Phase 3 randomized COMMODORE 2 trial: Crovalimab versus eculizumab in patients with paroxysmal nocturnal hemoglobinuria naive to complement inhibition.

Crovalimab is a novel C5 complement inhibitor that enables rapid and sustained C5 inhibition with subcutaneous, low-volume self-administration every 4 weeks. COMMODORE 2 (NCT04434092) is a global, randomized, open-label, multicenter, phase 3 trial evaluating the non-inferiority of crovalimab versus eculizumab in patients with paroxysmal nocturnal hemoglobinuria not previously treated with C5 inhibition. C5 inhibitor-naive patients with lactate dehydrogenase (LDH) ≥2 × upper limit of normal (ULN) were randomized 2:1 to crovalimab or eculizumab. Co-primary efficacy endpoints were proportion of patients with hemolysis control (centrally assessed LDH ≤1.5 × ULN) and proportion with transfusion avoidance. Secondary efficacy endpoints were proportions of patients with breakthrough hemolysis, stabilized hemoglobin, and change in FACIT-Fatigue score. The primary treatment period was 24 weeks. Two hundred and four patients were randomized (135 crovalimab; 69 eculizumab). Crovalimab was non-inferior to eculizumab in the co-primary endpoints of hemolysis control (79.3% vs. 79.0%; odds ratio, 1.0 [95% CI, 0.6, 1.8]) and transfusion avoidance (65.7% vs. 68.1%; weighted difference, -2.8 [-15.7, 11.1]), and in the secondary efficacy endpoints of breakthrough hemolysis (10.4% vs. 14.5%; weighted difference, -3.9 [-14.8, 5.3]) and hemoglobin stabilization (63.4% vs. 60.9%; weighted difference, 2.2 [-11.4, 16.3]). A clinically meaningful improvement in FACIT-Fatigue score occurred in both arms. Complete terminal complement activity inhibition was generally maintained with crovalimab. The safety profiles of crovalimab and eculizumab were similar with no meningococcal infections. Most patients who switched from eculizumab to crovalimab after the primary treatment period preferred crovalimab. These data demonstrate the positive benefit-risk profile of crovalimab.

Prevalence and clinical outcomes of germline variants among patients with myeloid neoplasms.

AIMS: Myeloid neoplasms (MNs) with germline predisposition have been recognised as a distinct entity. Emerging evidence suggests that sporadic myelodysplastic syndromes may also harbour undetected germline predispositions. We investigated germline alterations in a cohort of 122 adult Thai MNs. METHODS: MN patients were recruited and tested for germline variants using deep targeted next-generation sequencing. The germline variant was filtered using American College of Medical Genetics classifications and then evaluated for the association with clinical characteristics and outcomes. RESULTS: Our findings revealed pathogenic/likely pathogenic germline alterations in 12 (10%) of the patients. These germline lesions were commonly found in the DNA damage response pathway (n=6, 50%). We also identified novel deleterious FANCA A1219GfsTer59 variants in two patients diagnosed with secondary acute myeloid leukaemia (sAML) from aplastic anaemia and AML with myelodysplasia related. Among sAML, individuals with germline mutations had inferior overall survival compared with those with wild-type alleles (2 months vs 12 months) with HR 4.7 (95% CI 1.0 to 20), p=0.037. Therefore, the presence of pathogenic or likely pathogenic mutations may be linked to inferior survival outcomes. CONCLUSIONS: Our study highlighted that the prevalence of germline predisposition in Southeast Asian populations is comparable to that in Caucasians. This underscores the importance of germline genetic testing within the Asian population.

Thrombosis and Bleeding Risk Scores Are Strongly Associated with Mortality in Hospitalized Patients with COVID-19: A Multicenter Cohort Study.

