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Compared with 180 matched patients who received non-pola-based therapy, there was a significantly higher ORR in Pola-based salvage treatments (62.8% vs. 33.3%, hazard ratio [HR] 3.52, 95% confidence interval [CI] 1.39-8.95, I p i < 0.01). Treatments of patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) represent an unmet clinical need. Thirty-five patients who received Pola-based treatment (Pola-BR 54.3% and Pola-R 45.7%) were included. [Extracted from the article]

EXCELLENT OUTCOMES OF SUBCUTANEOUS PANNICULITIS-LIKE T-CELL LYMPHOMA TREATED WITH CYCLOSPORIN-BASED REGIMEN, A MULTICENTER RETROSPECTIVE STUDY IN THAILAND The patient demographic data, treatment regimens which divided into conventional chemotherapy or immunosuppressive agents, and treatment outcomes were retrieved from the Thai lymphoma registry database. B Background: b Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare form of cytotoxic T-cell lymphoma, characterized by primary cutaneous tissue involvement mimicking inflammatory panniculitis. [Extracted from the article]

Aim: Exposure to fine particulate matter, particularly PM2.5, has been associated with increased platelet activation and cardiovascular risks. However, its effect on platelet recovery after transfusion remains unclear., Purpose: This study aims to assess the influence of PM2.5 exposure on platelet recovery in patients with hematologic malignancies receiving prophylactic platelet transfusions., Patients and Methods: We conducted a cross-sectional study involving 66 patients with hematologic malignancies who developed chemotherapy-induced thrombocytopenia and received prophylactic platelet transfusions between January and December 2021. A total of 191 transfusion events were analyzed. Platelet increment and corrected count increment (CCI) were measured one hour post-transfusion. Transfusions were categorized based on mean PM2.5 levels one day prior to platelet collection: the control group (< 37.5 μg/m³) and the case group (≥ 37.5 μg/m³). Multivariate analyses were used to adjust for potential confounders., Results: No significant differences were observed in platelet increment (p = 0.128) or CCI (p = 0.828) between the PM2.5 exposure groups. Correlation analyses showed no significant association between PM2.5 levels and platelet increment (r = 0.0565, p = 0.437) or CCI (r = 0.0370, p = 0.614). These findings suggest that exposure to elevated PM2.5 levels one day before donation does not significantly impair platelet recovery., Conclusion: Short-term exposure to elevated PM2.5 levels does not significantly affect platelet recovery in patients receiving prophylactic platelet transfusions. These results provide important reassurance regarding the immediate effects of air pollution on transfusion outcomes, while highlighting the need for further research into potential long-term impacts., Competing Interests: The authors report no conflicts of interest in this work., (© 2025 Hantrakool et al.)

Background: Cerebral venous sinus thrombosis (CVST) is a rare type of thrombosis that affects the cerebral venous system. The data on neurological outcomes are limited., Objectives: This study aimed to investigate the neurological outcomes of CVST, contributing factors, clinical presentation, treatment and mortality., Methods: This was a single-center, retrospective study at a university-based referral hospital in Thailand. Consecutive patients diagnosed with CVST between January 2010 and December 2020 were included. Outcomes were neurological outcomes measured by modified Rankin Scale (mRS), anticoagulant treatment, recurrence, and mortality., Results: One hundred and seven CVST patients were included with a mean age (± SD) of 42.7 ± 20.4 years. Following the treatment, neurological outcomes significantly improved, with the proportion of patients with mRS 0-1 increasing from 18.7% at diagnosis to 83.2% and 85.1% at three and six months, respectively (P < 0.001). Clinical variables were associated with residual neurological symptoms (mRS≥1) included age ≥ 50 years (OR 4.1, 95% CI; 1.7-9.4, P 0.001), male sex (OR 3.0, 95%CI; 1.4-6.6, P 0.006), the thrombus involvement in deep sinus system (OR 6.1, 95%CI; 1.1-76.9, P 0.04) and cerebral vein and dural sinus thrombosis (CVT) risk score ≥ 1 (OR 3.1, 95%CI; 1.3-7.5, P 0.014). Patients whose CVST was associated with hormonal therapy were found to have a lower risk of residual neurological symptoms (OR 0.2, 95%CI 0.1-0.6, P 0.004). Hormonal therapy was associated with anticoagulant discontinuation (OR 2.7, 95% CI 1.1-7.0; P = 0.04). The presence of malignancy increased the risk of bleeding (OR 5.8, 95% CI 1.4-24.1; P 0.016). Overall mortality was 2.8%. Of which 50% were related to major bleeding., Conclusions: A significant improvement in neurological outcomes was observed at 3 and 6 months after diagnosis. Older age, male sex, thrombus involvement in deep sinus system were associated with residual neurological symptoms., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2025 Sitthilok et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare subtype of T-cell lymphomas with a characteristic feature of subcutaneous nodules associated with hemophagocytic lymphohistiocytosis (HLH). Treatment options for SPTCL are mainly chemotherapy (CMT) or immunosuppressive agents with selection currently dependent on physician decisions. Outcomes between the 2 treatment remedies have not yet been comprehensively compared. This study aimed to compare complete remission (CR) rates between SPTCL patients receiving cyclosporin (CSA)-based regimen (CSA +/- steroid) and CMT. The 5-year overall survival (OS) and 5-year progression free survival (PFS) were also analyzed. Clinical data from patients with SPTCL were drawn from the Thai Lymphoma Study Group registry who were newly diagnosed between 2007 and 2023. A total of 93 patients were selected with 45 cases having received CSA-based regimen and 48 cases having received CMT. There were more patients with limited stage at skin in the CSA group (63.8% vs. 36.2%, p = 0.003), while more patients with hepato- and/or splenomegaly were found in the CMT group (56.2% vs. 24.5%; p = 0.002). Germline HAVCR2 mutations were detected in 26/33 (78.8%) cases. The CR rate was significantly higher in patients treated with CSA (87% vs. 58.3%; OR = 6.5 [95%CI, 2.7-15.3]; p = 0.002). At a median follow-up of 87.8 months (range 0-185), the 5-year OS (98% vs. 87%, p = 0.19) and PFS (72.4% vs. 69.2%, p = 0.19) showed a trend favoring patients treated with CSA. Based on our study, CSA-based regimens are the preferred first-line treatment remedy for newly diagnosed SPTCL, especially in patients with limited cutaneous involvement., Competing Interests: Declarations. Ethics approval: The study has been approved by The Institutional Review Board of the Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand, which the following study in compliance with the International guidelines for human research protection as Declaration of Helsinki, The Belmont Report, CIOMS Guideline and International Conference on Harmonization in Good Clinical Practice (ICH-GCP).(Certificate of Full Board Approval (COA No. 0510/2023)) Informed consent was obtained from all patients for being included in the study. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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.

