Background: Hematopoietic stem cell transplantation (HSCT) is currently the only clinical cure for thalassemia major (TM). Graft-versus-host disease (GVHD) and transplant-related mortality (TRM) remain major barriers to clinical outcomes in TM-unrelated donor transplantation (MUD-HSCT). Aims: The role of Basiliximab in preventing acute graft-versus-host disease (aGVHD) after MUD-HSCT in thalassemia major (TM) is still unknown. We performed a prospective, multicenter, open-label, randomized controlled trial (RCT). The study is registered at www.clinicaltrials.gov as #NCT02342145. PATIENTS AND METHODS: Patients with TM with unrelated donor were randomly assigned to a basiliximab group (20 mg/kg basiliximab on days 0 and +4, respectively, plus tacrolimus [FK506], methotrexate [MTX], and mycophenolate mofetil [MMF]) and a control group (FK506, MTX, and MMF). The primary end point of this study was grade 2-4 aGVHD on day 100. Results: From April 2015 and September 2021, a total of 205 TM patients were enrolled. The ratio of male to female was 123 to 82 with a median age of 7 years (range, 2-19 years). Patients were randomly assigned to the basiliximab group of 102 and the control group of 103. Comparison of the basiliximab group and the control group, the cumulative incidence rate of grade 2-4 aGVHD was 24.5% and 29.1%, respectively (P=0.456), and the cumulative incidence rate of grade 3-4 aGVHD was 8.8% and 14.6% (P=0.201); the cumulative incidence rate of moderate or severe chronic GVHD was both 2.9%; median days of neutrophil engraftment were +11.8 and +11.6 days, respectively (P=0.701), platelets Implantation days were +15.4 and +13.5 days (P=0.126); TRM was 3.6% and 7.1% (P=0.249), over survival (OS) was 96.4% and 92.0% (P=0.188), respectively and thalassemia-free survival (TFS) of the two groups was also the same as the OS. There was no significant difference between the basiliximab and control groups with regard to cytomegalovirus reactivation, Epstein-Barr virus reactivation, and transplant-related complications. Subgroup analysis according to the degree of HLA matching showed that the 9/10 mismatch group had significantly lower OS and TFS than the 10/10 matched group (both 82.6% v 96.5%, P=0.004). The 3-year OS and TFS of the entire cohort (205 TM patients ) were 94.1% and 94.0%, respectively(Table 1, Fig 1). CONCLUSION: This first prospective randomized study showed basiliximab at a dose of 20 mg on day 0 and day+ 4 did not reduced the incidence of both aGVHD and cGVHD in patients with TM after MUD-HSCT. The incidence of aGVHD in unrelated donor transplants for TM patients is still high, 9/10 mismatched unrelated donor transplants had poor result when comparing 10/10 matched donor transplants for TM patients. Unrelated donors are still a very good alternative source of donors. The TFS of TM patients treated by unrelated donor transplantation can reach 94.0%. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Background: Acute graft-versus-host disease (aGvHD) is the primary cause of mortality following allogeneic hematopoietic cell transplantation (HCT). Objectives: This study aimed to predict the risk of aGvHD after HCT in patients with thalassemia major using a novel predictive nomogram. Design: A retrospective study was used to develop the prediction model. Methods: We performed retrospective analyses on 402 consecutive thalassemia patients who underwent HCT. Risk factors for aGvHD were analyzed using Cox proportional regression models. T-lymphocyte subsets were collected from 240 patients at the time of neutrophil engraftment. Least Absolute Shrinkage and Selection Operator regression was utilized to screen the indices, with cut-off values established through restricted cubic spline (RCS) regression. The predictive model was developed by integrating these T-lymphocyte subsets with clinical features, aiming to enhance the accuracy of aGvHD risk prediction. Results: Among 402 thalassemia patients analyzed post-transplantation, significant independent risk factors for aGvHD included matched unrelated donors, haploid-related donors, peripheral blood stem cell infusions, and donor age older than 40 years. Our RCS analysis indicated a marked increase in aGvHD risk when CD4+ T-cell counts exceeded 36 cells/μL and CD8+ T-cell counts exceeded 43 cells/μL during neutrophil engraftment. The integration of T-lymphocyte subsets with clinical risk factors into a Cox regression model demonstrated good predictive performance for assessing aGvHD risk. Conclusion: This study presents a novel model designed to predict aGvHD in thalassemia patients post-transplantation by utilizing T-lymphocyte data at the time of engraftment. The model facilitates the creation of personalized treatment plans, aiming to minimize the incidence of aGvHD and improve patient outcomes.

