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Bone Marrow Transplantation (2008) 42, 469–473 & 2008 Macmillan Publishers Limited All rights reserved 0268-3369/08 $32.00

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ORIGINAL ARTICLE

Evaluation of nutritional status in patients undergoing hematopoietic SCT M Hadjibabaie1, M Iravani2, M Taghizadeh1, A Ataie-Jafari3, AR Shamshiri2, SA Mousavi2, K Alimoghaddam2, S Hosseini3 and A Ghavamzadeh2 1

Faculty of Pharmacy, Department of Clinical Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; Hematology-Oncology and SCT Research Center, Department of Hematology-Oncology, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran and 3Endocrinology and Metabolism Research Center, Department of Nutrition, Tehran University of Medical Sciences, Tehran, Iran 2

The aims of this study were to establish the nutritional status of patients during hematopoietic SCT (HSCT) and to determine if body mass index (BMI) is a valid indicator of nutritional status in this population when compared with nitrogen balance (NB). In total, 50 patients were enrolled (mean age: 25.7±9.0 years). Patients (14%) were underweight (BMIo18.5 kg/m2), 58% in a normal BMI (between 18.5 and 24.9 kg/m2) and 28% were overweight or obese (BMIX25 kg/m2). NB dropped after transplantation and increased from days þ 5 to þ 20 after transplantation (P ¼ 0.006). There was a significant negative relationship between patients’ BMI and time to engraftment (r ¼ 0.45, P ¼ 0.001). Engraftment of underweight patients was 3.0 days (P ¼ 0.002) and 4.0 days (Po0.001) later than in normal and overweight or obese patients, respectively. There was no significant correlation between NB before transplantation and time to engraftment (r ¼ 0.22, P ¼ 0.16). The results of this study demonstrate that patients undergoing HSCT may have suboptimal nutritional status and that pre-HSCTBMI rather than NB may have a greater correlation in HSCT patients with the time of engraftment. Therefore, it may be useful to consider patient’s BMI before transplantation for earlier engraftment time. Bone Marrow Transplantation (2008) 42, 469–473; doi:10.1038/bmt.2008.188; published online 7 July 2008 Keywords: hematopoietic SCT; nutritional status; nutrition assessment; body mass index

Introduction Hematopoietic SCT (HSCT) including both BMT and peripheral blood SCT (PBSCT) is being used increasingly in an attempt to cure many hematological disorders, solid

Correspondence: Dr AR Shamshiri, Hematology-Oncology and SCT Research Center, Department of Hematology-Oncology, Shariati Hospital, Tehran University of Medical Sciences, Kargar Shomali Avenue, Tehran 14114, Iran. E-mail: [email protected] or [email protected] Received 5 September 2007; revised 19 May 2008; accepted 30 May 2008; published online 7 July 2008

tumors and autoimmune diseases. One of the major challenges in the post transplant period is nutrition.1 Impaired nutritional status before transplantation is a negative prognostic factor for outcome after HSCT.2 In fact, the better nourished patients have a shorter time to engraftment.3 Irrespective of nutritional status, however, nutritional support is frequently delivered routinely after HSCT to prevent malnutrition secondary to either gastrointestinal toxicity related to the conditioning regimen or to increased nutrient requirements. HSCT has a dramatic effect on the recipient, affecting protein, energy and micronutrient metabolism.4–7 Biochemical indices have been shown to not accurately reflect changes in nutritional status of HSCT recipients,8 and anthropometric measurements may be influenced by fluid and electrolyte disturbances.9–12 Negative nitrogen balance (NB) is common in HSCT patients13 as a consequence of both intestinal losses with diarrhea and catabolic effects on skeletal muscle. These effects are initially exerted by the underlying disease, then by conditioning regimens, and possible HSCT complications such as infections and GVHD.4,14 NB is a direct expression of the imbalance between protein breakdown and synthesis.14 It is considered the most accurate way to perform nutritional assessment in HSCT patients.15 In this study, we assessed nutritional status by using NB in patients undergoing HSCT before transplantation and at different time points thereafter. The use of body mass index (BMI) to determine nutritional status in pre-HSCT patients has been documented in previous studies and is used in many clinical centers. The secondary aim of our study was to determine if BMI is a valid indicator of nutritional status in this population when compared with NB.

