Pokpong Piriyakhuntorn

Increased gastrointestinal iron absorption contributes substantially to iron overload in non-transfusion-dependent thalassemia (NTDT) patients. Resveratrol (RVT) and omeprazole (OMP) may reduce intestinal iron absorption and potentially complement iron chelation therapy. This randomized, double-blind, placebo-controlled trial evaluated the efficacy and safety of adjunctive RVT or OMP in adults with NTDT receiving stable iron chelation therapy. The primary outcome was the change in serum ferritin; secondary outcomes influenced serum iron (SI), transferrin saturation (TS), erythroferrone (ERFE), hepcidin, fetal hemoglobin (HbF), and safety. Participants with serum ferritin ≥ 300 ng/mL were randomized (1:1:1) to receive RVT 250 mg, OMP 20 mg, or the placebo (PLA) twice daily for 6 months. Thirty participants were randomized (RVT, n = 10; OMP, n = 11; PLA, n = 9), with a baseline median serum ferritin value of 629 ng/mL, interquartile range (IQR) 484–975. Serum ferritin decreased numerically over 6 months in the RVT and OMP groups relative to PLA; however, no significant treatment × time interactions or adjusted between-group differences in changes from the baseline were observed. Although significant within-group changes were observed for selected iron-regulatory biomarkers, including hepcidin, ERFE, and TS, these were not accompanied by significant treatment × time interactions and did not demonstrate differential treatment effects. Both interventions were generally well tolerated, and no serious adverse events were reported. In this underpowered trial, neither adjunctive RVT nor OMP demonstrated statistically significant treatment-specific effects on serum ferritin or other iron-related outcomes when compared with the placebo. The observed numerical trends warrant evaluation in larger, adequately powered trials. Trial Registration: ISRCTN73258526.

Polycythemia vera (PV) is a myeloproliferative neoplasm frequently complicated by thromboembolic events. However, data regarding thrombotic burden and long-term outcomes among Asian patients remain limited. We conducted a retrospective cohort study at a tertiary referral center to evaluate thromboembolic events, treatment-related complications, disease progression, and overall survival in patients with PV. A total of 133 patients were included, with a median age of 61 years (range 18–88). Most patients were male (60.2%). Fifty-one patients (38.3%) experienced at least one thromboembolic event, with 54 events in total, of which 87% occurred before or at PV diagnosis. Arterial thrombosis accounted for 90.7% of all events. Age ≥60 years was significantly associated with thromboembolic events, with an odds ratio of 2.34 (95% confidence interval [CI], 1.07–5.11). After a median follow-up of 7.7 years, the 5-year overall survival was 82.7% (95% CI, 74.61–88.35). Prior thrombosis was associated with an increased risk of death (hazard ratio, 1.98; 95% CI, 1.15–3.42). Hydroxyurea resistance or intolerance occurred in 9.8% of patients. Bleeding complications were observed in 6.8%, including major bleeding in 4.5%. Fibrotic transformation, leukemic transformation, and secondary solid malignancies occurred in 4.5%, 3.8%, and 6.0% of patients, respectively. Thromboembolic events were common and predominantly arterial in this Asian PV cohort, occurring mainly before or at diagnosis. Prior thrombosis was associated with inferior survival. Long-term follow-up also revealed disease progression and secondary solid malignancies, underscoring the importance of continued surveillance.

The aim of this study was to characterize the clinical features and outcomes of patients with JAK2 V617F- and CALR-unmutated essential thrombocythemia (ET) and to identify potential driver mutations through whole-exome sequencing (WES). This was a cross-sectional study including patients diagnosed with ET between 2007 and 2024. Clinical characteristics and outcomes were compared between patients with and without JAK2V617F and CALR mutations. WES was analyzed in JAK2V617F- and CALR-unmutated ET patients. Thirty-nine out of 162 ET patients (24%) were JAK2V617F- and CALR-unmutated. This group was younger than patients in the JAK2V617F mutated group (mean age 53.7 vs. 61.1 years, p = 0.012) and had lower incidence of thrombotic events (5.1% vs. 9.1%, p = 0.327). The median overall survival was 13.51 years compared to 12.61 years in patients with JAK2V617F or CALR mutations (p = 0.63). There were no statistically significant differences in clinical symptoms, incidence of thrombosis, bleeding, myelofibrosis, or leukemic transformation. WES was analyzed in 15 patients. Uncommon MPL mutations were identified, including MPLL265F, MPLP70L, and MPLR321Q. Potential novel CALR mutations were detected in exon 5 (c.540C > T, N180 = ) and exon 6 (c.703-3del). Non-driver gene mutations were detected, including RUNX1 (57.1%), ASXL1, DNMT3A, SETBP1, and MSH6. Patients with JAK2V617F- and CALR-unmutated ET tend to present at a younger age and exhibit a lower incidence of thrombosis compared to those with JAK2V617F-mutated ET. The application of WES enabled the detection of uncommon and potential driver mutations in JAK2V617F- and CALR-unmutated ET.