Relapsed/refractory acute leukemia (R/R-AL) is associated with a low remission rate, short survival rate, and poor prognosis. Treating R/R-AL remains challenging as there is no standardized effective regimen; hence, there is a need for efficient therapies. CD38 expression has been observed in acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). Daratumumab is a humanized anti-CD38 monoclonal antibody used to treat multiple myeloma and has been reported to treat R/R-AL safely and effectively. The clinical data of 10 adult patients with R/R-AL who were treated with a daratumumab-based salvage regimen between July 2018 and May 2023 at our center were analyzed retrospectively. Seven AML and three ALL cases were included in the analysis. Seven (70%) patients showed responses to the treatments (complete response [CR], 60%; partial response [PR], 10%). Of the seven responders, three underwent allogenic stem cell transplantation (ASCT), including one who underwent a second ASCT. Among the five patients with R/R AML who had prior exposure to venetoclax, three achieved a therapeutic response (two CR and one PR) when re-treated with venetoclax in combination with daratumumab. The median follow-up time was 6.15 months (0.9-21 months). Overall survival and event-free survival rates at 12 months were 68.6% and 40.0%, respectively. The main adverse events included grade 3 febrile neutropenia (20%) and grade 3 hematological toxicities (60%). The daratumumab-based salvage regimen offers patients with R/R-AL the opportunity of remission with acceptable tolerability, creating the possibility of bridging ASCT.

Research into the pulmonary function of patients with transfusion-dependent thalassemia (TDT) is limited, with existing studies presenting conflicting results. We carried out a retrospective study involving 140 patients with TDT. The mean patient age was 8.7 ± 3.2 years, with a median serum ferritin (SF) level of 3791.4 ng/ml (IQR: 2424.1-5733.3 ng/ml). Pulmonary function abnormalities were detected in 46.43 % (65 out of 140) of patients, primarily manifesting as diffusion dysfunction (26.43 %), followed by ventilatory dysfunction (5.0 %), and mixed pulmonary dysfunction (15.0 %). A serum ferritin level above 2500 ng/ml significantly correlated with the occurrence of these abnormalities(OR = 3.187, 95%CI:1.312-7.741, P = 0.010), while higher hemoglobin concentrations demonstrated a protective effect (OR = 0.966, 95%CI: 0.943-0.989, P = 0.004). Our study highlights diffusion dysfunction as the most prevalent type of pulmonary function abnormalities in TDT patients. Furthermore, it establishes a correlation between elevated serum ferritin levels and pulmonary dysfunction.

Background: Previous studies have confirmed that the incidence of graft-versus-host disease (GVHD) remained still very high in patients with thalassemia major (TM) undergoing related haploidentical donor and unrelated donor hematopoietic stem-cell transplantation (HID-HSCT and MUD-HSCT), which seriously affected patients' overall survival and thalassemia-free survival, especially acute GVHD (aGVHD). This study aimed to investigate whether Daclizumab at a dose of 1 mg/Kg on days +7, +14, +28 and +42 reduced GVHD plus standard GVHD prophylaxis (tacrolimus [FK506] plus methotrexate [MTX] and mycophenolate mofetil [MMF]) in TM patients with HID-HSCT or MUD-HSCT. Methods: We retrospectively analyzed our data of TM patients who underwent HID-HSCT or MUD-HSCT at the First Affiliated Hospital of Guangxi Medical University in China from November 2022 to July 2023. TM patients enrolled all received the GVHD prophylaxis which included Daclizumab at a dose of 1 mg/kg on days +7, +14, +28 and +42 plus FK506 (0.03mg/kg/day), MTX (15mg/m 2 on days +1, 10mg/m 2 on days +3, +6, +11), and MMF (250mg/day × 90 days). The primary endpoint was grades 2-4 aGVHD on days +100. Results: Data of 37 patients' transplantation were evaluated. The ratio of male to female was 20 to 17 with a median age of 8 years (range, 3-17 years). Patients were assigned to the HID-HSCT of 24 and the MUD-HSCT of 13. Median follow-up period was 7 months (range, 3 to 11 months). The total of the cumulative incidence rate of grades 2-4 aGVHD was 18.9%, and the rate of grades 3-4 aGVHD was 10.8%. Subgroup analysis showed that the rate of grades 