Background/Objectives : The primary objective of this study was to investigate clinical manifestations, time to diagnosis, and number of biopsies in patients with extranodal natural killer T-cell lymphoma (ENKTL). The secondary objectives were to determine response rates, survival outcomes, prognostic factor for overall survival (OS), and validation of the Prognostic Index of Natural Killer Lymphoma (PINK), Ann Arbor staging system (AASS), and the CA system. Methods : This retrospective study included data pertaining to patients with newly diagnosed ENKTL in Chiang-Mai University Hospital from 2004 to 2020. Comparisons between the areas under the receiver operating characteristic curve (AUC) of prognostic models (PINK, AASS, and CA system) were made. Results : Sixty patients were enrolled (n = 60) with a mean age of 49.1 ± 13.4 years. The most frequent symptom of ENKTL was nasal obstruction (66%). The median time to diagnosis was 22 days (ranging from 3 to 84 days), with 36.7% requiring more than one biopsy for diagnosis. Most patients presented with limited stage disease (75%). The median OS was 49 months. Factors associated with increased mortality were advanced stage, bone marrow involvement, gastrointestinal tract involvement, and receiving chemotherapy. Following prognostic model validation, the CA system model scored the highest level of accuracy (AUC 0.61), followed by AASS (AUC 0.58) and PINK (AUC 0.54). Conclusions : Patients with ENKTL commonly presented with nasal obstruction, with 36.7% requiring more than one biopsy for diagnosis. An advanced stage, bone marrow involvement, or gastrointestinal tract involvement were associated with poor OS. The CA system model has the highest level of accuracy for prognostic determination.

Background/Objectives : Rivaroxaban and dabigatran are commonly used for thromboembolic disease management in active cancer patients. However, limited research explores the impact of concurrent chemotherapy on the pharmacodynamics of direct oral anticoagulants (DOAC). The aim of our study was to evaluate the impact of combined chemotherapy with rivaroxaban and dabigatran on the pharmacodynamics in patients with diffuse large B-cell lymphoma (DLBCL).; Methods : This was a prospective, pharmacodynamic study. Eligible subjects were ≥18 years old, diagnosed with DLBCL and initiating R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) immunochemotherapy. The enrolled adults received either rivaroxaban (10 mg once daily) or dabigatran etixalate (110 mg twice daily). Plasma anti-factor Xa (FXa) in participants on rivaroxaban and diluted thrombin time (dTT) in participants on dabigatran were assessed over the dosing interval before and after R-CHOP administration. Pharmacodynamic parameters of rivaroxaban and dabigatran were determined using a non-compartmental analysis.; Results : Twenty-six adults participated, with twelve in the rivaroxaban group and fourteen in the dabigatran group. The mean age was 59 ± 14.4 years. In the rivaroxaban group, the AUEC of FXa inhibition showed no significant change after R-CHOP (mean difference 3.8 ng·h/mL, 95% confidence interval (CI) -155.4 to 163.0, p = 0.96). Similarly, in the dabigatran group, the AUEC of dTT remained unchanged post R-CHOP (mean difference 54.41 ng·h/mL, 95% CI -99.09 to 207.9 ng/mL, p = 0.46). However, the median time-to-peak dTT was significantly faster with R-CHOP (3 h, [min-max, 1.5-8] compared to without it (4 h, [min-max, 3-8], p = 0.04); Conclusions : Concurrent R-CHOP chemotherapy did not significantly impact FXa inhibition by rivaroxaban or dTT by dabigatran. The time-to-peak dTT was faster when dabigatran was administered with R-CHOP.

