No Effect of Individualized Nutrition on Quality of Life, Acute Graft-Versus-Host Disease or Oral Mucositis after Allogeneic Stem Cell Transplantation: A Randomized Controlled Trial

Introduction: Patients with hematological cancers treated with allogeneic stem cell transplantation (allo-SCT) after myeloablative conditioning are at risk of malnutrition due to inadequate energy intake. This may cause or contribute to adverse outcomes. The best way to prevent and treat malnutrition and optimize nutritional status in these patients, remains unknown. We therefore conducted a randomized controlled trial to examine the effect of an individualized nutritional intervention to optimize energy intake, on quality of life (QoL), severe acute graft-versus-host disease (aGVHD) and severe oral mucositis 3 months after allo-SCT.

Methods: One-hundred and seventy-one patients were eligible for the trial, of whom 117 (68%) agreed to participate and were randomized to either the intervention- (n=57) or control (n=60) group. As the primary outcome we determined QoL using the 2 item-global QoL/health of the European Organisation for Research and Treatment of Cancer Quality of Life Core Questionnaire-30. Secondary outcomes were (i) the prevalence of aGVHD grades 3 and 4 diagnosed according to the modified Glucksberg criteria; and (ii) the prevalence and (iii) the number of days with oral mucositis. The goal of the intervention was to supply a daily minimum of 30 kcal/kg body weight from the day the patients commenced the conditioning regime and until discharge. Oral intake was monitored daily during the entire hospital stay. In addition to regular food, the intervention group also received energy-dense and low-lactose oral supplements while in hospital. A nasojejunal tube was inserted within day 5 after allo-SCT. If the energy needs were not met orally or tube feeding was not tolerated, these patients received additional parenteral nutrition. Prior to discharge the intervention group received dietary advices to optimize their nutrient- and energy intake. In the control group oral intake was not monitored while hospitalized, tube feeding was not given and a standard amount of parenteral nutrition was administered only if necessary. Three months after allo-SCT energy intake per body weight was calculated for both study groups using one-day unweighted dietary records. The study was registered in Clinical Trials (NCT01181076).

Results: Median age (n=117) at inclusion was 44 (range 18 - 65) years and 61% were males. The compliance with the intervention during hospital stay (median length 36 days, range 19-93 days) was high: The median energy intake in the intervention group was of 31.2 (14.4 - 42.9) kcal/kg corresponding to about 100% of the target of 30 kcal/kg. Three months after allo-SCT energy intake was available from 72 patients. The intervention group (n=36) had a median daily energy intake of 30.0 (7.7 - 65.0) kcal/kg, whereas the corresponding value was 26.7 (9.3-75.9) kcal/kg in the control group (n=36; p=0.84). A total of 88/117 (75%) patients were eligible for analysis of global QoL scores (40 in the intervention- and 48 in the control group) 3 months after allo-HSCT. The remaining 29 patients had either died (intervention group n= 9, control group n=5), relapsed (intervention group n=4, control group n=3), or had not returned the QoL questionnaire (intervention group n=4, control group n=4). The mean difference in global QoL between the intervention- and control group was not significant: 2.7 (95% CI -7.7 to 13.2; p=0.60; intervention group mean -11.7, SD 24.1; control group mean -14.4, SD 24.8). A total of 117 patients were included in the analyses of aGVHD and oral mucositis. Twenty patients were diagnosed with aGVHD grades 3 and 4 (intervention group n=8, control group n=12), yielding an odds ratio of 0.65 (95% CI 0.25 to1.74; p=0.39). Eighty-nine patients (intervention group n=43, control group n=46) were diagnosed with oral mucositis grades 3 and 4, yielding an odds ratio of 0.93 (95% CI 0.40 to 2.19; p=0.88). The mean difference in number of days with oral mucositis grades 3 and 4 between the intervention- and control group was not significant: -0.55 (95% CI -1.92 to 0.81; p=0.42).

Conclusion: In this first randomized controlled trial testing an individually tailored nutritional intervention in patients undergoing allo-SCT, we found no significant difference in global quality of life, prevalence of acute graft-versus-host disease, or prevalence or duration of oral mucositis 3 months after allo-SCT with myeloablative conditioning.