Transfusion-dependent Patients Research Articles

Role of Transient Elastography in Pediatric Transfusion Dependent Thalassemia Patients from Lower Socioeconomic Strata and its Correlation with Serum Ferritin: A Cross-Sectional Study

Role of Transient Elastography in Pediatric Transfusion Dependent Thalassemia Patients from Lower Socioeconomic Strata and its Correlation with Serum Ferritin: A Cross-Sectional Study

Mortality, Clinical Complications, and Healthcare Resource Utilization Associated with Managing Transfusion-Dependent β-Thalassemia and Sickle Cell Disease with Recurrent Vaso-occlusive Crises in Italy.

To examine the clinical burden and healthcare resource utilization (HCRU) among patients with transfusion-dependent β-thalassemia (TDT) and patients with sickle cell disease (SCD) with recurrent vaso-occlusive crises (VOCs) in Italy. Eligible patients were identified from an administrative claims database from 1 January 2010 and 1 February 2019. Patients with TDT had ≥ 1 iron chelation treatment, ≥ 8 red blood cell transfusions (RBCTs) during any 12-month period, and ≥ 12 months of available data pre- and post-index (i.e., first RBCT claim). Patients with SCD with recurrent VOCs had ≥ 2 VOCs/year in ≥ 2 consecutive years and ≥ 12 months of available data pre- and post-index (second VOC claim in the second of 2 consecutive years). Patients were propensity score matched to five controls by age, sex, geographic area, and index year. Clinical and HCRU outcomes were evaluated post-index. In total, 214 patients with TDT and 111 patients with SCD with recurrent VOCs were matched to 1070 and 555 controls, respectively. Both patient groups had substantially higher mortality rates than controls (TDT: 4.8 versus 0.8 deaths per 100 person-years; SCD: 1.6 versus 0.4 deaths per 100 person-years). Clinical complications were prevalent in both patient groups. Compared with controls, both patient groups had significantly higher mean rates of all-cause hospitalizations (TDT: 1.4 versus 0.1; SCD: 2.0 versus 0.1) and outpatient services (TDT: 21.9 versus 1.6; SCD: 6.2 versus 1.0) per patient per year (all: p < 0.05). Management of TDT and SCD in Italy is associated with significant clinical and health system burden, highlighting the need for new treatments that eliminate RBCTs and VOCs.

New therapy options for myelodysplastic syndrome—all for all or targeted?

SummaryThe OeGHO-Frühjahrstagung 2024 took place in Vienna. Thereby one session was dedicated specifically to the field of myelodysplastic syndrome (MDS). Just a few days before the meeting, the European Medicines Agency approved luspatercept for transfusion-dependent low-risk MDS patients in the first line. It was therefore more current than ever to discuss the future significance of this therapy for our patients in the low-risk field. In addition, there are other new substances in the pipeline; some of which already have mature phase III data (e.g., imetelstat), which have already led to the approval by the US Food and Drug Administration.

Transfusion burden and willingness to pay for temporary alleviation of anemia status in transfusion-dependent beta-thalassemia patients in China

BackgroundTransfusion-dependent β-thalassemia (TDT) is one of the global public health concerns highlighted by the World Health Organization. Patients with TDT require regular blood transfusion to survive. However, the availability of blood resources is extremely limited. The purpose of this study was to investigate transfusion burden and willingness to pay (WTP) for temporary remission of anemia status among patients with TDT and to explore the associated factors.MethodsAdult patients with TDT were recruited through cluster sampling across several high-incidence provinces in China. Consenting patients completed online questionnaires on demographic information, transfusion burden and WTP with real-time WeChat communication assistance from researchers. The guiding techniques of double-bounded dichotomous choices and open-ended questions in the contingent valuation method (CVM) were used to obtain participants’ WTP for 1 unit of leukocyte-depleted red blood cells. WTP calculations were performed using maximum likelihood estimation, with further insights gained through subgroup analysis based on gender, family monthly income level and convenience of blood transfusion.ResultsThe analysis included 149 TDT patients from five high-incidence provinces, with an average monthly income of $198.5. Patients received an average of 3.7 units per transfusion, 15.4 times annually, with an average WTP of $70.4 per unit (95% CI [62.0, 78.9]). Estimated WTP for temporary anemia alleviation per transfusion totaled $260.6, exceeding monthly income by 1.32 times. Higher WTP was observed among males, higher-income households, and those with at least junior education. Lower WTP was noted among patients with lower transfusion volumes and those needing to travel for transfusion or during hospitalization for blood transfusion.ConclusionHigh WTP indicated a strong desire for temporary anemia relief. Most TDT patients faced significant economic and transfusion burden. The evident gap in meeting clinical needed underscores the urgent demand for innovative treatments to reduce transfusion dependency, potentially transforming TDT care and improving socioeconomic well-being and clinical outcomes. These findings supported evidence-based decision-making for TDT pharmacoeconomics and efficient healthcare resource allocation in China.