BACKGROUND Autologous stem cell transplantation (ASCT) is the standard treatment for multiple myeloma (MM) and refractory/relapsed (R/R) lymphoma patients. Engraftment syndrome (ES) is a non-infectious febrile syndrome during ASCT. This study focused on the incidence, risk factors, manifestations, and outcomes of patients with ES receiving ASCT. MATERIAL AND METHODS This retrospective cohort study included MM and R/R lymphoma patients who underwent ASCT at Chiang Mai University Hospital from January 2014 to September 2020. ES was diagnosed by the consensus of independent reviewers based on clinical manifestations, laboratory, and radiological findings. RESULTS We included 124 patients, of whom 67 (54.1%) had lymphoma. The mean age was 48.0±12.3 years. The incidence of ES was 36.3%. The ES group had a significantly higher proportion of patients with fever, elevated liver enzymes, elevated bilirubin, hypoalbuminemia, and weight gain compared to the non-ES group. TNC more than 10×10⁸ cells/kg was an independent risk factor for ES (odds ratio 2.94 with a 95% confidence interval of 1.15-7.50, P=0.024). ES was associated with longer length of stay (22.5±8.2 vs 16.9±6.4 days, P<0.001) but was not associated with overall survival (OS). CONCLUSIONS The incidence of ES in this cohort was 36.3%. Features observed in ES patients were fever, elevated liver enzymes, elevated bilirubin, and hypoalbuminemia. TNC of more than 10×10⁸ cells/kg was an independent risk factor. ES was associated with longer length of stay but not survival outcomes.

Diffuse large B-cell lymphoma (DLBCL) is an aggressive type of non-Hodgkin lymphoma (NHL) that accounts for approximately 25-40% of all NHL cases. The objective of this study was to investigate the protein expression, clinical impact, and prognostic role of MYC, BCL2, and Ki-67 in Thai DLBCL patients. A retrospective analysis was conducted on 100 DLBCL patients diagnosed between January 2018 and December 2019. Immunohistochemistry was used to assess the expression of MYC, BCL2, and Ki-67. The study revealed a significant association between extranodal involvement and positive cases of MYC and BCL2. MYC expressions were associated with Ki-67 expression, while BCL2 positivity was associated with the non-germinal center B-cell (non-GCB) subtype. However, there were no significant differences in the three-year overall survival (OS) and three-year progression-free survival (PFS) rates when using cut-off points of ≥ 40% for MYC, ≥ 50% for BCL2, and ≥ 70% for Ki-67. Notably, DLBCL cases with co-expression of MYC and BCL2 exhibited significantly inferior three-year OS compared to other cases (0% vs. 53%; p = 0.020). Multivariate analysis identified age ≥ 60 years and Eastern Cooperative Oncology Group (ECOG) performance status as independent prognostic factors. In conclusion, MYC, BCL2, and Ki-67 expression can serve as prognostic biomarkers; however, their prognostic value may vary based on the specific cut-off values used. Therefore, determining the appropriate threshold for each biomarker based on individual laboratory analyses and clinical outcomes is crucial., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Yimpak et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Elevated ambient pollution exposure is potentially linked to thromboembolism. However, the mechanisms by which particulate matter (PM) interferes with the balance of hemostatic system remain unclear. This study investigates PM-mediated hemostatic changes in individuals across unique seasonal variations of ambient pollution., Methods: This prospective study was conducted between February and July 2020 during alterations in ambient pollution in Chiang Mai, Thailand. Blood tests from 30 healthy subjects were assessed at four-week intervals, four times in total. Various coagulation tests, including prothrombin time (PT), activated partial thromboplastin time (aPTT), von Willebrand factor (vWF), platelet count, and platelet functions, were evaluated. A mixed-effects model was used to analyze the impact of high PM2.5 and PM10 on hemostatic parameters., Results: Thirty male subjects with mean age of 38.9 ± 8.2 years, were included. High levels of PM2.5 and PM10 were significantly associated with PT shortening, with no such effect observed in aPTT. PM2.5 and PM10 values also positively correlated with vWF function, while vWF antigen levels remained unchanged. Soluble P-selectin showed a strong positive association with PM2.5 and PM10 levels. Platelet function analysis revealed no correlation with PM values., Conclusion: Short-term exposure to elevated PM2.5 and PM10 concentrations was linked to shortened PT and enhanced vWF function in healthy individuals. Exploring the impact of these changes on clinically relevant thrombosis is crucial. Additional studies on the pathogenesis of pollution-related thrombosis are warranted for maintaining good health., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Hantrakool, Sriwichai, Shaengkhamnang, Leetrakool, Niprapan, Kawichai, Wannakul, Panyasit, Tuntivate, Wongtagan, Natesirinilkul, Koonyosying, Phinyo, Punnachet, Hantrakun, Piriyakhuntorn, Rattanathammethee, Chai-Adisaksopha, Rattarittamrong, Tantiworawit, Norasetthada and Srichairatanakool.)

