Anorexia overcoming in patients with cytostatic therapy and hematopoietic stem cell transplantation

Summary

Cytostatic therapy and hematopoietic stem cell transplantation (HSCT) are treatment options for blood malignancy, often associated with the development of complications, including gastrointestinal toxicity in the early period and endocrine system dysfunction more typical as a late complication. One of the manifestations of which is anorexia, leading to protein-energy malnutrition, body mass wasting, and ultimately cachexia – negative impact factor of overall survival. We aimed to evaluate safety and clinical efficacy of existing appetite stimulants in order to overcome anorexia in the patients.

Patients and methods

Since 2014, 99 patients with acute myeloid leukemia (n=27), acute lymphoblastic leukemia (n=26), solid tumors (n=12), lymphomas (n=10), chronic myeloid leukemia (n=8), inherited (n=4) and other diseases (n=12) were enrolled to the prospective study. The median age was 20.6 years (2 months to 76 years), among them children (n=68) and adults (n=31). The groups included 59 males and 40 females. HSCT was performed in 75 patients: allogeneic unrelated (n=45), related donors (n=11), haploidentical donors (n=16), autologous (n=3); cytostatic therapy was performed in 20 cases; other methods of treatment (n=4). To treat protein-energy malnutrition in which anorexia was the leading syndrome. Appetite stimulant therapy was carried out in 58 patients, i.e., megestrol acetate (Megace, Bristol-Myers Squibb, USA), 40-320 mg/day (0.8-13.3 mg/kg) orally, divided into 2 doses, duration 1-3 months. 19 patients received levocarnitine (Elkar, PEAK-Pharma, Russia) – 0.3-0.9 g/day (0.61 g/day) orally for 1 month. Taking into the account that prednisolone, for which appetite increase is a common side effect, 22 patients who had received Prednisolone 1-2 mg/kg/day as a part of graft-versus-host disease (GvHD) therapy, were also included into the study. The groups of patients were homogeneous for the main clinical parameters (p=0.3).

Results

Appetite was restored in 79.3% of patients (n=46) in megestrol acetate group, р=0.0001; 63.6% (n=14) with prednisolone, р=0.0001; 22.2% (n=4), with levocarnitine. Body mass increase was observed in 81% (n=47) of the patients in megestrol acetate group (p=0.05); 50% (n=11) in prednisolone group (p=0.05) and 15.8% (n=3), among levocarnitine-treated patients. At the beginning of megestrol acetate treatment 27 patients (46.5%) had chronic GvHD of different localization and 29.3% (n=17) had cachexia. Initially, the patients had hypotrophic or cachectic nutritional status, presence or absence of GvHD didn’t affect efficiency appetite stimulants (р=0.3). Prednisolone treatment was associated with more frequent rate of complications, 45.4% (n=10) (metabolic disturbances in 7 patients, catabolism in 7 patients, steroid-induced diabetes mellitus in 3 cases, p=0.0001), in comparison with megestrol acetate (n=1, bronchial spasm), and levocarnitine (n=1, allergic reaction manifested by rash).

Conclusions

Low-dose megestrol acetate is a safe and effective option for anorexia and cachexia treatment in adults and children after HSCT and cytostatic therapy. Use of prednisolone as a GvHD treatment in HSCT recipients was less effective to overcome anorexia, moreover, it was accompanied with enhanced catabolism and metabolic alterations.

Keywords

Hematopoietic stem cell transplantation, graft-versus-host disease, anorexia, appetite stimulants.