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Table of Contents
ORIGINAL ARTICLE
Year : 2021  |  Volume : 12  |  Issue : 3  |  Page : 137-141

Altered oral intake during hematopoietic stem cell transplantation: Patterns and countermeasures


1 Department of Clinical Haematology and Stem Cell Transplantation, Dayanand Medical College and Hospital, Ludhiana, Punjab, India
2 Department of Medical Oncology, Dayanand Medical College and Hospital, Ludhiana, Punjab, India

Date of Submission26-Dec-2020
Date of Decision21-Feb-2021
Date of Acceptance22-Feb-2021
Date of Web Publication15-Jul-2021

Correspondence Address:
Dr. Suvir Singh
Department of Clinical Haematology and Stem Cell Transplantation, Dayanand Medical College, Ludhiana, Punjab
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/injms.injms_173_20

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  Abstract 


Introduction: Hospitalization for stem cell transplantation leads to reduced oral intake, often requiring parenteral nutrition (PN). Preserving enteral nutrition sustains gut mucosa and microbiota and potentially reduces long-term complications. We provide a short report on patterns of altered dietary intake in stem cell transplant recipients and simple measures that can be taken to mitigate the same. Methods: Patients undergoing autologous and allogeneic stem cell transplantation over an 11 month period were included. Baseline calorie and protein intake was calculated according to the National Institute of Nutrition (India) guidelines. Steps to maintain oral intake included: patient education pretransplant, allowance of home food and packaged food (cookies/chocolates), shift to semisolid or liquid diet, and symptomatic local analgesia for all patients with mucositis. Results: A total of 16 patients were included in the analysis, (male:female = 10:6), with a median age of 43 years (range, 6–67). Median body mass index at baseline was 22.5 kg/m2 (range, 11.9–31.8 kg/m2). Median calorie intake at baseline was 26.8 kcal/kg/day (range, 18–51) and protein intake was 0.47 g/kg/day (range 0.19–0.87). During the course of treatment, maximum grade of mucositis was grade III in 9 and grade II in seven patients. The median caloric deficit from baseline at lowest intake was -79% (range, +11 to − 96%), with the nadir occurring by median day 6.5 (range,-1–12). At the time of discharge, the median oral intake was 70% of baseline (range, −1.2% to + 175%). Most patients had a median of − 4.3% (range, −15% to + 0.4%) of weight loss at discharge. No patient required PN during admission. One patient died as a result of regimen-related toxicity. Conclusions: Patients undergoing stem cell transplantation demonstrated significantly low oral intake at admission which further significantly reduced over the course of hospitalization. Pretransplant optimization of calorie intake, patient education, dietary modification, and in-hospital symptomatic control along with daily monitoring of calorie intake is essential so that reduction can be picked up early and corrective actions are taken.

Keywords: Bone marrow transplant, cancer, diet, leukemia, transplant


How to cite this article:
Singh S, Singh K, Singh J, Paul D, Jain K. Altered oral intake during hematopoietic stem cell transplantation: Patterns and countermeasures. Indian J Med Spec 2021;12:137-41

How to cite this URL:
Singh S, Singh K, Singh J, Paul D, Jain K. Altered oral intake during hematopoietic stem cell transplantation: Patterns and countermeasures. Indian J Med Spec [serial online] 2021 [cited 2021 Sep 19];12:137-41. Available from: http://www.ijms.in/text.asp?2021/12/3/137/321459




