Transfusion-dependent Patients Research Articles

Cost-effectiveness of sutimlimab in cold agglutinin disease.

Primary cold agglutinin disease (CAD) is a rare autoimmune hemolytic anemia caused by cold-reactive antibodies that bind to red blood cells and lead to complement-mediated hemolysis. Patients with primary CAD experience the burden of increased health resource utilization and reduced quality of life. The standard-of-care (SOC) in patients with primary CAD has included cold avoidance, transfusion support, and chemoimmunotherapy. The use of sutimlimab, a humanized monoclonal antibody that selectively inhibits C1-mediated hemolysis, was shown to reduce transfusion-dependence and improve quality of life across two pivotal phase 3 studies, further supported by 2-year extension data. Using data from the transfusion-dependent patient population that led to sutimlimab's initial FDA approval, we performed the first-ever cost-effectiveness analysis in primary CAD. The projected incremental cost-effectiveness ratio (ICER) in our Markov model was $2 340 000/QALY, significantly above an upper-end conventional US willingness-to-pay threshold of $150 000/QALY. These results are consistent across scenarios of higher body weight and a pan-refractory SOC patient phenotype (i.e., treated sequentially with bendamustine-rituximab, bortezomib, ibrutinib, and eculizumab). No parameter variations in deterministic sensitivity analyses changed our conclusion. In probabilistic sensitivity analysis, SOC was favored over sutimlimab in 100% of 10 000 iterations. Exploratory threshold analyses showed that significant price reduction (>80%) or time-limited treatment (<18 months) followed by lifelong clinical remission off sutimlimab would allow sutimlimab to become cost-effective. The impact of sutimlimab on health system costs with longer term follow-up data merits future study and consideration through a distributional cost-effectiveness framework.

Serum Zinc and Copper Levels in Children with Thalassemia Major

Background: Thalassemia is a frequent hereditary genetic with different clinical manifestations from mild to severe based on its genetic. Beta thalassemia major is the worse form of this disease caused by decreased or absent beta globin chains of hemoglobin. Regular blood transfusion is the main aim leads to iron overload and deposition of iron in different organs.Objectives: To determine different serum distribution levels and correlation of copper and zinc in transfusion dependent thalassemia patients Material and Methods: This was a descriptive cross-sectional study in which a non-probability convenient sampling technique was used for sample collection. This study was conducted in KPK in a total of 137 patients, who were diagnosed cases of thalassemia major by hemoglobin electrophoresis, enzyme linked immunosorbent assay (ELISA) method and receiving iron and folate therapy. SPSS version 22 was used and Pearson's correlation coefficient was applied. P-value 0.05 was considered significant.Results: In this study mean age was 6.7±3.49 years. 77 (56%) percent children were male while 64 (44%) children were female. Mean hemoglobin (Hb) level was 7.43±1.3 gm/dl. Mean SGPT score was 26.28 ± 7.51. Mean blood urea was 21.10 ± 8.49 mmol/l while mean serum creatinine level was 0.56 ± 0.26 mg/dl. Mean serum zinc level was 13.36 ± 11.12mg/dl while mean serum copper level was 1.21± 0.60 mg/dl and mean serum ferritin level was 6682 ± 533 Ug/l.Conclusion: This study showed hypozincemia in thalassemia major patients, but copper deficit was not present. There was no substantial variance between serum ferritin level and mean serum concentration of zinc and copper in this study. Ancillary assessments in this respect is recommended. Keywords: Copper, Thalassemia, Zinc

Gene expression patterns of Sirtuin family members (SIRT1 TO SIRT7): Insights into pathogenesis and prognostic of Myelodysplastic neoplasm

