Nutritional Intake and Nutritional Status by the Type of Hematopoietic Stem Cell Transplantation

As the method for correcting bone marrow disorder by injecting normal hematopoietic stem cell after complete destroy of bone marrow with bone marrow suppression, malignant disease or genetic disorder, stem cell transplantation is the treatment method that is currently recognized as the only alternative for completely curing various blood diseases [1, 2]. However, complications accompanied during the treatment process serve as factors that disrupt successful hematopoietic stem cell transplantation and reduce long-term survival results. Transplantation-related complications largely include toxicity associated with conditioning regimen, toxicity caused by preventive drugs during the transplantation process, complications caused by immunity failure and graft-versus-host disease (GVHD), which integrates immunological side effects of the allogeneic hematopoietic stem cell transplantation [2]. In particular, as a majority of symptoms accompanied with the complications act as factors that hinder nutritional intake, studies related with nutritional intake, support and malnutrition have been continuously carried out in addition to efforts exerted to minimize complications related with hematopoietic stem cell transplantation [3].

The conditioning regimen composed of high-dose chemotherapy or total body irradiation (TBI) triggers various side effects that disturb nutritional intake, such as stomatitis, nausea, vomiting, loss of appetite and diarrhea [4]. Various studies report that nutritional intake and nutritional status are significantly reduced during the hematopoietic stem cell transplantation period [5], which not only postpones the period of engraftment [6], but also causes GVHD, veno-occlusive disease (VOD) and hospitalization in the ICU [7, 8]. Malnutrition is also triggered by other metabolic effects according to cancer diagnosis, such as cachexia, in addition to the reduction of nutritional intake caused by various therapeutic side effects. Malnutrition is generally reported to be experienced among 40-80% of cancer patients [9, 10], and various research results have reported malnutrition as the main factor that increases the infection rate, morbidity, mortality, length of hospital stay and medical cost of cancer patients [10-15]. Research results also show that malnutrition increases the length of hospital stay and the risk of early death for hematopoietic stem cell transplantation patients, and presents a correlation between poor prognosis and severe GVHD [8, 16-18].

In this regard, although various studies emphasize the importance of evaluating nutritional status, monitoring appropriate nutritional intake and the providing nutritional support for hematopoietic stem cell transplantation patients, accurate guidelines for nutritional support remain unestablished [19, 20]. By surveying the short-term nutritional status of 34 child transplantation patients, results showed a significant correlation between nutritional intake and nutritional status [21], presented that the nutritional status was more satisfactory in the group that received appropriate nutritional support and proposed that positive effect was presented in lean body mass. However, the results of various studies indicate that more efforts must be made in various aspects, such as the development of indicators for nutritional support [3, 22-24].

On the other hand, research results have indicated that the engraftment period of hematopoietic stem cell transplantation patients can differ according to the type of transplantation [25, 26], that high oral intake was generally presented in the early engraftment group with short engraftment period [6] and that the nutritional status during transplantation can become an important factor for determining the period of engraftment [27]. Therefore the type of hematopoietic stem cell transplantation can serve as an important variable in researching the nutritional intake and nutritional status of hematopoietic stem cell transplantation patients.

Hereupon, this study investigated changes in nutritional intake and nutritional status during the transplantation period in consideration of the type of hematopoietic stem cell transplantation and analyzed the correlation to provide evidence for establishing nutrition care guidelines of hematopoietic stem cell transplantation patients.

