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Health-related quality of life in patients with steroid-refractory acute graft-versus-host disease
Leeneman, B., Blommestein, H. M., van Dongen-Leunis, A., Algeri, M., Fibbe, W. E., Oosten, L., Uyl-de Groot, C. A., Thielen, F. W.
European journal of haematology. 2023
Abstract
BACKGROUND Evidence regarding health-related quality of life (HRQoL) in patients with steroid-refractory acute graft-versus-host disease (SR-aGvHD) is lacking. Evaluating HRQoL was a secondary objective of the HOVON 113 MSC trial. Here we describe the outcomes of the EQ-5D-5L, EORTC QLQ-C30, and FACT-BMT for all adult patients who completed these questionnaires at baseline (i.e., before the start of treatment; n = 26). METHODS Descriptive statistics were used to describe baseline patient and disease characteristics, EQ-5D dimension scores and values, EQ VAS scores, EORTC QLQ-C30 scale/item and summary scores, and FACT-BMT subscale and total scores. RESULTS The mean EQ-5D value was 0.36. In total, 96% of the patients reported problems with usual activities, 92% with pain/discomfort, 84% with mobility, 80% with self-care, and 72% with anxiety/depression. The mean EORTC QLQ-C30 summary score was 43.50. Mean scale/item scores ranged from 21.79 to 60.00 for functioning scales, from 39.74 to 75.21 for symptom scales, and from 5.33 to 91.67 for single items. The mean FACT-BMT total score was 75.31. Mean subscale scores ranged from 10.09 for physical well-being to 23.94 for social/family well-being. CONCLUSION Our study showed that HRQoL in patients with SR-aGvHD is poor. Improving HRQoL and symptom management in these patients should be a top priority.
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Efficacy and Safety of 1% Progesterone Gel to the Forehead for Ocular Chronic Graft-versus-Host Disease
Luo, Z. K., Domenech-Estarellas, E. A., Han, A., Lee, D., Khatri, R., Wahl, J. L., Cutler, C., Armand, P., Antin, J. H., Koreth, J., et al
Transplantation and cellular therapy. 2021
Abstract
There is no Food and Drug Administration-approved treatments for ocular chronic graft-versus-host disease (oGVHD) to date, and current therapeutic options are limited. Forehead application of 1% progesterone gel provides corneal antinociception in preclinical models, suggesting it may be useful in alleviating ocular irritations. This study was conducted to evaluate the efficacy and safety of 1% progesterone gel in treating moderate to severe symptomatic oGVHD. Thirty-three patients with oGVHD following allogeneic stem cell transplantation were enrolled in this single-center, sponsor-initiated, prospective exploratory randomized double-masked placebo-controlled phase II clinical trial. The inclusion criteria included a National Institutes of Health consensus score of =2, moderate to severe ocular discomfort level, and receipt of a stable immunosuppression regimen. Twenty-one of the 22 patients in the progesterone arm and all 11 patients in the placebo arm completed the course of twice-daily forehead drug application for 10 weeks. The changes from baseline of self-reported ocular symptom scores and physician-recorded cornea fluorescein staining scores were analyzed using mixed-model repeated-measures regression model in an intention-to-treat population. The 33 patients included 12 women and 21 men, with a median age of 66 years (range, 24 to 75 years). At 10 weeks, there was a significant reduction in ocular symptoms from baseline in the progesterone group compared with the placebo group in symptom frequency (-30.7 versus -2.2; P < .001) and severity (-19.8 versus +1.6; P = .005). At 10 weeks, there was also greater reduction of cornea fluorescein staining centrally (-1.2 versus +.1; P = .001) and inferiorly (-1.4 versus -0.2; P = .005). No difference was noted in superior cornea staining. There were no severe adverse events in the progesterone group. Forehead application of 1% progesterone gel significantly improved ocular signs and symptoms within 10 weeks. It appears to be a safe and effective new therapy for oGVHD, and a novel mechanism for neuroaxis drug delivery. A multicenter phase III clinical trial is planned for further validation.