2-4 aGVHD was 20.8% in HID-HSCT and 15.4% in MUD-HSCT, respectively; the rate of grades 3-4 aGVHD was 8.3% in HID-HSCT and 15.4% in MUD-HSCT, respectively. The median days of neutrophil engraftment were +12 days, platelets Implantation days were +14 days. The cytomegalovirus reactivation, Epstein-Barr virus reactivation, fungal infection and septicemia were seen in 16(43.2%), 3(8.1%), 6(16.2%) and 5(13.5%) patients, respectively. One patient in MUD-HSCT died of severe pulmonary infection, but no deaths were attributable to HID-HSCT (Figure 1, Table 1). CONCLUSION: The results of our study analysis suggest that Daclizumab at a dose of 1 mg/kg on days +7, +14, +28 and +42 provides clinically meaningful benefits when added to standard GVHD prophylaxis in TM patients undergoing haploidentical donor and unrelated donor transplantation, including decrease in the incidence rate of aGVHD without sever infection and transplant-related complications. Four doses of Daclizumab should be included in the GVHD prophylaxis of patients with thalassemia major selected for related haploidentical donor and unrelated donor transplantation.

Introduction Transfusion-dependent thalassemia (TDT) is a prevalent monogenic disorder characterized by an imbalance in hemoglobin peptide chain synthesis, leading to clinical manifestations such as anemia, hemolysis, and ineffective erythropoiesis. Iron overload, a consequence of repeated blood transfusions and increased intestinal iron absorption, is known to cause complications including heart failure, hepatic fibrosis, hypothyroidism, and hypopituitarism .etc. However, the impact of iron overload on pulmonary function has been relatively under-investigated. This study aimed to investigate the prevalence of pulmonary dysfunction in TDT patients and its association with iron overload. Method A retrospective analysis was conducted on patients selected from the hematopoietic stem cell transplantation candidates between January 2019 and December 2023. The inclusion criteria were: 1) a confirmed diagnosis of TDT based on genetic testing and clinical presentation; 2) absence of pneumonia within two weeks before pulmonary function testing and no recent symptoms indicative of respiratory infection; 3) availability of complete clinical data, including routine blood tests within one week of pulmonary function testing, and serum ferritin levels, liver iron MRI, and cardiac iron MRI within six months. The exclusion criteria included: 1) a history of asthma, pulmonary hypertension, or heart disease; 2) pulmonary function tests conducted post-transplantation.Pulmonary function tests were performed by experienced physicians using body plethysmography and spirography (Jaeger Master Scree, Germany). We performed statistical analyses using SPSS version 26.0. Independent t-test, non-parametric test, and chi-square test were used for comparison of normally distributed quantitative variables, non-normally distributed quantitative variables, and qualitative variables, respectively. Binary logistic regression was used for multivariate analysis. P<0.05 was considered statistically significant. Results A total of 140 TDT patients were included in the study. The mean age of the patients was 8.7 ± 3.2 years, with a median serum ferritin (SF) level of 3791.4 ng/ml (interquartile range: 2424.1-5733.3 ng/ml). Pulmonary function abnormalities were detected in 46.43% (65 out of 140) of the patients, predominantly as diffusion dysfunction (26.43%), followed by ventilatory dysfunction (5.0%), and mixed pulmonary dysfunction (15.0%). An elevated serum ferritin level above 2500 ng/ml was significantly correlated with the occurrence of these abnormalities (odds ratio [OR] = 3.187, 95% confidence interval [CI]: 1.312-7.741, P = 0.010), whereas higher hemoglobin concentrations were associated with a protective effect (OR = 0.966, 95% CI: 0.943-0.989, P = 0.004). Conclusion Our research has pinpointed SF levels exceeding 2500 ng/ml as a critical risk factor for impaired lung function in patients with TDT. In contrast, high hemoglobin levels serve as a protective factor. These findings emphasize the necessity of rigorous monitoring of iron levels and maintaining adequate hemoglobin concentrations to effectively manage TDT, ultimately enhancing patient care and survival.