Background: A common complication of thalassemia is secondary osteoporosis. This study aimed to assess the prevalence and factors associated with low BMD in thalassemic patients., Method: This is a cross-sectional study. Eligible patients were males aged within 18-49 years or premenopausal women diagnosed with thalassemia in Chiang Mai University Hospital between July 2021 and July 2022. The diagnosis of low BMD by dual-energy x-ray absorptiometry (DXA) was defined as a Z-score of -2.0 SD or lower in either the lumbar spine or femoral neck. Clinical factors associated with low BMD were analyzed using a logistic regression model., Results: Prevalence of low BMD was 62.4% from 210 patients with a mean age of 29.7 ± 7.6 years. The predominant clinical characteristics of low BMD thalassemia patients were being female, transfusion-dependent (TDT) and a history of splenectomy. From multivariable analysis, the independent variables associated with low BMD were transfusion dependency (odds ratio, OR 2.36; 95%CI 1.28 to 4.38; p=0.006) and body mass index (BMI) (OR 0.71; 95%CI 0.61 to 0.82; p<0.001). Among patients with low BMD, we observed a correlation between a Z-score with low IGF-1 levels (β=-0.42; 95% CI -0.83 to -0.01; p=0.040), serum phosphate levels (β=0.40; 95% CI 0.07 to 0.73; p=0.016) and hypogonadism (β=-0.48, 95% CI -0.91 to -0.04, p=0.031)., Conclusion: This study found a prevalence of low BMD in 62.4% of subjects. Factors associated with low BMD were TDT and BMI. Within the low BMD subgroup, hypogonadism, serum phosphate and low serum IGF-1 levels were associated with a lower Z-score., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ananvutisombat, Tantiworawit, Punnachet, Hantrakun, Piriyakhuntorn, Rattanathammethee, Hantrakool, Chai-Adisaksopha, Rattarittamrong, Norasetthada, Fanhchaksai and Charoenkwan.)

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 m 2 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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kunlayawutipong, Rattanathammethee, Punnachet, Hantrakun, Piriyakhuntorn, Hantrakool, Chai-Adisaksopha, Rattarittamrong, Tantiworawit, Norasetthada and Louthrenoo.)

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

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., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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.

Introduction: Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloid leukemia (AML) with a unique clinical presentation and prognosis. This study aimed to investigate the epidemiology, clinical characteristics, treatments, and clinical outcomes of Thai APL patients dominantly treated with all-trans-retinoic acid (ATRA) combined with a chemotherapy-based therapy., Methods: This was an eight-year prospective, observational study from nine academic hospitals in the Thai Acute Leukemia Working Group (TALWG) of the Thai Society of Hematology, which included newly diagnosed Thai APL patients, aged 18 years or older. The web-based registration collected baseline charateristic, and clinical outcomes., Results: From 992 newly diagnosed AML patients, 79 APL patients were enrolled in this study. Almost all subjects were de novo APL (94.9%), while the others were therapy-related APL. The commonest clinical presentation was disseminated intravascular coagulation (38%). One-third of the patients were categorized as high risk according to the initial WBC. Almost all patients received ATRA combined with idarubicin regimen. The complete response rate was as high as 95.7%, which translated into excellent four-year overall survival (OS) (75.6%) and four-year leukemia-free survival (LFS) (75.4%). The multivariate analysis demonstrated that the older age and WBC count >20 × 10 9 /L conferred a significantly unfavorable OS with the hazard ratios of 3.03 (95% confidence interval [CI]: 1.14-8.05) and 4.18 (95%CI: 1.69-10.35), respectively. Similarly, these two parameters remained independent of the poor prognosis factors for LFS., Conclusion: This report confirmed that APL had a favorable prognosis. However, advanced age and high WBC count >20 × 10 9 /L contributed to a worse outcome., Abbreviations: APL; acute promyelocytic leukemia; ATRA; all-transretinoic acid; CR; complete remission; DS; differentiation syndrome; ECOG; Eastern Cooperative Oncology Group; ED; early death; HR; hazard ratio; IQR; interquartile range; LFS; leukemia-free survival; OS; overall survival; WBC; white blood cell.

Introduction: To date, there is limited data regarding the incidence and risk prediction of cancer-associated thrombosis among South-East Asian patients who do not receive thromboprophylaxis., Materials and Methods: This was a prospective cohort study conducted at a tertiary medical center from June 2020 to December 2021 in Thailand. We enrolled cancer patients aged ≥ 18 years, with ECOG score ≤ 1, scheduled to receive the first cycle of chemotherapy. We measured incidence of venous thromboembolism (VTE), all-cause mortality and performance of risk prediction scores., Results: A total of 457 patients were included with a mean age of 58.18 ± 12.60 years. By the end of 6 months period, VTE had occurred in 30 patients (6.56 %, 95%CI 4.36-9.21). The median time to the first thrombosis was 1.94 months (IQR 0.26-3.19). Cancer associated thrombosis incidence was 14.58 % for Khorana score ≥ 3, 6.67 % for scores 1-2 and 2.13 % for score 0. C-statistics were 0.50 (95%CI 0.41-0.60) for Khorana score cut-off ≥ 2, 0.57 (95%CI 0.49-0.65) for Khorana score ≥ 3, 0.55 (95%CI 0.46-0.65) for PROTECHT score ≥ 3, and 0.57 (95%CI 0.49-0.65) for CONKO score ≥ 3. Classifying cholangiocarcinoma as very-high-risk increased the Khorana score cut-off ≥ 3's C-statistic to 0.62 (95%CI 0.53-0.71)., Conclusions: A significant proportion of ambulatory South-East Asian cancer patients without thromboprophylaxis developed VTE. Further prospective studies investigating the benefit of thromboprophylaxis in high-risk patients with active cancer are warranted., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

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., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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.

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., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Attachaipanich, Aungsusiripong, Piriyakhuntorn, Hantrakool, Rattarittamrong, Rattanathammethee, Tantiworawit, Norasetthada and Chai-Adisaksopha.)