Patients and methods Patients In this cross-sectional survey, 50 adult patients with malignant and nonmalignant diseases who underwent allogeneic (allo) or autologous BMT or PBSCT in the Hematology-Oncology and Bone Marrow Transplantation Research Center at Shariati Hospital in Tehran, Iran from February 2006 to 2007 were prospectively evaluated for their nutritional status. Informed consent was obtained for

Nutrition assessment in hematopoietic SCT M Hadjibabaie et al

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all patients. Characteristics of patients who participated in the study are shown in Table 1. Patients were excluded if they had respiratory, hepatic, renal and cardiac dysfunction. All parameters were evaluated 5 days before transplantation (5), and 5, 10 and 20 days after stem cells infusion ( þ 5, þ 10 and þ 20, respectively). Subjects were weighed to the nearest 0.05 kg using calibrated digital scales and height was measured to the nearest 0.1 cm using a wall-mounted stadiometer. BMI was calculated as weight (kg) divided by height (m) squared. BMI values were classified into three groups: BMI o18.5 kg/m2 as underweight, BMI between 18.5 and 24.9 kg/m2 as normal, and BMIX25 kg/m2 as overweight or obese.

Engraftment Myeloid engraftment following HSCT has conventionally been defined as the first of 3 consecutive days the patient presents an ANC of 0.5 109 per liter or more.21–24 Statistical analysis Statistical analyses were performed using the SPSS package for statistics version 11.5. Data were presented as mean±s.d. values; and Po0.05 was considered significant. Correlation analysis was performed to determine correlation of pre-HSCT NB values and BMI categories with the time to engraftment.

Results Conditioning regimen All patients received pretransplant conditioning regimen consisting of one of the following: BU/CY; CY/fludarabine; CY/anti-thymocyte globulin (ATG); CCNU (Lomustine)/VP16/CY or melphalan. GVHD prophylaxis and treatment Acute GVHD was diagnosed on the basis of clinical symptoms of skin, oral mucosa, gut and liver. Grading of GVHD was from 0 (absent) to IV according to published criteria.16 Prophylaxis against GVHD was given to all patients and consisted of CsA and low-dose MTX. Methylprednisolone was given to patients with uncontrolled GVHD. If no response was obtained, ATG was added to the regimen. Mucositis of the gastrointestinal tract Almost all patients undergoing HSCT, develop oroesophageal mucositis and gastrointestinal toxicity within 7–10 days after chemotherapy. As a result patients have decreased oral intake, nausea, diarrhea and vomiting. Even though both the severity and the duration of gastrointestinal toxicity may differ among individuals, but the condition significantly affects food intake and absorption for up to 2–3 weeks after HSCT.17 Dietary intakes, nitrogen balance and energy requirements Patients’ food intake was observed and recorded by a nutritionist for 3 consecutive days and daily intake of energy and protein was calculated using Food Processor software. Energy and protein amounts of parenteral nutrition (PN) were added to obtained values. Patients’ pre-HSCT energy requirements were calculated as 1.4Xbasal metabolic rate (BMR) and 1.7 BMR during 20 days after BMT.18 BMRs were estimated according to the Harris– Benedict equation.19 At 24 h urine collection was performed and urinary urea nitrogen (UUN) was measured enzymatically. NB was calculated using the following equation:20 NB ¼ grams of nitrogen intake(grams of nitrogen excretion (UUN) þ 3) Nitrogen intake was calculated by dividing the amount of protein intake to 6.25. Bone Marrow Transplantation