This study analyzed the nutritional intake and nutritional status by classifying subjects into groups according to the hematopoietic stem cell transplantation method. Compared with allogeneic transplantation, autologous transplantation generally presented a shorter length of hospital stay and engraftment period as well as a relatively favorable condition during hospital stay. Furthermore, As the source of stem cell can serve as factors that influence the period of engraftment, this study also surveyed bone marrow transplant and peripheral blood stem cell transplant [25, 26]. Analysis results showed that among 36 patients, 9 received autologous transplantation whereas 27 received allogeneic transplantation. The ratio of patients that received peripheral blood stem cell transplant accounted for 100% of the autologous transplantation group and 40.7% of the allogeneic transplantation group, showing a significant difference. The period of engraftment was nearly 3 days longer in the allogeneic transplantation group when compared with the autologous transplantation group. This is stipulated to be related with the source of stem cell when considering the research results that reported the correlation between the collect rate of hematopoietic stem cells and early engraftment [25, 26]. The allogeneic transplantation group presented a significantly longer period of receiving nutritional support due to the decline in oral intake. The autologous transplantation group received nutritional support for 9.3 days on average, thus analyzed to receive nutritional support for a shorter period than the 17.5 days presented in the study conducted by Roberts et al. [22], who studied breast cancer patients receiving autologous hematopoietic stem cell transplantation. On the other hand, the result presented in this study is similar to the 9 days reported in the study conducted on acute myeloid leukemia patients receiving hematopoietic stem cell transplantation [19]. The average period of engraftment was 10.7 days in autologous transplantation and 13.3 days in allogeneic transplantation, which are shorter than the 16.5 days presented in a study conducted on acute myeloid leukemia patients that received allogeneic transplantation [27]. A study conducted on 416 hematopoietic stem cell transplantation patients randomly established the early engraftment group as subjects below the 50 percentile. Results showed that the period of engraftment was longer than 11.2 days in the early engraftment group and shorter than 15.6 days in subjects above the 50 percentile [6]. This result is stipulated to be produced by the different classification standards for research subjects and control groups. The results gained from the study conducted by Kim et al. [6] presented high oral intake in the early engraftment group. Although Kim et al. [6] analyzed the days of vomiting and stomatitis, factors hindering oral intake, as variables for explaining the period of engraftment, the present study did not show significant results between the period of engraftment and nutritional intake. This can be assumed to be related with fact that the outcome of the bone marrow transplant is influenced by various factors, such as disease, age, medical history, condition of disease during transplantation, HLA-correspondence, conditions of donor and GVHD [2, 19]. In this regard, in order to provide efficient nutritional care for patients, it is important to analyze factors that can influence nutritional intake and nutritional status and develop a protocol based on the analysis results, rather than approaching the issue simply based on the transplant method.