Summary objectiveTo assess the clinical features and outcomes of hematological disease patients with Candida tropicalis bloodstream infections and determine the antifungal susceptibility of C. tropicalis.MethodsThis is a retrospective, single-center, observational study conducted in the Department of Hematology at The First Affiliated Hospital of Guangxi Medical University from January 2013 to December 2021. A total of 26 hematological disease patients with C. tropicalis bloodstream infections were enrolled, and their clinical features, treatment plans, and prognoses were assessed. Univariate analysis was performed by Kaplan–Meier analysis and multivariate analysis was conducted using a Cox regression model. The antifungal susceptibility of C. tropicalis was determined from patient blood cultures.ResultsThe patients had a mean age of 35 years (range: 10–65 years), 50% were male (13/26) and 88.5% had hematologic malignancies (23/26) while the remaining three patients included two cases of severe aplastic anemia and one case of β-thalassemia. All patients had neutropenia. Seven patients were initially given azole alone (26.9%), five of whom failed treatment and died (71.4%). Fifteen patients were treated with echinocandin (57.7%), three of whom failed treatment and died (20.0%), and eight patients were treated with amphotericin B (30.8%), two of whom failed treatment and died (25.0%). The total and attributable mortality rates were 42.3 and 34.6%, respectively. Univariate analysis showed that there are six risk factors for attributable deaths among hematological disease patients with C. tropicalis blood infections. These risk factors included septic shock, Pitt bacteremia scores ≥4, procalcitonin levels ≥10 ng/mL, positive plasma (1,3)- β-D glucan assay, serum albumin levels <30.0 g/L, time from fever to antifungal treatment initiation ≥5 days and time between neutropenia and antifungal treatment ≥10 days. Moreover, skin and mucosal infections and a treatment schedule that included amphotericin B and drug combinations are protective factors for attributable deaths. Multivariate analysis showed that septic shock (p = 0.006) was an independent risk factor for attributable death. All isolates were sensitive to flucytosine and amphotericin B. The intermediate or resistance of C. tropicalis to fluconazole, itraconazole and voriconazole were 41.7, 50, and 41.7%, respectively.ConclusionHematological disease patients with C. tropicalis bloodstream infections had a high mortality rate, and early antifungal therapy significantly reduced mortality. Candida tropicalis was highly resistant to azole drugs and sensitive to flucytosine and amphotericin B. According to our study, the preferred agent is amphotericin B and drug combinations should be considered for severe infections.

Background: Non-transfusion-dependent thalassemia (NTDT) characterized by ineffective hematopoiesis and increased intestinal iron absorption, and excessive iron deposits in the bone marrow, heart, and liver, causing progressive organ damage. It has been reported that oxidative stress damage caused by iron overload could induce apoptosis or ferroptosis. However, the related studies and mechanisms are not well unknown in NTDT disorders. Aims: To investigate the effects of iron overload on bone marrow erythropoiesis, heart and liver in NTDT patients and Hbb th3(th3/+) mice. Methods: Patients (19-47 y of age) and 12-month-old Hbb th3(th3/+) mice with NTDT were selected as thalassemia group, healthy human and normal mice were selected as control group. Iron overload related indexes, bone marrow erythropoiesis, oxidative stress, apoptosis and ferroptosis of each sample were detected by Elisa, flow cytometry, RT-PCR and Weston blot methods, respectively. Results: Compared with the control group, Serum ferritin is significantly increased in NTDT group, and there is imbalance of iron metabolism. And in NTDT patients, liver and myocardial iron deposition was assessed by MRI analysis, resonance results suggest that the degree of iron overload in liver is more significant than that in heart. The damage of erythropoiesis in NTDT group was more severe than that in control group, which showed active erythropoiesis, and the differentiation of erythroid precursor cells stagnated in early stage of erythroid precursor cells, and there were maturation disorders. The oxidative stress-related indexes reactive oxygen species (ROS), lipid peroxidation and malondialdehyde (MDA) induced by iron overload were also significantly increased in the NTDT group. However, significant signs of apoptosis were observed in the bone marrow of the NTDT group, including increased proportion of apoptotic cells, signs of apoptosis were mainly observed in the mitochondria of erythroid colony electron microscopy, and the level of GPX4 that is a key indicator of ferroptosis, was increased. But the expression of GPX4, VDAC2 and SLC7A11 of ferroptosis was decreased in the heart and liver with heavy iron deposition, and the signs of ferroptosis were also observed under electron microscopy. Summary/Conclusion: Our study found that there are differences in iron overload and injury performance among different organs in NTDT. Oxidative stress caused by iron overload in the bone marrow impairs erythropoiesis mainly through apoptosis, whereas signs of ferroptosis were observed in the liver and heart of Hbb th3(th3/+) mice.These results suggest that with the gradual accumulation of iron circulation, the damage is a dynamic process, and different organs show different signs of damage, which may be related to the different mechanisms of damage, tolerance and compensation of organs, but further studies are needed to confirm.

