الفهرس 
OVERVIEW OF ALLOGENEIC STEM CELL TRANSPLANTATIONOnly 14 pages are availabe for public view
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Abstract
A
llogeneic HSCT is the treatment of choice for treatment of patients with high risk features of acute leukemia or those who are relapsed after standard treatment. However this procedure have a lot of transplant related morbidity and mortality that are considerably decreasing now due to updates in selecting donors, conditioning regimens, early diagnosis and treatment of life threatening condition.
Nutritional support is one of the most important issues in the management of patients who undergo hematopoietic stem cell transplantation (HSCT). Many factors induce changes in the metabolism during HSCT including high-dose chemotherapy and total body irradiation, mucositis with painful ulcers, diminished ingestion, nausea, vomiting and diarrhea.
Nowadays, lots of nutritional assessment methods and indicators are being used both nationally and internationally, such as plasma albumin and prealbumin, serum creatinine and blood urea nitrogen, and anthropometric indexes. By now, there are few studies on nutritional assessment of hematological patients before and after HSCT, and additionally, most rely on one single assessment method.
This study aims at evaluating pre-transplant nutritional status in the recipients of allogeneic SCT, identifying the relationships between nutritional status of the recipients before transplantation from one side and the post-transplant outcomes including time to engraftment, incidence and severity of GvHD, infectious complications, relapse, transplant related mortality, relapse related mortality, overall survival as well as disease free survival along with assessment of quality of life (QoL).
The current study included 30 patients who underwent allogeneic stem cell transplantation at Bone Marrow Transplantation Unit, Ain-Shams University Hospitals, during period Jan-2019 till Jan-2023, as well as 30 patients with two or more years after allogeneic stem cell transplantation who were following up at Bone Marrow Transplantation Unit, Ain-Shams University Hospitals, during the same period.
As regards patient in group I, they were 23 males (76.7%) and 7 females (23.3%). Their age ranged between 19-52 years with mean age 29 ± 10.3. Their diagnoses were 17 cases AML (56.6%), 9 cases ALL (30%), 3 cases aplastic anemia (10%), 1 case biphenotypic leukemia (3.3%). All patients were in CR before undergoing HSCT and all patients underwent matched related donor HSCT from peripheral blood source. All patients were followed up during and after HSCT procedure for evaluation of transplant outcomes.
As regards nutritional status during transplant period among the studied population 21 patients (70%) received oral nutrition and didn’t require parenteral nutrition during transplant period, while other nine patients (30%) required either partial or total parenteral nutrition due to severe oral mucositis. We found that total parenteral nutrition (TPN) as well as partial parenteral nutrition (PPN) were associated with longer engraftment duration and this was statically significant. Also there was statistically significant higher incidence of post- transplant related complications including acute GVHD (p= 0.001), chronic GVHD (p= 0.006), post-transplant infections (p= 0.001) and transplant related mortality (p=0.02).
Nutritional lab biomarkers were assessed in the peri-transplant period for group I patients, we found statistically significant difference between nutritional lab biomarkers including serum albumin, prealbumin and serum 25 hydroxy-vitamin D early post-transplant compared to pre-transplant values.
We also found statistically significant negative correlation between peri-transplant serum albumin, prealbumin and 25 hydroxy-vitamin D with date of engraftment, as well as post-transplant early complications including mucositis and neutropenic fever. Lower levels of Albumin, pre-albumin was associated with higher incidence of incidence of infections as well as acute GVHD. 3 month post-transplant serum pre-albumin level has also statistically significant negative correlation with incidence of chronic GVHD (p= 0.043).
As regards anthropometric measurements during peri-transplant period, we found statistically significant difference in the distribution of weight values including BMI, waist circumference, hip circumference, waist-hip ratio at 1 month post-transplant period compared with pre-transplant measurements. We also found that pre-transplant as well as 1 month post-transplant BMI, WHR and body fat percentage were significantly correlated with transplant outcomes including duration of engraftment as well as incidence of acute GVHD, graft failure and TRM. On the other hand we didn’t find statistically significant correlation between quadriceps femoris thickness measured at pre-transplant periods as regards transplantation outcomes. Despite that there was statistically significant negative correlation between quadriceps femoris thickness measured at 1 month post-transplant and early transplant outcomes including duration of neutropenic fever as well as incidence of acute GVHD.
Quality of life of patients in group I was assessed at period of 6 months post-transplant using FACT-BMT questionnaire (Version 4). We found statistically significant positive correlation between albumin, pre-albumin and serum vitamin D level with all parameters of quality of life assessment and this was statistically significant correlation. However there was no statistically significant correlation between measurements including BMI, waist circumference, quadriceps thickness and all parameters of quality of life assessment.
We also studied 6 month overall survival among group I patients and impact of nutritional lab parameters as well as anthropometric parameters as prognostic markers for 6 month overall survival post-allogeneic stem cell transplantation. We found that six month survival post-transplant was estimated it was 90% in our studied group. We didn’t find statically significant prognostic impact of pre-transplant as well as 1-month post-transplant nutritional laboratory parameters including albumin, pre-albumin and vitamin D level with 6 months overall survival.
As regards patient in group II, they were 21 males (70%) and 9 females (30%). Their age ranged between 20 and 54 years with mean age 30.9 ± 9.9 years. All patients received peripheral blood stem cells from fully matched related siblings. Their diagnoses were 17 cases AML (56.7%), 12 cases ALL (40%), 1 case bi-phenotypic leukemia (3.3%).