Background: Internationally established guidelines mention pharmacological prophylaxis for all hospitalized COVID-19 patients. However, there are concerns regarding the efficacy and safety of anticoagulants. This study investigated the associations between thrombosis/bleeding risk scores and clinical outcomes. Methods: We conducted a retrospective review of adult patients admitted to two hospitals between 2021 and 2022. We analyzed clinical data, laboratory results, low molecular weight heparin (LMWH) use, thrombosis, bleeding, and 30-day survival. Results: Of the 160 patients, 69.4% were female, and the median age was 59 years. The rates of thrombotic complications and mortality were 12.5% and 36.3%, respectively. LMWH prophylaxis was administered to 73 of the patients (45.6%). The patients with high Padua prediction scores (PPS) and high IMPROVEVTE scores had a significantly higher risk of venous thromboembolism (VTE) compared to those with low scores (30.8% vs. 9.0%, p = 0.006 and 25.6% vs. 7.7%, p = 0.006). Similarly, elevated IMPROVEVTE and IMPROVEBRS scores were associated with increased mortality (hazard ratios of 7.49 and 6.27, respectively; p < 0.001). Interestingly, LMWH use was not associated with a decreased incidence of VTE when stratified by risk groups. Conclusions: this study suggests that COVID-19 patients with high thrombosis and bleeding risk scores have a higher mortality rate.

Genetic variations of type 2 and type 3 von Willebrand diseases in Thailand.

AIMS: Von Willebrand disease (VWD) is an inherited haemostatic disorder with a wide range of bleeding phenotypes based on von Willebrand factor (VWF) levels. Multiple assays including VWF gene analysis are employed to correctly diagnose VWD and its subtypes. However, data on VWF mutations among Southeast Asian populations are lacking. We, therefore, aimed to explore genetic variations in Thai patients with type 2 and type 3 VWD by whole exome sequencing (WES). METHODS: In this multicentre study, Thai patients with type 2 and type 3 VWD, according to the definitions and VWF levels recommended by the international guidelines, were recruited. WES was performed using DNA extracted from peripheral blood in all cases. The novel variants were verified by Sanger sequencing. RESULTS: Fifteen patients (73% females; median age at diagnosis 3.0 years) with type 2 (n=12) and type 3 VWD (n=3) from 14 families were enrolled. All patients harboured at least one VWF variant. Six missense (p.Arg1374Cys, p.Arg1374His, p.Arg1399Cys, p.Arg1597Trp, p.Ser1613Pro, p.Pro1648Arg) and one splice-site (c.3379+1G>A) variants in the VWF gene were formerly described. Notably, six VWF variants, including three missense (p.Met814Ile, p.Trp856Cys, p.Pro2032Leu), one deletion (c.2251delG) and two splice-site (c.7729+4A>C, c.8115+2delT) mutations were novelly identified. Compound heterozygosity contributed to type 2 and type 3 VWD phenotypes in two and one patients, respectively. CONCLUSIONS: Type 2 and type 3 VWD in Thailand demonstrate the mutational variations among VWF exons/introns with several unique variants. The WES-based approach potentially provides helpful information to verify VWD diagnosis and facilitate genetic counselling in clinical practice.

National strategic advocacy to manage patients with inherited bleeding disorders in low and lower-middle income countries.

INTRODUCTION: Inherited bleeding disorders (IBDs) including hemophilia, von Willebrand disease, platelet disorders, mucocutaneous bleeding disorders and coagulation factor deficiencies are rarely found and under-recognized in low and lower-middle-income countries. Some patients succumbed to serious bleeding without diagnosis and treatment during childhood. AREA COVERED: Diagnosis, management, and prevention should be integrated into the existing health care system. Although some countries have not implemented appropriate health care infrastructure, an initiative plan should be set up by cooperation of experienced experts and health care providers. Identification of patients with IBDs should be started in the antenatal setting to search for females at risk of carrier state. The investigations include bleeding assessment, mixing venous clotting time, coagulogram, coagulation factor assay and mutation detection. Genotypic analysis is helpful for confirming the definite diagnosis, carrier detection as well as prenatal diagnosis for females at risk of bearing an offspring with severe bleeding manifestations. Management involves replacement therapy ranging from blood component to virus-inactivated factor concentrate. Appropriate research is an essential backbone for improving patients' care. EXPERT OPINION: Effective national strategic advocacy to manage patients with IBDs requires intensive collaboration among policy makers, health care providers, patients, and family members.

Clinical characteristics and symptom burden of Thai myeloproliferative neoplasm patients.

