Transfusion-dependent Patients Research Articles

Is serum ferritin level or T2-sequence magnetic resonance imaging more effective in predicting liver iron in transfusion-dependent thalassemia cases?

Amaç: Transfüzyon bağımlı talasemi hastalarında aşırı demir yüklenmesi, sürekli şelasyon tedavisi ve demir düzeyi izlemini gerektiren bir durumdur. Serum ferritin düzeyinin tayini, demir yükünü takip etmek için basit bir yöntem olarak kabul edilmektedir. Bununla birlikte, karaciğer demir düzeyi tayininde manyetik rezonans görüntüleme (MRG) gibi yöntemlerin daha kesin olduğunu vurgulamaktadır.
 Gereç ve Yöntem: Talasemide demir yükünün anlaşılmasına katkıda bulunmak amacıyla, kök hücre transfüzyonuna hazırlık amacıyla karaciğer biyopsisi yapılan 14 transfüzyon bağımlı talasemi hastasının karaciğer demir düzeyi sonuçlarını karaciğer T2 MRG ve serum ferritin sonuçları ile karşılaştırıldı.
 Bulgular: Serum ferritin değeri ortalaması 2488,43±1520,18 mg/L idi. T2*MRG sonuçlarına göre karaciğer demir yükü değerlendirildiğinde sekiz hastada hafif düzey, beş hastada orta düzey, bir hastada ileri düzey demir birikimi saptandı. Modifiye Scheuer sınıflamasına göre biyopsilerde demir düzeyi iki hastada derece 1; yedi hastada derece 2; üç hastada derece 3 ve iki hastada derece 4 olarak değerlendirildi. Ferritin düzeyi arttıkça karaciğer demir biyopsi skoru da istatistiksel anlamlı olarak artmaktaydı (r=0,544 ve p=0,044). Karaciğer T2 MRG düzeyi ile karaciğer demir biyopsi skoru arasında ise istatistiksel olarak anlamlı ve ters yönlü korelasyon mevcuttu (r=-0,724 ve p=0,003). Karaciğer biyopsi demir skoruna göre demir düzeyini ayırt etmede ferritin düzeyi istatistiksel olarak anlamlı bulunmazken (p=0,096); T2*MRG ölçümlerine ilişkin ROC eğrisi altında kalan alan istatistiksel olarak anlamlı bulundu (AUC=0,967; 95% CI: 0,880-1,000 ve p=0,005).
 Sonuç: Çalışmamızda serum ferritin ve T2 MRG sonuçlarının karaciğer biyopsisi demir düzeyi ile korele olduğunu saptadık. Ancak ferritin düzeyinin karaciğer biyopsisi demir düzeyini göstermede sensitivite ve spesifitesinin düşük olduğu, T2 MRG ise sensitivite ve spesifitesinin yüksek olduğunu saptadık.

The role of MRI-R2* in the detection of subclinical pancreatic iron loading among transfusion-dependent sickle cell disease patients and correlation with hepatic and cardiac iron loading

ObjectivesPancreatic reserve could be preserved by early assessment of pancreatic iron overload among transfusion-dependent sickle cell disease (SCD) patients. This study aimed to measure pancreatic iron load and correlate its value with patients’ laboratory and radiological markers of iron overload.Materials and methodsSixty-six SCD children and young adults underwent MRI T2* relaxometry using a simple mathematical spreadsheet and laboratory assessment.ResultsThe results indicated moderate-to-severe hepatic iron overload among 65.2% of studied cases. None had cardiac iron overload. Normal-to-mild iron overload was present in the pancreas in 86% of cases, and 50% had elevated serum ferritin > 2500 ug/L. There was no significant correlation between pancreatic R2* level, serum ferritin, and hepatic iron overload. Patients with higher levels of hemolysis markers and lower pre-transfusion hemoglobin levels showed moderate-to-severe pancreatic iron overload.ConclusionChronically transfused patients with SCD have a high frequency of iron overload complications including pancreatic iron deposition, thereby necessitating proper monitoring of the body’s overall iron balance as well as detection of extrahepatic iron depositions.

Transfusion burden in early childhood plays an important role in iron overload in Diamond-Blackfan anaemia.