Background: Cytomegalovirus(CMV) is one of the most important infections following allogeneic haematopoietic stem cell transplantation (HSCT). Although Letermovir is licensed for prophylaxis of CMV infection in allogeneic hematopoietic cell transplant adult CMV seropositive patients. There are limited data for letermovir as primary CMV prophylaxis in pediatric patients . The objective of the study was to analyze the the use of letermovir for prophylaxis from CMV infection in β thalassemia major children undergoing allo-HSCT in a single center. M ethods : This study was an retrospective, single-center evaluation of β thalassemia major pediatric recipients treated by allo-HSCT in the First Affiliated Hospital of Guangxi Medical University. 34 patients included in the study were CMV-seropositive, underwent allo-HSCT, and were started on letermovir for primary CMV prophylaxis between June 2022 and July 2023. CMV monitoring was performed 2 times a week until day +100 after HSCT. The primary end point was CMV reactivation on days +100. Results: 34 patients were analyzed. 20 patients were transplanted from haploidentical donor, 9 patients were transplanted from matched-related donor, 5 patients were transplanted from matched-unrelated donor. The median followed-up was 129 days (range, 50-405 days).The median age was 9 years (range, 2-16 years). The GVHD prophylaxis for matched-related donor group was cyclosporine-based , and the GVHD prophylaxisfor haploidentical and matched-unrelated donor groups were tacrolimus-based. Letermovir start at median 21 days (range 10-35 days) after HSCT. The median weight at the initiation of letermovir was 18.8 kg (range, 12-25 kg). The dose of letermovir was 240mg and 120mg orally once daily in tacrolimus co-administration and cyclosporine co-administration, respectively. During the follow-up period , CMV reactivation was observed in 8 patients totally (23.5%). Among them, 6 patients(17.6%) were in haploidentical donor group. 1 patient (2.9%) in matched-related group and 1 patient (2.9%) in matched-unrelated donor group was CMV reactivated, respectively. Throughout letermovir prophylaxis, the median CMV DNAemia level was 1945 copies (range,526-3800 copies), and the CMV DNAemia lasting time were 17.5 days (range,15-59 days). No patients developed clinically significant CMV infection. 1 patient died because of pulmonary infection of mucor. No serious hepatotoxicity, nephrotoxicity or letermovir intolerance was described. Conclusion: Our data support letermovir prophylaxis efficacy and safety in β thalassemia major children after allo-HSCT.

Objective: This article primarily examines the clinical attributes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in transplant recipients with thalassemia, offering significant insights into the treatment and care of this patient population. Method: The present study retrospectively analyzed the data of all thalassemia patients who underwent Hematopoietic stem cell transplantation (HSCT) at the First Affiliated Hospital of Guangxi Medical University between December 2019 and December 2022. A total of 280 patients were included, of which 81 had confirmed coronavirus disease 2019 (COVID-19). The study collected information on patient demographics, transplantation type and timing, graft-versus-host disease (GVHD), use of immunosuppressive agents, onset time and severity of COVID-19, and prognosis. Follow-up was conducted until March 31, 2023.Univariate analysis was performed using SPSS v25.0, and GraphPad Prism was used for the cumulative incidence comparisons. Results: The median age was 3.6(2-19) years.The main type of thalassemia was β type (93.9%). Identical sibling donors accounted for 40%, haploidentical donors accounted for 25.4%, and identical unrelated donors accounted for 34.6% (10/10). The main source of hematopoietic stem cells was bone marrow combined with peripheral blood (85%).There were no significant differences in age, gender, diagnosis, donor type, graft type, use of immunosuppressive agents, GVHD, and pneumonia of pro-COVID-19 between infected patients and non-infected patients with SARS-CoV-2. Most of the patients were mild (74 cases, 91.3%) in terms of the severity of COVID-19 infection, only 8.6% of the moderate cases, and none severe and died. 74 cases were cured without drug treatment. Of the seven patients treated with medications, four were azvudine and three were nematasvir. The median number of days (IQR) of treatment for COVID-19 was 5(5) days. The cumulative incidence in the immunosuppressive group was higher than that in the non-immunosuppressive group over the same time frame. There was no significant difference in the final infection rate of COVID-19 among patients receiving transplantation in different years(2020,2021,2022), which was 24.7 26.8 36.5 ( p=0.368), respectively. Conclusion: The low infection rate and no severe cases may be due to scientific protection and timely medication. There are no special risk factors for COVID-19 infection in thalassemia patients after transplantation.

