Can chronic graft versus host disease (cGVHD) cause unintentional weight loss?

Can Chronic Graft-Versus-Host Disease Cause Unintentional Weight Loss?

Yes, chronic graft-versus-host disease (cGVHD) definitively causes unintentional weight loss and malnutrition, with 43% of cGVHD patients demonstrating malnutrition (BMI <21.9) and 14% showing severe malnutrition (BMI <18.5). 1

Magnitude and Clinical Significance of Weight Loss in cGVHD

Weight loss is a well-established and frequent complication of cGVHD that directly impacts patient outcomes. 1 The severity correlates with disease activity:

• Patients with active, ongoing cGVHD demonstrate significantly lower BMI values compared to those with inactive disease (P = 0.02). 1
• Weight loss is explicitly recognized as a late complication of hematopoietic stem cell transplantation (HSCT) in survivors with cGVHD. 2
• cGVHD has a profound impact on overall health status, particularly affecting functional impairment, activity limitation, and pain—all factors that can contribute to weight loss. 2

Mechanisms and Contributing Factors

The pathophysiology of weight loss in cGVHD is multifactorial and incompletely understood:

• Traditional explanations such as odynophagia (painful swallowing) and oral sensitivity do not correlate with weight loss in cGVHD patients, suggesting unknown mechanisms are responsible. 1
• Elevated resting energy expenditure and elevated serum tumor necrosis factor-alpha are potential contributors to weight loss that require further investigation. 1
• Multiple factors contribute to muscle weakness and muscle loss, including the underlying malignant disease, pre-HSCT therapy, immobilization during HSCT, and side effects of corticosteroids used to treat cGVHD. 2

Gastrointestinal Manifestations That Impair Nutrition

Symptomatic gastrointestinal cGVHD is a specific contraindication to enteral nutrition, indicating the severity of GI involvement that can prevent adequate oral intake. 2

The spectrum of GI complications includes:

• Severe mucositis, intractable vomiting, ileus, severe malabsorption, and protracted diarrhea are all manifestations of cGVHD that directly impair nutritional intake. 2
• Patients lose weight particularly in the first 40 days after admission for HSCT, with weight loss having a negative effect on clinical outcomes. 2

Clinical Implications and Mortality Risk

Weight loss and malnutrition in cGVHD patients may represent independent risk factors for mortality. 1

• cGVHD is the leading cause of non-relapse mortality in HSCT survivors. 2
• A BMI below 21.9 is an independent risk factor for mortality in this population. 1
• Death due to severe cGVHD is usually a consequence of infectious complications, which are exacerbated by the immunocompromised state and malnutrition. 3

Management Approach to Prevent and Treat Weight Loss

Aggressive treatment of cGVHD may help reverse weight loss and malnutrition. 1

Nutritional Monitoring and Support

• Patients should be screened and assessed for impending or overt malnutrition at admission and monitored weekly during HSCT for adequate nutrient intake, metabolism, and physical activity. 2
• If nutritional deficits are observed, nutrition support including counseling, oral nutritional supplements (ONS), enteral nutrition (EN), and/or parenteral nutrition (PN) should be initiated early to avoid or minimize further loss of weight and body cell mass. 2
• During intensive chemotherapy and after stem cell transplantation, maintaining physical activity and ensuring adequate nutritional intake is strongly recommended, which may require EN and/or PN. 2

Route of Nutritional Support

• Enteral tube feeding is preferred over parenteral nutrition unless there is severe mucositis, intractable vomiting, ileus, severe malabsorption, protracted diarrhea, or symptomatic gastrointestinal graft-versus-host disease. 2
• When symptomatic GI cGVHD is present, parenteral nutrition becomes necessary and should be supplied by an expert team tailored to individual patient requirements. 2

Physical Activity Interventions

• Patients should be encouraged and supported to perform muscle training and increase physical activity before, during, and after HSCT. 2
• Daily 30-minute ergometer training in HSCT patients results in higher maximal physical performance, less neutropenia, thrombocytopenia, diarrhea, and pain at discharge, as well as shorter hospital stays. 2

Common Pitfalls to Avoid

• Do not attribute weight loss solely to obvious symptoms like oral pain or difficulty swallowing, as these do not correlate with actual weight loss in cGVHD patients. 1
• Do not delay nutritional intervention—early initiation of nutrition support is critical to prevent further deterioration. 2
• Do not overlook the need for aggressive cGVHD treatment itself, as controlling the underlying disease may be necessary to reverse malnutrition. 1
• Do not assume all weight loss is reversible with nutrition alone, as metabolic disturbances from cGVHD may prevent substantial benefit from nutritional support alone. 4