Combined effects of exercise and nutritional interventions on sarcopenia and its associated quality of life in transfusion-dependent thalassemia patients: a single-arm, open-label study

Combined effects of exercise and nutritional interventions on sarcopenia and its associated quality of life in transfusion-dependent thalassemia patients: a single-arm, open-label study

Vitamin D Deficiency among Blood Transfusion-Dependent Beta Thalassemia Children Admitted to Tertiary Level Pediatric Hospital in Nepal: A Descriptive Cross-Sectional Study

Introduction: Children with beta thalassemia are on regular blood transfusions, which could result in iron deposition in the liver causing decreased synthesis of Vitamin D-25OH. There are limited publications on the association of Vitamin D deficiency with blood transfusion-dependent thalassemia in the Nepalese population. This study aims to determine the prevalence of Vitamin D deficiency among blood transfusion-dependent beta-thalassemia patients.Methods: This was a descriptive cross-sectional study conducted among beta-thalassemia major patients under 15 years of age, receiving regular blood transfusion, from July 17, 2022, to July 16, 2023, after ethical approval obtained from Ethical Review Committee, Kanti Children’s Hospital (reference number 155). Data were collected using convenience sampling, and descriptive analyses were performed using Microsoft Excel and Statistical Package for Social Sciences (SPSS) 2024.Results: A total of 127 blood transfusion-dependent beta-thalassemia major patients were included in the study, of whom 82 (64.56%) were male. Among these patients, 104 (81.88%) were aged between 5 and 14 year. Almost one-third 41 (32.28%) had Vitamin D insufficiency, and a quarter, 34 (26.77%), had Vitamin D deficiency. Ten percent of the children were underweight, and a quarter were stunted.Conclusions: Children with blood transfusion dependent beta thalassemia major are at a greater risk for Vitamin D deficiency and iron overload

Assessment of Cardiac, Hepatic and Pancreatic Iron Overload in Transfusion Dependent Thalassemia Patients Using T2* Magnetic Resonance Imaging

Assessment of Cardiac, Hepatic and Pancreatic Iron Overload in Transfusion Dependent Thalassemia Patients Using T2* Magnetic Resonance Imaging

Study of platelet activation, hypercoagulable state, and pulmonary hypertension in patients with transfusion-dependent beta-thalassemia

Abstract: BACKGROUND: Thalassemic patients require lifelong blood transfusions, which can lead to complications such as pulmonary arterial hypertension. The pathogenesis involves hypercoagulability, in which researches on coagulation abnormalities in this regard are limited. OBJECTIVES: The aims of the study was to investigate the mechanism of hypercoagulability and pulmonary hypertension in transfusion-dependent thalassemic patients and compare it with healthy controls. PATIENTS MATERIALS AND METHODS: This case–control analysis enrolled 50 transfusion-dependent thalassemia patients and 50 healthy controls. Complete blood counts, liver function tests, coagulation markers (P-selectin, protein C, antithrombin III, and fibrinogen), serum ferritin, and transthoracic echocardiography were performed, and blood transfusion/chelation history and splenectomy status were recorded. RESULTS: Thalassemia patients revealed severe anemia, leukocytosis, thrombocytosis, significantly elevated serum ferritin (1957.50 ± 2455.05 g/L), elevated liver enzymes serum glutamic oxaloacetic transaminase (22.01 ± 9.89 U/L), serum glutamic pyruvic transaminase (22.70 ± 9.78 U/L) in comparison to controls, and mean serum P-selectin was significantly higher in thalassemic patients (100.48 ± 53.29 ng/mL). Mean serum antithrombin-III and protein C were significantly lower in thalassemic patients (89.27 ± 16.08 units/h, 86.04 ± 25.21 μg/mL) in comparison to controls. CONCLUSIONS: Transfusion-dependent thalassemia is characterized by severe anemia and splenomegaly, leading to complex hemodynamic changes with evidence of platelet activation, hypercoagulable state, liver injury, and increased atherosclerosis. It induces pulmonary artery thrombosis contributing to the development of pulmonary artery hypertension.