  Introduction Top


Stem cell transplantation is a potentially curative approach to several hematologic diseases and requires administration of a preparative regimen comprising high-dose chemotherapy with or without radiotherapy. Preparative regimens have evolved over the years and are considerably less toxic, but can still be associated with significant nonhematologic toxicity.[1] Most transplant recipients experience reduction in oral intake due to a combination of mucositis, infections, or chemotherapy-induced nausea/vomiting (CINV). This is associated with short- and long-term malnutrition, which can adversely affect clinical outcomes.[2] Maintaining enteral intake has been shown to preserve gut flora and mucosal function, potentially reducing the risk of graft-versus-host disease (GVHD) and infections.[3] Several factors affect enteral nutrition, including toxicity of preparative regimen, previous dietary habits, and sociocultural factors. As the period of reduced oral intake is predictable, most guidelines recommend initiation of parenteral nutrition (PN) when oral intake falls below 50%60%.[4] However, PN is fraught with high costs and infectious complications and may constitute a significant proportion of overall transplant costs in resource-constrained settings. We present a short report detailing the patterns of dietary changes seen during stem cell transplantation and possible steps to mitigate the same.


  Methods Top


Setting

This study was conducted as a prospective, observational study in the division of stem cell transplantation of a tertiary care teaching hospital. All patients admitted for autologous or allogeneic stem cell transplantation from July 2019 to October 2020 were included in the analysis.

Aims and objectives

The primary objective was to describe the patterns of dietary intake in patients admitted for autologous and allogeneic stem cell transplantation. Secondary objectives included assessment of factors modifying oral intake.

Protocols to maintain dietary infection control

The universal protocol followed for dietary management for patients undergoing a transplant included the following.

  1. All patients admitted in the bone marrow transplant (BMT) unit met a trained dietician pre-admission to discuss dietary preferences
  2. To maintain sterility, all food was terminally pressure cooked. To ensure this, all food items were placed in a steel container which was steamed in a pressure cooker. The pressure cooker was opened only once it reached inside the BMT unit to avoid contamination
  3. A high threshold was kept for initiating PN to minimize costs and risk of fungal infections. Patients who had no oral intake at all for 48 h with severe mucositis were considered for PN
  4. Calorie and protein intake was calculated for all patients at baseline and on a daily basis by the BMT nursing staff based on 24 h recall. Caloric content of food was obtained from standardized tables published by the National Institute of Nutrition (NIN), which lists caloric and protein content of Indian foods
  5. Centre for International Blood and Marrow Transplant Research scoring system was used to document mucositis following preparative regimens.


Protocols adopted to maintain oral intake

The following steps were taken to reduce the requirement of PN and ensure oral intake as much as possible. For patients where no oral intake was possible, PN was considered as part of protocol:

  1. Patients and families met dietary services before admission to discuss food preferences
  2. BMT consent form included a detailed description of mucositis and reduced oral intake in detail to prepare patients beforehand
  3. Homemade food was allowed for local patients as long it was terminally pressure cooked
  4. During the period of hospital stay, no restrictions on dietary intake were imposed, with the exception of milk and processed milk products during the first 28 days
  5. Packaged food, such as chocolates and cookies were allowed for all patients if requested
  6. Ice chips were made with water and juice to provide local relief of pain and change of taste.


Statistical analysis

Data were described in terms of range; mean ± standard deviation (frequencies [number of cases]) and relative frequencies (percentages) as appropriate. All statistical calculations were done using Statistical Package for the Social Science (SPSS) SPSS 21 version (SPSS Inc., Chicago, IL, USA) statistical program for Microsoft Windows.


  Results Top


A total of 16 patients were included in the analysis, including 10 males and 6 females. The median age of the group was 43 years (range, 6–67). All patients were diagnosed to have hematologic malignancies, except three patients who had solid organ tumors undergoing autologous transplantation. The median body mass index (BMI) of the cohort at the time of admission to BMT was 22.5 kg/m2 (range, 11.9–31.8). The baseline median calorie intake per kg of body weight was 26 kcal/kg/day (range 18.5–51.2 kcal/kg/day) and median protein intake was 0.47 g/kg/day (range, 0.19–1.2 g/kg/day). All patients received myeloablative chemotherapy without irradiation as part of the conditioning regimen. [Table 1] summarizes baseline characteristics, and [Table 2] summarizes calorie and protein intake at baseline.
Table 1: Baseline characteristics of transplant recipients

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Table 2: Details of baseline caloric and protein intake

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After initiation of preparative regimens, a reduction in caloric intake was noted for all patients. The median lowest caloric intake was 5.8 kcal/kg/day (range, 1.03-23) and the maximal caloric deficit from baseline was −79% (range, −96 to +11%). The lowest point of oral intake was reached on day 6.5 (range, −1 to +12) posttransplantation. PN was not used for any patient.