In Diamond-Blackfan anaemia (DBA), iron overload (IO) is common in transfusion-dependent patients, yet has also been reported in non-transfusion-dependent patients. We explored the incidence of IO in transfusion-dependent and non-transfusion-dependent DBA patients. We observed hepatic IO in 65% of patients analysed with MRI, including three patients that were only treated with transfusions in the past. Whereas overall ferritin levels and liver iron content correlated, ferritin levels did not reflect total body iron adequately. Our data suggest that transfusion burden in the past plays an important role in IO in DBA, and should be taken into account during follow up.

Assessment of glucose metabolism in thalassemia patients with type two diabetes in Thi-Qar/ Southern of Iraq

The natural history of glucose metabolism in transfusion-dependent beta-thalassemia patients is characterized by deterioration of glucose tolerance over time. The current study involved 80 participate (40 thalassemia with diabetic 22 boy and 18 girl and 40 as control group 21 boy and 19 girl). The study was conducted at the Specialized Center for Endocrinology and Diabetes in Thi-Qar Governorate and some outpatient clinics for the period from January to April 2022. The results of the current study recorded a significant increase of involved parameters in thalassemia patients than control group in both compartment when compared all patients with all control, and when compared according to gender, also the results a non-significant difference between patients according age with except ALP.

Psychological distress and coping strategies among the caretakers of children with transfusion-dependent thalassemia.

IntroductionThalassemia is a chronic childhood disease that could result in psychological distress not only to the patients but also to their caretakers. Caretakers utilize different coping strategies to reduce stress and maintain a good quality of life.ObjectiveThe study aims to measure the level of psychological distress among caretakers of transfusion-dependent thalassemia patients and identify coping strategies used by them, as well as examine factors related to both outcome measures.MethodsSixty-eight (N = 68) caretakers of children with transfusion-dependent thalassemia agreed to participate in the study when they were approached during their visits to one of three major hospitals in Kelantan, Malaysia, for the children's medical treatment. They completed the Malay validated Depression Anxiety and Stress Scale 21 (DASS 21) and Brief-COPE self-report, in addition to a brief study proforma.ResultsThe majority of the participants reported feeling psychologically well, with no related scores in depression, anxiety, and stress sub-scales. The mean score for anxiety and stress sub-scales were 3.54 (SD = 3.54) and 4.25 (SD = 3.26) respectively. The median score for the depression sub-scale was 2.00 (IQR 4.00). The three mostly utilized coping strategies were religion, acceptance, and positive reframing. Those with depressed and anxious moods were found to engage more in negative coping strategies including substance abuse, denial, and behavioral disengagement. Being female, of younger age, employed, with higher educational level, and income status was found to significantly influence the adoption of positive reframing as a coping strategy.ConclusionPsychological distress such as elevated anxiety and depression was found among a small portion of caretakers who have children with thalassemia whose treatment required blood transfusion. They were noted to apply more maladaptive coping strategies compared to their psychologically well counterparts.

Ferric Carboxymaltose and Erythropoiesis-Stimulating Agent Treatment Reduces the Rate of Blood Transfusion in Refractory Anemia.

Background: Erythropoiesis-stimulating agents (ESAs) are used to treat refractory anemia (RA). Guidelines suggest iron supplementation for unresponsive patients, regardless of iron deficiency. The primary aim of this study was to evaluate the effect of iron supplementation with ferric carboxymaltose (FCM) on the reduction of red blood cell transfusion (RBCT) rate in transfusion-dependent RA patients. Methods: This was a prospective quasi-randomized study, wherein patients were randomly assigned into three groups: (A) ESAs alone, (B) ferric gluconate (FG) and ESAs, and (C) FCM and ESAs. Hemoglobin and ferritin levels, as well as the number of RBCTs at 4 and 28 weeks were compared. Economic evaluation was also performed. Results: A total of 113 RA patients were enrolled. In total, 43 were treated with intravenous FG and ESAs, 38 with FCM and ESAs, and 32 with ESAs alone. At both follow-ups, erythropoietic response was increased in those receiving iron as compared with those with ESAs alone (p = 0.001), regardless of the type of iron. At one month, ferritin levels were higher in the FCM and ESA groups (p = 0.001). RBCTs were lower in both iron groups. The less costly treatment strategy was FCM, followed by FG, and lastly ESAs. Conclusions: Addition of iron to ESAs in RA reduced RBCT requirement and improved hemoglobin values.

