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

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

Essential genetic modifiers and their measurable impact in a community-recruited population analysis for non-severe hemoglobin E/ß-thalassemia prenatal genetic counseling.

The study aimed to identify essential phenotype-modulating factors among the pre-existence of several important ones and clarify their measurable impact on the clinical severity of hemoglobin (Hb) E/ß-thalassemia in a community-recruited population analysis. This prospective study was designed to compare modifiers between community- (less or no symptoms) and hospital-recruited individuals with Hb E/ß-thalassemia. The formerly included couples previously assessed for prenatal thalassemia at-risk status at 42 community and 7 referral hospitals in Thailand through on-site investigations between June 2020 and December 2021. The control included Hb E/ß-thalassemia patients undergoing transfusions. The Mahidol score classified disease severity. Beta-globin, α0-thalassemia (-SEA, -THAI), α+-thalassemia (-α3.7, -α4.2), Hb Constant Spring (αCS) alleles, rs766432 in BCL11A, rs9399137 in HBS1L-MYB, and rs7482144-XmnI were evaluated. Modifiers were compared between 102 community- and 104 hospital-recruited cases. Alleles of ß+, -SEA, -α3.7, αCS, and a minor allele of rs9399137 were prevalent in the community and mild severity groups (p < 0.05). Multiple linear regression analysis associated modulating alleles with -4.299 (-SEA), -3.654 (ß+), -3.065 (rs9399137, C/C), -2.888 (αCS), -2.623 (-α3.7), -2.361 (rs7482144, A/A), -1.258 (rs9399137, C/T), and -1.174 (rs7482144, A/G) severity score reductions (p < 0.05). Certain modifiers must be considered in routine prenatal genetic counseling for Hb E/ß-thalassemia.

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

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

Prevalence and predictors of peripheral arterial disease determined by ankle brachial index in diabetes population treated within primary care services in a non-urban area of lower northern Thailand.

In diabetes patients, urban lifestyle has been concerned as one of the risk factors for peripheral arterial disease (PAD). The aims of this study were to find out the prevalence and associated risk factors of PAD in type 2 diabetes patients who live in a non-urban community area. A total of 885 participants with type 2 diabetes mellitus were enrolled from six primary care units in the health network centered at Naresuan University Hospital, Phitsanulok, between May and June 2018. Ankle-brachial index (ABI) was performed in all subjects using a vascular screening device. PAD was defined by an ABI value of 0.9 or lesser at least on one leg. The predictors of PAD were analyzed using multiple logistic regression. The prevalence of PAD was 7.2% among 884 evaluable patients. Diabetic neuropathy and a history of macrovascular complications were significant predictors of PAD.

Event-free survival at 12 months is a strong surrogate endpoint for stage 1 diffuse large B cell lymphoma: a report from Nation Wide Registry Thai Lymphoma Study Group.

Event-free survival at 12 months (EFS12) is a surrogate endpoint for long-term outcomes in many histologic lymphoma subtypes. However, most reports have primarily investigated the implication of EFS12 in advanced-stage non-Hodgkin lymphoma (NHL). There are limited data regarding the significance of EFS12 in early-stage NHL. Herein, we evaluated the prognostic significance of EFS12 in patients with stage 1 diffuse large B-cell lymphoma (DLBCL). Out of 282 patients with stage 1 DLBCL who received intensive therapy, 227 (80.5%) achieved EFS12. The 4-year overall survival (OS) was 91.4% and 4.0% for patients who achieved and failed to achieve EFS12, respectively. Multivariable analyses demonstrated response to treatment and achievement of EFS12 as independent predictors for OS. In conclusion, our study demonstrated EFS12 as a powerful prognostic factor for stage 1 DLBCL. Further validation in more extensive prospective studies is warranted.

Lessons learned from a prenatal diagnosis program for thalassemia in Thailand.

