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.

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.

Comparison of risk prediction scores for cancer-associated thrombosis in ambulatory cancer patients not receiving thromboprophylaxis: A prospective cohort study in a South-East Asian population.

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.

Efficacy of ESHAP versus ICE plus dexamethasone (DICE) as salvage chemotherapy for relapsed or refractory diffuse large B-cell lymphoma.

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.

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.

The efficacy of alendronate for the treatment of thalassemia-associated osteoporosis: a randomized controlled trial.

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/cm2, p = 0.004), while there was no change in the placebo group (0.69 ± 0.09 vs 0.70 ± 0.06 g/cm2, 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.

D-index and invasive fungal infections (IFIs) in adult acute myeloid leukemia (AML) patients with the first episode of febrile neutropenia.

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.

Long-Term Outcomes with Sequential Tyrosine Kinase Inhibitors Treatment in Chronic Myeloid Leukemia Patients.

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.

Longitudinal Profiles of Anti-Platelet Factor 4 Antibodies in Thai People Who Received ChAdOx1 nCoV-19 Vaccination.

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.

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.

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 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.

Alteration of monocyte subsets and their functions in thalassemia patients.

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.

A randomized placebo-controlled clinical trial of oral green tea epigallocatechin 3-gallate on erythropoiesis and oxidative stress in transfusion-dependent ß-thalassemia patients.

ß-Thalassemia patients suffer from ineffective erythropoiesis and increased red blood cell (RBC) hemolysis. Blood transfusion, erythropoietic enhancement, and antioxidant supplementation can ameliorate chronic anemia. Green tea extract (GTE) is comprised of catechin derivatives, of which epigallocatechin-3-gallate (EGCG) is the most abundant, presenting free-radical scavenging, iron-chelating, and erythropoiesis-protective effects. The present study aimed to evaluate the effects of GTE tablets on the primary outcome of erythropoiesis and oxidative stress parameters in transfusion-dependent ß-thalassemia (TDT) patients. Twenty-seven TDT patients were randomly divided into placebo and GTE tablet (50 and 100 mg EGCG equivalent) groups and assigned to consume the product once daily for 60 days. Blood was collected for analysis of hematological, biochemical, and oxidative stress parameters. Accordingly, consumption of GTE tablets improved blood hemoglobin levels when compared with the placebo; however, there were more responders to the GTE tablets. Interestingly, amounts of nonheme iron in RBC membranes tended to decrease in both GTE tablet groups when compared with the placebo. Importantly, consumption of GTE tablets lowered plasma levels of erythroferrone (p < 0.05) and reduced bilirubin non-significantly and dose-independently. Thus, GTE tablets could improve RBC hemolysis and modulate erythropoiesis regulators in transfusion-dependent thalassemia patients.

Psychometric Properties of MD Anderson Symptoms Inventory for Acute Myeloid Leukemia Patients in Thailand.

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.

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.

Effects of Particulate Matter on Inflammation and Thrombosis: Past Evidence for Future Prevention.

Ambient air pollution has become a common problem worldwide. Exposure to pollutant particles causes many health conditions, having a particular impact on pulmonary and cardiovascular disease. Increased understanding of the pathological processes related to these conditions may facilitate the prevention of the adverse impact of air pollution on our physical health. Evidence from in vitro, in vivo, and clinical studies has consistently shown that exposure to particulate matter could induce the inflammatory responses such as IL-6, TNF-α, IL-1ß, as well as enhancing the oxidative stress. These result in vascular injury, adhesion molecule release, platelet activation, and thrombin generation, ultimately leading to a prothrombotic state. In this review, evidence on the effects of particulate matter on inflammation, oxidative stress, adhesion molecules, and coagulation pathways in enhancing the risk of thrombosis is comprehensively summarized and discussed. The currently available outcomes of interventional studies at a cellular level and clinical reports are also presented and discussed.

Prevalence and clinical outcomes of polycythemia vera and essential thrombocythemia with hydroxyurea resistance or intolerance.

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.

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.