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., Competing Interests: Disclosure of conflicts of interest All authors declare that there are no potential competing interests., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: This study aimed to evaluate the performance of the D-index, a calculated measure of neutropenic burden, in predicting the risk of invasive fungal infections (IFIs) in acute myeloid leukemia (AML) patients., Methods: A retrospective study of adult AML patients who received the first induction chemotherapy and developed febrile neutropenia was conducted. Clinical characteristics, laboratory data, and the calculation of the D-index and cumulative D-index (c-D-index) were collected and analyzed between patients with and without IFIs., Results: A total of 101 patients were included, with 16 (15.8%) patients who developed IFIs. Clinical characteristics, antifungal prophylaxis, and AML cytogenetic risk were similar between patients with or without IFIs. The results showed that the D-index and c-D-index were more effective in predicting IFIs than the duration of neutropenia. With the D-index cutoff of 7083, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 81.3%, 83.5%, 48.2%, and 95.9%, respectively. c-D-index at 5625 revealed sensitivity, specificity, PPV, and NPV for IFIs of 68.8%, 68.2%, 28.9%, and 92.1%, respectively. Using this cutoff of c-D-index, patients without IFIs were overtreated with an antifungal regimen in 45 (52.9%) cases., Conclusion: The D-index and c-D-index were helpful indicators for defining the risk of IFIs in AML patients with febrile neutropenia., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Rattanathammethee et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: With adequate blood transfusion and iron chelation, thalassemia patients have a longer life expectancy and experience long-term metabolic complications, including osteoporosis, fractures, and bone pain. Alendronate, an oral bisphosphonate, is currently used to treat various types of osteoporosis. However, the efficacy for the treatment of thalassemia-associated osteoporosis remains unclear., Methods: We conducted a randomized controlled trial to evaluate the efficacy of alendronate for the treatment of osteoporosis in thalassemia patients. Patients were included if they were males (18-50 years) or premenopausal females with low bone mineral density (BMD) (Z-score < -2.0 SD) or positive vertebral deformities from vertebral fracture analysis (VFA). Stratified randomization was performed according to sex and transfusion status. Patients were 1:1 allocated to receive once weekly alendronate 70 mg orally or placebo for a total duration of 12 months. BMD and VFA were re-evaluated at 12 months. Markers of bone resorption (C-terminal crosslinking telopeptide of type I collagen; CTX) and bone formation (Procollagen type I N-terminal propeptide; P1NP), and pain scores were measured at baseline, 6 months, and 12 months. The primary outcome was the change of BMD. The secondary endpoints were changes in bone turnover markers (BTM) and pain scores., Results: A total of 51 patients received the study drug, 28 patients were assigned to receive alendronate and 23 patients to receive placebo. At 12 months, patients in the alendronate group had significant improvement of BMD at L1-L4 compared to their baseline (0.72 ± 0.11 vs 0.69 ± 0.11 g/cm 2 , p = 0.004), while there was no change in the placebo group (0.69 ± 0.09 vs 0.70 ± 0.06 g/cm 2 , p = 0.814). There was no significant change of BMD at femoral neck in both groups. Serum BTMs were significantly decreased among patients receiving alendronate at 6 and 12 months. The mean back pain score was significantly reduced compared to the baseline in both groups (p = 0.003). Side effects were rarely found and led to a discontinuation of the study drug in 1 patient (grade 3 fatigue)., Conclusion: Alendronate 70 mg orally once weekly for 12 months effectively improves BMD at L-spine, reduces serum BTMs, and alleviates back pain in thalassemia patients with osteoporosis. The treatment was well tolerated and had a good safety profile., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Piriyakhuntorn, Tantiworawit, Phimphilai, Srichairatanakool, Teeyasoontranon, Rattanathammethee, Hantrakool, Chai-Adisaksopha, Rattarittamrong, Norasetthada, Fanhchaksai and Charoenkwan.)

Objective: Tyrosine kinase inhibitor (TKI) is the standard treatment for chronic myeloid leukemia (CML). In the national list of essential medicines in Thailand, the first, second, and third-line treatments are imatinib, nilotinib, and dasatinib, sequentially, different from the European Leukemia Net guidelines. This study aimed to evaluate the outcomes of CML patients who received sequential treatment with TKI., Methods: This study enrolled CML patients diagnosed between 2008 and 2020 at Chiang Mai University Hospital who received TKI. Medical records were reviewed for demographic data, risk score, treatment response, event-free survival (EFS), and overall survival (OS)., Result: One hundred and fifty patients were included in the study, 68 patients (45.3%) were female. The mean age is 45.9 ± 15.8 years. Most patients (88.6%) had good ECOG status (0-1). The CML diagnosis was in the chronic phase in 136 patients (90.6%). The EUTOS long-term survival (ELTS) score revealed a high of 36.7%. At the median follow-up of 8.3 years, 88.6% of patients were in complete cytogenetic response (CCyR), whereas 58.0% were in major molecular response (MMR). The 10-year OS and EFS were 81.33% and 79.33%, respectively. The factors associated with poor OS were high ELTS score (P = 0.01), poor ECOG performance status (P < 0.001), not achieved MMR within 15 months (P = 0.014), and not achieved CCyR within 12 months (P < 0.001)., Conclusion: The sequential treatment for CML patients had a good response. Factors predicting survival were ELTS score, ECOG performance status, and early achieving MMR and CCyR.

