Incidence of venous thromboembolism and predictive ability of age-adjusted international prognostic index for prediction of venous thromboembolism in Asian patients with diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is one of the malignancies at high risk for the development of venous thromboembolism (VTE). We aimed to evaluate the incidence of VTE and the predictive ability of the age-adjusted international prognostic index (aaIPI) for the prediction of VTE among DLBCL patients. This was a retrospective cohort study including adult patients with newly diagnosed DLBCL. Differences in VTE occurrence within one year after diagnosis of DLBCL were estimated across aaIPI groups using the Kaplan-Meier model, Cox's model, and Gray's model with deaths regarded as competing events. Five hundred and ninety-one newly diagnosed DLBCL patients with a median age of 58 (range 16-93) years were included in this study. At a median follow-up time of 365 (range 2-365) days, VTE events were objectively diagnosed in 32 patients, giving a one-year cumulative incidence of VTE of 5.4% (95% confidence interval [CI], 3.7-7.6). Patients with aaIPI ≥ 2 had a significantly higher risk of VTE than patients with aaIPI < 2 (hazard ratio, 3.5; 95% CI, 1.6-7.8; p = 0.001 based on Cox's model and sub-distribution hazard ratio, 3.0; 95% CI, 1.3-6.7; p = 0.007 using Gray's model). The C-statistic of aaIPI was 0.65 (95% CI, 0.58-0.72). We demonstrated that the incidence of VTE in Asian DLBCL patients was not uncommon. The aaIPI was effective in determining the risk of VTE in DLBCL patients, even when including death as a competing event. aaIPI may be helpful in identifying patients at higher risk of VTE in DLBCL patients.

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.

Endothelial activation and stress index as a prognostic factor of diffuse large B-cell lymphoma: the report from the nationwide multi-center Thai Lymphoma Study Group.

Several prognostic models have been introduced to predict outcomes of patients with diffuse large B-cell lymphoma (DLBCL). Endothelial activation and stress index (EASIX) is a surrogate of endothelial dysfunction which has been shown to predict outcomes of patients with various hematologic malignancies. However, the prognostic implication of EASIX for DLBCL is limited and warrants exploration. We conducted a retrospective study enrolling adult DLBCL patients including a discovery cohort from the single-centered university hospital database and a validation cohort from the independent nationwide multi-center registry. EASIX scores were calculated using creatinine, lactate dehydrogenase, and platelet levels. The receiver operating characteristic curve analysis was used to determine optimal cutoff. Statistical analysis explored the impact of EASIX on survival outcomes. A total of 323 patients were included in the discovery cohort. The optimal EASIX cutoff was 1.07 stratifying patients into low (53.9%) and high EASIX (46.1%) groups. Patients with high EASIX had worse 2-year progression-free survival (PFS) (53.4% vs. 81.5%, p<0.001) and overall survival (OS) (64.4% vs. 88.7%, p<0.001) than patients with low EASIX. Multivariate analysis revealed that older age, bulky disease, impaired performance status, and high EASIX were associated with an unfavorable OS. In the validation cohort of 499 patients, the optimal EASIX cutoff was 1.04. Similar to the discovery cohort, high EASIX score was associated with high-risk diseases, worse PFS, and inferior OS. In conclusion, EASIX score was significantly associated with survival outcomes and may be used as a simple prognostic tool to better risk-classify DLBCL.

Outcomes of polatuzumab vedotin-containing regimens in real-world setting of relapsed and or refractory diffuse large B-cell lymphoma patients: a matched-control analysis from the Thai Lymphoma Study Group (TLSG).

Relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) is a challenging condition to treat, and there is an unmet clinical need for effective therapies. Recently, polatuzumab vedotin (Pola), an anti-CD79b antibody-drug-conjugate (ADC), combined with bendamustine-rituximab (BR), has been approved for R/R DLBCL patients. However, real-world data on Pola-based regimens in R/R DLBCL patients, especially in Thailand, are limited. This study aimed to evaluate the efficacy and safety of Pola-based salvage treatment in R/R DLBCL patients in Thailand. Thirty-five patients who received Pola-based treatment were included in the study, and their data were compared to 180 matched patients who received non-Pola-based therapy. The overall response rate (ORR) in the Pola group was 62.8%, with complete remission and partial remission rates of 17.1% and 45.7%, respectively. The median progression-free survival (PFS) and overall survival (OS) were 10.6 months and 12.8 months, respectively. The study found a significantly higher ORR in Pola-based salvage treatments compared to non-Pola-based therapy (62.8% vs. 33.3%). The survival outcomes were also significantly superior in the Pola group, with longer median PFS and OS than the control group. Grades 3-4 adverse events (AEs) were mainly hematological, and they were tolerable. In conclusion, this study provides real-world evidence of the efficacy and safety of Pola-based salvage treatment in R/R DLBCL patients in Thailand. The results of this study are promising and suggest that Pola-based salvage treatment could be a viable option for R/R DLBCL patients who have limited treatment options.

The long-term efficacy in blood transfusions, hematologic parameter changes, and complications after splenectomy in patients with transfusion-dependent thalassemia.

BACKGROUND: A splenectomy can reduce transfusion requirements in patients with thalassemia. However, the role of a splenectomy remains controversial because its efficacy has not yet been fully determined and there are concerns over potential complications. The purpose of this study was to assess the efficacy, potential changes in hematologic parameters, and any complications associated with splenectomy. METHODS: Medical records of 50 patients with transfusion-dependent thalassemia (TDT) who had undergone a splenectomy, along with those of 20 control subjects with intact spleens, were retrospectively reviewed. RESULTS: The primary outcomes indicate the efficacy of a splenectomy in reducing red cell transfusions. Fifty TDT post-splenectomy patients were included in this study, of which 28 (56%) were female. The median age of all patients was 20.5 (18-28 years of age). Twenty-seven patients (54%) transformed from TDT to non-transfusion-dependent thalassemia (NTDT) after the splenectomy; 100% with Hb H disease, 58.3% with beta-thalassemia/Hb E disease, and 23.5% with homozygous beta-thalassemia. According to multivariable logistic regression analysis, Hb H disease (adjusted OR 55.23, 95% CI 1.35-22.8.10) and receiving a splenectomy at > ten years of age (adjusted OR 25.36, 95% CI 1.62-396.47) were associated with higher responses. The prevalence of pulmonary hypertension and thromboembolic events were similar between the splenectomy patients and non-splenectomy patients. CONCLUSION: Splenectomy reduced transfusion requirements in TDT patients. The predictive factors as a response to a splenectomy included Hb H disease amongthose receiving a splenectomy at > ten years of age.

Impact of dabigatran dose on drug levels in asian patients with atrial fibrillation or venous thromboembolism: evidence from pharmacological to clinical outcomes.

Dabigatran is commonly used in atrial fibrillation (AF) or venous thromboembolism (VTE). However, there was limited data on dabigatran levels in Asian patients. This study aimed to investigate plasma levels of dabigatran 110 mg (D110) or 150 mg (D150) twice daily and their impact on clinical outcomes in Thai patients. This was a prospective cohort study including patients who were diagnosed with AF or VTE and were prescribed either D110 or D150. Plasma dabigatran levels were measured using the diluted thrombin time method. All patients were observed for bleeding and thrombotic complications for 12 months after enrollment. Ninety patients were included in the study (45 in the D110 group and 45 in the D150 group). For the D110 group, there was no significant difference in trough and peak levels in patients with creatinine clearance (CrCl) < 50 ml/min compared to those with CrCl ≥ 50 ml/min. For the D150 group, patients with CrCl < 50 ml/min had significantly higher trough and peak levels compared to those with CrCl ≥ 50 ml/min (P = 0.016 for trough, P = 0.005 for peak). Multivariate regression analysis showed females and low CrCl were independent risk factors for high dabigatran levels. Most patients (83.33%) who experienced bleeding complications had peak levels within the expected range. D150 was associated with higher plasma dabigatran levels, especially in those with impaired renal function.