Prevalence of hypogonadism in transfusion-dependent β-thalassemia patients of Bangladesh: investigating the role of serum ferritin level as a diagnostic tool

IntroductionHypogonadism is one of the most frequent complications in transfusion-dependent thalassemia patients and early recognition and treatment is the core element in restoring impaired gonadal function. Despite the high burden of disease, relevant studies are scarcely addressing the gonadal function of such patients in Bangladesh. The pattern of gonadal function in transfusion-dependent thalassemia patients must be characterized before planning a generalized management plan. Moreover, since iron overload is a key reason behind hypogonadism in thalassemia patients, investigating the role of serum ferritin level as a diagnostic tool for hypongadism was also an aim of this study. MethodsThis cross-sectional study was conducted at the Department of Transfusion Medicine of the Bangabandhu Sheikh Mujib Medical University. According to the inclusion and exclusion criteria, a total of 94 patients were enrolled in this study. A detailed history and thorough clinical examination were carried out in each patient and recorded using a pretested structured questionnaire. In addition, the laboratory assessment of serum ferritin, luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone and estradiol in serum were also performed. The data were analyzed using the STATA (v.16). ResultsThe mean age of the patients with transfusion-dependent thalassemia was 18.81 ± 4.65 (SD), with 53.3% of the patients being male. The overall prevalence of hypogonadism was 35.11%, 18.1% being normogonadotropic, 11.7% being hypogonadotropic and 5.3% being hypergonadotropic. The serum ferritin level was significantly higher (p < 0.001) in patients with hypogonadism (Eugonadal: 2,174.79 (± 749.12) ng/ml; Hypogonadal: 3,572.59 (± 1,199.49) ng/ml). The area under the receiver operating characteristic (ROC) curve of serum ferritin was high (0.83) and the p-value was highly significant (< 0.001). ConclusionTherefore, the serum ferritin level and gonadal hormone analysis of transfusion-dependent thalassemia patients can be considered a screening tool for assessing gonadal function and early detection and prevention of hypogonadism.

Evaluation of Quantitative Aspects of Craniofacial Deformities in Transfusion Dependent Beta-Thalassemia Major Patients: A Cephalometric Study.

To evaluate the quantitative (cephalometric) aspects of the craniofacial deformities in transfusion-dependent beta-thalassemia (TDT) patients. Sixty-five TDT patients receiving a regular blood transfusion in the Department of Pediatrics of age group 5 to 8 years (younger) and 15 years and above (older) were compared with control groups of similar age using cephalograms (lateral and posterior-anterior view). The prevalence of skeletal class II tendency is higher in thalassemic patients that do not improve with age. The thalassemic patients were found to show large angle ANB i.e. Angle between points point a, nasion and point B (ANB), large flexure angle, small angle SNB i.e. Angle between points sella, nasion and point B (SNB), and normal angle SNA i.e. Angle between points sella, nasion and point A (SNA) angles suggestive of retrognathic mandible. The thalassemic patients were observed to have smaller transverse widths and thickened calvarium on the posterior-anterior view. The skeletal class II malocclusion appears to be a manifestation of generalized growth retardation/delayed puberty in thalassemic patients leading to diminished mandibular growth, rather than maxillary prognathism due to marrow hyperplasia.

Association between transfusion status and clinical and economic outcomes in patients with myelodysplastic syndromes from the physicians' perspective.

The current study investigated physicians' understanding of the impact of transfusion status (TS) on clinical and economic outcomes in patients with myelodysplastic syndromes (MDS). 378 physicians primarily specializing in hematology/oncology across five European countries completed the survey. The survey asked physicians for their perspectives on the impact of TS on risk of death, risk of progression to acute myeloid leukemia (AML), chance of leukemia-free survival, and number of significant bleeding events, infection events, hospitalizations, and emergency room (ER) visits. Physicians estimated that compared to transfusion-dependent (TD) patients, transfusion-independent (TI) patients had a 37.6% reduced risk of death, lower risk of progression to AML, and lower risk of non-leukemic death, for all MDS risk levels. TD patients who became TI after treatment were estimated to have 40.6% reduced risk of death and 34% reduced risk of progression to AML, compared to TD patients who remained TD. Compared with TD patients, physicians estimated that TI patients have fewer events of infection and significant bleeding, and experience fewer hospitalizations and ER visits per person per year. Overall, physicians reported better outcomes for TI patients. New treatment options for patients with MDS to reduce or eliminate transfusion burden are warranted.