ABSTRACTObjective Patients living with myeloproliferative neoplasms (MPNs) suffer from symptom burden that affect quality of life. Due to the differences in cultures, climates, and genetic background, we aimed to investigate the symptom burden of Thai MPN patients Methods A comprehensive survey using the MPN-10 questionnaire was carried out between September 1, 2014, and September 30, 2017. The scores obtained were then correlated with clinical outcomes.. Results A total of 145 patients were enrolled. Nearly 90% of patients reported being symptomatic. The mean MPN-10 score was 13.6 (SD = 11). The mean MPN-10 score was highest in PMF, whereas the mean score and intensity of individual items were surprisingly low in ET and PV. Notably, the mean MPN-10 score was significantly higher in patients with documented splenomegaly compared to those with a normal-sized spleen. However, there were no correlations between MPN-10 scores and the mutation status, disease complications such as thrombosis and hemorrhage, progression to myelofibrosis or leukemia, and mortality. Patients who needed regular transfusions reported a higher MPN-10 score compared to those who did not. Conclusion The MPN-10 score did not predict survival outcomes among Thai MPN patients. Higher MPN-10 was associated with more transfusion. Thai MPN patients reported lower MPN-10 compared to western population especially PV and ET.

How do we translate gaps and unmet needs of blood management for thalassemia into a collaborative implementation framework?

BACKGROUND AND OBJECTIVE: The mainstay of management for thalassemia is regular blood transfusions. However, gaps and unmet needs of blood services for thalassemia are still not clearly identified and addressed in Thailand, a country prevalent with thalassemia. What can be a collaborative implementation framework that helps advance practices and policies relating to blood management for thalassemia? METHODS: The first Blood & Beyond Roundtable Discussion was held in July 2022 to gather the current situation, gaps, and unmet needs of blood services for thalassemia from multidisciplinary experts and thalassemic patients. The Implementation Guide as suggested by the Centre for Effective Services was applied as a tool to consolidate information from the discussions and construct the collaborative implementation framework. RESULTS: The National Blood Center and hospitals in Thailand followed the missions specified in the National Blood Policy and the standard guidelines to ensure the best practice of blood management for thalassemia. However, there were six gaps and unmet needs identified from the discussions. After all discussion points were mapped onto the framework, an implementation plan comprised of five specific activities became clear and actionable. CONCLUSION: Without the complete information from both experts and patients, the implementation plan would not have been successfully constructed. The method that we employed to translate all information into the framework can be adapted by other countries to develop their own specific framework efficiently.

Management of classical Philadelphia chromosome-negative myeloproliferative neoplasms in Asia: consensus of the Asian Myeloid Working Group.

Myeloproliferative neoplasms (MPN) are a heterogeneous group of clonal hematopoietic stem cell disorders characterized clinically by the proliferation of one or more hematopoietic lineage(s). The classical Philadelphia-chromosome (Ph)-negative MPNs include polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF). The Asian Myeloid Working Group (AMWG) comprises representatives from fifteen Asian centers experienced in the management of MPN. This consensus from the AMWG aims to review the current evidence in the risk stratification and treatment of Ph-negative MPN, to identify management gaps for future improvement, and to offer pragmatic approaches for treatment commensurate with different levels of resources, drug availabilities and reimbursement policies in its constituent regions. The management of MPN should be patient-specific and based on accurate diagnostic and prognostic tools. In patients with PV, ET and early/prefibrotic PMF, symptoms and risk stratification will guide the need for early cytoreduction. In younger patients requiring cytoreduction and in those experiencing resistance or intolerance to hydroxyurea, recombinant interferon-α preparations (pegylated interferon-α 2A or ropeginterferon-α 2b) should be considered. In myelofibrosis, continuous risk assessment and symptom burden assessment are essential in guiding treatment selection. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) in MF should always be based on accurate risk stratification for disease-risk and post-HSCT outcome. Management of classical Ph-negative MPN entails accurate diagnosis, cytogenetic and molecular evaluation, risk stratification, and treatment strategies that are outcome-oriented (curative, disease modification, improvement of quality-of-life).