The Long-Term Efficacy of Deferiprone in Thalassemia Patients With Iron Overload: Real-World Data from the Registry Database.

Deferiprone (DFP) is an oral iron-chelating agent that is widely used in thalassemia patients with iron overload. This study aimed to investigate the long-term efficacy of DFP monotherapy on serum ferritin (SF) and adverse events. All thalassemia patients aged 15 years or older who received DFP monotherapy were identified from the thalassemia registry database between November 2008 and October 2019. After treatment, patients who achieved a target SF level, defined as <1000.0 ng/mL in transfusion-dependent thalassemia (TDT) and <800.0 ng/mL in non-TDT (NTDT) for two consecutive visits, were categorized as the achievable group. We used multivariate analysis to identify factors that contribute to differences between groups. One hundred and five patients were enrolled in the study with a median age of 28 (19-41) years and median initial SF level of 1399.0 (1141.0-2169.0) ng/mL. Of these, 61.0% carried Hb E (HBB: c.79G>A)/ß-thalassemia (ß-thal) and 60.0% were TDT patients. The median DFP dose was 63 (47-73) mg/kg/d and the median follow-up duration of treatment was 36 (20-54) months. A total of 58 (55.24%) patients were in the achievable group. The initial SF level <1350.0 ng/mL was significantly associated with achieving a targeted SF level (p = 0.002). Ten adverse events resulted in withholding DFP. The most common was gastrointestinal irritation in four patients and three patients with agranulocytosis. In conclusion, DFP is an effective iron chelator in thalassemia patients. Slightly more than half the patients (55.0%) achieved a target SF level. Lower SF levels at the beginning were an important factor.

Outcome of patients with newly diagnosed primary CNS lymphoma after high-dose methotrexate followed by consolidation whole-brain radiotherapy and cytarabine: an 8-year cohort study.

BACKGROUND: Addition of cytarabine to high-dose methotrexate (HD-MTX) chemotherapy improves outcome of primary CNS lymphoma (PCNSL); however, the combination therapy increases toxicity. Sequential chemotherapy and cranial radiation may decrease toxicity without altering efficacy. METHODS: This was a single-center, retrospective cohort study of consecutive newly diagnosed immunocompetent PCNSL patients treated with HD-MTX (5 cycles of 3 g/m2 every 2 weeks) followed by consolidation whole-brain radiotherapy (WBRT) and cytarabine (2 cycles of 3 g/m2/d for 2 days every 3 weeks) from January 2013 to December 2020. Initial WBRT before HD-MTX was allowed in patients with significant disability or brain edema at presentation. Primary outcome was progression-free survival (PFS). Key secondary outcomes were response rate, treatment-related toxicity, and overall survival (OS). RESULTS: Of 41 patients, 25 patients had a complete response (CR) and ten patients had a partial response, inferring an overall response rate (ORR) of 85.4% and a CR rate of 60.9%. More than 90% of patients were able to tolerate and complete the HD-MTX. The incidence of ≥ grade 3 hematologic and non-hematologic toxicities were 4.8% and 17.1%, respectively. Treatment-related mortality rate was 2.4%. There was no difference in toxicity between patients with age < 60 and ≥ 60 years. At the median follow-up duration of 39.8 months, the median PFS was 35.2 months (95% CI 12.4-69.3) and median OS was 46.5 months (95% CI 21.8-NR). CONCLUSION: High-dose methotrexate followed by consolidation whole-brain radiotherapy and cytarabine has acceptable efficacy, great tolerability, and low toxicity in newly diagnosed PCNSL patients.

Correlation Between Serum Ferritin and Viral Hepatitis in Thalassemia Patients.