Frequency of consanguineous marriage among the thalassaemia major patients in Bangabandhu Sheikh Mujib Medical University

Thalassaemia is a commonly occurring hereditary disorder. There is a high prevalence of thalassaemia disease in South-East Asia as well as Bangladesh. It is an autosomal recessive disorder, so consanguineous marriage is a very important factor for this disease. Mutated beta globin gene of haemoglobin from both parents is responsible for this disease to occur. But when the number of thalassaemia carriers is miserably high, then only avoidance of consanguineous marriage can’t prevent the birth of children with thalassaemia major. So, this cross sectional study was conducted among 120 diagnosed (by haemoglobin electrophoresis or high performance liquid chromatography) thalassaemia major patients in the Department of Haematology, Bangabandhu Sheikh Mujib Medical University, Dhaka from July 2019 to May 2020. History from each patient was taken and blood samples were collected from their parents to confirm carrier state by haemoglobin electrophoresis. Blood samples were also collected from patients and their parents toperform complete blood count and peripheral Blood Film. This study showed the mean age of the participants was 15±9.34 and 73 (60.8%) patients were male and 47 (39.2%) were female. About, 71% of the study population lived in urban area, 81 (67%) patients were transfusion dependent thalassaemia patients. 15% thalas- saemia major patients had the history of consanguinity of their parents. Among the parents of the thalassaemia major patients, 62.5% were Beta thalassaemia trait (heterozygous state), 25.83% parents were Hb E trait ( heterozygous state), 7.08% parents were suffering from Beta Thalassaemia Major(homozygous state) and 11 (4.58%) parents were suffering from Hb E/Beta Thalassaemia which is a compound heterozygous state. Though consanguinity is a very influential factor, but the most important causative factor is the presence of high number of thalassaemia carrier in the population. So, it’s a burning issue for the nation to perform a routine carrier screening for all rather than focusing on consanguinity only, to lessen the burden of thalassaemia disease in Bangladesh. BSMMU J 2022; 15(1): 25-28

Prospective, Case-Control Study of Serological Response after Two Doses of BNT162b2 anti-SARS-CoV-2 mRNA Vaccine in Transfusion-Dependent Thalassemic Patients.

Prospective, Case-Control Study of Serological Response after Two Doses of BNT162b2 anti-SARS-CoV-2 mRNA Vaccine in Transfusion-Dependent Thalassemic Patients.

Comparative risk of pulmonary adverse events with transfusion of pathogen reduced and conventional platelet components.

BackgroundPlatelet transfusion carries risk of transfusion‐transmitted infection (TTI). Pathogen reduction of platelet components (PRPC) is designed to reduce TTI. Pulmonary adverse events (AEs), including transfusion‐related acute lung injury and acute respiratory distress syndrome (ARDS) occur with platelet transfusion.Study designAn open label, sequential cohort study of transfusion‐dependent hematology‐oncology patients was conducted to compare pulmonary safety of PRPC with conventional PC (CPC). The primary outcome was the incidence of treatment‐emergent assisted mechanical ventilation (TEAMV) by non‐inferiority. Secondary outcomes included: time to TEAMV, ARDS, pulmonary AEs, peri‐transfusion AE, hemorrhagic AE, transfusion reactions (TRs), PC and red blood cell (RBC) use, and mortality.ResultsBy modified intent‐to‐treat (mITT), 1068 patients received 5277 PRPC and 1223 patients received 5487 CPC. The cohorts had similar demographics, primary disease, and primary therapy. PRPC were non‐inferior to CPC for TEAMV (treatment difference −1.7%, 95% CI: (−3.3% to −0.1%); odds ratio = 0.53, 95% CI: (0.30, 0.94). The cumulative incidence of TEAMV for PRPC (2.9%) was significantly less than CPC (4.6%, p = .039). The incidence of ARDS was less, but not significantly different, for PRPC (1.0% vs. 1.8%, p = .151; odds ratio = 0.57, 95% CI: (0.27, 1.18). AE, pulmonary AE, and mortality were not different between cohorts. TRs were similar for PRPC and CPC (8.3% vs. 9.7%, p = .256); and allergic TR were significantly less with PRPC (p = .006). PC and RBC use were not increased with PRPC.DiscussionPRPC demonstrated reduced TEAMV with no excess treatment‐related pulmonary morbidity.