Good prognosis of adult hemophagocytic lymphohistiocytosis associated with the germline HAVCR2 mutation.

Hemophagocytic lymphohistiocytosis (HLH) in adults may be idiopathic or secondary to various conditions. Recent studies identified germline hepatitis A virus-cellular receptor 2 (HAVCR2) mutations in subcutaneous panniculitis-like T-cell lymphoma (SPTCL) with HLH. The roles of this mutation in HLH, especially in idiopathic group, have never been explored. Of the 65 HLH cases, we detected germline HAVCR2Y82C mutations in nine (13.8%) cases (five SPTCL and four idiopathic HLH). Other causes of HLH were hematologic malignancies excluding SPTCL (32.3%), idiopathic HLH without HAVCR2 mutation (29.2%), infections (15.3%), and autoimmune diseases (9.2%). Germline HAVCR2 mutation was significantly associated with less anemia and better survival. This defines a distinct subgroup of HLH.

Exploring Toxin Genes of Myanmar Russell's Viper, Daboia siamensis, through De Novo Venom Gland Transcriptomics.

The Russell's viper (Daboia siamensis) is a medically important venomous snake in Myanmar. Next-generation sequencing (NGS) shows potential to investigate the venom complexity, giving deeper insights into snakebite pathogenesis and possible drug discoveries. mRNA from venom gland tissue was extracted and sequenced on the Illumina HiSeq platform and de novo assembled by Trinity. The candidate toxin genes were identified via the Venomix pipeline. Protein sequences of identified toxin candidates were compared with the previously described venom proteins using Clustal Omega to assess the positional homology among candidates. Candidate venom transcripts were classified into 23 toxin gene families including 53 unique full-length transcripts. C-type lectins (CTLs) were the most highly expressed, followed by Kunitz-type serine protease inhibitors, disintegrins and Bradykinin potentiating peptide/C-type natriuretic peptide (BPP-CNP) precursors. Phospholipase A2, snake venom serine proteases, metalloproteinases, vascular endothelial growth factors, L-amino acid oxidases and cysteine-rich secretory proteins were under-represented within the transcriptomes. Several isoforms of transcripts which had not been previously reported in this species were discovered and described. Myanmar Russell's viper venom glands displayed unique sex-specific transcriptome profiles which were correlated with clinical manifestation of envenoming. Our results show that NGS is a useful tool to comprehensively examine understudied venomous snakes.

Germline HAVCR2 mutations and their relation to the clinical spectrum of subcutaneous panniculitis-like T-cell lymphoma and hemophagocytic lymphohistiocytosis: results from a multicenter study and meta-analysis.

Germline HAVCR2 mutations are frequently detected in subcutaneous panniculitis-like T-cell lymphoma (SPTCL) patients with/without hemophagocytic lymphohistiocytosis (HLH) but factors associated with variable manifestations remain undetermined. To evaluate clinical variations and associated factors in SPTCL and/or HLH with/without HAVCR2 mutations, we performed direct sequencing of HAVCR2 exon 2 using DNA from patients with SPTCL or idiopathic HLH/HLH-like systemic illnesses, defined by HLH alone without secondary causes. The systematic review and individual patient data (IPD) level meta-analysis which included the present and previously published studies reporting HAVCR2 mutations in SPTCL with/without HLH populations was subsequently conducted using random-effects meta-analysis and multivariate logistic regression. Among 34 patients enrolled, ten of 28 SPTCL patients developed HLH/HLH-like systemic illnesses. Six cases with HAVCR2Y82C mutation manifested with HLH without panniculitis. Male sex (P=0.03) and age <18 years (P=0.04) were associated with HLH, corresponding to the inverse correlation between age and HLH-2004 score (r=-0.40; P=0.02). Homozygous HAVCR2Y82C mutation was more common in the presence of HLH compared with the absence (75.0% vs. 44.4%; P=0.02). Using IPD from the present and the other three eligible cohorts (N=127), male sex, heterozygous and homozygous/compound heterozygous HAVCR2 mutations were associated with HLH by the adjusted odds ratio of 2.93 (95% confidence interval [CI]: 1.22-7.06), 4.77 (95% CI: 1.05-21.63) and 8.48 (95% CI: 2.98-24.10), respectively. Patients with male sex and/or germline HAVCR2 mutations showed an increased risk of developing HLH. Younger patients tended to manifest with HLH, while older patients typically presented with SPTCL with less frequent HLH/HLH-like systemic illnesses.