Patients’ body weight, energy intake, the ratio of energy intake/energy requirements and NB during the study are shown in Table 2. Distribution of patients in different categories of BMI and NB, and the time of engraftment in each subgroup are shown in Table 3. The trends in body weight, energy intake and NB changes are presented in Figures 1–3. Body weight and energy intake declined until 10 days after transplantation and thereafter increased from days þ 10 to þ 20 after transplantation. The NB dropped after transplantation and increased from days þ 5 to þ 20 after transplantation. The changes in body weight and NB during the 1-year study period were significant (Po0.001 and P ¼ 0.006, respectively). Correlation analysis showed that there was a significant and negative relationship between patients’ BMI and time to engraftment (r ¼ 0.45, P ¼ 0.001; Figure 4). Engraftment of underweight patients was 3.0

Table 1

Characteristics of patients

Gender (male/female) Age (Mean±s.d.; years) Transplant type (allogeneic/autologous) Diagnosis AML ALL CML HD Others

22/28 25.76±9.5 34/16 18 11 6 4 11

(36%) (22%) (12%) (8%) (22%)

Abbreviation: HD ¼ Hodgkin’s disease.

Table 2 Body weight, energy intake and nitrogen balance of patients in different stages of the study (n ¼ 50) Days

T(5) T(+5) T(+10) T(+20)

Body weight Energy intake (kg) (kcal) (mean±s.d.) (mean±s.d.) 63.1±15.8 62.0±15.3 61.5±15.1 61.8±14.9

1984±702 1530±668 1286±804 1726±645

Energy intake/ energy need (mean±s.d.)

Nitrogen balance (mean±s.d.)

0.94±0.29 0.61±0.28 0.51±0.34 0.69±0.28

1.1±0.8 1.7±3.9 0.7±4.0 0.9±5.3

T(5) ¼ 5 days before SCT; T(+5) ¼ 5 days after SCT; T(+10) ¼ 10 days after SCT; T(+20) ¼ 20 days after SCT.


471 Table 3 Distribution of patients in different categories of BMI and Nitrogen Balance, and the time of engraftment in each subgroup Time to engraftment (days) (mean±s.d.)

BMI (kg/m2) o18.5 18.5–24.9 X25

7 (14%) 29 (58%) 14 (28%)

15.0±3.2 12.0±1.7 11.0±1.3

N balance o0 X0

22 (46%) 28 (54%)

12.6±2.5 11.4±1.3

1.00

Nitrogen balance

N (%)

0.00

–1.00

64.0

63.0

+5

+10 Time (days)

+20

Figure 3 Patients’ nitrogen balance at different stages of the study. T(5)=5 days before SCT; T( þ 5)=5 days after SCT; T( þ 10)=10 days after SCT; T( þ 20)=20 days after SCT.

62.0

20

18

61.0

60.0 –5

+5

+10 Time (days)

+20

Figure 1 Patients’ body weight at different stages of the study. T(5)=5 days before SCT; T( þ 5)=5 days after SCT; T( þ 10)=10 days after SCT; T( þ 20)=20 days after SCT.

Time of engraftment (days)

Weight (kg)

–5

16

14

12

10 2000 8 10

20

30

40

Energy intake (kcal)

BMI (kg/m2) Figure 4 Correlation between patients’ BMI before SCT and time of

1800

engraftment.

days (P ¼ 0.002) and 4.0 days (Po0.001) later than in normal and overweight or obese patients, respectively. There was no significant correlation between NB before transplantation (day 5) and the time of engraftment (r ¼ 0.22, P ¼ 0.16; Figure 5). In addition, no significant correlation was observed between NB after transplantation (days þ 5, þ 10 and þ 20) and engraftment either. Sixteen patients (32%) had a bacteremia with one positive blood culture. There were no significant differences in the length of hospitalization and time to engraftment between allogeneic and autologous transplanted patients.