P1523: DEMOGRAPHICS, CLINICAL CHARACTERISTICS, AND REAL-WORLD TREATMENT PATTERNS AMONG PATIENTS WITH BETA-THALASSEMIA: A RETROSPECTIVE MEDICAL RECORD ABSTRACTION STUDY

Background: Beta-thalassemias (BTs) are genetic disorders of hemoglobin (Hb) synthesis defined by deficient or absent synthesis of the beta-globin subunit. As a result, patients with BT experience hypochromic anemia and excess alpha-globin chain, causing ineffective erythropoiesis and low-grade hemolysis; however, patient characteristics and treatment patterns are not well understood. Aims: This retrospective medical record abstraction study evaluated patients prior to introduction of luspatercept with transfusion-dependent (TD) and non-transfusion-dependent (NTD) BT for demographics, clinical characteristics, and treatment patterns. Methods: Medical records of adults with TD or NTD BT in the United Kingdom (UK), France, Germany, Spain, and Canada with ≥5 years of visit history within the practice were evaluated. The target sample size was 50 patients in all countries (except Canada: N=20 patients), with an even distribution of patients with TD and NTD BT. Information on demographics, clinical characteristics, and treatment patterns was abstracted from the medical records. Results: In total, 118 patients with TD and 96 patients with NTD BT were identified. Among patients with TD BT, mean (standard deviation [SD]) patient age was 36.1 (11.9) years, and 28.8% were female; among patients with NTD BT, mean (SD) patient age was 36.6 (9.8) years, and 38.5% were female (Table). Table shows characteristics and results per country. Among patients with TD BT, 90/118 (76.3%) were receiving transfusions at least once every 4 weeks, with 5.1% receiving transfusions weekly, 16.1% every 2 weeks, 28.8% every 3 weeks, 26.3% every 4 weeks, 3.4% every 5 weeks, 17.8% every 6 weeks, and 2.5% other or unknown. Patients with TD BT had an average (SD) of 2.4 (0.6) units of blood transfused per session (range, 1.9 in Spain to 2.7 in UK), with an average (SD) Hb level before the transfusion of 6.9 (1.3) g/dL (range, 5.9 in Canada to 7.3 in Germany). Patients with TD BT had been on the transfusion regimen for an average of 72.6 months (range, 45.2 in Canada to 104.9 in UK) during the observation period. All patients with NTD BT had previously had ≥1 transfusion at any point in time that the physician was aware of, with an average (SD) of 2.9 (0.9) transfusions per patient (range, 2.6 in Canada to 3.1 in Germany). Among patients with NTD BT with detailed transfusion data available post-index date (N=81; 84.4%), the mean (SD) number of units of blood per transfusion was 2.2 (0.6) (range, 1.9 in Spain to 2.7 in France), and the mean (SD) Hb level before transfusion was 7.4 (1.2) g/dL (range, 6.2 in Canada to 8.2 in Spain). Iron chelation therapy was received in 70.3% of TD patients (range, 44.4% in the UK and 92.6% in Germany) and in 45.8% of NTD patients (range, 37.0% in France to 80.0% in Canada). The percentages of patients with hepatitis B, C, and D were low (ie, all <2%) for both the TD and NTD cohorts, as were the percentages of patients with cerebrovascular disease (2.5% for TD and 1.0% for NTD) and congestive heart failure (5.1% for TD and 2.1% for NTD). Image:Summary/Conclusion: Real-world data on clinical practice and outcomes in patients with BT are lacking. This study found that NTD and TD patients with BT have similarly low pre-transfusion Hb levels. A high number of patients, especially TD patients, are not treated according to the current recommendations, highlighting the importance of national reference centers to improve outcomes and quality of life in these patients.

