Cachectic muscle wasting in acute myeloid leukaemia: a sleeping giant with dire clinical consequences

Abstract

Acute myeloid leukaemia (AML) is a haematological malignancy with poor survival odds, particularly in the older (>65 years) population, in whom it is most prevalent. Treatment consists of induction and consolidation chemotherapy to remit the cancer followed by potentially curative haematopoietic cell transplantation. These intense treatments are debilitating and increase the risk of mortality. Patient stratification is used to mitigate this risk and considers a variety of factors, including body mass, to determine whether a patient is suitable for any or all treatment options. Skeletal muscle mass, the primary constituent of the body lean mass, may be a better predictor of patient suitability for, and outcomes of, AML treatment. Yet skeletal muscle is compromised by a variety of factors associated with AML and its clinical treatment consistent with cachexia, a life-threatening body wasting syndrome. Cachectic muscle wasting is associated with both cancer and anticancer chemotherapy. Although not traditionally associated with haematological cancers, cachexia is observed in AML and can have dire consequences. In this review, we discuss the importance of addressing skeletal muscle mass and cachexia within the AML clinical landscape in view of improving survivability of this disease.

Keywords: Acute myeloid leukaemia; Cachexia; Cancer; Chemotherapy; Myopathy; Risk stratification; Skeletal muscle.

Figure 1

Proposed muscle‐related risk stratification criteria in acute myeloid leukaemia (AML). Improved risk stratification criteria for AML could consider, measure, and utilize skeletal muscle mass because muscle loss is correlated with higher morbidity and mortality rates. Patients could be stratified through the identification of (i) cachexia by the CAchexia SCOre (CASCO), which utilizes pro‐inflammatory status [measured by interleukin‐6 (IL‐6)], and the Glasgow prognostic score (GPS), which measures serum C‐reactive protein (CRP) and albumin; (ii) sarcopenia/obesity by the body mass index (BMI) using the rudimentary measures of patient height and weight; or (iii) myopenia/sarcopenia by the skeletal muscle index (SMI), the gold standard assessment of skeletal muscle mass by abdominal computed tomography (CT). This could occur before, during, and after AML treatment to determine acceptable chemotherapy exposure (e.g. type of anthracycline, dose, and number of consolidation cycles) and eligibility for haematopoietic cell transplantation (HCT) and increase overall survival.

Figure 2

Potential drivers of muscle mass loss in acute myeloid leukaemia (AML). Chemotherapy administration has been shown to directly induce skeletal muscle wasting and dysfunction. This can be exacerbated by the effect of chemotherapy on the gastrointestinal tract (GIT), which dysregulates motility and microbiota composition and compromises the intestinal barrier. Collectively, these symptoms reduce nutrient absorption and nutrient status signalling through the microbiome and increase the risk of infection and passage of inflammatory mediators. Furthermore, chemotherapy extirpates blood cells causing hypoxia and supressing the immune response. Consequently, patients are incapacitated, because of both fatigue and risk of infection, respectively. Ultimately, processes that maintain muscle mass and function are compromised, and muscle damage and wasting is potentiated. The outcome is cachexia, which further drives muscle wasting and dysfunction through dysregulated signalling, malnutrition, and muscle de‐loading.