At discharge, median caloric intake as percentage of baseline was 70% (range 1.1%–175%). Reduction of caloric intake from baseline was present in 11 patients, while an increase above baseline was noted for five patients. [Figure 1] shows median caloric intake with interquartile ranges at baseline and at the time of discharge. Weight loss was noted in most patients at the time of discharge, with median weight loss being − 4.3% (range, −15.3% to + 0.42%). The corresponding BMI loss was − 4.5% (range, −18.11 to + 0.4%), demonstrated in [Figure 2]. Change in weight at discharge compared to baseline weight is summarized for all patients in [Figure 3]. Early transplant-related mortality was noted in one patient with germ cell tumor as a result of hepatic and renal dysfunction due to regimen-related toxicity. All other patients were uneventfully discharged and are on regular follow-up.
Figure 1: Median, lower and upper quartiles of data intake for all patients at the time of admission and discharge. The two dots in the first group indicate outliers

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Figure 2: Line chart showing the comparison of body mass index at baseline and at discharge. A fall in body mass index is noted for all except one patient at discharge

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Figure 3: Graph showing percentage weight deficit for all patients

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  Discussion Top


Enteral nutrition during stem cell transplantation is affected due to a combination of high-dose chemo/radiotherapy, mucositis, bleeding, and infections, placing transplant recipients at the risk of malnutrition and potentially inferior clinical outcomes. Our report provides a glimpse into patterns of nutritional disturbances seen during the process of transplantation in an Indian setting. We observe suboptimal caloric intake for all patients at baseline, which is reduced significantly during the period of hospitalization. Reduced oral intake persists at the time of discharge and is associated with discernible weight loss. With basic measures in liaison with dietary and nursing services, we were able to avoid the use of PN for all patients.

There are several incentives in maintaining enteral nutrition during transplantation. Loss of gut microbiota diversity caused by chemotherapy is shown to increase the risk of GVHD and infections.[5] This is potentiated by the use of broad-spectrum antibiotics, ubiquitously used during transplantation.[6] Enteral nutrition promotes the recovery of gut microbiota and improves diversity, potentially reducing the risk of GVHD.[3] It also maintains gut mucosal integrity and favorably modifies local immune responses. This is shown to translate into lower nonrelapse mortality and improved GVHD and relapse-free survival), providing an impetus to maintain oral nutrition as far as possible.[7]

When compared to dietary recommendations, our study indicates suboptimal caloric intake at baseline for all patients. The NIN guidelines recommend a caloric intake of 38–58 kcal/kg/day for adult males and 34–51 kcal/kg/day for females, based on the level of physical activity, which is much higher than that noted in our cohort.[8] A suboptimal caloric intake may be expected due to the recent administration of chemotherapy before admission for transplantation. Additionally, the high cereal – low protein nature of Indian diets may also exacerbate the above deficit.[9] These factors must be considered and optimized before admission for transplant.

We noted the lowest caloric intake during the 1st week posttransplantation, with a median deficit of approximately 80% from baseline. This is in keeping with other reports, which indicate maximum reduction in oral intake by the first seven days.[10] This timeline coincides with the maximum severity of physical symptoms such as mucositis, CINV, and oral pain which preclude oral intake. Mucositis is noted with up to 60% of patients receiving high-dose chemotherapy-based conditioning and is one of the most important factors affecting oral intake.[11] Multiple nonphysical factors also contribute to reduced oral intake and must be actively identified and corrected. Patients with excessive psychological stress and a negative perception toward treatment outcomes have a greater reduction in dietary intake posttransplant.[12] Alteration of “taste” also contributes to reduced oral intake, but is difficult to characterize and must be discussed upfront with patients.[13] All our patients were educated on the same, which presumably allowed preservation of some enteral nutrition to tide over the worst symptoms.