P1630: WEARABLES IN TRANSFUSION MEDICINE: CHALLENGES AND FUTURE PERSPECTIVE

Background: The digital era has granted us new techniques like photoplethysmogram or ECG-based wearable devices, that can remotely monitor physiological parameters of patients, including heart rate and activity measures continuously. These developments yield many opportunities but also great challenges. For instance, in the Myelodysplastic syndrome (MDS), most patients will become RBC transfusion dependent during the course of their disease. It has been well established that Hb-level alone is an insufficient marker to guide in RBC transfusions. Nonetheless, we base transfusion regiments on Hb-thresholds combined with a subjective interpretations of the patient’s quality of life. This leads to great variability in transfusion strategies causing patients to often be over- or undertransfused. We therefore need objective parameters to evaluate and guide our transfusion strategies. Aims: We intend to share our practical knowledge of the encountered challenges. Methods: Following pilots with the Withings Steel HR and VitalPatch (Table 1.), we have started the REMOTE 2 trial (NTR: NL9289) and are collaborating internationally to initiate larger trials. Here we have gathered the experiences we deem important for researchers new to the field. Results: When choosing the device, first establish the desired outcomes. Is a true continuous heart rate collection necessary, or will a semi-continuous measurement suffice? Within an elderly MDS population a more manageable device with a long battery-life can help reduce data missingness. On the other hand, with only daily averages of parameters, a deeper understanding of interaction of the collected parameters is challenging. Also, product placement will impact the outcome, as wrist-worn devices are more susceptible to noise than chest-worn devices. Importantly, inter-device variability has been reported to be high. Therefore, it is strongly preferable to use one device only in a study. Many wearable biosensors are not medically validated (yet). We believe, however, this should not discourage the investigator to use such a device. Unvalidated continuous heart rate measurements have been shown to produce very accurate data. And importantly, there are currently no validated – or unvalidated – parameters to evaluate these patients. Physiological parameters are highly impacted by numerous factors like weather and daily schedules. Large sample sizes should reduce this natural variability, but trials involving MDS-patients have thus far been unable to collect more than 38 patients in one study. Combining groups, like thalassemia and myelofibrosis, will increase the sample size. However, subgroup analysis will still lack power. Therefore, international collaborations are necessary to acquire sufficient sample sizes to answer questions like: What parameters are of value to evaluate transfusion strategies? How do these parameters respond to different 1) amounts of RBCs; 2) thresholds; and 3) timing of transfusion? After answering these first questions, we can look at how these parameters change with longer-standing changes, and how deleterious the fluctuations in Hbmass are to the patient. Image:Summary/Conclusion: Depending on the research context, intervention and the desired outcomes, one should carefully choose the required device. While various devices may mork, the trade-off between ease of use and data granularity can make a substantial difference when analysing the data. For sufficient sample sizes, international collaborations are required to answer the many questions in order to improve the care of chronic transfusion dependent patients.

P1060: REAL-WORLD CLINICAL OUTCOMES AFTER 3 AND 6 MONTHS OF TREATMENT WITH FEDRATINIB FOLLOWING RUXOLITINIB FAILURE

Background: Relief of symptoms and splenomegaly is an important treatment (Tx) goal for patients with myelofibrosis (MF). Fedratinib (FEDR) and ruxolitinib (RUX) are approved in the USA for Intermediate (Int)- or High-risk (HR) primary or secondary MF. Aims: To describe spleen size, and hematologic and MF-specific symptoms, during the first 6 months of FEDR therapy after prior Tx with RUX in US clinical practices. Methods: Adults with Int- or HR MF who initiated FEDR on or after August 16, 2019 (FEDR approval date) and with ≥90 days of follow-up were identified from community oncology practices. Eligible patients were those treated with RUX and then FEDR, who had spleen palpation at FEDR initiation, and who had completed ≥1 cycle of FEDR. Treating physicians completed electronic case report forms for the selected eligible patients, extracting patient characteristics, Tx pattern data, and clinical outcomes such as spleen size, MF-related symptoms per the Myelofibrosis Symptom Assessment Form version 4.0 (MFSAF v4.0), hemoglobin (Hb), and platelet and white blood cell (WBC) counts, at each visit in the first 6 months of FEDR Tx. Data were collected from February to March 2021. Mean spleen size, symptom count, Hb, and platelet and WBC counts at FEDR initiation vs at 3 and 6 months post-FEDR were compared via paired 2-sided t-test. Percentage reduction in spleen size and proportion of transfusion-dependent patients between FEDR initiation and 3 and 6 months post-FEDR were compared via 1-sided chi-square test. Only patients assessed at FEDR initiation (with palpable spleen or complete blood count available) and with a corresponding assessment at 3 or 6 months were included in the comparative analysis. Results: Among 150 eligible patients, the mean age at FEDR initiation was 68 years (range, 36–85). Median duration of RUX Tx prior to FEDR was 7.6 months (range, 0.7–65.5). At FEDR initiation, MF risk was categorized as International Prognostic Scoring System (IPSS)/Dynamic IPSS HR in 43% of patients, Int-2 in 37%, Int-1 in 9%, and unknown in 10%. A total of 74% of patients started FEDR at the recommended dosage of 400 mg daily. Median duration of post-FEDR follow-up was 5.1 months (IQR, 3.0–17.3) for patients initiated at FEDR 400 mg daily and 4.4 months (IQR, 3.0–14.3) for those initiating at <400 mg daily. At data cutoff, 55% of patients were still on FEDR. The primary reason for FEDR discontinuation was disease progression (43%). Mean duration of FEDR Tx was 4.7 months. Of 67 patients who discontinued FEDR, 44 were deceased at data cutoff. At FEDR initiation, 88% of patients had palpable spleen; mean spleen size was 16.0 cm (standard deviation [SD] 5.8) above the costal margin, which decreased to 13.2 cm (SD 7.9) at 3 months (P=0.0001) and 7.2 cm (SD 7.4) at 6 months (P=0.012). Mean number of MF-related symptoms declined significantly at 3 and 6 months; mean platelet count increased significantly at 6 months, from 160×109/L to 186×109/L (Table). Overall, 65.2% of patients experienced spleen size reduction, 18.8% had no change, and 16.0% had an increase. Mean best percentage change in spleen size was −29.2% (median −9.8%); complete resolution of palpable spleen occurred in 21% of patients. Image:Summary/Conclusion: This study illustrates the real-world effectiveness of FEDR after RUX failure in patients with Int- or HR MF. FEDR provided significant reductions in spleen size and reported number of MF-related symptoms after 3 months of Tx, including complete spleen responses. Greater benefits were observed with longer Tx duration.