1600

1400

–5

+5 +10 Time (days)

+20

Figure 2 Patients’ energy intake at different stages of the study. T(5)=5 days before SCT; T( þ 5)=5 days after SCT; T( þ 10)=10 days after SCT; T( þ 20)=20 days after SCT.

Nutrition Most patients were able to tolerate oral intake during their hospital stay, but PN was given as a supplement to almost Bone Marrow Transplantation


472

Time of engraftment (days)

20

18

16

14

12

10

8 –10

0 Nitrogen balance

10

Figure 5

Correlation between patients’ nitrogen balance before SCT and time of engraftment.

all patients every other day. Five patients were unable to tolerate oral intake for an average of 3 days (2–7 days) and they received total parenteral nutrition.

Post transplant complications GVHD grade 0 developed in 44%, grade I in 8.8%, grade II in 26.5% and grade III in 20.6% of patients after alloHSCT. Mucositis stage 0 developed in 32.4 and 12.5%, stage I in 41.2 and 65.5%, stage II in 11.8 and 25% and stage III in 14.7 and 0% of patients after allogeneic and autologous transplantation, respectively. We did not find any correlation between BMI and the incidence and severity of the mucositis or GVHD. In addition, there was no correlation between NB (days before and after HSCT) and mucositis but the NB at days þ 10 and þ 20 was significantly higher in grade I compared with grades II and III GVHD (Po0.05).

Discussion HSCT is a highly stressful condition requiring a high level of energy. This stressful condition results from a hypermetabolic state in which increased catabolism and anabolism are intertwined as a consequence of cytoreductive therapy, occurrence of complications such as infections, multiple organ failure and tissue repairing.25 In addition, increased energy requirement, fluid restrictions and hepatotoxicity of PN make it difficult to provide adequate nutrition consistently.26 To ensure the nutritional status of patients during HSCT is optimal, it is crucial that nutritional status be monitored accurately and that individual energy requirements provided. Impaired nutritional status before HSCT has been known to be a negative prognostic factor, whereas well-nourished patients having a shorter engraftment time.27 The aims of this study were to determine the nutritional status of patients undergoing HSCT and to examine Bone Marrow Transplantation

whether BMI and NB are good predictive methods of assessing the days to engraftment in this population. The nutritional status of patients during HSCT is not well documented in the literature and different methods have been used to determine nutritional status. One study showed that 100 patients undergoing HSCT were at or above ideal body weight and none had a history of significant weight reduction (410% in previous 6 months).28 However, in another study, 73% of patients were well nourished, 23% were moderately malnourished or at risk of malnutrition and 4% were severely malnourished.29 Our study found that 14% of patients undergoing HSCT were underweight (BMI below 18.5 kg/m2) and 40% were in a negative state of NB. Considering our findings of suboptimal nutritional status in our HSCT patients and the results of previous studies, which have demonstrated that weight and NB decrease further after HSCT in adult subjects, it is recommended that patients undergoing HSCT be provided with nutritional support and that nutritional status closely monitored to ensure early identification of malnutrition. Although the occurrence of acute GVHD could be regarded as a positive event because of GVL effect, this is a major complication occurring from 7–10 days to p3 months after allo-BMT in 30–60% of patients.30 One study showed that poor oral intake early after HSCT may be associated with an increased risk of developing severe acute GVHD.31 Mucositis after chemotherapy can also affect oral intake and food absorption. In our study, we did not find any correlation between BMI and incidence and severity of mucositis or GVHD. There was no correlation between NB and mucositis but the NB at days þ 10 and þ 20 was significantly higher in grade I in comparison with grades II and III. This can be explained by toxicity of gastrointestinal tract that can cause decreased nutrient absorption and loss of nutrients from the gut, especially amino acids due to altered transmembrane transport of nutrients. The results of this study demonstrate that engraftment occurs earlier in patients with higher levels of BMI. This is also true for patients with higher levels of NB, but we found that BMI was a better predictive of engraftment time than NB (r ¼ 0.45, P ¼ 0.001 versus r ¼ 0.22, P ¼ 0.16). A limitation of our study is that we did not assess body composition to distinguish the effective component of body mass. In our patients, pre-HSCT BMI was a strong predictor of engraftment time. This is a simple measurement, so it is recommended for clinicians to consider the weight of patients who will undergo HSCT in the future and well nourishment of underweight patients’ pre-HSCT period. Further studies on body composition of patients’ preHSCT are required to identify the effective component of body mass.