At present, the main therapies for ß-thalassemia patients include regular blood transfusion and iron chelation, associating with a number of limitations. Thalidomide, a fetal hemoglobin (HbF) inducer that promotes γ-globin gene expression, has been reported to be effective for ß-thalassemia. Thus, this meta-analysis was conducted to assess the efficacy and safety of thalidomide for treating patients with ß-thalassemia. We searched the related studies from eight databases published from inception until December 1, 2021. The R 4.0.5 language programming was used to perform meta-analysis. After screening of retrieved articles, 12 articles were included that enrolled a total of 451 patients. The Cochrane Collaboration risk assessment tool was used to evaluate the quality and the bias risk of the randomized controlled trials (RCTs), and non randomized trials were assessed using Newcastle-Ottawa Scale (NOS). After treatment with thalidomide, the pooled overall response rate (ORR) was 85% (95% confidence interval (CI): 80–90%), and the pooled complete response rate (CRR) was 54% (95% confidence interval: 31–76%). Compared with the placebo group, the thalidomide group had higher odds of overall response rate (odds ratio = 20.4; 95% CI: 6.75–61.64) and complete response rate (odds ratio = 20.4; 95% CI: 6.75–61.64). A statistically significant increase in hemoglobin level and HbF level after treatment, while there was no statistically significant difference in adult hemoglobin (HbA) level, spleen size, and serum ferritin. According to the results of ORR and CRR, transfusion-dependent thalassemia (TDT) patients showed remarkable efficacy of thalidomide, 83 and 52% respectively. So we analyzed 30 transfusion-dependent thalassemia patients from three studies and found that the most frequent ß-globin gene mutations were CD41-42 (-TCTT), while response to thalidomide did not show any statistically significant relationship with XmnI polymorphism or CD41-42 (-TCTT) mutation. About 30% of patients experienced mild adverse effects of thalidomide. Collectively, thalidomide is a relatively safe and effective therapy to reduce the blood transfusion requirements and to increase Hb level in patients with ß-thalassemia.

Iron overload is the most common complication in patients with β-thalassaemia major (β-TM). Iron overload cardiomyopathy remains the leading cause of morbidity and mortality in patients with β-TM.1, 2 About ten years ago, β-TM patients in mainland China rarely survived past the age of 30 years. Chinese β-TM patients with iron overload were younger and had a greater iron burden than those in western countries.3 Therefore, regular and long-term iron chelation therapy (ICT) was necessary in Chinese β-TM patients to achieve long-term survival. Deferasirox (DFX), a once-daily oral iron chelator, was licensed as first-line therapy by the FDA and the EMA in 2005 and 2006, respectively. Since then, numerous randomized controlled trials (RCTs) have compared DFX to other iron chelators, demonstrating similar effects to deferoxamine and compliance superior to deferoxamine and deferiprone.4-6 Nevertheless, so far, no study examined the long-term effect (over a 10-year period) of DFX. Moreover, according to recent meta-analysis and reviews, the long-term safety and benefits of DFX need to be further examined using a high-quality RCT and long-term follow-up.5, 6 Thus, the aim of this study was to investigate the long-term effectiveness and the safety of DFX in β-TM patients over a period of 15 years. This study is an extension of the EPIC trial (Evaluation of Patients' Iron Chelation with Exjade®, Clinicaltrials.gov identifier: NCT 00171821) conducted in our centre. We followed up 17 patients who finished the one-year core study and two-years extension phase of EPIC in our centre for 15 years (April 2005 to December 2019) by observing the dynamic changes of serum ferritin (SF) and cardiac T2* value and monitoring the adverse effects (AEs). Among the 17 patients, 10 were male and 7 female, with a mean age of 7·2 years. At baseline, the mean ± SD of SF was 5 555·80 ± 2 464·78 ng/ml (baseline characteristics are shown in supplementary data Table S1). The initial dose of DFX was 20 mg/kg/day, which was applied for 12 months (core study of EPIC trial). There was no significant decrease in SF compared to baseline after 12 months. Consequently, the dose was gradually increased. After 18 months, all 