To assess and validate the gene expression profile of SIRTs (SIRT1, SIRT2, SIRT3, SIRT4, SIRT5, SIRT6, and SIRT7) in relation to the pathogenesis and prognostic progression of Myelodysplastic neoplasm (MDS). Eighty bone marrow samples of patients with de novo MDS were diagnosed according to WHO 2022 and IPSS-R criteria. Ten bone marrow samples were obtained from elderly healthy volunteers and used as control samples. Gene expression levels of all SIRTs were assessed using RT-qPCR assays. Downregulation of SIRT2 (p = 0.009), SIRT3 (p = 0.048), SIRT4 (p = 0.049), SIRT5 (p = 0.046), SIRT6 (p = 0.043), and SIRT7 (p = 0.047) was identified in MDS patients compared to control individuals. Also, we identified that while SIRT2-7 genes are typically down-regulated in MDS patients compared to normal controls, there are relative expression variations among MDS patient subgroups. Specifically, SIRT4 (p = 0.029) showed increased expression in patients aged 60 or above, and both SIRT2 (p = 0.016) and SIRT3 (p = 0.036) were upregulated in patients with hemoglobin levels below 8 g/dL. SIRT2 (p = 0.045) and SIRT3 (p = 0.033) were highly expressed in patients with chromosomal abnormalities. Different SIRTs exhibited altered expression patterns concerning specific MDS clinical and prognostic characteristics. The downregulation in SIRTs genes (e.g., SIRT2 to SIRT7) expression in Brazilian MDS patients highlights their role in the disease's development. The upregulation of SIRT2 and SIRT3 in severe anemia patients suggests a potential link to manage iron overload-related complications in transfusion-dependent patients. Moreover, the association of SIRT2/SIRT3 with genomic instability and their role in MDS progression signify promising areas for future research and therapeutic targets. These findings underscore the importance of SIRT family in understanding and addressing MDS, offering novel clinical, prognostic, and therapeutic insights for patients with this condition.

Frequency and potential risk factors of polyneuropathy in transfusion-dependent Β-thalassemia major patients: a cross-sectional study

BackgroundNeurological complications, including peripheral polyneuropathy, have been reported in β-thalassemia patients that negatively impact their quality of life. Chronic hypoxia, iron overload, average age, and iron chelators-induced neurotoxicity might contribute to the development of neuropathy. However, the leading offender of this complication remains not clear. We aimed to study the frequency and potential risk factors of polyneuropathy in β-thalassemia patients. We performed a cross-section study on 150 transfusion-dependent β-thalassemia major patients with a mean age of 16.44 ± 3.32 years. We performed electrophysiological studies for motor and sensory nerves.ResultsWe found that 31.3% of cases had neurological manifestations with significant relation to age, duration of the disease, and frequent transfusion. Out of 47 patients with neurological manifestations, 12 (25.5%) had abnormal nerve conduction velocity (NCV). Abnormal median, peroneal, and tibial nerve motor amplitudes were detected in 10.6%, 10.6%, and 14.9% of patients respectively. Abnormal median, peroneal, and sural nerve sensory amplitudes were detected in 4.3%, 2.2%, and 10.6% of patients respectively. Apart from a significant relation between abnormal NCV and older ages, no significant relation was detected with other studied clinical and laboratory parameters.ConclusionWe detected a high frequency of motor and sensory polyneuropathy in B-thalassemia patients. Polyneuropathy was predominately detected in older ages highlighting that neuropathy in thalassemia patients is probably age-dependent. Other factors including disease duration, transfusion frequency, and iron overload might have a contributing effect, however, that could not be confirmed in this study. Further studies are needed to verify the frequency and predictors of polyneuropathy in B-thalassemia patients.

Hearing loss in beta-thalassaemia: An Italian multicentre case-control study.