The reliability of FEbrile Neutropenia after ChEmotherapy (FENCE) scores in predicting granulocyte colony-stimulating factor breakthrough febrile neutropenia among patients with lymphoma undergoing first-cycle chemotherapy: A prospective observational study.

Background: A tool for estimating risk of febrile neutropenia (FN) after chemotherapy, namely the FEbrile Neutropenia after ChEmotherapy (FENCE) score, has been developed but has not been widely validated. This study aimed to validate the FENCE score as a tool for predicting granulocyte colony-stimulating factor (G-CSF) breakthrough FN among patients with lymphoma who underwent chemotherapy. Methods: This was a prospective observational study of treatment-naive adult patients with lymphoma who underwent their first cycle of chemotherapy between 2020 and 2021. The patients were followed up until the next cycle of chemotherapy to identify any infection events. Results: Among the 135 patients with lymphoma, 62 (50%) were men. In a comparison of the value of each FENCE parameter for predicting G-CSF breakthrough infection, the parameter of advanced-stage disease showed high sensitivity of 92.8%, and receipt of platinum chemotherapy showed high specificity of 95.33%. With a FENCE score of 12 as a cutoff for low risk, analysis across all patients with lymphoma resulted in a high AUROCC of 0.63 (95% CI = 0.5-0.74%; p = 0.059), and analysis across only patients with diffuse large B-cell lymphoma (DLBCL) resulted in an AUROCC of 0.65 (95% CI = 0.51-0.79%; p = 0.046). With a cutoff point of 12, FENCE score can predict breakthrough infection events at 30.0% (95% CI = 17.8-47.4%). Conclusion: This study divided patients with lymphoma into risk groups according to FENCE score, showing that this instrument has discriminatory ability in predicting FN events, these being more likely to occur in patients in the intermediate- and high-risk groups. Multicenter studies are needed to validate this clinical risk score.

Stability of Hemoglobin Constant Spring Identified by Capillary Electrophoresis.

OBJECTIVE: Hemoglobin Constant Spring (HbCS) is often missed by routine hemoglobin analysis. The aim of this research was to study HbCS stability as identified by capillary electrophoresis (CE) to determine the specimen storage time limit. METHODS: The EDTA blood of 29 HbCS samples were kept at 4°C and analyzed every workday until CE could not detect HbCS or until 7 weeks after blood collection. The genotypes were confirmed by multiplex polymerase chain reaction. RESULTS: The median subject age was 27 years and 10 subjects were male. The HbCS levels were stable during the first 7 days but became undetectable in 5 cases (17.2%) after 1 week. All of them were heterozygous HbCS. Longer detection times were correlated with the higher baseline HbCS levels, with a correlation coefficient of 0.582 (P  ≤ 0.001). CONCLUSION: Routine hemoglobin typing and quantitation should be performed within 1 week after blood collection to detect low HbCS levels, especially in heterozygous HbCS.

Comparison of Molecular International Prognostic Scoring System (M-IPSS) and Revised International Prognostic Scoring System (R-IPSS) in Thai patients with myelodysplastic neoplasms.

INTRODUCTION: Risk stratification is essential for treatment decision in myelodysplastic neoplasms (MDS). Molecular international prognostic scoring system (M-IPSS) has been recently developed combining somatic mutations and clinical information being used in the revised international prognostic scoring system (R-IPSS). OBJECTIVE: We aimed to explore the performances of M-IPSS and R-IPSS in Thai patients with MDS. METHOD: MDS patients were stratified into risk categories using R-IPSS and M-IPSS scores. The performance of both models were evaluated for prognostic prediction. RESULTS: One hundred and sixty-two MDS patients were recruited from the multicenter study. Survival analysis revealed that both R-IPSS and M-IPSS were good prediction models with the Concordance Index (C-index) of 0.71 (95% Confidence interval [CI] 0.64-0.78) and 0.75 (95% CI 0.69-0.80), respectively (p = 0.22). Comparing the two, 13 of 162 (8%) cases were re-staged between lower and higher risks which would have affected treatment decisions. CONCLUSION: Our study showed that R-IPSS score can be used for risk stratification in most Thai patients. A prediction model using somatic mutations specifically in Asian patients should be formulated in the future.