17 patients received a dose of 30 mg/kg/day and stayed on this dose for a long time. Until 2010, Cappellini et al. and Pennell et al. demonstrated that DFX ameliorates iron overload in a dose-dependent manner and recommended the maximum dose of DFX can be up to 40 mg/kg/day.7, 8 After that, the dose of DFX increased further, especially in patients with cardiac siderosis (up to 40 mg/kg/day). Then, constantly adjusting the dose of DFX according to the monitoring indexes, weight and blood transfusion, the last dose was 29·27 ± 5·79 mg/kg/day. During the 15 years of follow-up, SF was collected from all patients and was classified in groups (every two years), and then compared to the baseline data (Table I). The SF levels significantly decreased compared with baseline to 2 373·97 ± 3 793·57 ng/ml (P < 0·001) in 2019. However, in the sixth year of DFX treatment, the SF levels began to decrease significantly compared with the baseline, which was considered to be related to the higher age of patients starting DFX treatment, heavy iron overload, and lack of DFX treatment experience causing relatively deficient dosing. After the 15 years of DFX treatment, the number of patients with SF <2 500 ng/ml was increased from two to 13; among these 13 patients, five patients had SF <1 000 ng/ml. However, there are still four patients with SF >2 500 ng/ml. SF of all patients, n = 17 (mean ± SD) (ng/ml) In 2010, cardiac T2* value was measured. There were three patients with severe cardiac siderosis, five with mild-to-moderate cardiac siderosis, and nine patients without cardiac siderosis. After 10 years intensive ICT, the cardiac T2* value in the mild-to-moderate cardiac siderosis increased to the normal range (13·26 ± 2·37 ms to 24·87 ± 11·93 ms), and severe cardiac siderosis increased to the mild-to-moderate range (6·62 ± 2·46 ms to 18·43 ± 9·03 ms). Detailed cardiac T2* changes are shown in the supplementary data (Table SII). Yet, there were still three patients who developed severe cardiac siderosis, among whom one patient irregularly received DFX because he had Adult-Onset Still's Disease at the age of 15 and was treated with glucocorticoid and methotrexate for a long time (Fig 1A, Case 1); one patient stopped taking drugs for about two years because of a pregnancy (Fig 1B, Case 3); one was unable to take drugs regularly due to lack of awareness of the dangers of β-TM (Fig 1C, Case 6). No serious Adverse Events (AEs) were observed during the 15 years of DFX treatment. No patients stopped treatment due to serious AEs, and no deaths occurred. There were only transitory and mild AEs that appeared in the early stage of treatment. All these AEs reslved spontaneously after a short while without stopping DFX. To the best of our knowledge, our study is the longest follow-up study that examined the effect of deferasirox in β-TM patients. Our data demonstrate that long-term iron chelation therapy of deferasirox could effectively and safely ameliorate iron overload in β-TM. Our study also suggests that iron chelation therapy needs to be taken as early as possible and must be sufficient and persevered to achieve the best iron chelation effect. However, due to the small sample size, we were unable to examine whether long-term deferasirox monotherapy is superior to other iron chelation therapy strategies. Therefore, more long-term follow-up data and studies from other centres are needed to further explore the effect of deferasirox in β-TM patients. We wish to thank all patients and their families for their participation in this study. We are very grateful to Novartis Pharmaceuticals for all their help and support. This work was supported by the National Natural Science Foundation of China (81460025 and 81260090), Guangxi Natural Science Foundation (GKG1598011-1), and The Second Batch of Guangxi Medicine and Health Self-financing Projects (Z20180908). ZBW, RRL, GHY, YMH, YL, XPH and XMZ collected the data. PP and LLL contributed analysis tools. ZBW, RRL and YRL analyzed the data and wrote the paper. YRL supervised the study. The final version was approved by all authors. The authors declare to have no potential conflicts of interest regarding the present work. Table SI. Baseline patients' characteristics. Table SII. Comparisons of mean Cardiac T2* between 2010 and 2015 or 2019 in patients with different degrees of myocardial iron overload in 2010. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.