The main factor that disrupts oral intake during the hematopoietic stem cell transplantation period is side effects produced by conditioning regimen. As the oral intake is generally reduced by such side effects for 1-2 weeks during the transplantation period, it is common to receive nutritional support. In this regard, many studies are conducted in relation to this issue [22, 23, 31], but accurate guidelines have not been provided. The study conducted by Arfons & Lazarus [24], who evaluated the necessity of parenteral nutrition support by analyzing the period of engraftment, infection rate, survival rate and length of hospital stay of hematopoietic stem cell transplantation patients, proposes that it is essential to consider the use of parenteral nutrition support for patients that are unable to ingest orally. The study conducted by Iestra et al. [19] reports that TPN is not required by all patients and concludes that support must be provided through appropriate assessment of nutritional status and oral intake monitoring at the beginning of treatment. However, it is difficult to find accurate guidelines in relation to this matter. Hereupon, this study judged that it is essential to accurately assess the nutritional intake of hematopoietic stem cell transplantation patients in order to provide appropriate nutritional support and thus evaluated the appropriateness of nutritional intake during the hematopoietic stem cell transplantation period. The nutritional intake was largely classified into oral intake, oral intake to recommended amount and nutritional intake including TPN to recommended amount. In both groups, the nutritional intake was gradually decreased from Pre-1day and reached the lowest value during Post+1wk. The oral calorie intake to recommended amount was presented as 4.6% and 15.2% in the autologous transplantation group and allogeneic transplantation group, respectively. Furthermore, it was analyzed that both groups presented nutritional intake that fell below the recommended amount by 47.7% and 60.2%, respectively, even when considering TPN. This is similar to the results presented by Hadjibabaie et al. [32], who evaluated the nutritional status of 50 hematopoietic stem cell transplantation patients and reported that the lowest intake quantity was measured as 51% of the recommended amount and was shown on the 10th day after transplantation. Another study conducted on hematopoietic stem cell transplantation patients reported that the early engraftment group presenting relatively satisfactory intake quantity ingested 1,555.0 mL during admission, 1,053.2 mL during Pre-1day, 765.7 mL during Post+1wk and 893.3 mL during Post+2wk, which is generally higher than the intake quantity of this study [6]. This result is judged to be produced from the difference generated by analyzing food intake in volume and in accurate calories [6]. Nutritional intake was very low in hematopoietic stem cell transplantation even when compared with solid cancer patients that are mainly treated through chemotherapy due to the high-intensity conditioning regimen composed of the high-dose chemotherapy and total body irradiation. The study conducted by Kim et al. [33], who studied solid cancer patients receiving chemotherapy, presented that the average calorie intake as 1,476 kcal/d, 47.8 g/d, which is higher than those measured in this study. The study conducted by Yang & Lee [34] showed that the intake quantity decreased from 1,450.48 cc/d to 1,120.52 cc/d, thus presenting a smaller decrease than hematopoietic stem cell transplantation patients. The study conducted by Yang et al. [35], who researched gastric cancer patients, presented that the nutritional intake was decreased from 863.12 kcal to 802.63 kcal during the chemotherapy period. In particular, it is important to note that both control groups presented 20% of oral calorie intake to recommended amount during Post+2wk. Also, it is most essential to increase the oral intake to the recommended level as quickly as possible before discharge. This is related with the fact that various studies have reported that nutritional intake and nutritional status can decrease even after discharge due to factors such as chronic graft-versus-host disease and changes in palate, thus influencing the survival rate after transplantation. Also, there are no effective alternatives related with recovery and increased oral intake after receiving hematopoietic stem cell transplantation. In the retrospective study conducted by Barker et al. [7], most of the 132 hematopoietic stem cell transplantation patients complained of stomach-related side effects, such as stomatitis, vomiting, abdominal pain and diarrhea, even after being discharged. These side effects are presented as the main factors that increase GVHD, vein occlusion syndrome, ICU hospitalization rate and the death rate within 100 days after transplantation. The study conducted by Iestra et al. [36] evaluated nutrition-related physical symptoms and compliance with recommended intake level 50, 75, 125, 200, 350 days after transplantation. Results showed that 66% of patients experienced meal intake disorders 50 days after transplantation. The main factors were analyzed as nausea, drying of mouth, changes in palate and fatigue. Studies focused on palate changes presented that patients experienced palate changes related with sweet and salty tastes according to the assessment of palate and salivation rate of 3 groups: 150 days after hematopoietic stem cell transplantation (n = 20), 151-1,095 days after hematopoietic stem cell transplantation (n = 20) and more than 1,095 days after hematopoietic stem cell transplantation (n = 21). As the symptoms are reported to last more than 3 years after receiving transplantation, it can be viewed as a long-term problem [37]. The cohort study conducted by Epstein et al. on patients that received hematopoietic stem cell transplantation (day 90-100 post HCT) also proposes that subjects experienced various oral complications that can also affect their quality of life [38]. Thus, although this study focused on nutritional intake during the hematopoietic stem cell transplantation period, results showed that it is more important to find post-discharge nutritional care methods that can increase the overall transplant success rate.

On the other hand, although this study predicted that different nutritional intake will be presented in autologous transplantation and allogeneic transplantation groups, no significant difference was shown in the changes of nutritional intake according to the transplantation period. Although the autologous transplantation group presented a significantly favorable level of oral intake during Pre-1day, the allogeneic transplantation group presented a relatively higher level of oral calorie intake and significantly higher level of oral protein intake during Post+1wk. The effect of intensity of conditioning regimen can be considered according to the source of stem cell [25, 26]. Nutritional care considering stomach-related side effects according to the intensity of conditioning regimen is required based on the research results that analyzed the symptoms disturbing oral intake, such as vomiting and stomatitis, as significant factors that influence early engraftment [6]. Furthermore, by comparing the transplantation progress of the TPN group and oral intake group among autologous hematopoietic stem cell transplantation patients, the TPN group was shown to ingest 1,494 kcal/d, 60 g protein/d whereas the oral intake group ingested 951 kcal/d, 36 g protein/d on average. The weight and body measurement indicators were favorably maintained in the TPN group. Nutritional care plan focused on the regulation of nutritional support quantity according to period can be viewed efficient when considering the fact that the provision of TPN to patients must be considered for patients suffering from nutritional deficit due to transplantation, patients experiencing complications after the transplantation and patients that have reduced oral intake for a long period [22].