Role of Quercetin Supplementation on Iron Parameters in Blood Transfusion-Dependent Thalassemia Patients

Background: Thalassemia is a group of inherited blood disorders that affect the production of hemoglobin, a protein in red blood cells that carries oxygen throughout the body. Iron overload is a condition in which the body absorbs and stores too much iron. In addition to repeated blood transfusions, increased gastrointestinal tract (GIT) iron absorption plays an important role in iron overload with thalassemia. Quercetin, a common flavonoid present in fruits and vegetables, exhibits diverse biological effects. Objective: To assess the effect of quercetin on iron overload parameters in blood transfusion-dependent thalassemia patients (TDT). Methods: A randomized, double-blind, placebo-placebo group-led study was conducted on 110 TDT patients, more than 12 years of age, who were supplemented with either quercetin or a placebo capsule daily (500 mg) for 3 months. A blood sample was obtained for laboratory parameters at baseline and at the end of 3 months. Results: At the baseline time of the study, the demographic features and iron overload parameters of patients and the placebo group were not statistically different, while after three months of supplementation, there was a significant decrease in levels of serum iron, UIBC, serum ferritin and ferritin saturation rate, and a significant increase in TIBC in the patients compared with the placebo group. Conclusions: The study shows the significant role of quercetin on iron overload parameters in blood transfusion-dependent thalassemia patients.

Genotype Distribution and Clinical Characteristics of Thalassemia Patients Needing Transfusion in Yangjiang, Western Guangdong

Plain Language SummaryThis study is a retrospective research that investigates the genotype distribution and iron metabolic imbalance in thalassemia patients requiring blood transfusion. Eighty-four thalassemia patients needing transfusion were enrolled in the study and underwent genotype analysis. Among these patients, 56 were transfusion-dependent and 28 were non-transfusion-dependent. Of the 56 transfusion-dependent patients, 48 were observed for 3 years, and their iron overload status was analyzed in this study. Our research found that among the 84 thalassemia patients needing transfusion, there were six types of α-thalassemia deletions and nine types of β-thalassemia mutations. Among the 56 transfusion-dependent patients, three types of α-thalassemia genotypes and 15 types of β-thalassemia genotypes were identified. Among the 48 transfusion-dependent thalassemia patients observed for 3 years, 40 patients exhibited iron overload with SF levels exceeding 1,000 ng/mL. The recent SF levels were lower than those 3 years ago. Our study found that β-thalassemia is the most common type of transfusion-dependent thalassemia. Standard blood transfusion and iron chelation therapy are necessary for transfusion-dependent thalassemia patients. While some patients show a reduction in SF levels after 3 years of treatment, there are still individuals who exhibit elevated levels necessitating ongoing management.

Investigation of SEN virus prevalence in hemophilia patients

BackgroundHemophilia and transfusion-dependent patients are at high risk of a wide range of blood-borne agents. Among these, SEN virus (SENV) stands out as a significant concern due to its association with transfusion-induced non-A to non-E hepatitis. This study, therefore, aimed to investigate the prevalence of this virus in hemophilia patients, focusing on potential complications and risk factors. MethodThis was a cross-sectional study conducted in a hemophilia center in the east of Iran. Blood samples were taken from patients and healthy people, and demographic and clinical information was collected. The sera samples were then subjected to DNA extraction. PCR-based methods detected SENV and its genotype, and then phylogenetic analysis was performed. The collected data were analyzed and interpreted by SPSS22 software. ResultsThe mean age of patients and the healthy group was 26.18 ± 14.97 and 41.69 ± 14.05, respectively. Among the patient and healthy groups, 94.5 % and 36.4 % were male, and the rest were female, respectively. Most of the participants in the patient group had hemophilia type A (85.5 %), then type B (7.3 %), VWD type (3.6 %), and F and plt type (1.8 %) were in the next categories. SENV-DNA was detected in 58.2 % of patients and 20 % of healthy groups (P-value: 0.00). Among these, H and D genotypes were found in 35 % and 23.7 % of patients and 12.7 % and 7.3 % of healthy groups, respectively. The prevalence of the virus was significantly related to minor elevation of AST and was higher in hemophilia type A (63.8 %) and severe type of disease (63.2 %). ConclusionThis study underscore the significant prevalence of the SENV virus in hemophilia patients, a particularly noteworthy finding compared to the healthy population. With the limited information available about this virus, our findings highlight the importance of continuous monitoring and follow-up of high-risk groups in relation to blood-borne pathogens, providing reassurance about the ongoing efforts in the field.

