvHD symptom scoring and chief eye symptom score. 2,13 Apart from removing the Schirmer's tear test from the severity scoring scale, these recommendations did not change in 2014. 14 The ability of these criteria to predict ocular cGvHD diagnosis based on expert ophthalmologic examination is not known. In addition, there are no evidence-based recommendations regarding when transplant clinicians should suspect ocular cGvHD diagnosis and refer patients to an ophthalmologist for evaluation.Accepted therapeutic response measures in ocular cGvHD are also lacking. The NIH cGvHD Consensus conference in 2005 proposed the Schirmer's tear test as a measure of response, but a large prospective longitudinal study by Inamoto et al. demonstrated that the Schirmer's tear test did not correlate well with either provider-or patient-reported perceptions of change in ocular cGvHD severity. 16 Additional investigations are needed to identify which specific measures are most strongly associated with ocular cGvHD activity, and thus might have been expected to have the best performance characteristics in measuring ocular cGvHD response in a clinical trial or in clinical practice.Despite the high frequency of ocular cGvHD post HSCT, risk factors and clinical characteristics of ocular cGvHD are not completely understood. Matched related donor HSCT, male gender, prior acute skin GvHD, and oral and skin cGvHD involvement have been found to be associated with ocular cGvHD. 1,17 Reliable identification of risk factors for ocular cGvHD could select patients that might benefit from early intervention and provide insight into the pathophysiology of this condition.The objective of this study is to determine which aspects of the NIH cGvHD severity scoring criteria are most predictive of ocular cGvHD diagnosis in a large, well-characterized cohort with moderate to severe cGvHD enrolled on a cross-sectional natural history study. Patients underwent a standardized ophthalmology specialist examination and each patient was determined as having ocular cGvHD diagnosis or not. Since there are no standard definitions for ocular cGvHD activity, a second objective of this study was to use ophthalmology expert decision as the gold standard (active vs. inactive ocular cGvHD) and determine which factors of the ophthalmology examination and transplant clinician examination correlate most closely with the presence of active ocular cGvHD. MethodsThe National Cancer Institute (NCI) cGvHD natural history protocol is a cros...

Although fatigue is common after allogeneic hematopoietic cell transplantation, little is known about fatigue in patients with chronic GvHD (cGvHD). The aim of this study was to explore factors associated with fatigue in cGvHD. Data were drawn from a sequentially recruited, cross-sectional study of adults with moderate or severe cGvHD (n = 263). Respondents were classified as fatigued or not fatigued based on their response to a single item regarding loss of energy from the Lee cGvHD Symptom Scale. In univariate analysis, factors significantly associated with fatigue included performance status, number of prior cGvHD therapies, cGvHD symptom bother, self-assessed physical and mental health, nutritional status, walk velocity and self-reported physical activity. There were no significant associations between fatigue and disease-related cGvHD variables. Multivariable logistic regression demonstrated that being less active and having pulmonary and/or muscle/joint symptoms were independently associated with fatigue. In conclusion, clinically significant fatigue was prevalent in more than one-third of subjects with cGvHD, and was disabling. Absence of association with measures of cGvHD severity underscores the need to elucidate the pathogenesis of fatigue and its relationship with inflammatory activity. Pulmonary and muscle/joint symptoms and physical inactivity represent potential targets for intervention in clinical studies.