Assessment of long-term quality of life in patients with thalassemia major diagnosis following hematopoetic stem cell transplantation

Introduction: Beta-thalassemia major is a hemoglobinopathy group characterized by hemolytic anemia which is caused by congenital synthesis of β globin chains in autosomal recessive inheritance. The classical treatment of the cases is based on correcting anemia by blood transfusion every 3-4 weeks and effective removal of iron accumulated in the body as a result of ineffective erythropoiesis and blood transfusions. In thalassemia major patients, both anemia and iron accumulated in the body and especially in tissues cause organ complications over time and shorten the life span. The main complications are related to the heart, liver, pancreas and endocrine system. Nowadays, the survival of these cases has been prolonged and the development of complications has been delayed with good-safe transfusion and effective chelation therapy. However, quality of life is impaired and maximum life expectancy is limited. Hematopoietic stem cell transplantation is the only curative option currently available. However, stem cell transplantation itself carries a risk of mortality and morbidity in the short and long term. Current experience in the world shows that more than 90% of patients with thalassemia major currently survive hematopoietic stem cell transplantation and disease-free survival is around 80%. Stem cell transplantation allows individuals to live without thalassemia, but studies and information on the long-term impact on the quality of life are limited. Objective: The aim of this study was to determine the long-term quality of life in patients with allogeneic hematopoietic stem cell transplantation with beta-thalassemia major in childhood and to compare the results of physical and psychosocial quality of life with standard scales to healthy children in the same age group (healthy peers within or outside the XV family). The secondary objective is to identify treatment-related factors that affect long-term quality of life. Hypothesis: Long-term quality of life in patients with HSCT in childhood due to thalassemia major is similar to healthy peers. Metods: The study included 38 patients over 5 years of age who had undergone HSCT for thalassemia major between 2005 and August 2017 in Ege University Faculty of Medicine, Pediatric Stem Cell Transplantation Unit. Healthy children in the same age group (siblings of patients or children and siblings who applied to the general pediatric outpatient clinic with acute problems) and young healthy adults were selected as the control group. The Universal quality of life scale (PediatricQuality of Life Inventory (PedsQLTM) Version 4.0), in which its validity and reliability has been proved in Turkish, were used to assess the quality of life in children aged 5-18 years. The World Health Organization Quality of Life Instrument, Short Form (WHOQOL-BREF) also was used in patients over 18 years of age. In accordance with The Pediatric Quality of Life Inventory, the questionnaire was administered to both the child and the parent in cases under the age of 18, and physical, emotional, social and school-related functionality was questioned. In the WHOQOL-BREF scale, physical, psychological, social and environmental functions were answered by the patient himself/herself. In addition, education and work status of the patients under the age of 18 and their parents; their education and working status of the patients over the age of 18 were evaluated with separate questionnaires considering that it may have an impact on the quality of life. Results: A total of the 38 patients included in the study, 16 were female (42.1%) and 22 were male (57.9%) with a mean age of 16.1 ± 4.3 (min 6.5, max 25.3) years. These cases; The mean age of transplantation was 8.7 ± 3.4 years and the mean time from transplantation to study was 7.3 ± 3.2 years (min 2 - max 11.6 years). The total of the 38 healthy cases selected to the control group, 21 were female (55.3%) and 17 were male (44.7%). The mean age was 16.7 ± 5.5 (min 5, max 27.6 years). XVI Both healthy and patient groups were divided into 4 age groups; 2 patients (2.6%) between 5-7 years, 5 patients (6.6%) between 8-12 years (6.6%), 18 patients (23.7%) between 13-18 years and 13 patients above 18 years of age in both patient and healthy groups (17.1%). The mean ferritin levels of the patients before transplantation were 2105 ± 1124 (min 368, max 5470) ng / dl, and when risk classification was made according to Pesaro criteria, 21% of 38 patients were evaluated as Class 3. When thalassemic complications were examined before HSCT; liver dysfunction was detected in 16 cases (42.1%), endocrine complications in 7 cases (18.4%) and cardiac complications in one case (2.6%). During HSCT, the donor was MSD-compatible sibling (76.3%) in 29 patients, MRDcompatible relative (5.3%) in 2 patients, and MUD-compatible non-relative donor (18.4%) in 7 patients. Bone marrow was used in 16 cases (42.1%), peripheral blood in 15 cases (39.5%), bone marrow and cord blood in 6 cases (15.8%), bone marrow + cord blood + peripheral blood in 1 case (2.6%). Four of the 38 patients underwent HSCT for the second time because of graft failure. When the complications after HSCT were evaluated; Grade 3-4 acute GVHD was seen in only one case, CFSV was limited in 5 cases (limited in 2 cases, common in 3 cases) and endocrine complications in 17 cases (44.7%). When the educational and occupational status of the parents of all patients under 18 years of age were evaluated, a statistically significant difference was found between the patient and the healthy group; As 60% of the mothers of the sick children were primary school graduates, 52% of the mothers were college-university in healthy control cases, 76% of the mothers of the sick children were housewives, and 52% of the mothers of the healthy cases worked as civil servants (p <0.001 ). In addition, as 60% of the fathers of the sick children were primary school graduates, 52% of the fathers of the healthy cases were collegeuniversity graduates, 56% of the fathers of the sick cases worked as workers, and 56% of the fathers of healthy cases were tradesmen-merchant-manager. The rates of education and employment in the patient