Prevalence of hemoglobinopathies detected by high performance liquid chromatography in tertiary care centre, Kota, Rajasthan

Background: Hemoglobinopathies are the most common heterogeneous group of monogenetic disorder in the world. Their prevalence varies with geographical regions. India is developing country and many studies have shown a significant burden of hemoglobinopathies in India. Our aim is to estimate prevalence of various hemoglobinopathies in our region. Methods: The present study was conducted at the department of pathology, Government Medical College, Kota on patients referred for antenatal or voluntary premarital checkup, patients with clinical history and complete blood count (CBC) suggestive of hemolytic anemia, and family members of known cases of hemoglobinopathies. Transfusion-dependent patients were also included. However, patients with history of blood transfusion within the last 1 month were excluded. EDTA samples were used for CBC using 6-part differential cell counter and high-performance liquid chromatography (HPLC) using BIORAD D10 analyzer. The results were tabulated and analyzed. Results: Of the 226 cases studied, 139 (61.5%) were females and 87 (38.5%) were males. Most common age group was 21 to 30 years. The number of thalassemia traits were 26 (11.5%), sickle cell traits were 7 (3.1%), sickle cell homozygous was 1 (0.4%), compound heterozygous for sickle cell and thalassemia were 2 (0.9%), while the remaining 190 patients (84.07%) were found to have normal HPLC, with presence or absence of nutritional deficiency. Conclusions: In our study, we found a high prevalence of hemoglobinopathies among patients. The most common disorder detected was beta thalassemia trait. Most of the hemoglobinopathies found in our study could be accurately quantified by HPLC which is a rapid, sensitive, and reproducible method for the detection of different hemoglobinopathies.

Clinico-Laboratory Profile of Hypertriglyceridemia Thalassemia Syndrome: A Case Series in a Paediatric Tertiary Care Centre.

Increased hemolysis and repeated blood transfusion trigger oxidative stress resulting in numerous adverse effects in beta-thalassemia patients. Extreme elevation of triglyceride level is a rare clinical entity seen in these patients. It is presumed to be caused due to an increase in oxidative stress and is termed Hypertriglyceridemia Thalassemia Syndrome. To assess the clinical and laboratory characteristics of beta-thalassemia patients presenting with hypertriglyceridemia and its correlation with the pre-transfusion hemoglobin level. Methods: This hospital record-based retrospective study was conducted at the Dr B C Roy Post Graduate Institute of Paediatric Sciences, Kolkata, India. The study comprised 12 pediatric beta-thalassemia patients whose plasma appeared milky or chylous during a complete hemogram. Clinical examination and laboratory investigations were done to describe their clinico-laboratory features. A whole exome sequencing was carried out to assess their genetic background. Blood hemoglobin and serum triglyceride estimation was carried out initially and at follow-up to determine any correlation between the two. Results: Out of 1482 patients, 12 (0.80 %) were diagnosed with Hypertriglyceridemia Thalassemia Syndrome. The median age of presentation was 12.5 months (Q1:10 months, Q3:14 months)., and the pretransfusion hemoglobin was 4.82 ± 1.16 g/dL. The lipid profile showed a triglyceride level of 858.3 ± 198.4 mg/dl and a total cholesterol level of 117.4± 16.15 mg/dl. Analysis revealed that the triglyceride levels were negatively correlated with the pretransfusion hemoglobin level (repeated measures correlation (rmcorr) = -0.65, 95% CI[-0.794, -0.425], p < 0.001). A genetic study highlighted c.92+5G>C as the commonest mutation. Hypertriglyceridemia was a rare presentation in transfusion-dependent beta-thalassemia patients. The serum triglyceride level significantly reduced when blood transfusion at regular intervals restored the patient's hemoglobin level.