The effect of posttransplant weight loss on transplant outcomes is contentious. Western data indicate that short-term weight loss is common but does not correlate with adverse posttransplant outcomes.[14] However, posttransplant weight loss of more than 10% in Asian populations has been shown to predict for worse long-term outcomes and requires further validation in indigenous cohorts.[15]

Guidelines for nutritional intake during transplantation have been published by the American Society for Parenteral and Enteral Nutrition[16] and European Society for Clinical Nutrition and Metabolism (ESPEN).[4] Both guidelines suggest screening patients at risk of malnutrition and initiation of PN if caloric intake is expected to fall below 60% for a period of ten or more days. However, PN significantly adds to the cost of hospitalization and is associated with a risk of hyperglycemia[17] and fungal infections,[18] and cannot be universally recommended in resource-constrained settings.

Dietary habits are shaped by socioeconomic, geographic, and personal factors, and implementing uniform guidelines without local modifications is onerous. Several reports indicate marked variability from published guidelines in real-world practice, even in high-income countries with established protocols.[19],[20]

To keep costs low and promote enteral nutrition, we adopted several simple interventions. Home-cooked food was allowed for local patients, allowing individual food preferences to be met. Packaged foods such as cookies or chocolates were allowed on a short-term basis. Ice candy or frozen juice ice chips are shown to improve taste and reduce local pain and were liberally allowed.[21]

Our report provides a glimpse into the pattern of dietary changes observed in stem cell transplant recipients, with most patients having marked and persistent reduction in oral intake after admission, associated with weight loss. It is essential to discuss the same with patients before admission so that they are equipped to handle this expected complication. Most importantly, simple short-term modifications to local foods may allow the continuation of enteral feeding and avoid costs and complications associated with PN.

Financial support and sponsorship

None.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Sakellari I, Mallouri D, Gavriilaki E, Batsis I, Kaliou M, Constantinou V, et al. Survival Advantage and Comparable Toxicity in Reduced-Toxicity Treosulfan-Based versus Reduced-Intensity Busulfan-Based Conditioning Regimen in Myelodysplastic Syndrome and Acute Myeloid Leukemia Patients after Allogeneic Hematopoietic Cell Transplantation. Biol Blood Marrow Transplant 2017;23:445-51.  Back to cited text no. 1
    
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Brotelle T, Lemal R, Cabrespine A, Combal C, Hermet E, Ravinet A, et al. Prevalence of malnutrition in adult patients previously treated with allogeneic hematopoietic stem-cell transplantation. Clin Nutr 2018;37:739-45.  Back to cited text no. 2
    
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D'Amico F, Biagi E, Rampelli S, Fiori J, Zama D, Soverini M, et al. Enteral Nutrition in Pediatric Patients Undergoing Hematopoietic SCT Promotes the Recovery of Gut Microbiome Homeostasis. Nutrients 2019;11:2958.  Back to cited text no. 3
    
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Bozzetti F, Arends J, Lundholm K, Micklewright A, Zurcher G, Muscaritoli M, et al. ESPEN Guidelines on Parenteral Nutrition: Non-surgical oncology. Clin Nutr 2009;28:445-54.  Back to cited text no. 4
    
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Shono Y, van den Brink MRM. Gut microbiota injury in allogeneic haematopoietic stem cell transplantation. Nat Rev Cancer 2018;18:283-95.  Back to cited text no. 5
    
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Holler E, Butzhammer P, Schmid K, Hundsrucker C, Koestler J, Peter K, et al. Metagenomic analysis of the stool microbiome in patients receiving allogeneic stem cell transplantation: Loss of diversity is associated with use of systemic antibiotics and more pronounced in gastrointestinal graft-versus-host disease. Biol Blood Marrow Transplant 2014;20:640-5.  Back to cited text no. 6
    