Despite numerous studies, the true scenario of hearing loss in beta-thalassaemia remains rather nebulous. Pure tone audiometry, chelation therapy, demographics and laboratory data of 376 patients (mean age 38.5 ± 16.6 years, 204 females, 66 non-transfusion-dependent) and 139 healthy controls (mean age 37.6 ± 17.7 years, 81 females) were collected. Patient and control groups did not differ for age (p = 0.59) or sex (p = 0.44). Hypoacusis rate was higher in patients (26.6% vs. 7.2%; p < 0.00001), correlated with male sex (32.6% in males vs. 21.8% in females; p = 0.01) and it was sensorineural in 79/100. Hypoacusis rate correlated with increasing age (p = 0.0006) but not with phenotype (13/66 non-transfusion-dependent vs. 87/310 transfusion-dependent patients; p = 0.16). Sensorineural-notch prevalence rate did not differ between patients (11.4%) and controls (12.2%); it correlated with age (p = 0.01) but not with patients' sex or phenotype. Among adult patients without chelation therapy, the sensorineural hypoacusis rate was non-significantly lower compared to chelation-treated patients while it was significantly higher compared to controls (p = 0.003). Sensorineural hypoacusis rate is high in beta-thalassaemia (about 21%) and it increases with age and in males while disease severity or chelation treatment seems to be less relevant. The meaning of sensorineural-notch in beta-thalassaemia appears questionable.

Magnitude of Bone Disease in Transfusion-Dependent and Non-Transfusion-Dependent β-Thalassemia Patients.

Introduction β-Thalassemia is a common inherited disease in the northern part of Iraq. A considerable number of transfusion-dependent (TDT) and non-transfusion-dependent (NTDT) β-thalassemia patients suffer bone problems. The objective of this study was to evaluate the degree of bone disease in the TDT and NTDT patients using a dual-energy X-ray absorptiometry (DEXA) scan. Patients and methods In this study, 53 TDT and 20 NTDT patients aged ≥10 years were enrolled. Their bone status was assessed using the DEXA scan at the lumbar spine (L1-L4) and femoral neck. The effect of physical, biochemical, and hormonal characteristics on the bone mineral density (BMD) parameters was evaluated. The value of the BMD Z-score was the measureto decideonthemagnitude of bone disease. Results and discussion The mean age of the enrolled patients was 24.1 years. The BMD Z-score values were significantly lower among the TDT patients at the lumbar spine and femoral neck (BMD Z-score: -2.05 and -1.51 versus -2.29 and -0.71; p=0.044 and 0.009, respectively). The proportion of osteoporosis at the lumbar spine was significantly higher in the TDT group than in the NTDT group (69.8% versus 40%; p <0.001).The BMD Z-score correlated significantly with patient BMI and parathyroid hormone (PTH) level in both the TDT and NTDT groups. No correlation was found withage, hemoglobin (Hb), and serum levels of calcium, vitamin D, ferritin, phosphorus, and alkaline phosphatase (ALP). Conclusions Impaired bone density was encountered at high proportions in our thalassemia patients. TDT patients suffered more severe bone disease thanNTDT patients.

Treatment of refractory/relapsed Diamond-Blackfan anaemia with eltrombopag.

Diamond-Blackfan anaemia (DBA) is a rare, inherited bone marrow failure syndrome with a ribosomal defect causing slowed globin chain production with normal haem synthesis, causing an overabundance of reactive iron/haem and erythroid-specific cellular toxicity. Eltrombopag, a non-peptide thrombopoietin receptor agonist, is a potent intracellular iron chelator and induced a robust durable response in an RPS19-mutated DBA patient on another trial. We hypothesized eltrombopag would improve RBC production in DBA patients. We conducted a single-centre, single-arm pilot study (NCT04269889) assessing safety and erythroid response of 6 months of daily, fixed-dose eltrombopag for DBA patients. Fifteen transfusion-dependent (every 3-5 weeks) patients (median age 18 [range 2-56]) were treated. One responder had sustained haemoglobin improvement and >50% reduction in RBC transfusion frequency. Of note, 7/15 (41%) patients required dose reductions or sustained discontinuation of eltrombopag due to asymptomatic thrombocytosis. Despite the low response rate, eltrombopag has now improved erythropoiesis in several patients with DBA with a favourable safety profile. Dosing restrictions due to thrombocytosis may cause insufficient iron chelation to decrease haem production and improve anaemia in most patients. Future work will focus on erythropoiesis dynamics in patients and use of haem synthesis inhibitors without an impact on other haematopoietic lineages.

Switching from Deferasirox Dispersible Tablets to Deferasirox Film-Coated Tablets: Is There an Effect on Ferritin Levels in Children and Adolescents with Transfusion-Dependent Anemia?