Acknowledgements We acknowledge the personnel of Shariati Hospital BMT ward-1 for their contributions to this study and Dr R Namdar for her valuable assistance in final editing of the paper. This research


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has been supported by Hematology-Oncology and Stem Cell Transplantation Research Center/Tehran University of Medical Sciences.

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References

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1 Rzepecki P, Barzal J, Sarosiek T, Szczylik C. Biochemical indices for the assessment of nutritional status during hematopoietic stem cell transplantation: are they worth using? A single center experience. Bone Marrow Transplant 2007; 40: 567–572. 2 Schulte C, Reinhardt W, Beelen D, Mann K, Schaefer U. Low T3-syndrome and nutritional status as prognostic factors in patients undergoing bone marrowtransplantation. Bone Marrow Transplant 1998; 22: 1171–1178. 3 Weisdorf S, Hofland C, Sharp HL, Teasley K, Schissel K, McGlave PB et al. Total parenteral nutrition in bone marrow transplantation: a clinical evaluation. J Pediatr Gastroenterol Nutr 1984; 3: 95–100. 4 Guiot HF, Biemond J, Klasen E, Gratama JW, Kramps JA, Zwaan FE. Protein loss during acute graft versus host disease: diagnostic and clinical significance. Eur J Haematol 1987; 38: 187–196. 5 Donaldson SS, Lenon RA. Alterations of nutritional status: impact of chemotherapy and radiation therapy. Cancer 1979; 43: 2036–2052. 6 Ohnuma T, Holland JF. Nutritional consequences of cancer chemotherapy and immunotherapy. Cancer Res 1977; 37: 2395–2406. 7 Gauvreau-Stern JM, Cheney CL, Aker SN, Lenssen P. Food intake patterns and foodservice requirements on a marrow transplant unit. J Am Diet Assoc 1989; 89: 367–372. 8 Muscaritoli M, Conversano L, Cangiano C, Capria S, Laviano A, Arcese W et al. Biochemical indices may not accurately reflect changes in nutritional status after allogeneic bone marrowtransplantation. Nutrition 1995; 11: 433–436. 9 Keenan AM. Nutritional support of the bone marrow transplant patient. Nurs Clin North Am 1989; 24: 383–393. 10 Cheney CL, Abson KG, Aker SN, Lenssen P, Cunningham BA, Buergel NS et al. Body composition changes in marrow transplant recipients receiving total parenteral nutrition. Cancer 1987; 59: 1515–1519. 11 Aker SN, Lenssen P, Darbinian J, Cheney CL. Nutritional assessment in the marrow transplant patients. Nutr Support Serv 1983; 3: 22–37. 12 Cohn SH, Ellis KJ, Vartsky D, Sawitsky A, Gartenhaus W, Yasumura S et al. Comparison of methods of estimating body fat in normal subjects and cancer patients. Am J Clin Nutr 1981; 34: 2839–2847. 13 Herrmann VM, Petruska PJ. Nutrition support in bone marrow transplant recipients. Nutr Clin Pract 1993; 8: 19–27. 14 Weisdorf SA, Salati LM, Longsdorf JA, Ramsay NK, Sharp HL. Graft versus host disease of the intestine: a protein losing enterophathy characterized by fecal alpha-1-antitrypsin. Gastroenterology 1983; 85: 1076–1081. 15 Muscaritoli M, Grieco G, Capria S, Iori AP, Rossi Fanelli F. Nutritional and metabolic support in patients undergoing bone marrow transplantation. Am J Clin Nutr 2002; 75: 183–190. 16 Glucksberg H, Storb R, Fefer A. Clinical manifestations of graft-versus-host-disease in human recipients of marrow

