1.
Statin-based endothelial prophylaxis and outcome after allogeneic stem cell transplantation
Pabst, C., Schreck, N., Benner, A., Hegenbart, U., Schönland, S., Radujkovic, A., Schmitt, M., Müller-Tidow, C., Orsatti, L., Dreger, P., et al
European journal of clinical investigation. 2022;:e13883
Abstract
BACKGROUND Allogeneic hematopoietic stem cell transplantation (alloSCT) often remains the only curative therapy for hematologic malignancies. Although the management of transplant-associated adverse events considerably improved over the last decades, non-relapse mortality (NRM) remains a challenge, and endothelial dysfunction was identified as a major contributor to NRM. METHODS Statin-based endothelial prophylaxis (SEP) has been implemented in the standard-of-care in our transplant centre to reduce NRM caused by endothelial injury. Here, we retrospectively analyzed the impact of SEP on clinical outcome in a cohort of 347 alloSCT patients. RESULTS SEP (n=209) was associated with significantly reduced NRM (hazard ratio 0.61, 95% CI 0.38-0.96) and better overall survival (OS) after acute graft-versus-host disease (HR 0.59, 95% CI 0.37-0.93). Subgroup analyses showed that the NRM benefit was mainly found in patients with an intermediate endothelial activation and stress index (EASIX), while relapse risk was not affected. On day 100 post alloSCT, patients receiving SEP had significantly higher levels of the rate-limiting enzyme of tryptophan metabolism, indoleamine 2,3-dioxygenase (IDO), higher kynurenine to tryptophan ratios as a proxy of IDO activity, and tended to have lower levels of the endothelial injury marker ST2 (p=0.055). No significant differences in interferon-gamma or IL18 levels were observed. These biomarker signatures suggest that the beneficial effects of SEP might be mediated by both endothelial protection and immunomodulation. CONCLUSIONS Together, these data suggest that SEP improves NRM and OS post alloSCT in particular in patients with intermediate endothelial risk and provide first mechanistic clues about its potential mode of action.
2.
Determinants of exercise adherence and contamination in a randomized controlled trial in cancer patients during and after allogeneic HCT
Kuehl, R., Schmidt, M. E., Dreger, P., Steindorf, K., Bohus, M., Wiskemann, J.
Supportive Care in Cancer. 2016;24(10):4327-37
Abstract
BACKGROUND Evidence from randomized controlled trials is growing that exercise interventions are beneficial in cancer patients receiving allogeneic stem cell transplantation (allo-HCT). However, information about adherence to exercise interventions and exercise contamination in control groups is lacking. This information is crucial for the interpretation of study results. We therefore examined the determinants of exercise adherence and contamination in different treatment periods during (inpatient) and after (outpatient) allo-HCT. METHODS One hundred fifty-three patients scheduled for allo-HCT were randomized to a 1-year partly supervised exercise intervention (endurance and resistance exercise) or to a control group. Adherence was assessed via exercise logs and contamination via questionnaires. RESULTS Adherence varied between 66 % (inpatient) and 78 % (outpatient) in different treatment periods. During (inpatient) transplantation period, higher adherence was significantly associated with lower fatigue (P=0.004) and with having children at home (P=0.049). Adherence after discharge was positively associated with endurance performance (P=0.003); higher adherence after day 100 was associated with exercise activity prior allo-HCT (P=0.010) and higher adherence after discharge (P=0.001). Contamination among controls was high with 54 % and significantly associated with muscle strength (P=0.025) and fatigue (P=0.050). CONCLUSION Exercise adherence in different treatment periods was determined by different variables, and contamination among controls was evident. These findings may have important implications for correct interpretation of randomized exercise intervention trials.