Serum ferritin is an acute phase protein; importantly, its level is noticeably increased in response to iron overload and systemic inflammation. The iron overload status in thalassemia patients has been recognized as a potential way to measure liver iron concentration (LIC) levels using magnetic resonance imaging (MRI). The aim of this study was to investigate the effect of chronic viral hepatitis on the level of serum ferritin in patients with thalassemia. A cross-sectional study was conducted involving chronic viral hepatitis infection. Mean serum ferritin and LIC levels were recorded. The LIC values were used to divide the patients into two groups; a higher LIC group (>5 mg Fe/g) and a lower LIC group (<5 mg Fe/g). Mean serum ferritin levels were then compared between the two LIC groups. We identified 32 thalassemia patients comprising of 13 chronic viral hepatitis patients, seven patients with hepatitis B virus (HBV), and six patients with hepatitis C virus (HCV). With regard to the group with higher LIC values, the mean serum ferritin levels in the hepatitis group were significantly higher than for those in the non hepatitis group (1776 ± 488 vs. 967 ± 860 ng/mL, p = 0.03). Furthermore, the linear correlation between the mean serum ferritin levels and the viral load in the non transfusion-dependent thalassemia (NTDT) group were found to be significantly correlated (r = 0.7, p = 0.04). Chronic viral hepatitis was determined to be a possible casualty of disproportionately high ferritin levels in the NTDT group.

The effects of text messaging for promoting the retention of the first-time blood donors, a randomized controlled study (TEXT study).

BACKGROUND: Donor recruiting remains a challenging process to obtain sufficient blood product supply worldwide. This was a randomized controlled trial aimed to evaluate the efficacy of text messaging for promoting the retention of first-time blood donors. STUDY DESIGN AND METHODS: Participants enrolled were 18 years of age or older who were first-time blood donors and able to understand text messages. Participants were randomized in a 1:1 ratio (text group vs control group). Only participants who were allocated in the "text group" received a text message once their blood product was dispatched from the transfusion service. The content of the text message was "We would like to inform you that your blood has been used for patients on the date (DD/MM/YY)." The primary outcome of the study was the rate of returning at 9 months after the first donation. RESULTS: In an intention-to-treat analysis, 1270 participants were allocated to the text group and 1270 participants to the control group. The primary outcome occurred in 199 in the text group (22.4 per 100 donor-years) and 152 in the control group (16.9 per 100 donor-years). The incidence rate ratio was 1.31 (95% confidence interval, 1.06-1.63; P = .005). The number needed to treat was 22. The median time to return for blood donation was 112 days (interquartile range [IQR], 98-146) in the text group and 113 days (IQR, 97-144) in the control group. CONCLUSION: Among first-time blood donors, text messaging after blood product being dispatched is an effective and simple intervention to increase the retention rate for subsequent donations.

Comparison of hemoglobin and hematocrit levels at 1, 4 and 24 h after red blood cell transfusion.

Previous studies have shown that equilibration following a red cell transfusion had occurred by 24 h. A shorter time to follow the hemoglobin (Hb) and hematocrit (Hct) after transfusion may help physicians to provide earlier and more pertinent treatment. This was a prospective study conducted from December 2014 to August 2015. This research aimed to determine the equilibration time point of the level of Hb and Hct after one unit red blood cell (RBC) transfusion. Patients were randomized into three groups and Hb level and Hct were assessed at one, four or 24 h after transfusion. The mean differences in Hb level and Hct before and after transfusion were compared between each group. Sixty patients were eligible for enrollment onto this study; 20 patients were therefore allocated to each group. The median age was 51 years old, male predominating (83.33%). The most common indication for transfusion was post-operative anemia (88.33%). There were no significant differences between the baseline characteristics baseline Hb, Hct and volume of RBC transfusion in each group. The mean differences in Hb (g/dl)/Hct (%) level at the different time points of one, four and 24 h were 1.21/3.62, 1.19/3.63, and 0.95/3.09 respectively (P = 0.109 and P = 0.398, respectively). The equilibration of Hb and Hct did not differ between one, four and 24 h after a RBC transfusion. The target Hb and Hct can be determined at one hour after transfusion.

Cardiorenal syndrome in thalassemia patients.