As regards long term complications in group II patients, we found that six (30%) patients had developed chronic GVHD, two patients (6.6%) had disease relapse during follow up period, three patients (10%) had transplant related mortality due infection or complications of chronic GVHD and one patient had mortality secondary to disease relapse.
Nutritional lab parameters including albumin, prealbumin and serum25 hydroxy-vitamin D were assessed for long term survivals, we found that lower levels of these biomarkers were associated with higher incidence of long term post-transplant complications including chronic GVHD and TRM and this relationship was statistically significant. Lower serum albumin level were also associated with statistically significant higher incidence of disease relapse.
As regards anthropometric measurements in allogeneic stem cell survivors, we found that BMI was negatively correlated with incidence of chronic GVHD, disease relapse and TRM and this relationship was statistically significant. While waist hip ratio, body fat percentage, and quadriceps femoris thickness were biomarkers for chronic GVHD and disease relapse and didn’t correlate with transplant related mortality.
Quality of life of patients in group II was assessed at during follow up visits using FACT-BMT questionnaire (Version 4). We found statistically significant positive correlation between nutritional lab parameters as well as anthropometric measurements with all parameters of quality of life assessment.
Patients in group II (long term survivors) were followed up for 3 or more years post-transplant. We studied disease free survival as well as overall survival among studied grouped and showed 93.3% 3-year DFS while 3-year overall survival was 83.3%. We found that only body mass index was significant prognostic factor for 3 year survival among group II patients.
LIMITATIONS
Limitations of our study included:
D
uring our study there were no dedicated clinical nutritionist for patients undergoing stem cell transplantation in BMT unit Ain shams university, there were no records about ongoing caloric need based on clinical estimations, even for patients receiving partial parenteral nutrition and total parenteral nutrition the main justifications were inability of oral intake rather than the patient actual caloric need. Which may reflect with non-optimum caloric correction and hence correction of malnutrition state during stem cell procedure.
We faced the same concern for patients who were stem cell survivors undergoing regular fellow up, especially patients with chronic GVHD, who required special nutritional care and dietary supplementation based on caloric requirements and nutritional assessments.
Also patients BMT records didn’t mention the patient nutritional status during transplant procedure whether they required parenteral nutrition or not.
In addition for patients with stem cell transplantation survivors who were under regular follow up we recognized a trend for patients who had more complications after transplantation were those who had frequent visits in BMT follow up clinic, for assessment or for call for medications. While patients who had less complications and even longer survival 5-10 years post-transplant from records didn’t have regular visits and some of them only have remote follow up with their treating physicians. They may be reflected with more complication in our studied group.
CONCLUSION AND RECOMMENDATIONS
I
n conclusion we found assessment of nutritional lab parameters including serum albumin, pre-albumin and hydroxyl cholecalciferol as well as anthropometric measurements including, BMI, waist circumference, body composition analysis and quadriceps femoris thickness using bedside B-mode ultrasound during peri-transplant period, were a low cost, non-invasive biomarkers for early transplant outcomes including engraftment duration, infections, acute and chronic GVHD.
Also for patients who were long term survivors, assessment of nutritional lab parameters as well as anthropometric measurements were a low cost, non-invasive biomarkers for long term complications including chronic GVHD, disease relapse, and transplant related mortality.
Good nutritional support during early transplant procedure, proper management of mucositis and enhancing oral nutrition, improves early transplant outcomes in patients undergoing allogeneic stem cell transplantation.
Quality of life is an important endpoint after allogeneic stem cell transplantation. Nutritional parameters are good indicators for quality of life, while malnutrition is associated with higher complications post-transplant and poor quality of life.
from previous results we recommend that:
Nutritional assessment of patients undergoing allogeneic stem cell transplantation using anthropometric measurements including body mass index, waist hip ratio are non-invasive prognostic tools that predict outcomes of hematopoietic stem cell transplantation and complications post-transplant.
In addition combining nutritional laboratory parameters including serum albumin, pe-albumin with anthropometric measurements for patient undergoing stem cell transplantation add simple, less expensive tools for nutritional assessment and prognostic parameters for clinical outcomes after allogeneic stem cell transplantation.
Bedside ultrasound to assess quadriceps femoris thickness is a simple biomarker for muscle bulk and nutritional status post-transplant, also biomarker for sarcopenia and may be a prognostic tool for patients undergoing stem cell transplantation as well as long term transplant survivors.
Follow up of serum vitamin D level post-transplant may be a biomarker for stem cell transplantation outcomes as well as patient survival post-transplant. Early correction of serum vitamin D level may improve not only patient’s general condition but also immune dysregulation post-transplant and improve quality of life. Further studies are required to establish role of vitamin D as prognostic biomarker post-transplant as well as underlying mechanism for possible association between vitamin with acute and chronic GVHD.
Importance of establishment of well-trained nutritional team including clinical nutritionist and dietitian nurse in BMT unit for assessment of nutritional requirements during and after stem cell transplantation procedure to improve transplant outcomes as well as patient quality of life.
We recognized very few studies in literature especially in our country about assessment of quality of life post-stem cell transplantation. We recommend more studies targeting assessment of quality of life and aspects to improve quality of life post-transplant especially in increasing number of BMT centers and numbers of stem cell transplant survivors.