Prevalence and characteristics of inflammatory rheumatic diseases in patients with thalassemia.

Reports of inflammatory rheumatic diseases (IRD) in thalassemia are limited. This study aimed to determine the prevalence and clinical characteristics of IRD in patients with thalassemia disease. Consecutive adult patients with thalassemia disease, confirmed by hemoglobin typing, attending the Hematology Clinic between June 2019 and May 2021 were invited to join this study. All of them had their history taken and a physical examination for IRD. Those with IRD had their medical records reviewed. Sixty-three patients (transfusion-dependent in 50) were included in this study. There was α-, β-, and co-inheritance of α- and β-thalassemia in 22.22%, 73.02%, and 4.76% of the patients, respectively, with β-thalassemia/Hb E disease in 53.97%. Twenty-three patients had IRD (rheumatoid arthritis in 9, gout in 6, systemic lupus erythematosus in 3, spondyloarthropathy in 2, and one patient each with dermatomyositis, overlap syndrome, and unclassified polyarthralgia). Clinical manifestations and laboratory findings were similar to IRD patients in general. In 40 patients without IRD, direct and indirect Coombs tests and antinuclear antibody (ANA) were positive in 51.72%, 27.59%, and 10.26%, respectively. When comparing among these 40 patients, between those with non-transfusion-dependent thalassemia (n = 10) and those with transfusion-dependent thalassemia (n = 30), the latter had non-significantly more positive direct Coombs (60.87% vs. 16.67%), indirect Coombs (30.43% vs. 16.67%), and ANA tests (13.33% vs. 0%). The prevalence of IRD in patients with thalassemia disease was rather high. Positive direct Coombs test and ANA were common in transfusion-dependent patients.

Post-COVID-19 Lymphocytopenia and Opportunistic Pathogens Infection in a Thalassemia Major Patient

Transfusion-dependent thalassemia patients undergo transfusion immunomodulating effects, which result in a general immune response depression and, consequently, an increase in the frequency of infectious episodes and neoplastic events due to a reduction in phagocytic function. Altered natural killer functions and IL-2-mediated lymphocytic response, defects in antigen presentation due to monocyte–macrophage cells, and decreases in bone marrow precursors and HLA II+ cells all play key roles in immunodepression in thalassemia major. SARS-CoV-2 infection presents marked lymphopenia, occurring in 96.1% of severe cases. COVID-19-related lymphopenia is due to various mechanisms, which lead to an increase in lymphocytic apoptosis. Post-COVID-19 lymphocytic quantitative and functional disorders may compromise immune response and promote the onset of infections via opportunistic pathogens. Herein, we report a case of a thalassemia major patient who developed severe post-COVID-19 lymphocytopenia, which may have facilitated the onset of a severe Klebsiella Pneumoniae infection.

