Changes in Immunosuppressive Treatment of Chronic Graft-versus-Host Disease: Comparison of 2 Surveys within Allogeneic Hematopoietic Stem Cell Transplant Centers in Germany, Austria, and Switzerland.

Chronic graft-versus-host disease (cGVHD) remains the leading cause of late morbidity and mortality. Despite the growing number of treatment options in cGVHD, evidence remains sparse. The German-Austrian-Swiss GVHD Consortium performed a survey on clinical practice in treatment of cGVHD among transplant centers in Germany, Austria, and Switzerland in 2009 and 2018 and compared the results. The survey performed in 2009 contained 20 questions on first-line treatment and related issues and 4 questions on second-line scenarios followed by a survey on all systemic and topic treatment options known and applied, with 31 of 36 transplant centers (86%) responding. The survey in 2018 repeated 7 questions on first-line treatment and 3 questions on second-line scenarios followed by an updated survey on all current systemic treatment options known and applied, with 29 of 66 centers (43%) responding. In summary, the results show a large overlap of first-line treatment practice between centers and the 2 surveys because of a lack of new data that changes practice, except significant heterogeneity of treatment of cGVHD progressive onset type, which can be explained by the lack of trials focusing on this high-risk entity. In contrast, treatment options applied to second-line therapy vary considerably, with new agents like ibrutinib and ruxolitinib entering clinical practice. Moreover, treatment of bronchiolitis obliterans syndrome demonstrates heterogeneity in applied therapeutic options and sequence because of a lack of controlled data and different conclusions from already existing evidence. In summary, the survey results demonstrate an increasing number of treatment options applied to cGVHD accompanied by a significant heterogeneity in second-line treatment and underline the urgent need for clinical trials and registry analyses on rare entities with high mortality like progressive onset type and lung involvement of cGVHD.

The Effect of Low Frequency Sound on Heart Rate Variability and Subjective Perception: A Randomized Crossover Study.

BACKGROUND: Vibroacoustic therapy (VAT) uses low-frequency sound, often combined with listening to music, for therapeutic purposes. However, the impact of low-frequency vibration (LFV) on physiological functions and subjective perception is relatively unknown. METHODS: We conducted a randomized cross-over study with the aim of comparing the effect of constant LFV of 40 Hz, its amplitude modulation, and the placebo condition on heart rate variability (HRV), stress perception (measured by visual analogue scales for stress) and mood (measured by UWIST Mood Adjective Check List). RESULTS: Research experiments with various interventions (constant LFV with sound of nature (river in forest), amplitude modulation of the same LFV with sounds of nature and sounds of nature without LFV) were realised involving 24 participants. It was found there was an effect on HRV, stress perception and mood after the interventions. However, there were only seldomly experienced, and mostly nonsignificant, differences between the intervention conditions, so the effects may be attributed to factors other than LFV. CONCLUSIONS: Large scale experimental studies are needed to verify the preliminary findings and to explore various coinciding factors that may have influenced the results of this study, e.g., type of autonomic nervous system. We propose that the effect of LFV exposure may differ when combined with listening to music, and this hypothesis should be investigated in future studies.

Therapy of sclerodermatous chronic graft-versus-host disease with mammalian target of rapamycin inhibitors.

This retrospective study analyzes 34 patients with severe sclerodermatous chronic graft-versus-host disease (cGVHD) treated with inhibitors of the mammalian target of rapamycin (mTOR-I). Twelve patients received mTOR-I as monotherapy and 22 a combination therapy. Four patients also received extracorporal photopheresis. mTOR-I were applied as first-line therapy (n = 15) or in refractory disease (n = 19). Drug doses were adjusted to low therapeutical levels (3-8 ng/mL). Six and 20 patients had a complete and a partial response, respectively, with an overall response rate of 76%. Two additional patients had stable disease. Six refractory patients required alternative therapy. Comedication, especially steroids, could be tapered and stopped in a significant number of patients. No difference in response was observed in everolimus- and sirolimus-treated patients. Major adverse events possibly related to mTOR-I were hyperlipidemia and impaired wound healing. Two patients developed thrombotic microangiopathy. Eight patients died, 5 of the nonresponders (cGVHD; n = 3, infection; n = 2) and 3 of the responders (relapse of the underlying malignancy; n = 1, secondary malignancy; n = 1, unknown cause; n = 1). Twenty-six of the 34 patients remain alive, 18 still on therapy with mTOR-I. Median follow-up for surviving patients is 723 days (range 88-1621). The overall survival at 3 years since mTOR-I is 72%. In conclusion, mTOR-I seem to be an effective and well-tolerated treatment option for patients with sclerodermatous cGVHD.