To investigate the effect of switching from deferasirox dispersible tablet (DT) to deferasirox film-coated tablet (FCT) on serum ferritin (SF) levels in transfusion-dependent patients. Patients who received regular erythrocyte transfusion and whose treatment was switched from DT to FCT were included in the study. FCT start date was taken as the index date. Patients were followed over 2 equal and long periods, both before and after index date. Thirty-two patients were included, and the comparison periods ranged from 4 to 12 months. The SF values increased from a median of 1723 ng/mL (range 717-5369 ng/mL) to 1.853 ng/mL (range 924-5478 ng/mL) after switching from DT to FCT (P = .036). While there was a significant increase in median SF after switching in Turkish patients (1467 ng/mL to 1778 ng/ mL, P = .010) and patients ≥12 years (1598-1848 ng/mL, P = .009), there was an insignificant (P = .859) decrease in SF in immigrant children. Considering only the post-switch period, there was a non-significant increase in median SF in the entire cohort, while SF decreased significantly in immigrant children (P = .026). No serious side effects were observed in any patient that would cause discontinuation of treatment. Overall, higher SF value was observed with FCT compared to DT in short term. There were different results between patient groups. Our results suggest that FCT is more effective than DT in patients with high basal ferritin and who are actually incompatible with treatment and should be preferred first in these patients.

Imetelstat: Finally a disease-modifying treatment for lower-risk myelodysplastic syndromes?

Favorable results were achieved in a phase 3 clinical trial (IMerge) with the telomerase inhibitor imetelstat in transfusion-dependent patients with lower-risk myelodysplastic syndromes (MDSs) who relapsed or were refractory to erythropoiesis-stimulating agents.1 Imetelstat is likely to become a useful addition to our limited therapeutic options for patients with MDS.

Impact of COVID-19 on patients with beta-thalassemia major: an observational study.

The prevalence of COVID-19 is slightly lower, and its mortality is higher in beta-thalassemia patients than in the general population. We evaluated the impact of COVID-19 in terms of incidence, clinical course, management, and specific antibody response to vaccination in a cohort of patients with beta-thalassemiamajor. We retrospectively enrolled all transfusion-dependent beta-thalassemia major patients attending the Thalassemia Day Care Center of the University Hospital of Sassari, Italy, from March 1, 2020, to May 31, 2021. For each patient, demographic, clinical, laboratory, instrumental, and therapy data were collected. Patients aged ≥16 years received two doses of mRNA COVID-19 vaccine. Anti-SARS-CoV-2 serum antibodies were tested before and after the first vaccine dose. A total of 68 patients (median age: 36.5 years; IQR: 13-42 years) were included. Nasopharyngeal swab (NPS) for SARS-CoV-2 detection by RT-PCR was positive in 5 (7.35%) of 68 patients (4 symptomatic). No COVID-19-related complications, hospitalizations, or deaths were observed. The transfusion regimen and iron chelation therapy were not significantly changed. Prior to COVID-19 vaccination, anti-SARS-CoV-2 antibodies were tested in 61 patients, 51 negative and 10 positive; five of the latter were also positive for SARS-CoV-2 on NPS. The 46 vaccinated subjects had an antibody response, with higher levels in subjects previously infected with SARS-CoV-2. Our findings suggest that patients with beta-thalassemia major are not at a higher risk of contracting SARS-CoV-2 infection and developing a severe form of COVID-19 despite being considered more vulnerable than the general population.

Analysis of Hepcidin and Interleukin-6 Levels among Transfusion-Dependent Thalassemia Patients With and Without Alloimmunization/Autoimmunization

Analysis of Hepcidin and Interleukin-6 Levels among Transfusion-Dependent Thalassemia Patients With and Without Alloimmunization/Autoimmunization

A Cross-Sectional, Multicentric, Disease-Specific, Health-Related Quality of Life Study in Greek Transfusion Dependent Thalassemia Patients.