Anti-platelet factor 4 (anti-PF4) antibodies were identified as pathogenic antibodies for vaccine-induced immune thrombocytopenia and thrombosis (VITT) in subjects receiving ChAdOx1 nCoV-19 vaccinations. We performed a prospective cohort study to determine the prevalence of anti-PF4 and the effect of the ChAdOx1 nCoV-19 vaccine on anti-PF4 in healthy Thai subjects. Anti-PF4 antibodies were measured before and four weeks after receiving the first vaccination. Participants with detectable antibodies were scheduled for repeat anti-PF4 analysis at 12 weeks after the second vaccination. Of 396 participants, ten participants (2.53%; 95% confidence interval [CI], 1.22-4.59) were positive for anti-PF4 before receiving vaccinations. Twelve people (3.03%; 95% CI, 1.58-5.23) had detectable anti-PF4 after the first vaccination. There was no difference in the optical density (OD) values of anti-PF4 antibodies when comparisons were made between pre-vaccination and four weeks after the first vaccination ( p = 0.0779). There was also no significant difference in OD values in participants with detectable antibodies. No subjects experienced thrombotic complications. Pain at the injection site was associated with an increased risk of being anti-PF4 positive at an odds ratio of 3.44 (95% CI, 1.06-11.18). To conclude, the prevalence of anti-PF4 was low in Thais and did not significantly change over time.

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., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Infection is one of the leading causes of mortality in thalassemia patients. This study aimed to examine qualitative and quantitative changes in monocytes in thalassemia patients. Monocytes were isolated from peripheral blood mononuclear cells and separated into subpopulations by flow cytometry. Cytokine levels were measured using quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) and sandwich enzyme-linked immunosorbent assay (ELISA). The primary endpoint was monocyte-derived TNF-α expression. A total of 78 patients and 26 controls were included. The mean log (TNF-α fold-change) by qRT-PCR was significantly lower in all thalassemia groups, at 1.27 in controls, versus 0.97 (p = 0.0014) in non-transfusion-dependent thalassemia (NTDT), 0.96 (p = 0.0004) in non-splenectomized transfusion-dependent thalassemia (TDT-NS), and 0.87 (p < 0.0001) in splenectomized transfusion-dependent thalassemia (TDT-S). Similarly, the mean 2-h TNF-α level measured by sandwich ELISA assay was significantly lower in all thalassemia groups, at 98.16 pg/mL in controls, versus 56.45 pg/mL (p = 0.0093) in NTDT, 39.05 pg/mL (p = 0.0001) in TDT-NS and 32.37 pg/mL (p < 0.0001) in TDT-S. Likewise, TDT patients had a significantly decreased percentage of non-classical monocytes, by approximately half compared to controls. Our results show that thalassemia major patients have clearly impaired monocyte counts and function., (© 2022. The Author(s).)

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-β2-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., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Kansuttiviwat et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: To compare the efficacy and side effects of salvage chemotherapy between etoposide, methylprednisolone, cytarabine and cisplatin (ESHAP) and ifosfamide, carboplatin and etoposide plus dexamethasone (DICE) for relapsed or refractory diffuse large B-cell lymphoma (DLBCL)., Methods: Medical records of patients with relapsed or refractory DLBCL receiving second-line ESHAP or DICE chemotherapy with or without rituximab from January 2007 to November 2022 were retrospectively reviewed. The primary objective was progression-free survival (PFS). The secondary objectives were overall survival (OS), overall response rate (ORR) and adverse events (AEs)., Results: Seventy patients were enrolled including 21 patients who received ESHAP and 49 patients who received the DICE regimen. Six patients (28.6%) and 19 patients (38.8%) in the ESHAP and DICE groups underwent ASCT, respectively. The ORR was 47.6% for ESHAP and 53.1% for DICE ( p  = .67). The two-year PFS was 14.3% for ESHAP and 26.5% for DICE ( p  = .33) with median PFS of 5 months and 14 months, respectively (hazard ratio 0.74; 95% CI 0.39-1.36, p  = .330). The two-year OS was 14.3% for ESHAP and 26.5% for DICE ( p  = .37) with median OS of 8 months and 19 months, respectively. Patients in ESHAP group have more all-grade renal impairment than DICE group (23.8% vs. 6.1%, p  = .047)., Discussion and Conclusions: Efficacy between ESHAP and DICE regimens as salvage chemotherapy for relapsed or refractory DLBCL was not significantly different in terms of two-year PFS, two-year OS and ORR. DICE regimen had less renal AE than ESHAP.

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 × 10 9 /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 × 10 9 /L; p  < 0.001). Patients with U2AF1 mutations were associated with more severe leukopenia than wild-type (3 vs. 4.18 × 10 9 /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 × 10 9 /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.