OBJECTIVE: To assess the outcome of a thalassemia screening program at community hospitals by determining the proportion of at-risk couples able to obtain a prenatal diagnosis (PND) in relation to gestational age (GA). METHODS: We accessed records documenting prenatal screening for thalassemia in lower northern Thailand between January 2014 and December 2016. The proportion of at-risk pregnancies able to obtain a PND was determined and median GAs at the time of at-risk notification were compared. Reasons for failures to obtain PNDs were analyzed. RESULTS: Among 4633 screen-positive couples, 259 (5.6%) were identified as at-risk while 23 were excluded due to unconfirmed outcomes. Forty-one declined a PND and were excluded from the final calculations. Of the 195 remaining couples, 140 (71.8%) obtained a PND. Their median GA at the time of at-risk notification was 12.4 (5.6-29.1) weeks, which was earlier than the median GA of 17.7 (6.9-34.6) weeks for couples not undergoing PND (P < .001). Risks for various types of thalassemia and GA were associated with the chances of achieving a PND. CONCLUSION: In practice, one quarter of couples identified as at-risk were unable to obtain a PND. Time-influencing factors seem to be a major determinant.

Characteristics, treatment patterns, prognostic determinants and outcome of peripheral T cell lymphoma and natural killer/T cell non-Hodgkin Lymphoma in older patients: The result of the nationwide multi-institutional registry Thai Lymphoma Study Group.

INTRODUCTION: Peripheral T cell NHL (PTCL) and natural killer/T cell NHL (NKTCL) are relatively rare disorders. Data on clinical presentation, treatment and outcome are limited especially in older age groups. METHODS: We identified 127 patients with PTCL and NKTCL, excluding cutaneous T/NK cell lymphoma, aged over 60 years old from Thailand nationwide multicenter registry. RESULTS: Of 127 patients, median age of diagnosis was 67 years old. Patients aged older than 75 years old had similar characteristics to younger (60-74 years old) but higher comorbidity index. Seventy-nine patients (62.2%) received intensive/definite multi-agent chemotherapy, however, the proportion was significant lower in older patients (70.4% vs 34.5%, p < .001). After a median follow up duration of 17.3 months, 2-year progression free survival and overall survival were 38.1% and 48.5%. Univariate and multivariable analysis demonstrated older age, poor performance status and absence of definite multi-agent chemotherapy were associated with inferior survival. Definite multi-agent lymphoma specific chemotherapy was an independent factor for overall survival after adjustment for age, comorbidity index, performance status and prognostic index for T cell lymphoma. CONCLUSION: Despite overall poor prognosis of PTCL and NKTCL in older adults, chemotherapy could result in objective response and long-term survival in selected patients of this vulnerable age group thus emphasizing the importance of comprehensive geriatric evaluation.

Event free survival at 24 months is a strong surrogate prognostic endpoint of peripheral T cell lymphoma.

Event free survival at 24 months (EFS24) has been described as a powerful predictor for outcome in several subtypes of B cell lymphoma. However, it was limitedly described in T cell lymphoma. We explored the implication of EFS24 as a predictor marker for peripheral T cell lymphoma (PTCL). We reviewed 293 systemic PTCL patients at 13 nationwide major university hospitals in Thailand from 2007 to 2014. The median event free survival (EFS) and overall survival (OS) of PTCL patients in our cohort was 16.3 and 27.7 months with corresponding 2-year EFS and 2-year OS of 45.8% and 51.9%, respectively. A total of 118 patients achieved EFS24 (no events during the first 24 mo). Patients who achieved EFS24 had better OS than patients who did not (2-y OS 92% vs 18.8%; HR, 0.1; P < .001). The standardized mortality ratio of patients achieving EFS24 was 18.7 (95% CI, 14.6-22.8). Multivariable analysis demonstrated performance status, histologic subtype, remission status, and EFS24 achievement as independent predictors for OS. Our study affirmed the value of EFS24 as a powerful prognostic factor for PTCL. Further validation in prospective study setting is warranted.

Non-Hodgkin lymphoma in South East Asia: An analysis of the histopathology, clinical features, and survival from Thailand.