19

20

21

22

23

24

25

26

27

28

29

30

31

from HLA-matched sibling donors. Transplantation 1974; 18: 295–304. Wolford JL, McDonald GB. A problem-oriented approach to intestinal and liver disease after marrow transplantation. J Clin Gastroenterol 1988; 10: 419–433. Hutchinson ML, Clemans GW, Springmeyer SC, Flournoy N. Energy expenditure estimation in recipients of marrow transplants. Cancer 1984; 54: 1734–1738. Harris JA, Benedict FG. A Biometric Study of Basal Metabolism in Man. Publication no 279 Carnegie Institute of Washington: Washington, DC, 1919. Holcombe BJ, Gervasio JM. Adult parenteral nutrition. In: Troy D (ed). Applied Therapeutics: the Clinical Use of Drugs, 8th edn. Lippincott Whilliams & Wilkins: Baltimore, 2005, pp 37.15–37.16. Ali MY, Oyama Y, Monreal J, Winter J, Tallman M, Gordon LI et al. Reassessing the definition of myeloid engraftment after autotransplantation: it is not necessary to see 0.5 10(9)/l neutrophils on 3 consecutive days to define myeloid recovery. Bone Marrow Transplant 2002; 30: 749–752. Laughlin MJ, Barker J, Bambach B, Koc ON, Rizzieri DA, Wagner JE et al. Hematopoietic engraftment and survival in adult recipients of umbilical-cord blood from unrelated donors. N Engl J Med 2001; 344: 1815–1822. Mehta J, Powles R, Singhal S, Horton C, Middleton G, Eisen T et al. Early identification of patients at risk of death due to infections, hemorrhage, or graft failure after allogeneic bone marrow transplantation on the basis of the leukocyte counts. Bone Marrow Transplant 1997; 19: 349–355. Madero L, Dı´ az MA, Ortega JJ, Olive T, Martı´ nez A, Badell I et al. Recombinant human granulocyte-macrophage colonystimulating factor accelerates engraftment kinetics after allogeneic bone marrow transplantation for childhood acute lymphoblastic leukemia. Haematologica 1999; 84: 133–137. Paauw JD, McCamish MA, Dean RE, Ouellette TR. Assessment of caloric needs in stressed patients. J Am Coll Nutr 1984; 3: 51–59. Papadopoulou A. Nutritional considerations in children undergoing bone marrow transplantation. Eur J Clin Nutr 1998; 52: 863–871. Mazzi T. Supportive care. In: Apperley J, Carreras E, Gluckman A, Gratwohl A, Mazzi T (eds). The European Group for Blood and Marrow Transplantation: Haemopoietic Stem Cell Transplantation. Forum Service Editore: Italy, 2004, pp 119–131. Scolapio JS, Tarrosa VB, Stoner GL, Moreno-Aspitia A, Solberg Jr LA, Atkinson EJ. Audit of nutrition support for hematopoietic stem cell transplantation in a single institution. Mayo Clin Proc 2002; 77: 654–659. Horsley P, Bauer J, Gallagher B. Poor nutritional status prior to peripheral blood stem cell transplantation is associated with increased length of hospital stay. Bone Marrow Transplant 2005; 35: 1113–1116. Bross DS, Tutschka PJ, Farmer ER, Beschorner WE, Braine HG, Mellits ED et al. Predictive factors for acute graft versus host disease in patients transplanted with HLA identical bone marrow. Blood 1984; 63: 1265–1270. Mattsson J, Westin S, Edlund S, Remberger M. Poor oral nutrition after allogeneic stem cell transplantation correlates significantly with severe graft-versus-host-disease. Bone Marrow Transplant 2006; 38: 629–633.

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