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A Randomized Phase II Crossover Study of Imatinib or Rituximab for Cutaneous Sclerosis after Hematopoietic Cell Transplantation
Arai, S., Pidala, J., Pusic, I., Chai, X., Jaglowski, S., Khera, N., Palmer, J., Chen, G. L., Jagasia, M. H., Mayer, S. A., et al
Clinical Cancer Research. 2016;22(2):319-27
Abstract
PURPOSE Cutaneous sclerosis occurs in 20% of patients with chronic graft-versus-host disease (GVHD) and can compromise mobility and quality of life. EXPERIMENTAL DESIGN We conducted a prospective, multicenter, randomized, two-arm phase II crossover trial of imatinib (200 mg daily) or rituximab (375 mg/m(2) i.v. weekly x 4 doses, repeatable after 3 months) for treatment of cutaneous sclerosis diagnosed within 18 months (NCT01309997). The primary endpoint was significant clinical response (SCR) at 6 months, defined as quantitative improvement in skin sclerosis or joint range of motion. Treatment success was defined as SCR at 6 months without crossover, recurrent malignancy or death. Secondary endpoints included changes of B-cell profiles in blood (BAFF levels and cellular subsets), patient-reported outcomes, and histopathology between responders and nonresponders with each therapy. RESULTS SCR was observed in 9 of 35 [26%; 95% confidence interval (CI); 13%-43%] participants randomized to imatinib and 10 of 37 (27%; 95% CI, 14%-44%) randomized to rituximab. Six (17%; 95% CI, 7%-34%) patients in the imatinib arm and 5 (14%; 95% CI, 5%-29%) in the rituximab arm had treatment success. Higher percentages of activated B cells (CD27(+)) were seen at enrollment in rituximab-treated patients who had treatment success (P = 0.01), but not in imatinib-treated patients. CONCLUSIONS These results support the need for more effective therapies for cutaneous sclerosis and suggest that activated B cells define a subgroup of patients with cutaneous sclerosis who are more likely to respond to rituximab. Copyright ©2015 American Association for Cancer Research.
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A Clinical Trial Comparing the Safety and Efficacy of Topical Tacrolimus versus Methylprednisolone in Ocular Graft-versus-Host Disease
Abud, T. B., Amparo, F., Saboo, U. S., Di Zazzo, A., Dohlman, T. H., Ciolino, J. B., Hamrah, P., Dana, R.
Ophthalmology. 2016;123(7):1449-57
Abstract
PURPOSE To evaluate the safety and efficacy of topical tacrolimus 0.05% versus topical methylprednisolone 0.5% in patients with ocular graft-versus-host disease (GVHD). DESIGN Phase 1/2 prospective, randomized, double-masked clinical trial. PARTICIPANTS Eighty eyes of 40 patients diagnosed with chronic ocular GVHD were enrolled. METHODS Forty patients with ocular GVHD were randomized; 24 patients were treated with topical tacrolimus 0.05% and 16 patients were treated with topical methylprednisolone 0.5% twice daily for 10 weeks, in addition to continuing their baseline treatment regimen. MAIN OUTCOME MEASURES Safety was evaluated based on occurrence of adverse events. Tolerability was assessed based on subject reports of discomfort after drop instillation. Intraocular pressure (IOP) was monitored. The main efficacy end points were corneal fluorescein staining (CFS), tear film break-up time (TBUT), Schirmer test results, and expression of the ocular surface inflammatory markers human leukocyte antigen-DR (HLA-DR) and intercellular adhesion molecule-1 (ICAM-1). Symptoms were evaluated using the Ocular Surface Disease Index (OSDI). RESULTS After 10 weeks of treatment, no major adverse events occurred in either treatment group, and there was no significant difference in the composite tolerability scores between the 2 groups (P = 0.06). However, burning sensation was more pronounced with tacrolimus (P = 0.002). Topical tacrolimus was more effective than methylprednisolone in reducing the CFS score at week 10 (55% vs. 23% reduction, respectively; P = 0.01) and achieved significant improvement in TBUT when compared with baseline (P < 0.001). Reduction in OSDI score achieved statistical significance with tacrolimus (27% reduction; P = 0.02), but was marginal with methylprednisolone (32% reduction; P = 0.06). Expression of ICAM-1 by ocular surface epithelium decreased significantly in both groups (tacrolimus, P = 0.003; methylprednisolone, P = 0.008), whereas HLA-DR expression decreased significantly only in the tacrolimus group (P = 0.03). Schirmer test scores did not change significantly in either group during the study; IOP increased significantly with methylprednisolone at week 10 (P = 0.04). CONCLUSIONS Topical tacrolimus 0.05% is safe, generally well tolerated, and effective for the treatment of ocular GVHD without the hypertensive effects of topical corticosteroids. Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.