Molecular genotyping versus serological diagnosis for RH blood group typing in sickle cell patients

ABSTRACT Objectives High rate of alloimmunization in sickle cell disease (SCD) patients poses a significant challenge in finding compatible blood unit. Accurate determination of the blood group genotype of them can help reduce the alloimmunization risk. Tetra ARMS PCR is a novel method that has been utilized recently to investigate SNPs in diseases in a fast and reliable way. Methods Our study included 104 SCD and sickle thalassemia (Sβ) patients referred to Baghaei-2-Hospital of Ahvaz in 2019 using a nonrandom sampling method. Blood samples were collected for serological and molecular tests. Rh genotyping was performed using Tetra ARMS PCR and compared with the serological results. Results Based on the Tetra ARMS PCR method, out of 104 patients, 7 (6.7%) were d/d, 40 (38.5%) were D/d, 57 (54.8%) were D/D, 25 (24%) were C/C, 59 (56.7%) were C/c, 20 (19.3%) were c/c, 4 (3.8%) were E/E, 25 (24%) were E/e, and patients 75 (72.2%) were e/e. There were discrepancies in the serological and molecular results for 11 patients. Conclusion Use of Tetra ARMS PCR in combination with serological methods for determining the Rh blood group system in donors and transfusion-dependent patients represents a remarkable transformation in the field of immunohematology.

Evaluation of microstructural changes in the brain in transfusion dependent thalassemia patients with advanced magnetic resonance imaging techniques

PurposeTransfusion-dependent thalassemia (TDT) is associated with iron accumulation in the body and an increased tendency for thrombosis. With the increased life expectancy in these patients, the detection of neurocognitive complications has gained importance. This study investigates the microstructural changes in TDT patients using advanced diffusion MRI techniques and their relationship with laboratory parameters.MethodsThe study included 14 TDT patients and 14 control subjects. Tract-based spatial statistics (TBSS) were used to examine differences in DTI parameters such as fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) in thalassemia patients using multi-shell DWI images. The mean kurtosis (MK) difference was investigated using diffusion kurtosis imaging. Fiber density (FD), fiber cross-section (FC), and fiber density and cross-section (FDC) differences were examined using fixel-based analysis. In the patient group, correlative tractography was used to investigate the relationship between DTI parameters and platelet (PLT) and ferritin levels.ResultsIncrease in RD and MD was observed, particularly in the white matter tracts of the corona radiata in patient group. Additionally, an increase in AD was detected in a limited area. Correlative tractography in thalasemia patients showed a positive correlation between increases in RD, MD, and AD with PLT and ferritin. Fixel-based analysis demonstrated a dispersed distribution in white matter fibers, with a more pronounced decrease in FD, FC, and FDC in the internal capsule.ConclusionThere is widespread involvement in the white matter and fiber tracts in thalassemia patients, which is highly correlated with thrombotic parameters.

Plateletcrit and absolute immature platelet count are not impacted by platelet transfusions: a single-centre prospective study

BACKGROUND This is the first study in which the impact of platelet transfusions on seven platelet indices was evaluated in platelet transfusion-dependent patients admitted in the ICU. STUDY DESIGN AND METHODS Among a cohort of 21 ICU patients prospectively studied over eleven months, a total of 19 ICU patients were enrolled. Seven platelet indices were measured before and then, within 18–24 h, after platelet transfusions using the Sysmex XN-10 analyser and statistically investigated as follows: i) apheresis vs. pooled platelet transfusions; ii) pre– vs. post–platelet transfusions; and iii) platelet count (PC) increment vs. PC decrement group. RESULTS A 79.2% of platelet transfusion episodes in ICU patients showed an increase in PC increment within 18–24 h, of which 73.7% had a peak percentage immature platelet fraction (%-IPF) above 10.0% during their stay. No difference was observed in the measurements of platelet indices between the apheresis and pooled platelet transfusion doses (all p > 0.05). Of the seven platelet indices investigated, plateletcrit (PCT) and absolute immature platelet count (A-IPF) were not influenced by platelet transfusions and thus proven to be stable (0.06 vs. 0.07%, p = 0.0901 and 4.6 vs. 4.9 × 109/L, p = 0.4559, respectively), despite their close proximity to platelet transfusion. But the overall effectiveness of these indices in detecting changes over time was not hindered. CONCLUSION A-IPF and PCT are stable after platelet transfusions, regardless of whether patient’s respond to or do not respond to platelet transfusion doses. PCT and A-IPF may thus prove useful in monitoring patient transfusion support and guiding management in thrombocytopenic patients.