and control groups over 18 years of age were different between the two groups (p = 0.04). Both university-level education and graduation, and the rate of working in a job was higher in the control group. In this study, when we examined the total quality of life scores of all patients and control groups in all age groups, no statistically significant difference was found between patient and healthy group. XVII There was no statistically significant difference in quality of life between the patient and control groups in adult cases over 18 years of age. In this study, The survey data filled by children in school activities, there was a significant difference in the quality of life of the patients under the age of 18, while in the questionnaire filled in by the parents, there were statistically significant differences in physical functionality and total quality of life scores in favor of the healthy group. (p = 0.41, p = 0.003, p = 0.009). When the patients under the age of 18 were examined according to the age groups, the comparison of the quality of life in the 5-7 age group could not be made because of the small number of patients (2 control groups in total 2 patients). However, when we examined the scores, it was observed that patients scored lower in school activities than healthy cases in the child questionnaires, whereas low scores in participation in physical, social and school activities were observed in the parent questionnaire.. In the 8-12 age group, there are significant differences in physical, emotional, school and total scores according to the data of the child, and this difference was observed in favor of the healthy child in all scores according to the parental data. (p = 0.008, p = 0.031, 0.029, p = 0.003, p = 0.009, p = 0.015, p = 0.025, p = 0.013, p = 0.005). The quality of life of the 13-18 age group was evaluated, it was seen that there was no statistically significant difference in all areas, while the factors affecting the quality of life of HSCN cases were evaluated, it was seen that donor type, Pesaro risk grouping, K GVHD, endocrine and other developing complications did not significantly affect the mean of total quality scores. Discussion: In our study, no difference was found between peers and total quality of life scores of the patients in all age groups. However, when comparisons are made according to age groups; While there was no difference between the general quality of life scale scores above the age of 18, there were differences between the different age groups in the age group below 18 years. In the study, as a result of evaluating the quality of life of all cases under the age of 18, statistically significant differences were found in favor of the healthy group in terms of physical functioning and total quality of life scores in the child data and in the parental data (p = 0.41, p = 0.003, p = 0.009). The limited number of cases (2 patients, 2 control groups) in the XVIII younger age group (5-7 years old) makes interpretation difficult. When we evaluate the cases in the 8-12 age group, there are significant differences in health and activities, emotions, school, and total score according to child data. However, these differences become different according to parental data in favor of healthy children in all scores. In other words, it was observed that school children between 8-12 years of age had lower physical energy, less adaptation to school and less emotionally fragile. When the literature is examined, it is seen that quality of life is increased with HSCT in thalassemic children of the same age group (47). The comparison with healthy children is not available for this age group. When the quality of life of 13-18 age group was evaluated, it was seen that there was no statistically significant difference in both child and parent data. In our study, the rates of education and employment in the patient and control groups over 18 years of age were found to be different between the two groups. Both university-level education and graduation, and the rate of working in a job was higher in the control group. This can be interpreted as a measure of quality of life and lower quality of life in patients. However, while making this interpretation, we need to consider that the control group is not selected from the same social group as the patients and only 7 of them are a member of the patient families We observed that the families of the healthy cases under the age of 18 who were included in the study were more educated and had a better income than the patients' families. In addition, we see that the families in the patient group are more crowded in terms of the number of siblings. This is the weakness of this study. In the literature, there are studies comparing the quality of life of thalassemic and HSCN cases. However, there are fewer studies comparing HSHN cases with healthy peers. (44) (57 In these two studies, the quality of life was compared in the adult age group and it was shown that thalassemias undergoing HSCT were very similar in terms of quality of life to healthy individuals. In our study, when all age groups were evaluated together, no difference was found between healthy individuals over the age of 13 and only the younger age group (8- 12 years) was found to be different. Comparison with healthy peers in this age group has not been found in the literature. However, the limited number of cases (5 patients vs 5 controls) makes it difficult to comment on this issue. Adolescent children in this age group may have been more difficult to adapt to school and normal life after a serious treatment, or their parents may be less educated and have lower SES, which may be disadvantageous. XIX Studies in the literature show that CSVHD especially affects the quality of life negatively (51). In our study, there were 5 cases of CSVHD, 3 of which were severe, and 2 of them had lower quality of life scores. No significant difference was found in terms of pesaro risk, donor type, presence of GVHD and long-term organ complications. As a result; In our study, quality of life was found to be similar to healthy peers in patients who underwent HSCT for thalassemia major from different donors in childhood. Key words: Beta thalassemia major, Hematopoietic Stem Cell Transplantation, Quality of Life