BACKGROUND: Cardiorenal syndrome (CRS), a serious condition with high morbidity and mortality, is characterized by the coexistence of cardiac abnormality and renal dysfunction. There is limited information about CRS in association thalassemia. This study aimed to investigate the prevalence of CRS in thalassemia patients and also associated risk factors. METHODS: Thalassemia patients who attended the out-patient clinic of a tertiary care university hospital from October 2016 to September 2017 were enrolled onto this cross-sectional study. Clinical and laboratory findings from 2 consecutive visits, 3 months apart, were assessed. The criteria for diagnosis of CRS was based on a system proposed by Ronco and McCullough. Cardiac abnormalities are assessed by clinical presentation, establishment of acute or chronic heart failure using definitions from 2016 ESC guidelines or from structural abnormalities shown in an echocardiogram. Renal dysfunction was defined as chronic kidney disease according to the 2012 KDIGO guidelines. RESULTS: Out of 90 thalassemia patients, 25 (27.8%) had CRS. The multivariable analysis showed a significant association between CRS and extramedullary hematopoiesis (EMH) (odds ratio (OR) 20.55, p = 0.016); thalassemia type [ß0/ßE vs ß0/ß0 thalassemia (OR 0.005, p = 0.002)]; pulmonary hypertension (OR 178.1, p = 0.001); elevated serum NT-proBNP (OR 1.028, p = 0.022), and elevated 24-h urine magnesium (OR 1.913, p = 0.016). There was no association found between CRS and frequency of blood transfusion, serum ferritin, liver iron concentration, cardiac T2*, type of iron chelating agents, or urine neutrophil gelatinase-associated lipocalin level. CONCLUSIONS: CRS is relatively common in thalassemia patients. Its occurrence is associated with laboratory parameters which are easily measured in clinical practice.

Hyperuricemia, urine uric excretion, and associated complications in thalassemia patients.

Thalassemia patients have a high cell turnover rate due to chronic hemolysis and ineffective erythropoiesis; therefore, hyperuricemia is anticipated. This study aimed to identify the prevalence of hyperuricemia, gout and nephrolithiasis, conditions associated with serum uric acid (SUA), and urine uric acid excretion (UUA) in thalassemia patients. This was a cross-sectional study in patients aged 15 years or older at Chiang Mai University Hospital. All patients had blood and 24-h urine collection test. We enrolled 112 thalassemia patients in which 67.0% were female, 64.3% had beta thalassemia/Hb E, 76.8% were transfusion dependent, and 59.8% were post splenectomy. The median age was 29 (16-58) years. Mean SUA was 6.7 ± 2.0 mg/dl and hyperuricemia (SUA > 6.8 mg/dl) was found in 47 cases (45.2%). Intact spleen (ORs 4.3, 95%CI 1.55-12.50, p = 0.01) and lower FEuric (ORs 2.08, 95%CI 1.35-3.33, p < 0.01) were associated with hyperuricemia significantly. Seven (6.3%) had gouty arthritis and nine (8%) had microscopic hematuria, one case being confirmed nephrolithiasis. The mean UUA excretion was 981.3 ± 335.0 mg/day and UUA hyperexcretion (> 700 mg/24 h) was found in 83.3%. UUA hyperexcretion patients had renal hyperfiltration 46%, glomerular dysfunction 84%, and tubular dysfunction 7.7%. From our study, hyperuricemia was found in approximately 40% of thalassemia patients but gouty arthritis occurred only in few patients (6%). This may be explained by urinary uric hyperexcretion which is found in over 80%. The significant risk factors for hyperuricemia were intact spleen and lower fraction excretion of uric acid.

Prevalence and risk factors for hyperuricemia and hyperuricosuria in patients with hematologic malignancies.