Deferiprone, an iron chelator, alleviates platelet hyperactivity in patients with ß-thalassaemia/HbE.

Background: Hyperfunctional platelets play important roles in thromboembolism in patients with ß-thalassaemia/ haemoglobin E (ß-thal/HbE). Our previous study revealed ex vivo inhibitory effects of deferiprone on normal platelets. Herein, we aimed to investigate the in vivo effects on platelets in patients with ß-thal/HbE. Methods: A prospective, self-controlled clinical study on 30 patients with ß-thal/HbE who had received therapeutic deferiprone (20.8-94.5 mg/kg/day) was conducted. The study included a 4-week washout period followed by 4 and 12 weeks of deferiprone treatment. Platelet aggregation was performed by a turbidimetric method. Levels of deferiprone and soluble platelet (sP)-selectin in serum were measured by high-performance liquid chromatography (HPLC) and enzyme-linked immunosorbent assay (ELISA) kit, respectively. Results: The washout period significantly enhanced platelet hyperactivity both in patients who had undergone splenectomy and in those who had not. At 2 hours following the administration of a single dose of deferiprone, platelet sensitivity to ADP and arachidonic acid was significantly reduced. The inhibitory effects of deferiprone were gradually increased over the period of 4 and 12 weeks. Deferiprone also depressed sP-selectin levels, but the effect was stable over longer follow-up periods. Correlation analysis demonstrated the relationship between serum levels of deferiprone, sP-selectin, and platelet activities induced by ADP and arachidonic acid. Conclusion: We first demonstrated the in vivo antiplatelet effect and benefit of short-term treatment of deferiprone in patients with ß-thal/HbE. The impact on thrombotic outcomes deserves further study.

Immunogenicity and risks associated with impaired immune responses following SARS-CoV-2 vaccination and booster in hematologic malignancy patients: an updated meta-analysis.

Patients with hematologic malignancies (HM) have demonstrated impaired immune responses following SARS-CoV-2 vaccination. Factors associated with poor immunogenicity remain largely undetermined. A literature search was conducted using PubMed, EMBASE, Cochrane, and medRxiv databases to identify studies that reported humoral or cellular immune responses (CIR) following complete SARS-CoV-2 vaccination. The primary aim was to estimate the seroconversion rate (SR) following complete SARS-CoV-2 vaccination across various subtypes of HM diseases and treatments. The secondary aims were to determine the rates of development of neutralizing antibodies (NAb) and CIR following complete vaccination and SR following booster doses. A total of 170 studies were included for qualitative and quantitative analysis of primary and secondary outcomes. A meta-analysis of 150 studies including 20,922 HM patients revealed a pooled SR following SARS-CoV-2 vaccination of 67.7% (95% confidence interval [CI], 64.8-70.4%; I2 = 94%). Meta-regression analysis showed that patients with lymphoid malignancies, but not myeloid malignancies, had lower seroconversion rates than those with solid cancers (R2 = 0.52, P < 0.0001). Patients receiving chimeric antigen receptor T-cells (CART), B-cell targeted therapies or JAK inhibitors were associated with poor seroconversion (R2 = 0.39, P < 0.0001). The pooled NAb and CIR rates were 52.8% (95% CI; 45.8-59.7%, I2 = 87%) and 66.6% (95% CI, 57.1-74.9%; I2 = 86%), respectively. Approximately 20.9% (95% CI, 11.4-35.1%, I2 = 90%) of HM patients failed to elicit humoral and cellular immunity. Among non-seroconverted patients after primary vaccination, only 40.5% (95% CI, 33.0-48.4%; I2 = 87%) mounted seroconversion after the booster. In conclusion, HM patients, especially those with lymphoid malignancies and/or receiving CART, B-cell targeted therapies, or JAK inhibitors, showed poor SR after SARS-CoV-2 vaccination. A minority of patients attained seroconversion after booster vaccination. Strategies to improve immune response in these severely immunosuppressed patients are needed.