During the hematopoietic stem cell transplantation period, the autologous transplantation group presented 5.1% weight loss whereas the allogeneic transplantation group presented 3.7% weight loss, thus presenting similar results with the 3.5% weight loss reported in the study carried out on allogeneic transplantation patients [27]. The decrease rate was lower than the 5.6% reported in the study conducted by Iestra et al. [19] on acute myeloid leukemia patients that received hematopoietic stem cell transplantation. Appropriate nutritional support complying with the recommended oral intake is required when considering the fact that weight loss is a representative indicator that presents nutritional status and the fact that the period of engraftment is delayed by excessive weight loss and deficit of albumin and protein [27, 32]. Although significant difference in weight changes was not presented, the PG-SGA score, as the nutritional assessment results presenting food intake, symptoms disturbing oral intake, activity and function, showed that the autologous transplantation group presented significantly poor nutritional status during Post+1wk. On the other hand, the results of PG-SGA assessment presented that the ratio of patients with poor nutritional status was significantly high in the allogeneic transplantation group during Pre-1day. Furthermore, although there was only 1 malnourished patient (3.7%) when the patients were admitted, 35 patients (97.2%) were malnourished during Post+1wk. The study conducted by Horsely et al. [16], who analyzed the nutritional condition of 66 patients before transplantation through PG-SGA, presented that 27% of patients with favorable nutritional status showed a rapid deterioration in nutritional status after transplantation. This corresponds with the results of various studies that during the hematopoietic stem cell transplantation period, subjects not only lose body tissue due to catabolic metabolism, but also present rapid decrease in nutritional status due to reduced oral intake [5, 6, 32, 39]. On the other hand, the severity of malnutrition is indisputable [40] as it can lead to weight loss, reduced nutritional status due to chronic GVHD and changes in palate, which in turn reduces the quality of life [39] and increases death rate [17, 18]. The study conducted by Jacobsohn et al. [41] reported that among the 93 patients diagnosed with chronic GVHD, 43% presented malnutrition (BMI below 21.9) whereas 14% presented severe malnutrition (BMI below 18.5). In this regard, it can be assumed that a considerable number of subjects cannot solve malnutrition even after transplantation. Thus, active nutritional care is required to recover the nutritional status of patients during the hematopoietic stem cell transplantation period and after discharge.

By conducting the correlation analysis to analyze nutritional intake factors that influence the nutritional status at discharge, this study analyzed that the oral intake reduced from Post+1wk was not recovered by Post+2wk. Hereupon, it is more effective to analyze the oral intake for 1 week after transplantation to provide education for enhancing the food intake of patients with reduced oral intake after discharge. Furthermore, although nutritional support was appropriately provided according to the decrease in oral intake, nutritional support was not provided according to changes in oral intake during Post+2wk. This can be viewed in relation to the intentional reduction of TPN to prevent loss of appetite, it is essential to provide timely education for increasing food intake to prevent reduced nutritional status according to the decrease in oral intake.

On the other hand, this study holds significance in that it minimized the quantitative error in data collection between surveyors by using a structured food intake questionnaire and a simple food model and reflected TPN in the nutritional intake survey. Furthermore, it is judged that the accuracy of research was increased by using the validated PG-SGA assessment method for evaluating the nutritional status of cancer patients. However, the limitations of this study are as follows: the calorie and protein intake was calculated by using Food Exchange System, the lack of research subjects due to short research period and the cross-sectional design of study. These limitations must be complemented in follow-up studies.

When considering the fact that the changes in nutritional intake did not present significant differences according to the hematopoietic stem cell transplantation method, it is more important to analyze factors that can influence nutritional intake and nutritional status and develop a protocol based on the analysis results, rather than approaching the issue simply based on the transplant method, in order to achieve efficient nutritional care of patients. On the other hand, when considering the fact that the oral intake reduced from Post+1wk did not recover by Post+2wk and the fact that appropriate nutritional support was not provided despite the low recovery rate of oral intake during the Post+2wk, it is important to provide intensive education for increasing food intake during Post+1wk and discharge. Furthermore, to increase the overall transplant success rate, it is crucial to search nutritional care methods that can be applied during hospitalization and after discharge.