Systemic reports on the descriptive epidemiology of non-Hodgkin lymphoma (NHL) from Southeast Asia are scarce. A nationwide multi-institutional registry was conducted to compare the histopathology, clinical features, and survival of Thai adult patients with NHL using large registries, especially those from Far East Asia (FEA). Using a web-based registry system, 13 major medical centers from the 4 geographic regions of Thailand prospectively collected, from 2007 to 2014, the diagnostic pathology, according to the World Health Organization classification, 2008, clinical features and survival of 4056 patients who were newly diagnosed with NHL. The median age of the patients was 56 years (range, 16-99 years). The male-to-female ratio was 1.3:1. From the total of 4056 patients, T/NK-cell lymphoma (TNKCL) accounted for 12.6% of cases, and 5.1% had human immunodeficiency virus-associated lymphoma. The four leading histological subtypes were diffuse large B-cell lymphoma, not otherwise specified (58.1%); follicular lymphoma (5.6%); extranodal mucosa-associated lymphoid tissue lymphoma (5.2%); and peripheral T-cell lymphoma, not otherwise specified (4.0%). With a median follow-up duration of 46.1 months, the median overall survival of B-cell NHL was significantly longer than that of patients with TNKCL (76.5 vs 28.8 months, P = .0001). Compared to FEA, the Thai registry had an approximately one-half lower relative frequency of TNKCL; the prevalence of extranodal mucosa-associated lymphoid tissue lymphoma was much lower than in Korea, and the frequency of extranodal TNKCL, nasal type, was strikingly low compared to China. It is concluded that while the median age of Thai patients with NHL was approximately a decade younger than for Caucasians, the long-term survival rates for most histological subtypes were comparable. While the histological distribution generally complied with the characteristic Asian features, some differences from FEA were observed.

Prevalence and predictors of cardiac and liver iron overload in patients with thalassemia: A multicenter study based on real-world data.

Prevalence of cardiac and liver iron overload in patients with thalassemia in real-world practice may vary among different regions especially in the era of widely-used iron chelation therapy. The aim of this study was to determine the prevalence of cardiac and liver iron overload in and the management patterns of patients with thalassemia in real-world practice in Thailand. We established a multicenter registry for patients with thalassemia who underwent magnetic resonance imaging (MRI) as part of their clinical evaluation. All enrolled patients underwent cardiac and liver MRI for assessment of iron overload. There were a total of 405 patients enrolled in this study. The mean age of patients was 18.8±12.5years and 46.7% were male. Two hundred ninety-six (73.1%) of patients received regular blood transfusion. Prevalence of cardiac iron overload (CIO) and liver iron overload (LIO) was 5.2% and 56.8%, respectively. Independent predictors for iron overload from laboratory information were serum ferritin and transaminase for both CIO and LIO. Serum ferritin can be used as a screening tool to rule-out CIO and to diagnose LIO. Iron chelation therapy was given in 74.6%; 15.3% as a combination therapy.

Secondary central nervous system relapse in diffuse large B cell lymphoma in a resource limited country: result from the Thailand nationwide multi-institutional registry.

Secondary central nervous system (CNS) relapse is a serious and fatal complication of diffuse large B cell lymphoma (DLBCL). Data on secondary CNS (SCNS) relapse were mostly obtained from western countries with limited data from developing countries. We analyzed the data of 2034 newly diagnosed DLBCL patients enrolled into the multi-center registry under Thai Lymphoma Study Group from setting. The incidence, September 2006 to December 2013 to represent outcome from a resource limited pattern, management, and outcome of SCNS relapse were described. The 2-year cumulative incidence (CI) of SCNS relapse was 2.7 %. A total of 729, 1024, and 281 patients were classified as low-, intermediate-, and high-risk CNS international prognostic index (CNS-IPI) with corresponding 2-year CI of SCNS relapse of 1.5, 3.1, and 4.6 %, respectively (p < 0.001). Univariate analysis demonstrated advance stage disease, poor performance status, elevated lactate dehydrogenase, presence of B symptoms, more than one extranodal organ involvement, high IPI, and high CNS-IPI group as predictive factors for SCNS relapse. Rituximab exposure and intrathecal chemoprophylaxis offered no protective effect against SCNS relapse. At the time of analysis, six patients were alive. Median OS in SCNS relapsed patients was significantly shorter than relapsed patients without CNS involvement (13.2 vs 22.6 months) (p < 0.001). Primary causes of death were progressive disease (n = 35, 63.6 %) and infection (n = 9, 16.7 %). In conclusion, although the incidence of SCNS relapse in our cohort was low, the prognosis was dismal. Prophylaxis for SCNS involvement was underused even in high-risk patients. Novel approaches for SCNS relapse prophylaxis and managements are warranted.

Q Sepharose micro-column chromatography: A simple screening method for identifying beta thalassemia traits and hemoglobin E carriers.