Background: Secondary acute myeloid leukemia (sAML) and AML with myelodysplasia-related changes (AML-MRC) both result in dismal outcomes. This retrospective study aimed to determine whether these features are poor prognostic factors independent of older age and adverse cytogenetics, which are commonly associated with a poor prognosis., Methods: The characteristics and real-world outcomes of sAML and AML-MRC from the Thai AML registry database were investigated., Results: From a total of 992 newly diagnosed AML patients, 315 (31.8%) patients were classified into sAML or AML-MRC subtypes. Older age, low white blood cell (WBC) count, low bone marrow blast, and adverse cytogenetic risk were commonly present in sAML and AML-MRC compared to de novo AML. Complete remission after 7 + 3 induction therapy occurred in 42.3% of patients with sAML or AML-MRC and 62.4% of de novo AML (P < .001). The median overall survival (OS) of sAML, AML-MRC, and de novo AML were 6.9, 7.0, and 12.2 months, respectively (P < .001). The independent prognostic factors for inferior OS were older age, intermediate-risk or adverse-risk cytogenetics, WBC count > 100 × 10 9 /L, poor performance status, and a subgroup of AML-MRC with the morphologic criteria of multilineage dysplasia (AML-MRC-M). In addition, sAML, AML-MRC, and a WBC count > 100 × 10 9 /L were pre-treatment prognostic factors associated with poor relapse-free survival (P = .006, P = .017, and P < .001, respectively)., Conclusion: Both sAML and AML-MRC are independently associated with poor outcomes in Thai patients. Our study supports AML-MRC-M as an adverse prognostic factor for OS., (Copyright © 2022 Elsevier Inc. All rights reserved.)

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.

Introduction: To determine the prevalence, clinical outcomes, and factors associated with hydroxyurea (HU) resistance or intolerance among polycythemia vera (PV) and essential thrombocythemia (ET) patients., Methods: This study was a retrospective cohort study including PV and ET patients diagnosed by WHO criteria and treated with HU between January 2000 and June 2020. Clinical features, laboratory data, and resistance or intolerance of HU were collected. The prevalence, clinical outcomes, and associated factors of HU resistance or intolerance were analyzed., Results: There were 260 patients including 144 ET and 116 PV. The prevalence of HU resistance or intolerance was 11.9% (31 patients) which was more frequent in ET patients (14.6% vs. 8.6% in PV). Patients who had HU resistance or intolerance significantly increased the risk of bleeding events (HR 2.64; 95% CI 1.19-5.85, P  = 0.017). The risk factors of HU resistance or intolerance were low baseline hemoglobin levels (HR 0.90; 95%CI 0.84-0.97, P  = 0.01), age more than 60 years old (HR 3.98; 95% CI 2.08-7.62, P  < 0.001) and splenomegaly (HR 2.08; 95% CI 1.03-4.21, P  = 0.04)., Conclusions: The prevalence of HU resistance or intolerance in PV and ET patients was 11.9%. Patients with HU resistance or intolerance significantly increased the risk of bleeding complications.

Background: Intermediate or high doses of cytarabine (IDAC or HiDAC) were recommended as postremission chemotherapy for acute myeloid leukemia (AML). This retrospective study investigated the real-world outcomes of 3-different cytarabine doses from the multicenter Thai AML registry database., Patients and Methods: The intermediate- and adverse-risk AML patients (N = 258) who achieved complete remission and proceeded to single-agent cytarabine consolidation were enrolled., Results: The median relapse-free survival (RFS) using IDAC 1.5 g/m 2 , high-dose cytarabine (HiDAC) 2 g/m 2 , and HiDAC 3 g/m 2 were 12.6, 11.7, and 13 months, respectively. The median overall survival (OS) using IDAC 1.5 g/m 2 , HiDAC 2 g/m 2 , and HiDAC 3 g/m 2 were 34.9, 22.7, and 23.7 months, respectively. No significant difference in RFS and OS was detected between the 3 doses. Secondary AML, white blood cell > 100×10 9 /L and the adverse-risk AML were independent prognostic factors for inferior survival (P= .008, P < .001, P= .014). Patients who completed 3 to 4 cycles of consolidation had significantly superior RFS and OS (P< .001, P< .001). Febrile neutropenia occurred in 72.9% of IDAC, 73.8% of HiDAC 2 g/m 2 , and 78.1% of HiDAC 3 g/m 2 without statistical significance. However, the incidence of septic shock was significantly higher after HiDAC 3 g/m 2 compared to IDAC regimen (8% vs. 3%, P= .037)., Conclusion: IDAC is an appropriate regimen for postremission chemotherapy for intermediate- and adverse-risk AML. The higher dosing levels may not produce any benefits to patients and may increase incidence of septic shock. The number of consolidation cycles may impact on survivals rather than the intensity of cytarabine., Competing Interests: Disclosure All authors report no conflict of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: The MD Anderson Symptoms Inventory for acute myeloid leukemia/myelodysplastic syndrome (MDASI-AML/MDS) is a specific patient-reported outcome measure (PROM) and widely used to assess the quality of life of acute myeloid leukemia (AML) patients. This study aimed to validate the inventory in Thai AML patients., Methods: After receiving permission, the original MDASI-AML/MDS was translated and cross-culturally adapted to Thai. Twenty AML patients were included in the study. Internal consistency was evaluated using Cronbach's alpha and test-retest reliability was analyzed using intraclass correlation coefficient (ICC). Spearman's rank correlation was used to investigate the subscales of Thai MDASI-AML/MDS and Thai version of European Quality of Life-5 Dimension-5 Level (Thai EQ-5D-5L)., Results: All subscales of Thai MDASI-AML/MDS showed an acceptable Cronbach's alpha (0.64-0.91). The test-retest reliability of each subscale was adequate (ICC = 0.88-0.95). The core symptoms subscale in the Thai MDASI-AML/MDS strongly correlated to the anxiety/ depression subscale in the Thai EQ-5D-5L (r = 0.69, p = 0.0006). A strong correlation was demonstrated between the interference subscale of the Thai MDASI-AML/MDS and the usual activities subscale of Thai EQ-5D-5L (r = 0.77, p = 0.0001). A weak correlation was found between the MDS/AML specific symptoms subscale in the Thai MDASI-AML/MDS and anxiety and depression subscale in the Thai EQ-5D-5L (r = 0.49, p = 0.0285). The Thai MDASI-AML/MDS had strong correlation with Thai EQ-5D-5L (r = 0.71, p = 0.0050)., Conclusions: The Thai MDASI-AML/MDS provides adequate internal consistency in all subscales as well as good construct validity and reliability for Thai patients.

