Sarcopenia among patients after allogeneic hematopoietic stem cell transplantation and the impact of chronic graft-versus-host disease

Kelečić, Dina Ljubas; Lelas, Antonela; Karas, Irena; Desnica, Lana; Vukić, Tamara; Sabol, Ivan; Bender, Darija Vranešić; Seiwerth, Ranka Serventi; Perić, Zinaida; Duraković, Nadira; Čepo, Dubravka Vitali; Vrhovać, Radovan; Nemet, Damir; Pavletić, Steven Z.; Pulanić, Dražen; Krznarić, Željko

doi:10.1007/s00432-020-03280-0

Cited by 6 publications

(6 citation statements)

References 34 publications

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“…In our population eGFR was no significant covariate on clearance, but the small number of samples included with an eGFR < 60 mL/min imposes a limitation to our study. As sarcopenia is common in allo-HSCT recipients [36][37][38], eGFR might fail to detect minor renal dysfunction in our cohort. Fourth, other pharmacokinetic properties might be modified, e.g., reduced gastrointestinal absorption due to modification of the gut microbiota.…”

Section: Discussionmentioning

confidence: 94%

Ruxolitinib exposure in patients with acute and chronic graft versus host disease in routine clinical practice—a prospective single-center trial

Isberner

Kraus

Grigoleit

et al. 2021

Cancer Chemother Pharmacol

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Purpose Knowledge on Ruxolitinib exposure in patients with graft versus host disease (GvHD) is scarce. The purpose of this prospective study was to analyze Ruxolitinib concentrations of GvHD patients and to investigate effects of CYP3A4 and CYP2C9 inhibitors and other covariates as well as concentration-dependent effects. Methods 262 blood samples of 29 patients with acute or chronic GvHD who were administered Ruxolitinib during clinical routine were analyzed. A population pharmacokinetic model obtained from myelofibrosis patients was adapted to our population and was used to identify relevant pharmacokinetic properties and covariates on drug exposure. Relationships between Ruxolitinib exposure and adverse events were assessed. Results Median of individual mean trough serum concentrations was 39.9 ng/mL at 10 mg twice daily (IQR 27.1 ng/mL, range 5.6–99.8 ng/mL). Applying a population pharmacokinetic model revealed that concentrations in our cohort were significantly higher compared to myelofibrosis patients receiving the same daily dose (p < 0.001). Increased Ruxolitinib exposure was caused by a significant reduction in Ruxolitinib clearance by approximately 50%. Additional comedication with at least one strong CYP3A4 or CYP2C9 inhibitor led to a further reduction by 15% (p < 0.05). No other covariate affected pharmacokinetics significantly. Mean trough concentrations of patients requiring dose reduction related to adverse events were significantly elevated (p < 0.05). Conclusion Ruxolitinib exposure is increased in GvHD patients in comparison to myelofibrosis patients due to reduced clearance and comedication with CYP3A4 or CYP2C9 inhibitors. Elevated Ruxolitinib trough concentrations might be a surrogate for toxicity.

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Section: Discussionmentioning

confidence: 94%

Ruxolitinib exposure in patients with acute and chronic graft versus host disease in routine clinical practice—a prospective single-center trial

Isberner

Kraus

Grigoleit

et al. 2021

Cancer Chemother Pharmacol

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“…For example, using the frequency, intensity, time, and type of specific resistance and aerobic exercises (FITT) framework could ensure that a specific exercise dosage is being delivered, optimizing the results of the exercise 25. An exercise program should be tailored to specific symptoms and health needs of a population,25,34 and the HSCT population has particular issues, such as decreased overall strength, gait, and balance impairments, reduced exercise capacity, sarcopenia, and malnutrition, among others 1-13. Although there are no guidelines for the FITT components in the HSCT population, parameters from published randomized controlled trials involving the rehabilitation of hematological cancers could be adapted in HSCT patients 25…”

Section: Discussionmentioning

confidence: 99%

“…25 An exercise program should be tailored to specific symptoms and health needs of a population, 25,34 and the HSCT population has particular issues, such as decreased overall strength, gait, and balance impairments, reduced exercise capacity, sarcopenia, and malnutrition, among others. [1][2][3][4][5][6][7][8][9][10][11][12][13] Although there are no guidelines for the FITT components in the HSCT population, parameters from published randomized controlled trials involving the rehabilitation of hematological cancers could be adapted in HSCT patients. 25 Patients undergoing HSCT continue to have rehabilitation needs at the time of discharge.…”

Section: Exercise Therapy Characteristicsmentioning

confidence: 99%

“…Collectively, the potentially long hospitalization for HSCT may result in reduced physical function. 1,2 Consequently, numerous symptoms and physical impairments may arise, such as: (a) physical: decreased core strength and upper and lower extremity strength, decline in gait, and balance deficits [1][2][3][4][5] ; (b) cardiopulmonary: decreased peak VO 2 and exercise capacity and increased cardiovascular disease [6][7][8][9] ; (c) nutritional: malnutrition and loss of lean muscle body mass [10][11][12][13] ; and (d) pulmonary: decreased forced vital capacity and expiratory volume and increased risk of respiratory complications. [14][15][16] Rehabilitation interventions can mitigate symptoms and physical impairments when administered during acute hospitalization for HSCT.…”

Section: Introductionmentioning

confidence: 99%

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Assessment of Rehabilitation Practices During Hematopoietic Stem Cell Transplantation in the United States: A Survey