OBJECTIVES: For beta thalassemia control program in pregnancy, mass screening of the carrier state by determination of the hemoglobin (Hb) A2 and Hb E proportions and mutation analysis is a preferred method for making prenatal diagnoses. Q Sepharose micro-column chromatography, developed for the determination of Hb A2 and Hb E for screening purposes, was compared with high performance liquid chromatography (HPLC) to ascertain its relative accuracy and reliability. DESIGN AND METHODS: Results using Q Sepharose micro-column chromatography in 350 blood specimens, including 50 samples genetically proven to be beta thalassemia heterozygotes, were compared to HPLC for validation. An additional study was conducted to test a clinical application on a large-scale survey for beta thalassemia in 1581 pregnant women and their spouses. RESULTS: The mean (±SD) Hb A2 proportions in the normal and genetically proven beta thalassemia heterozygotes were 2.70±0.40% and 6.30±1.23%, respectively, as determined by Q-Sepharose micro-column chromatography, and 2.65±0.31% and 5.37±0.96%, respectively, as determined by HPLC. The mean Hb E proportions in the Hb E heterozygotes were 23.25±4.13% and 24.72±3.5% as determined by Q Sepharose micro-column chromatography and HPLC, respectively. In the large-scale survey for beta thalassemia, 23 at risk couples were detected. Seven affected fetuses were identified by prenatal diagnosis. CONCLUSIONS: Q Sepharose micro-column chromatography was found to be reliable, reproducible and well-suited for large-scale surveys. Additionally, by being reusable and convenient, this simple and economical chromatography method may be an alternative means to screen for beta thalassemia and Hb E carriers in the mass population.

Hemoglobin Analysis in the First Year of Life.

BACKGROUND AND OBJECTIVES: In newborns and infants during their first year of life, there is a dynamic change in the fraction of hemoglobin (Hb). To apply Hb analysis as a phenotypic diagnosis of thalassemia in newborns and infants, we need normal values of each Hb fraction for reference. METHODS: Seventeen cord bloods from normal deliveries were collected for analysis. One hundred and thirty-seven infants from the pediatric outpatient clinic were recruited and were categorized by their ages into a series of short periods (month±2 weeks). Both alpha and beta thalassemia carriers detected were excluded. Samples with an Hb level less than 10.0 g/dL were also excluded. The proportion of Hb A (α2ß2), A2 (α2δ2), and F (α2γ2) was obtained from high-performance liquid chromatography and analyzed according to its categorized periods. RESULTS: There were 90 (58.4%) specimens left for evaluation. The percentage of Hb A, A2, and F gradually changed with increasing age. The percentage of Hb A was 21.14±7.04% (mean±SD) in cord blood and increased substantially to 83.38±1.31% at the sixth month. The level was sustained thereafter. The incremental pattern of Hb A2 was similar to Hb A. The value was 0.32±0.19% at the beginning and reached a plateau with 2.78±0.25% at the sixth month. The percentage of Hb F started at 78.39±7.59% in cord blood and decreased rapidly in the first 6 months. CONCLUSIONS: The data possibly can be applied as quick guidance for interpretation of Hb analysis in newborns and infants during their first year of life.

Evaluation of a cryopreservation procedure to set up a new bone marrow transplant unit using lymphocyte proliferation test.

A bone marrow transplant (BMT) is one kind of standard treatment modality in advanced hemato-oncology. In order to set up a BMT unit, one of the important steps before starting a clinical program is to evaluate the cryopreservation procedure for stem cell storage. Twenty one bags of buffy coat were used to be the testing specimens. They were processed and frozen according to cryopreservation protocol and kept in liquid nitrogen for 2 weeks. The evaluation process was carried out with a lymphocyte proliferation test together with trypan blue staining. By measuring the optical density of each lymphocyte containing well after stimulation, the lymphocyte proliferation value (LPV) could be obtained. When comparing them before and after cryopreservation, the LPV was 2.064 ± 0.379 (mean ± SD) and 1.913 ± 0.546, (p = 0.314), respectively. At 2 weeks after cryopreservation, comparing between the frozen group and the unfrozen control, the LPV was 1.913 ± 0.546 and 0.486 ± 0.453, (p < 0.05), respectively. The LPV showed clear efficacy of the procedure, especially for preserving the cellular proliferation function. Our model of the cryopreservation procedure evaluation at pre-clinical phase by use of a buffy coat and lymphocyte proliferation test seems feasible for newly-established small BMT units. With these results, clinical transplantations can be performed with more confidence.

Iron-chelating therapies in a transfusion-dependent thalassaemia population in Thailand: a cost-effectiveness study.