The assessment of health-related quality of life (HRQoL) in thalassemia offers a holistic approach to the disease and facilitates better communication between physicians and patients. This study aimed to evaluate the HRQoL of transfusion-dependent thalassemia (TDT) patients in Greece. This was a multicentric, cross-sectional study conducted in 2017 involving 283 adult TDT patients. All participants completed a set of two QoL questionnaires, the generic SF-36v2 and the disease-specific TranQol. Demographic and clinical characteristics were used to predefine patient subgroups. Significant factors identified in the univariate analysis were entered into a multivariate analysis to assess their effect on HRQoL. The SF-36 scores of TDT patients were consistently lower compared to the general population in Greece. The mean summary score of TranQol was relatively high (71 ± 14%), exceeding levels observed in national surveys in other countries. Employment emerged as the most significant independent factor associated with better HRQoL, whereas age had the most significant negative effect. This study represents the first comprehensive QoL assessment of a representative sample of the TDT population in Greece. The implementation of TranQol allowed for the quantification of HRQoL in Greece, establishing a baseline for future follow-up, and identifying more vulnerable patient subgroups.

Cardiac effects of deferasirox in transfusion-dependent patients with myelodysplastic syndromes: TELESTO study.

Iron overload from repeated transfusions has a negative impact on cardiac function, and iron chelation therapy may help prevent cardiac dysfunction in transfusion-dependent patients with myelodysplastic syndromes (MDS). TELESTO (NCT00940602) was a prospective, placebo-controlled, randomised study to evaluate the iron chelator deferasirox in patients with low- or intermediate-1-risk MDS and iron overload. Echocardiographic parameters were collected at screening and during treatment. Patients receiving deferasirox experienced a significant decrease in the composite risk of hospitalisation for congestive heart failure (CHF) or worsening of cardiac function (HR = 0.23; 95% CI: 0.05, 0.99; nominal p = 0.0322) versus placebo. No significant differences between the arms were found in left ventricular ejection fraction, ventricular diameter and mass or pulmonary artery pressure. The absolute number of events was low, but the enrolled patients were younger than average for patients with MDS, with no serious cardiac comorbidities and a modest cardiovascular risk profile. These results support the effectiveness of deferasirox in preventing cardiac damage caused by iron overload in this patient population. Identification of patients developing CHF is challenging due to the lack of distinctive echocardiographic features. The treatment of iron overload may be important to prevent cardiac dysfunction in these patients, even those with moderate CHF risk.

Awareness and practices regarding thalassemia among parents of transfusion dependent beta thalassemia patients registered with Hamza Foundation Peshawar, Pakistan

Thalassemia, a pervasive and chronic condition that impacts an estimated 200 million people worldwide, is predominantly caused by the beta-thalassemia gene, which is found in approximately 3% of the global population. The purpose of this research, which was carried out from June to December 2022 at the Haemophilia Hospital of the Hamza Foundation Welfare Thalassemia, was to evaluate the knowledge and behaviours of guardians of transfusion-dependent beta-thalassemia patients who were registered with the foundation. The findings of the research, which utilised non-probability convenience sampling to select 150 parents, indicated that 38.7% of the parents surveyed were cognisant of thalassemia, whereas permanent treatment was conspicuously unknown to them. Furthermore, it is noteworthy that a substantial proportion (94%) of parents readily shared food, underscoring the criticality of implementing educational and awareness campaigns targeting not only parents but the broader populace in order to rectify the lack of understanding regarding thalassemia. The fact that genetic counselling was availed of by a minuscule proportion (13.3%) of parents underscores a possible avenue for enhancement in comprehensive care approaches.

Assessment of Serum Ferritin Levels in Transfusion Dependent Thalassaemic Patients at Rajasthan Southern Region

Assessment of Serum Ferritin Levels in Transfusion Dependent Thalassaemic Patients at Rajasthan Southern Region

Health-related quality of life with standard and curative therapies in thalassemia: A narrative literature review.