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Beckerson J, Szydlo RM, Hickson M, Mactier CE, Innes AJ, Gabriel IH, et al. Impact of route and adequacy of nutritional intake on outcomes of allogeneic haematopoietic cell transplantation for haematologic malignancies. Clin Nutr 2019;38:738-44.  Back to cited text no. 7
    
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Dietary Guidelines for Indians: A manual. Accessed at https://nin.res.in/downloads/dietaryguidelinesforNINwebsite.pdf. [Last accessed on 2020 Dec 20].  Back to cited text no. 8
    
9.
Sharma M, Kishore A, Roy D, Joshi K. A comparison of the Indian diet with the EAT-Lancet reference diet. BMC Public Health 2020;20:812.  Back to cited text no. 9
    
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So EJ, Lee JS, Kim JY. Nutritional intake and nutritional status by the type of hematopoietic stem cell transplantation. Clin Nutr Res 2012;1:3-12.  Back to cited text no. 10
    
11.
Valeh M, Kargar M, Mansouri A, Kamranzadeh H, Gholami K, Heidari K, et al. Factors Affecting the Incidence and Severity of Oral Mucositis Following Hematopoietic Stem Cell Transplantation. Int J Hematol Oncol Stem Cell Res 2018;12:142-52.  Back to cited text no. 11
    
12.
Ames S, Ames G, Lange L, Heckman M, Niazi S, Foran J, et al. Psychological factors associated with body weight loss following hematopoietic stem cell transplantation: A preliminary study. Biolo Blood Marrow Transplant 2016;22:S286-7.  Back to cited text no. 12
    
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Farhadfar N, Kelly DL, Mead L, Nair S, Colee J, Irizarry Gatell V, et al. Dietary intake and diet quality of hematopoietic stem cell transplantation survivors. Biol Blood Marrow Transplant 2020;26:1154-9.  Back to cited text no. 13
    
14.
Rieger CT, Wischumerski I, Rust C, Fiegl M. Weight loss and decrease of body mass index during allogeneic stem cell transplantation are common events with limited clinical impact. PLoS One 2015;10:e0145445.  Back to cited text no. 14
    
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Fuji S, Mori T, Khattry N, Cheng J, Do YR, Yakushijin K, et al. Severe weight loss in 3 months after allogeneic hematopoietic SCT was associated with an increased risk of subsequent non-relapse mortality. Bone Marrow Transplant 2015;50:100-5.  Back to cited text no. 15
    
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August DA, Huhmann MB. A. S. P. E. N. clinical guidelines: Nutrition support therapy during adult anticancer treatment and in hematopoietic cell transplantation. JPEN J Parente Enteral Nutr 2009;33:472-500.  Back to cited text no. 16
    
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Sheean PM, Freels SA, Helton WS, Braunschweig CA. Adverse clinical consequences of hyperglycemia from total parenteral nutrition exposure during hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2006;12:656-64.  Back to cited text no. 17
    
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Quesada C, Aceituno J, Suárez R, Mazariegos C. Fungemia related to parenteral nutrition. Curr Trop Med Rep 2017;4:172-7.  Back to cited text no. 18
    
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Peric Z, Botti S, Stringer J, Krawczyk J, van der Werf S, van Biezen A, et al. Variability of nutritional practices in peritransplant period after allogeneic hematopoietic stem cell transplantation: A survey by the Complications and Quality of Life Working Party of the EBMT. Bone Marrow Transplant 2018;53:1030-7.  Back to cited text no. 19
    
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Andersen S, Banks M, Brown T, Weber N, Kennedy G, Bauer J. Nutrition support during allogeneic stem cell transplantation: Evidence versus practice. Support Care Cancer 2020;28:5441-7.  Back to cited text no. 20
    
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Loves R, Plenert E, Tomlinson V, Palmert S, Green G, Schechter T, et al. Changes in taste among pediatric patients with cancer and hematopoietic stem cell transplantation recipients. Qual Life Res 2019;28:2941-9.  Back to cited text no. 21
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

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