Background: Unexplained cytopenia (UC) and low-risk myelodysplastic syndrome (MDS) are distinguished mainly by morphologic dysplasia, which sometimes shows inter-observer discrepancy. We hypothesized that gene mutations are strong prognostic factors for these low-risk patients., Materials and Methods: We enrolled patients from 4 medical centers with unexplained cytopenia of at least 1 lineage. Diagnosis of low-risk MDS was made according to WHO 2016 classification and a revised international prognostic scoring system (R-IPSS) score of ≤ 3.5. DNA was extracted from bone marrow or blood and sequenced by targeted next generation sequencing (NGS)., Results: One hundred twenty-one patients were recruited: 25% with UC and 75% with low-risk MDS. Complete blood counts were similar, but low-risk MDS patients carried higher numbers of mutations (1 vs. 0; P = .04) than UC patients. Overall, the most frequent mutated genes were TET2 (14.6%), SF3B1 (12.2%), and ASXL1 (9.7%). Survival rates of low-risk MDS patients versus UC patients were not significantly different. UC patients and low-risk MDS patients without genetic abnormalities showed superior 5-year progression free survival compared to MDS patients with mutations (100% vs. 76.0%; P = .005). Overall, ASXL1 mutations were associated with decreased 4-year overall survival compared to wild-type (59% vs. 31%; P = .01). In a multivariate analysis, ASXL1 and DNMT3A mutations in low-risk MDS patients were associated with a higher risk of disease progression with hazard ratios of 7.88 (95% CI 1.76-35.32, P = .01) and 7.45 (95% CI 1.61-34.46, P = .01), respectively., Conclusion: Mutation detection is important for proper risk stratification of patients presenting with idiopathic cytopenia., (Copyright © 2021. Published by Elsevier Inc.)

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)/β-thalassemia (β-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.

Objectives: To evaluate any association between pre-transfusion hemoglobin (Hb) levels and thalassemia complications and to identify the Hb cutoff values to predict thalassemia complications., Methods: We performed a cross-sectional study in thalassemia patients who attended the Adult Hematology Clinic of the tertiary care University Hospital from October 2017 to October 2018. A point-biserial correlation was used to identify any association between Hb levels and thalassemia complications. A receiver operating characteristic (ROC) curve was used to identify the diagnostic ability of Hb levels to predict thalassemia complications and identify Hb cutoff values., Results: Out of the 102 patients, there were 53 transfusion dependent thalassemia (TDT) patients and 49 non-transfusion dependent thalassemia (NTDT) patients. In theTDT group, Hb levels showed a negative correlation with severe hepatic iron overload and hypogonadism. The cutoff Hb levels to predict severe hepatic iron overload and hypogonadism were ≤7.01 and 6.81 g/dL, respectively, at which points the area under the ROC curve (AUC) were 0.721 and 0.708, respectively. In the NTDTgroup, Hb levels were negatively correlated with hepatic iron overload, osteoporosis, and pulmonary hypertension. The cutoff values of Hb levels to predict hepatic iron overload, osteoporosis, and pulmonary hypertension were ≤8.24, 7.16, and 7.16 g/dL, respectively, at which points the AUC were 0.923, 0.715, and 0.725, respectively., Conclusions: Lower Hb level was associated with more frequent complications in both TDT and NTDT patients. The Hb cutoff levels to predict these complications were identified.

Objectives: The primary objective was to compare the efficacy of intermediate-dose cytarabine (IDAC) and high-dose cytarabine (HiDAC) as consolidation chemotherapy for acute myeloid leukemia (AML) in terms of a one-year-relapse-free survival rate (RFS). The secondary objectives were one-year-overall survival rate (OS) and adverse effects., Methods: This was a retrospective study conducted at Chiang Mai University Hospital. AML patients who achieved complete remission after 7 + 3 induction regimen and received consolidation therapy with either IDAC or HiDAC during January 2015 and January 2018 were eligible. Data about clinical characteristics, efficacy and safety of IDAC and HiDAC regimens were collected., Results: Sixty-two AML patients were enrolled (30 patients in IDAC and 32 patients in the HiDAC regimen). The one-year RFS in the IDAC group was 63.33% and 46.87% in the HiDAC group ( P  = 0.137). The 1-year OS was 93.33% and 84.37% in the IDAC and HiDAC, respectively ( P  = 0.691). The duration of grade 3-4 thrombocytopenia was significantly shorter in IDAC than HiDAC (mean duration 14.69 vs. 23.84 days; P  = 0.045). There was no significant difference in other parameters including hemoglobin nadir, absolute neutrophil count nadir, platelet nadir, febrile neutropenia, duration of grade 3-4 neutropenia, and duration of hospitalization., Discussion and Conclusions: There was no significant difference in the one-year RFS and OS between IDAC and HiDAC. The IDAC regimen is an acceptable option for consolidation treatment in AML.