Health-related quality of life (HRQOL) is a patient-reported outcome that assesses the impact of a disease or illness on different domains of a patient's life. Different general and disease-specific measures can be used to evaluate HRQOL. This article aimed to summarize the evidence for HRQOL among patients with transfusion-dependent (TDT) and non-transfusion-dependent thalassemia (NTDT). We included HRQOL data related to standard therapy with blood transfusions, iron chelation, and/or luspatercept in TDT and NTDT, as well as curative therapies for TDT, including hematopoietic stem cell transplant (HSCT) and gene therapy. Patients with thalassemia had worse HRQOL scores compared to the general population, and chronic pain was seen to increase in frequency and severity over time with age. NTDT patients reported worse physical health and functioning, mental health, general health, and vitality than TDT patients. However, TDT patients reported worse pain, change in health, and social support than NTDT. Most therapies improved overall HRQOL among thalassemia patients. Deferasirox, an oral iron chelator, was associated with more HRQOL benefits compared to deferoxamine, an intravenous iron chelator. Luspatercept showed clinically meaningful improvement in physical functioning among TDT and NTDT. Furthermore, HSCT and gene therapy were associated with better physical, emotional, and mental domains scores.

Audiologic and vestibular assessment in children and adolescents with transfusion dependent beta thalassemia major: The era of deferasirox film coated tablet

BackgroundHearing impairment has frequently been described in β-thalassemia patients with a significant impact on the patients’ quality of life. Most studies provided evidence of deferoxamine (DFO) dose-related ototoxicity, however, the data is scarce regarding deferasirox (DFX) as a sole iron chelator. AimWe aimed to assess the prevalence and risk factors of sensorineural hearing loss (SNHL) and vestibular dysfunction in regularly transfused β-thalassemia patients who had been treated with DFX film coated tablets. MethodsWe conducted a case control study on 57 transfusion dependent β-thalassemia patients with a mean age of 15.3 years who received DFX FCT as monotherapy for at least one consecutive year, and 57 healthy age and sex-matching controls. Comprehensive audiological evaluations using pure tone audiometry (PTA) and transient evoked otoacoustic emission (TEOAE) as well as vestibular evaluation using Video-nystagmography (VNG) were done. ResultsSNHL was identified in 12 patients (21.1 %) using PTA and a statistically significant difference was detected between controls and patients at 6 KHz and 12 KHz frequencies. A higher incidence of SNHL was detected using TEOAE, 22 patients (43.1 %) failed to pass TEOAE, with a statistically significant decrease in the signal at frequencies 1, 4 KHz bilaterally and at frequencies 1.5, 2 KHz in the right ear compared to controls. Canal paresis was detected in 21 (36.8 %) of thalassemic children using bithermal caloric test with significantly more unilateral weakness than control children (P = 0.008). We found no significant correlation between audio-vestibular dysfunction and age, sex, serum ferritin, frequency of blood transfusion and dose of DFX FCT in thalassemic children. ConclusionWe conclude that the incidence of SNHL and vestibular dysfunction was high among transfusion dependent β-thalassemia patients. Therefore, we recommend performing pre-treatment baseline audio-vestibular assessment and yearly audio-vestibular monitoring to early detect high risk patients and initiate timely management to prevent permanent damage.

First Report of Filipino β0-Thalassemia/β-Thalassemia in a Chinese Family

A pregnant woman living in Fujian Province, southeastern China, presented due to a risk of having a baby with β-thalassemia major, during her second pregnancy, since she and her husband were suspected as β-thalassemia carriers and their affected daughter was a transfusion-dependent patient. Using the common α-thalassemia and β-thalassemia genotypes test, the pregnant woman was diagnosed as a β-thalassemia carrier with βIVS−2 − 654 (C→T)/βN genotype and her daughter had a homozygosity for IVS − 2 − 654 (C→T) mutation, however, no abnormalities were detected in her husband. SMRT identified a Filipino β0-deletion in her husband, and MLPA also revealed an unknown deletion in the HBB gene. Electrophoresis showed approximately 350 bp of the PCR product, and the β-Filipino genotype presented novel fracture fragments ranging from 5,112,884 to 5,231,358 bp, and lacked a 118,475 bp fragment relative to the wild-type sequence. The daughter was therefore diagnosed with the βIVS−2 − 654 (C→T)/βFilipino genotype. Prenatal diagnosis with umbilical cord blood at 27th week of gestation showed heteroztgosity for IVS − 2 − 654 (C→T) mutation in the fetus and continued pregnancy was recommended. In conclusion, we identified the Filipino β0-deletion in a Chinese family, from Fujian area, for the first time, during prenatal screening.