Pediatric acute lymphoblastic leukemia (ALL) has a cure rate above 90%, but outcomes in adult remain poor, with 3-year survival around 40%. Adolescents and young adults (AYAs) fall between these groups, often facing worse disease features and treatment-related risks. While pediatric-inspired regimens improve survival in AYAs, they also raise the issue of infection due to treatment intensity. A retrospective analysis was conducted on AYA-ALL patients treated at Chiang Mai University Hospital from 1 January 2007 to 31 December 2023. Data were accessed for research purpose from 10 January 2024 to 31 December 2024. Patients received either pediatric-inspired (TPOG) or adult regimens (Hyper-CVAD or GMALL). Infections were classified as clinically (CDI) or microbiologically documented (MDI). Logistic regression identified infection risk factors. Among 94 patients (62.8% male; median age 22.9 years), 56.4% received TPOG and 43.6% adult regimens. Infections occurred in 79.8%, higher with adult regimens (90.2% vs. 71.7%, p = 0.03). CDI was more frequent in adult regimens (73.4% vs. 52.8%, p = 0.04), while fungal infections predominated in TPOG (26.4% vs. 9.8%, p = 0.04). Adult regimens independently increased infection risk (OR 3.55; 95% CI 1.02-12.36, p = 0.04). Infection peaks occurred during induction (47.8%) and consolidation (51.8%). Gram-negative bacteria were most common (85%), mainly Escherichia coli (27%) and Salmonella spp. (21%). The invasive pulmonary aspergillosis was 11.7%. AYA-ALL patients are highly susceptible to infections, particularly with adult regimens. Fungal infections were more frequent with TPOG. Strengthening infection prevention and providing early treatment are vital.

Objective: This study investigated the prevalence of arterial stiffness among individuals diagnosed with myeloproliferative neoplasms (MPNs), specifically essential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis (PMF). Methods: We performed a cross-sectional study at Chiang-Mai University Hospital, Thailand, defining arterial stiffness as a mean cardio-ankle vascular index (CAVI) ≥8.0. Patients were compared to age-, sex-, and Thai cardiovascular (CV) risk score-matched controls with CV risk factors. Additional outcomes included the 10-year CV risk in MPN patients, estimated by the Thai CV risk score, and the correlation between plasma C-reactive protein (CRP) levels and CAVI. Results: Eighty participants were included (50 with PV, 24 with ET, 6 with PMF; median age: 63.5 years). Arterial stiffness was present in 63.8% of MPN patients overall, with respective rates for ET, PV, and PMF being 70.8%, 60.0%, and 66.7% (p = 0.655). When compared to matched non-MPN controls with CV risk, prevalence of arterial stiffness did not differ significantly (65.2% vs. 60.9%, p = 0.539). The median estimated 10-year CV risk for patients with MPNs was 13.6% (range 0.7–30.0). No significant association was observed between CRP levels and mean CAVI (R = 0.208, p = 0.073). Conclusions: Arterial stiffness was detected in 63.8% of individuals with MPNs, a prevalence like that of matched non-MPN patients with CV risk factors.

Deferasirox (DFX) is an oral iron chelator for thalassemia patients with iron overload. DFX was FDA-approved as a first-line treatment for chronic iron overload. In Thailand, DFX was indicated as second-line therapy for patients unresponsive to deferiprone. Objectives: This study aimed to investigate the efficacy and safety of DFX monotherapy. Methods: All transfusion-dependent thalassemia patients who received second-line DFX monotherapy were identified from the thalassemia registry between May 2007 and May 2022. The primary endpoint was the change in body iron stores, measured by serum ferritin at week 24. At treatment end, patients with a serum ferritin (SF) level < 1000 ng/mL in transfusion-dependent thalassemia (TDT) were categorized as the ferritin response group. Multivariate analysis identified factors driving group differences. Results: Forty-two patients were enrolled with a mean age of 35.5 (13–57) years. Of these, 73.81% had beta-thalassemia. The median initial DFX dose was 20.26 (17.85–22.22) mg/kg/day, with a median treatment follow-up of 2 (1.80–2.45) years. Median SF was decreased from 2516 (1712 to 3065) ng/mL to 1027.5 (598–1867) ng/mL (p < 0.001). Of 21 (50%) patients in the ferritin response group, independent factors were age > 15 years and lower initial SF, with OR = 7.13 (95% CI 1.05–48.49, p = 0.045) and OR = 0.93 (95% CI 0.87–1.00, p = 0.039). The most common adverse events were gastric irritation symptoms (11.90%). Conclusions: Deferasirox is an effective oral iron chelator for thalassemia, with manageable side effects. Half of patients reached target SF levels. Adults (>15 years) with lower initial SF levels had a better response to DFX.

Background/Objectives: Imatinib, a first-generation tyrosine kinase inhibitor, is the standard treatment for chronic myeloid leukemia (CML). Although generic formulations have improved access, concerns regarding their efficacy and safety remain. This study aimed to compare the clinical outcomes and adverse events of original and generic imatinib in patients with CML in Thailand. Methods: We conducted a retrospective cohort study of patients with chronic-phase CML receiving frontline imatinib at Chiang Mai University Hospital between January 2012 and September 2022. Treatment responses, event-free survival (EFS), overall survival (OS), and adverse events were also analyzed. Results: Among the 71 patients, 46 (64.8%) received original imatinib, and 25 (35.2%) received generic imatinib. The median follow-up period was 80.3 months (IQR: 52.0–106.4). At 12 months, there were no significant differences in the cumulative complete cytogenetic response (73.3% vs. 70.8%, p = 0.825) or major molecular response (35.6% vs. 41.7%, p = 0.618). Although EFS was not significantly different between the groups, OS was significantly longer in patients receiving original imatinib (p < 0.001). Conclusions: Although early treatment responses and EFS were similar, generic imatinib was associated with an inferior OS. These findings highlight the need for close monitoring and further evaluation of long-term outcomes when using generic formulations.

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/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 10x10(8) 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 10x10(8) cells/kg was an independent risk factor. ES was associated with longer length of stay but not survival outcomes.