Leite,

Oza,

Parke

et al. 2024

Rehabilitation Oncology

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Background: Rehabilitation therapy is important to treat physical and functional impairments that may occur in individuals receiving physically taxing, yet potentially curative hematopoietic stem cell transplants (HSCTs). However, there are scarce data on how rehabilitation is delivered during HSCT in real-life setting. Our objective is to assess the rehabilitation practices for adult patients hospitalized for HSCT in the United States. Methods: We conducted a 48-question online survey with cancer centers with the top 10% HSCT volumes (per American registries). We obtained data on patient characteristics, rehabilitation therapy details (timing, indication, and administering providers), physical function objective and subjective outcome measures, and therapy activity precautions. Results: Out of 21 institutions, 14 were included. Rehabilitation therapy referrals occurred at admission for all patients at 35.7% of the centers for: functional decline (92.9%), fall risk (71.4%), and discharge planning (71.4%). Participating institutions had physical therapists (92.9%), occupational therapists (85.7%), speech-language pathologists (64.3%), and therapy aides (35.7%) in their rehabilitation team. Approximately 71% of centers used objective functional measures including sit-to-stand tests (50.0%), balance measures (42.9%), and 6-minute walk/gait speed (both 35.7%). Monitoring of blood counts to determine therapy modalities frequently occurred and therapies held for low platelet or hemoglobin values, but absolute neutrophil values were not a barrier to participate in resistance or aerobic therapies (42.9%). Conclusion: Rehabilitation practices during HSCT varied among the largest volume cancer centers in the United States, but most centers provided skilled therapy, utilized objective, clinician- and patient-reported outcomes, and monitored blood counts for safety of therapy administration.

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“…Patients who undergo alloSCT are usually admitted for several weeks, thus risking to lose muscle strength and function over time ( 10 , 11 ). Furthermore patients develop acute Graft-versus-Host Disease (GVHD) in approximately 30-50% of cases ( 12 ) and chronic GVHD in 30-70% of cases ( 13 ).…”

Section: Introductionmentioning

confidence: 99%

Monitoring of strength, inflammation and muscle function in allogenic stem-cell transplantation patients – a pilot study for novel biomarker and risk stratification determination

Schulz,

Bizjak,

Moebes

et al. 2023

Front. Immunol.

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BackgroundLow aerobic capacity is associated with an increased mortality risk in allogenic stem-cell transplantation (alloSCT) patients, but currently used risk scores in the pre-transplantation workup are still underestimating physical activity as a prognostic factor.AimTo examine the physical condition, muscle function, blood inflammation and training adherence of alloSCT patients during inpatient time to identify potential biomarkers associated with development of myopathy and sarcopenia.MethodsPatients undergoing alloSCT were examined at four time points (T0: before alloSCT; Tha: hospital admission; T1: engraftment; T2: inpatient discharge). T0 included cardiopulmonary performance, body composition, grip and knee strength, motor skill tests (One-leg stand/Tinetti/Chair-rising), blood sampling (blood cell profiling and inflammation targets (Kynurenin/high sensitivity C-reactive Protein (hsCRP)/Tumor necrosis factor alpha (TNF-alpha)/Musclin/Galectin-3) and quality of life, state of health, fatigue, muscle weakness and physical activity by questionnaires (IPAQ/BSA/SARC-F/Fatigue). At T1 and T2, blood samples, grip strength and motor skill tests were repeated. Glucocorticoid dose and daily physical activity were documented during inpatient stay.Results26 of 35 included patients (4 females; age 55.58 ± 12.32 years; BMI 24.70 ± 3.27 kg/m2; VO2peak 16.55 ± 4.06 ml/min/kg) could proceed to alloSCT. Grip strength and Tinetti decreased from T0 until T2, no difference in Chair-rising test, One-leg and Tandem stand. All patients engrafted after 24.9 days ± 3.9 days. HsCRP and Kynurenine increased from T0 to T1, decreased at T2. TNF-alpha (T0vsT2/T1vsT2) and Musclin (T0vsT1) decreased. At T2, Galectin-3 was higher compared to T0/T1. Correlation analysis of grip strength and inflammatory markers revealed a positive correlation with TNF-alpha at T2. 50% of patients documented physical activity and questionnaire and reported a 50%-reduction of daily endurance and strength training between T1 to T2.ConclusionAllogeneic stem-cell transplantation is associated with immune system vulnerability due to conditioning, increased inflammation and fatigue, and loss of muscle strength and function. In addition to hsCRP, Kynurenine seems to be a reliable biomarker to monitor acute and regenerative inflammation status of alloSCT patients, while Musclin and Galectin-3 may be added to physiological assessment regarding myopathy and sarcopenia. Grip strength and daily activity level should be documented by professionals to identify risk patients early and support them with optimal (exercise) therapy.

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Sarcopenia among patients after allogeneic hematopoietic stem cell transplantation and the impact of chronic graft-versus-host disease

Cited by 6 publications

References 34 publications

Ruxolitinib exposure in patients with acute and chronic graft versus host disease in routine clinical practice—a prospective single-center trial

Ruxolitinib exposure in patients with acute and chronic graft versus host disease in routine clinical practice—a prospective single-center trial

Assessment of Rehabilitation Practices During Hematopoietic Stem Cell Transplantation in the United States: A Survey

Monitoring of strength, inflammation and muscle function in allogenic stem-cell transplantation patients – a pilot study for novel biomarker and risk stratification determination

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