Introduction: Hyperuricemia is a common complication of hematologic malignancies, and hyperuricosuria in this population has shown conflicting results. This study aimed to determine the prevalence of hyperuricemia and parameters associated with serum uric acid (SUA) and urine uric acid (UUA) in patients with lymphoma and myeloproliferative neoplasms (MPN). Methods: This cross-sectional study included adult patients with newly diagnosed lymphoma and MPN at the university-based hospital. Clinical characteristics were collected, and independent risk factors for hyperuricemia and hyperuricosuria were determined using multiple logistic regression. Results: One hundred and sixty-five patients were included with a median age of 55 years (45.5-64) and 51.5% were males. There were 91 patients (55.2%) with lymphoma and 74 cases (44.8%) of MPN. Overall, hyperuricemia was prevalent in 43.6% with a median SUA of 6.3 mg/dl (4.6-8) and hyperuricosuria was detected in 39.4% with a median 24-h UUA of 545 mg (365.4-991). Hyperuricemia was observed in patients with lymphoma and MPN in 20.9% and 71.6%, respectively, and hyperuricosuria in 15.4% and 68.9%, respectively. In lymphoma patients, estimated glomerular filtration rate (eGFR) <90 ml/min/1.73 m2 and serum lactate dehydrogenase (LDH) ≥ 250 U/L were associated with hyperuricemia with odds ratio (OR) 3.24, 95% confidence interval (CI) 1.95-11.07, p = 0.006 and OR 2.07, 95%CI 1.62-6.97, p = 0.039), and only elevated serum LDH was related to hyperuricosuria (OR 2.37, 95%CI 1.56-14.29, p = 0.036). In MPN patients, hemoglobin levels <10 g/dl and serum LDH ≥ 640 mg/dl were independent risk factors of hyperuricosuria (OR 1.88, 95%CI 1.42-8.39, p = 0.045 and OR 6.21, 95%CI 1.49-25.74, p = 0.012). Conclusion: Hyperuricemia in patients with hematologic malignancies was common, notably MPN, and parameters associated with hyperuricosuria were provided. In addition to the utilization of allopurinol in patients at high risk of tumor lysis syndrome, patients without hyperuricosuria may also be of significant interest.

Survival and causes of death in patients with alpha and beta-thalassemia in Northern Thailand.

BACKGROUND: Thalassemia is the most prevalent hereditary anaemia worldwide. Severe forms of thalassemia can lead to reduced life expectancy due to disease-related complications. OBJECTIVES: To investigate the survival of thalassemia patients across varying disease severity, causes of death and related clinical factors. PATIENTS AND METHODS: We conducted a retrospective review of thalassemia patients who received medical care at Chiang Mai University Hospital. The analysis focused on survival outcomes, and potential associations between clinical factors and patient survival. RESULTS: A total of 789 patients were included in our study cohort. Among them, 38.1% had Hb H disease, 35.4% had Hb E/beta-thalassemia and 26.5% had beta-thalassemia major. Half of the patients (50.1%) required regular transfusions. Sixty-five patients (8.2%) had deceased. The predominant causes of mortality were infection-related (36.9%) and cardiac complications (27.7%). Transfusion-dependent thalassemia (TDT) (adjusted HR 3.68, 95% CI 1.39-9.72, p = 0.008) and a mean serum ferritin level ≥3000 ng/mL (adjusted HR 4.18, 95% CI 2.20-7.92, p < 0.001) were independently associated with poorer survival. CONCLUSIONS: Our study highlights the primary contributors to mortality in patients with thalassemia as infection-related issues and cardiac complications. It also underscores the significant impact of TDT and elevated serum ferritin levels on the survival of thalassemia patients.

Prevalence, Outcomes and Impact of Disease-Related Complications in the Survival of Multiple Myeloma Patients.

There are limited data regarding the impact of disease-related complications on the survival of multiple myeloma (MM) patients. The primary objective of this study was to determine the prevalence of disease-related complications, including hypercalcemia, renal insufficiency, anemia, and bone lytic lesions in MM patients. The secondary objectives were to determine clinical characteristics, treatment outcomes, and the association of disease-related complications and mortality. A retrospective chart review of MM patients from November 2014 to December 2019 was conducted. A total of 200 MM patients were enrolled. The median age at diagnosis was 63 years. The bone lytic lesion was the most common disease-related complication found in 85% during first-line therapy, followed by anemia (71.5%), renal insufficiency (28.5%), and hypercalcemia (20%). While anemia was the most common complication during the second (51.2%) and third-line therapy (72%). The development of skeletal-related events (SREs) after treatment is a disease-related complication that is associated with decreased overall survival (HR 4.030, 95% CI 1.97-8.24, p < 0.001). The most common disease-related complication of MM at initial diagnosis is bone lytic lesions, whereas anemia is more common with subsequent relapses. The presence of SRE after treatment is associated with the increased mortality of MM patients.