BACKGROUND AND OBJECTIVE: ß-Thalassaemia is a major public health problem in Thailand. Use of appropriate iron-chelating agents could prevent thalassaemia-related complications, which are costly to the healthcare system. This study aimed to evaluate the cost effectiveness of deferoxamine (DFO), deferiprone (DFP) and deferasirox (DFX) in Thai transfusion-dependent ß-thalassaemia patients from the societal perspective. METHODS: A Markov model was used to project the life-time costs and outcomes represented as quality-adjusted life-years (QALYs). Data on the clinical efficacy and safety of all therapeutic options were obtained from a systematic review and clinical trials. Transition probabilities were derived from published studies. Costs were obtained from the Thai Drug and Medical Supply Information Center, Thai national reimbursement rate information and other Thai literature sources. A discount rate of 3% was used. Incremental cost-effectiveness ratios (ICERs) were presented as year 2009 values. A base-case analysis was performed for thalassaemia patients requiring regular blood transfusion therapy, while a separate analysis was performed for patients requiring low (i.e. symptom-dependent, less frequent) blood transfusion therapy. A series of sensitivity analysis and cost-effectiveness acceptability curves were constructed. RESULTS: Compared with DFO, using DFP was dominant with lifetime cost savings of $US91 117. Comparing DFX with DFO, the incremental cost was $US522 863 and incremental QALY was 5.77 with an ICER of $US90 648 per QALY. When compared with DFP, the ICER of DFX was $US106 445 per QALY. A cost-effectiveness analysis curve showed the probability of DFX being cost effective was 0% when compared with either DFO or DFP, based on the cost-effectiveness cut-off value of $US2902 per QALY. When compared with DFP, DFX was cost effective only if the DFX cost was as low as $US1.68 per 250 mg tablet. The results of the analysis in patients requiring low blood transfusion therapy were not different from those of the base-case analysis. CONCLUSIONS: Our findings suggest that using DFP is cost saving when compared with conventional therapy, while using DFX is not cost effective compared with either DFO or DFP in Thai patients with transfusion-dependent ß-thalassaemia. Policy-makers and clinicians may consider using such information in their decision-making process in Thailand.

Risk of a couple having a child with severe thalassemia syndrome, prevalence in lower northern Thailand.

Thalassemia screening in pregnant women and their spouses was performed at Buddhachinaraj Provincial Hospital and 8 community hospitals in Phitsanulok; lower northern Thailand. The prevalence of thalassemic carrier state was determined of 1,198 couples. Of these, 4.8% had heterozygous alpha thalassemia-1, 1.6% had heterozygous beta thalassemia, 12.4% had heterozygous hemoglobin (Hb) E, 2.7% had homozygous Hb E and 0.25% of others had abnormal Hb. Eighteen at risk couples (1.5%) were identified. Fifteen couples were at risk for compound heterozygous Hb E / beta thalassemia and the remaining 3 were at risk for homozygous alpha thalassemia-1. Prenatal diagnosis (cordocentesis) was performed in 4 couples at risk, but no fetuses with severe thalassemic disease were detected.

Hospital-acquired anemia.

OBJECTIVE: The incidence and etiologies of hospital-acquired anemia has not been well defined A prospective study was conducted to determine the incidence and etiologies of hospital-acquired anemia developed in patients admitted in the medical ward of a tertiary care university hospital. MATERIAL AND METHOD: All non-anemic (hemoglobin (Hb) > or = 13 g/dl in male, > or = 12 g/dl in female) patients who were admitted to the general medical wards for at least 1 week, between March 2001 to October 2001, were included in the present study. Outcome of interest was anemia developed during hospital stay. The total volume of blood collected for investigations were recorded. RESULTS: Of the 98 evaluable patients, 64 (65.3%) developed anemia. Thirty-five percent of the patients had mild anemia (Hb > 10.0 g/dl) and 7% had severe anemia (Hb < or = 8.0 g/dl). Anemia of chronic disease was the most common cause found in 57.4% of anemic patients. Mean total volume of blood collected for investigation was higher in the anemic compared with the non-anemic group (147.0 ml vs. 52.0 ml, p < 0.05). Total volume of investigational blood also correlated significantly with degree of anemia (r = 0.638, p < 0.05). CONCLUSION: Anemia was a common complication occurring in almost two-thirds of patients admitted to the hospital. Even though anemia of chronic disease was the leading cause, investigational blood loss was also an important contributing factor.