Efficacy and Tolerability of Twice-Daily Dosing Schedule of Deferasirox in Transfusion-Dependent Paediatric Beta-Thalassaemia Patients: A Randomized Controlled Study

Background: Deferasirox has proved good efficacy and acceptable safety for the management of thalassaemia patients. However, some patients are unresponsive or intolerant to once-daily administration of deferasirox even at a high dose. The current study evaluated the effectiveness and tolerability of twice-daily dosing of deferasirox among transfusion-dependent paediatric beta-thalassaemia patients. Methods: This prospective randomized single-blinded parallel study included all transfusion-dependent paediatric beta-thalassaemia patients prescribed with deferasirox, who visit the study site for their regular blood transfusions and follow-up. The enrolled patients were randomized into intervention and control groups by using a simple block randomization method. In the intervention group, the once-daily dosing of deferasirox was changed to twice-daily dosing with the same total daily dose. Whereas, in the control group, the patients continued with the once-daily deferasirox dosing. The serum ferritin levels of both groups were determined on the enrolment day and after 6 months of follow-up. Results: Forty-one patients were included for analysis. A statistically significant mean decrease in serum ferritin levels was detected in the intervention group, while the serum ferritin levels of the control group significantly increased from baseline. The twice-daily dosing of deferasirox was better tolerated by the thalassaemia patients when compared to once-daily dosing. Conclusion: This study concludes that twice-daily dosing of deferasirox with the same total daily dose significantly enhances the iron chelation efficacy and tolerability among transfusion-dependent paediatric beta-thalassaemia patients when compared to once-daily regimen.

Clodronate inhibits alloimmunization against distinct red blood cell alloantigens in mice.

Alloimmunization can be a significant barrier to red blood cell (RBC) transfusion. While alloantigen matching protocols hold promise in reducing alloantibody formation, transfusion-dependent patients can still experience RBC alloimmunization and associated complications even when matching protocols are employed. As a result, complementary strategies capable of actively preventing alloantibody formation following alloantigen exposure are warranted. We examined whether pharmacological removal of macrophages using clodronate may provide an additional strategy to actively inhibit RBC alloimmunization using two preclinical models of RBC alloimmunization. To accomplish this, mice were treated with clodronate, followed by transfusion of RBCs expressing the HOD (HEL, OVA, and Duffy) or KEL antigens. On days 5 and 14 post transfusion, anti-HOD or anti-KEL IgM and IgG antibodies were evaluated. Low dose clodronate effectively eliminated key marginal zone macrophage populations from the marginal sinus. Prior treatment with clodronate, but not empty liposomes, also significantly inhibited IgM and IgG anti-HOD alloantibody formation following transfusion of HOD RBCs. Similar exposure to clodronate inhibited IgM and IgG antibody formation following KEL RBC transfusion. Clodronate can inhibit anti-HOD and anti-KEL antibody formation following RBC transfusion in preclinical models. These results suggest that clodronate may provide an alternative approach to actively inhibit or prevent the development of alloantibodies following RBC transfusion, although future studies will certainly be needed to fully explore this possibility.

Red blood cell transfusion burden in myelodysplastic syndromes (MDS) with ring Sideroblasts (RS): A retrospective multicenter study by the Groupe Francophone des Myélodysplasies (GFM).

MDS-RS patients are characterized by chronic anemia and a low risk of Acute Myeloid Leukemia (AML) progression and they generally become Red Blood Cell (RBC) transfusion dependent (TD). We performed a retrospective "real-life" observational study of 6months in 100 MDS-RS TD patients, recruited in 12 French centers, to describe transfusion characteristics, and evaluate the frequency and causes of hospitalizations, health costs, and morbidity, associated with transfusion dependency, in a French population of RBC transfusion-dependent MDS-RS patients. 79% of the patients had high transfusion burden (HTB) and 21% low transfusion burden (LTB). HTB patients had a longer disease duration (6 vs. 3.7 years, p=0.0078), more frequent iron chelation (82% vs. 50%, p=0.0052) and higher serum ferritin (p=0.03). During the 6-month study period, 22% of the patients required inpatient hospitalization, 36% of them for symptomatic anemia requiring emergency RBC transfusion. The 6-month median transfusion costs, including the cost of the day care facility, transportation to and from the hospital, iron chelation, and lab tests, was 16,188€/patient. MDS-RS represents the archetypal type of chronically transfused lower-risk MDS. Most of those patients have a high transfusion burden and thus frequently need visits to the hospital's day care facility, and frequent hospitalizations, with an overall high median treatment cost. Those costs should be compared with costs of new treatments potentially able to avoid RBC transfusion dependence and to reduce the complications of chronic anemia in MDS-RS patients.