Genetic mutations associated with blood count abnormalities in myeloid neoplasms.

INTRODUCTION: Myelodysplastic syndromes (MDS) predominantly present with varying degrees of cytopenia, while myelodysplastic syndromes/myeloproliferative neoplasms (MDS/MPN) exhibit proliferative features. Genetic defects underlying different complete blood count (CBC) alterations remain to be defined. OBJECTIVE: We aimed to evaluate mutations and impacts on abnormal blood counts in MDS and MDS/MPN. METHOD: MDS and MDS/MPN patients were recruited and sequenced by targeted next-generation sequencing. Clinical parameters, especially CBC, were evaluated for the association with genetic abnormalities and clinical outcomes. RESULTS: A total of 168 patients with myeloid neoplasms were recruited (92 cases of low-risk MDS, 57 cases of high-risk MDS and 19 cases of MDS/MPN). Compared to low-risk MDS and MDS/MPN, patients with high-risk MDS were presented with more severe neutropenia with 17.5% showing absolute neutrophil counts (ANC) lower than 0.5 × 109/L. Patients with MDS/MPN more commonly harboured mutations and had a higher number of mutations per case than low-risk MDS (94.7% vs. 56.5%; p < 0.001 and 3 vs. 1; p < 0.001, respectively). Patients with SF3B1 mutations showed lower haemoglobin levels than wild-type (7.9 vs. 8.4 g/dL, p = 0.02), but were associated with normal platelet counts (286 vs. 93 × 109/L; p < 0.001). Patients with U2AF1 mutations were associated with more severe leukopenia than wild-type (3 vs. 4.18 × 109/L; p = 0.02). KRAS mutations were associated with monocytosis (p < 0.001). Multivariate analysis revealed high-risk MDS, MDS/MPN, severe neutropenia (ANC < 0.5 × 109/L), and mutations in ASXL1 and SETBP1 were associated with inferior survival outcomes. CONCLUSION: Certain mutations were related to more severe anaemia, lower white blood cell count or monocytosis in Asian MDS and MDS/MPN patients.

Randomised controlled trial of glucose-6-phosphate dehydrogenase deficient versus non-deficient red blood cell transfusion in patients with hypoproliferative anaemia.

BACKGROUND: Recent studies revealed the glucose-6-phosphate dehydrogenase (G-6-PD) deficiency prevalence of 7.7-10% among Thai blood donors. Transfusion of red blood cells (RBCs) from these subjects potentially causes haemolysis in recipients. METHODS: RBC units from the National Blood Centre were sampled to assess G-6-PD levels using spectrophotometry. Patients with pure underproduction anaemia requiring blood transfusion were randomised to receive G-6-PD-deficient versus normal ABO-matched RBCs. Pre- and 48-h post-transfusion indirect bilirubin, haemoglobin, haematocrit, lactate dehydrogenase (LDH) and haptoglobin were measured. RESULTS: From April 2020 to March 2021, 374 RBC units were tested for G-6-PD, and that 25 were found to be G-6-PD deficient. Twelve units of G-6-PD-deficient RBCs and 14 units of normal RBCs were given to patients who met the inclusion criteria. The median (interquartile range) increases of indirect bilirubin in G-6-PD-deficient (N = 11) versus normal RBCs (N = 13) were + 0.12 (0.27) versus + 0.01 (1.3) mg/dl, p = 0.030), respectively. The median increases of haemoglobin were 1.00 (0.50) versus + 0.80 (0.95), p = 0.910, respectively. The increases in haematocrit were 2.59 (1.9) versus 2.29 (2.1), p = 0.733, respectively. There were no significant differences in changes of LDH and haptoglobin levels and no transfusion reactions. DISCUSSION: G-6-PD-deficient packed red cells were associated with mildly elevated indirect bilirubin after transfusion, but there was no observed clinical symptoms.