Longitudinal prospective comparison of pancreatic iron by magnetic resonance in thalassemia patients transfusion-dependent since early childhood treated with combination deferiprone-desferrioxamine vs deferiprone or deferasirox monotherapy.

In transfusion-dependent thalassemia patients who started regular transfusions in early childhood, we prospectively and longitudinally evaluated the efficacy on pancreatic iron of a combined deferiprone (DFP) + desferrioxamine (DFO) regimen versus either oral iron chelator as monotherapy over a follow-up of 18 months. We selected patients consecutively enrolled in the Extension-Myocardial Iron Overload in Thalassemia network who received a combined regimen of DFO+DFP (No.=28) or DFP (No.=61) or deferasirox (DFX) (No.=159) monotherapy between the two magnetic resonance imaging scans. Pancreatic iron overload was quantified by the T2* technique. At baseline no patient in the combined treatment group had a normal global pancreas T2* (≥26 ms). At follow-up the percentage of patients who maintained a normal pancreas T2* was comparable between the DFP and DFX groups (57.1 vs 70%; p=0.517).Among the patients with pancreatic iron overload at baseline, global pancreatic T2* values were significantly lower in the combined DFO+DFP group than in the DFP or DFX groups. Since changes in global pancreas T2* values were negatively correlated with baseline pancreas T2* values, the percent changes in global pancreas T2* values, normalized for the baseline values, were considered. The percent changes in global pancreas T2* values were significantly higher in the combined DFO+DFP group than in either the DFP (p=0.036) or DFX (p=0.030) groups. In transfusion-dependent patients who started regular transfusions in early childhood, combined DFP+DFO was significantly more effective in reducing pancreatic iron than was either DFP or DFX.

Incidence of blast phase in myelofibrosis patients according to anemia severity at ruxolitinib start and during therapy.

Anemia is frequently present in patients with myelofibrosis (MF), and it may be exacerbated by treatment with the JAK2-inhibitor ruxolitinib (RUX). Recently, a relevant blast phase (BP) incidence has been reported in anemic MF patients unexposed to RUX. The authors investigated the incidence of BP in 886 RUX-treated MF patients, included in the "RUX-MF" retrospective study. The BP incidence rate ratio (IRR) was 3.74 per 100 patient-years (3.74 %p-y). At therapy start, Common Terminology Criteria for Adverse Events grade 3-4 anemia (hemoglobin [Hb] <8g/dL) and severe sex/severity-adjusted anemia (Hb <8/<9g/dL in women/men) were present in 22.5% and 25% patients, respectively. IRR of BP was 2.34 in patients with no baseline anemia and reached respectively 4.22, 4.89, and 4.93 %p-y in patients with grade 1, 2, and 3-4 anemia. Considering the sex/severity-adjusted Hb thresholds, IRR of BP was 2.85, 4.97, and 4.89 %p-y in patients with mild/no anemia, moderate, and severe anemia. Transfusion-dependent patients had the highest IRR (5.03 %p-y). Progression-free survival at 5years was 70%, 52%, 43%, and 27% in patients with no, grade 1, 2, and 3-4 anemia, respectively (p<.001). At 6months, 260 of 289 patients with no baseline anemia were receiving ruxolitinib, and 9.2% had developed a grade 3-4 anemia. By 6-month landmark analysis, BP-free survival was significantly worse in patients acquiring grade 3-4 anemia (69.3% vs. 88.1% at 5years, p<.001). This study highlights that anemia correlates with an increased risk of evolution into BP, both when present at baseline and when acquired during RUX monotherapy. Innovative anemia therapies and disease-modifying agents are warranted in these patients.