Soluble fms-like tyrosine kinase-1 as a predictive marker for iron overload in adult patients with transfusion-dependent beta-thalassemia major

Background The excessive iron accumulation has been identified as a contributing factor in the development of several issues in individuals with beta thalassemia, as those affecting the heart, liver, and endocrine glands. Soluble fms-like tyrosine kinase-1 (sFLT-1) belongs to the family of vascular endothelial growth factor receptors and acts as an inhibitor of signaling mediated by vascular endothelial growth factor and placental growth factor. The condition of iron excess has been associated with the potential to induce low-grade inflammation. The observed inflammatory condition is noteworthy due to the shown ability of sFLT-1 to stimulate a pro-inflammatory reaction. Consequently, this phenomenon could clarify the association between iron overload, inflammation, and elevated sFLT-1 levels in individuals with thalassemia. Aim The purpose of this work was to assess role of sFLT-1 as a predictive marker for iron overload in adults with transfusion-dependent beta-thalassemia major (BTM). Patients and methods Forty-five transfusion-dependent BTM patients were recruited and divided into 15 poor-chelated individuals with levels of serum ferritin more than 2500 ng/ml and 30 well-chelated individuals with levels of serum ferritin less than 2500 ng/ml. Serum sFLT-1 was measured using the enzyme-linked immunoassay technique. Results Serum sFLT-1 was substantially greater in the poor-chelated beta thalassemia compared with well chelated. sFLT-1 at a cutoff-value of 8.09 pg/ml had a high-diagnostic efficacy to differentiate poor chelated from the well-chelated group. Conclusion Elevated sFLT-1 levels may act as a biomarker for poor iron chelation in transfusion-dependent BTM patients.

Cognitive debriefing and the validity of the Malay EQ-5D-3L in transfusion-dependent thalassemia patients from Sabah, Malaysia

Cognitive debriefing and the validity of the Malay EQ-5D-3L in transfusion-dependent thalassemia patients from Sabah, Malaysia

Association of serum ferritin trends with liver enzyme patterns in β-thalassemia major: A longitudinal correlational study.

β-Thalassemia major patients require lifelong blood transfusions, leading to iron overload and liver injury. This study examines the longitudinal association between serum ferritin and liver function over 5 years in pediatric patients. This retrospective study included 582 transfusion-dependent thalassemia patients aged 1-18 years. Serum ferritin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and albumin were measured annually. Correlation and linear regression analyses assessed associations between ferritin trajectories and liver enzymes. Mean ferritin rose from 1820 ± 960 ng/mL at baseline to 4500 ± 1900 ng/mL at year 5, indicating worsening iron overload. AST and ALT levels also steadily climbed over follow-up, whereas albumin declined slightly. Ferritin correlated positively with AST (r = 0.675, P < 0.01) and ALT (r = 0.607, P < 0.01), but not with albumin (r = -0.143, P = 0.153) annually. The regression interaction term showed within-patient ferritin increases over time were independently associated with escalating AST and ALT (P < 0.05), after adjusting for confounders. Rising ferritin levels predict progressive liver injury in regularly transfused pediatric thalassemia patients. Tighter control of iron overload may help preserve hepatic function.

Safety and efficacy of luspatercept for the treatment of anemia in patients with myelofibrosis

AbstractThe ACE-536-MF-001 trial enrolled patients with myelofibrosis (n = 95) into 4 cohorts: patients in cohorts 1 and 3A were non–transfusion dependent (NTD) and had anemia; patients in cohorts 2 and 3B were transfusion dependent (TD); and patients in cohort 3A/3B had stable ruxolitinib treatment before and during the study. All patients received luspatercept (1.0-1.75 mg/kg, 21-day cycles). Treatment was extended if clinical benefit was observed at day 169. The primary end point was anemia response rate (NTD, ≥1.5 g/dL hemoglobin increase from baseline; TD, transfusion-independence) over any 12-week period during the primary treatment period (weeks 1-24). Overall, 14% of patients in cohorts 1 and 3A, 10% in cohort 2, and 26% in cohort 3B met the primary end point. In cohorts 1 and 3A (NTD), 27% and 50% of patients, respectively, had mean hemoglobin increase of ≥1.5 g/dL from baseline. Among TD patients, ∼50% had ≥50% reduction in transfusion burden. Reduction in total symptom score was observed in all cohorts, with the greatest response rate seen in cohort 3A. Overall, 94% of patients had ≥1 adverse event (AE); 47% had ≥1 treatment-related AE (TRAE; 11% grade ≥3), most frequently hypertension (18%), managed with medical intervention. One patient had a serious TRAE leading to luspatercept discontinuation. Nine patients died on treatment (unrelated to study drug). In most patients, ruxolitinib dose and spleen size remained stable. In patients with myelofibrosis, luspatercept improved anemia and transfusion burden across cohorts; the safety profile was consistent with previous studies. This trial was registered at www.ClinicalTrials.gov as #NCT03194542.