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.

Impact of antiphospholipid antibodies on thrombotic events in ambulatory cancer patients.

BACKGROUND: Despite the conflicting data, the positivity of antiphospholipid antibodies (aPL) in cancer patients may be associated with an increased risk of thrombosis. OBJECTIVE: To identify the prevalence and impact of aPL on venous thromboembolic events (VTE) and arterial thrombosis (ATE) in ambulatory cancer patients. METHODS: In this single-center, prospective cohort study, we enrolled newly diagnosed ambulatory cancer patients receiving chemotherapy. Non-cancer controls were age- and sex-matched. Participants were evaluated for aPL. Primary outcomes were the composite outcome of VTE or ATE and the prevalence of aPL positivity in cancer patients. Secondary outcomes included the risk of VTE and ATE in cancer patients and all-cause mortality at six-month follow-up duration. RESULTS: There were 137 cases and 137 controls with mean age of 56.0±12.3 and 55.5±12.1 years, respectively. Cancer patients were more likely to have positive aPL compared to controls, with the risk difference of 9.4% (95%CI 1.5 to 17.5). Composite of ATE or VTE occurred in 9 (6.6%) in cancer patients and 2 (1.5%) in controls. Cancer patients with aPL positivity were associated with higher risk of ATE or VTE (risk ratio [RR] 3.6, 95% CI 1.04-12.4). Positive LA in cancer patients were associated with higher risk of composites of ATE or VTE (RR 5.3 95%CI 1.3-21.0), whereas the anti-ß2-GPI positivity were associated with increased risk of VTE (RR 4.7, 95%CI 1.1-19.2). CONCLUSION: aPL was more prevalent in active cancer patients and positive aPL in cancer patients was associated with arterial or venous thrombosis.

Antithrombotic therapy in antiphospholipid syndrome with arterial thrombosis: a systematic review and network meta-analysis.

Introduction: The optimal secondary thromboprophylactic strategies for patients with antiphospholipid syndrome (APS) and arterial thrombosis remain controversial. This study aimed to evaluate the comparative efficacy and safety of various antithrombotic strategies in APS with arterial thrombosis. Methods: A comprehensive literature search was conducted using OVID MEDLINE, EMBASE, Web of Science, and the Cochrane Controlled Register of Trials (CENTRAL) from inception until 30 September 2022, with no language restrictions. The inclusion criteria for eligible studies were as follows: inclusion of APS patients with arterial thrombosis, treatment with either antiplatelet agents, warfarin, direct oral anticoagulants (DOACs), or a combination of these therapies, and reporting of recurrent thrombotic events. Results: We conducted a frequentist random-effects network meta-analysis (NMA) involving 13 studies with a total of 719 participants, comprising six randomized and seven non-randomized studies. In comparison to single antiplatelet therapy (SAPT), the combined use of antiplatelet and warfarin demonstrated a significant reduction in the risk of recurrent overall thrombosis, with a risk ratio (RR) of 0.41 (95% CI 0.20 to 0.85). Dual antiplatelet therapy (DAPT) showed a lower risk of recurrent arterial thrombosis compared to SAPT although the difference did not reach statistical significance, with an RR of 0.29 (95% CI 0.08 to 1.07). DOAC was associated with a significant increase in the risk of recurrent arterial thrombosis, with an RR of 4.06 (95% CI 1.33 to 12.40) when compared to SAPT. There was no significant difference in major bleeding among various antithrombotic strategies. Discussion: Based on this NMA, the combination of warfarin and antiplatelet therapy appears to be an effective approach in preventing recurrent overall thrombosis in APS patients with a history of arterial thrombosis. While DAPT may also show promise in preventing recurrent arterial thrombosis, further studies are needed to confirm its efficacy. Conversely, the use of DOACs was found to significantly increase the risk of recurrent arterial thrombosis.