Prognostic factors of adult hemophagocytic lymphohistiocytosis and clinical utility of HLH-2004 diagnostic criteria and HScore: A real-world multicenter study from Thailand.

INTRODUCTION: Adult hemophagocytic lymphohistiocytosis (HLH) is a rare disease with a dismal prognosis. Early diagnosis and prompt management are necessary for improved outcomes. METHODS: This multicenter retrospective study investigated the etiologies, survival, and prognostic factors of HLH, including the utility of HLH-2004 criteria and HScore in real-life clinical practice. RESULTS: A total of 147 HLH patients were identified by using a combination of hemophagocytosis identification in bone marrow and the HLH-related international classification disease-10. A total of 116 (78.9%) patients fulfilled the HLH diagnosis by HScore, while 91 (61.9%) patients fulfilled 5 of 8 HLH-2004 criteria. In Thailand, the clinical application of HLH-2004 criteria needed to be reduced from 8 to 6 due to a lack of sCD25 and natural killer cell activity tests. Using the adapted HLH-2004 with a cutoff value of 4 resulted in 132 (89.9%) cases meeting the diagnostic criteria. Among these 132 confirmed HLH patients by using adapted HLH-2004, HLH was triggered by infection (29.5%), autoimmune disease (12.9%), malignancy (40.9%), and unknown cause (16.7%). Median overall survival of HLH patients was extremely short (67 days). Ferritin >6,000 µg/L, HLH from infection, malignancy, and unknown etiology were demonstrated as independent prognostic factors for inferior survival (hazard ratio (HR) 2.47; 95%CI 1.39-4.37, HR 4.69; 95%CI 1.38-15.92, HR 6.09; 95%CI 1.84-20.14, and HR 6.02; 95%CI 1.64-22.05, respectively). CONCLUSION: Ferritin is a helpful biomarker for HLH diagnosis and prognostic prediction. Autoimmune disease triggered HLH has favorable outcomes. Future prospective study is required to verify use of the adapted HLH-2004 criteria.

The association of growth differentiation factor-15 levels and osteoporosis in patients with thalassemia.

BACKGROUND: Ineffective erythropoiesis (IE) is a significant risk factor for osteoporosis in individuals with thalassemia. Growth differentiation factor-15 (GDF15), a biomarker of IE, was found to be elevated in thalassemia patients. This study aimed to examine the association between GDF15 levels and osteoporosis in patients with thalassemia. METHODS: A cross-sectional study was conducted in 130 adult patients with thalassemia in Thailand. Bone mineral density (BMD) at the lumbar spine was evaluated by dual-energy X-ray absorptiometry (DXA), and with a Z-score of less than -2.0 SD was defined as osteoporosis. GDF-15 was measured using the enzyme-linked immunosorbent assay (ELISA). Logistic regression analysis was used to examine the associated factors with the development of osteoporosis. Receiver operator characteristic (ROC) curve analysis was used to estimate the threshold of GDF15 in predicting osteoporosis. RESULTS: Osteoporosis was detected in 55.4% (72/130) of the patients. Advanced age and high GDF15 levels were positively associated with osteoporosis, while an increased hemoglobin level was negatively associated with osteoporosis in patients with thalassemia. In this study, the GDF15 level's ROC demonstrated a good performance in predicting osteoporosis (AUC=0.77). CONCLUSIONS: The prevalence of osteoporosis is high among adult thalassemia patients. Age and high GDF15 levels were significantly associated with osteoporosis in this study. A higher hemoglobin level is associated with a lower risk of osteoporosis. This study suggest that GDF15 could be used as a predictive biomarker for osteoporosis in patients with thalassemia. Adequate red blood cell transfusions and suppression of GDF15 function may be beneficial in preventing osteoporosis.

Does leukocytosis remain a predictive factor for survival outcomes in patients with acute promyelocytic leukemia receiving ATRA plus a chemotherapy-based regimen? A prospective multicenter analysis from TALWG.

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 × 109/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 × 109/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.

Clinical features and risk factors of renal dysfunctions in thalassemic patients.

INTRODUCTION: Chronic anemia, iron overload, and iron chelation therapy are the main contributing factors for renal complications in thalassemia, e.g., nephrolithiasis, glomerular disease, and renal tubular dysfunction. The prevalence and associated factors for developing renal dysfunctions in Thai patients with thalassemia, however, remained limited. This study aimed to determine the prevalence and risk factors of renal dysfunctions in patients with thalassemia. METHODS: A cross-sectional study was conducted on adult patients with thalassemia disease at Srinagarind Hospital, Khon Kaen University, Thailand. All patients were evaluated for complete blood count, blood chemistry, urinalysis, and urine biochemistry. Renal tubular dysfunction was defined as existing in at least one of the following parameters including; proteinuria, hypercalciuria, hypouricemia with uricosuria, or hypophosphatemia with phosphaturia. Logistic regression analysis was used to identify associated factors for renal dysfunctions. RESULTS: Of 105 patients, renal tubular dysfunction was found in 60 patients (57.1%). In multivariate analysis of the clinical risk factors for renal tubular dysfunction in thalassemia patients, age per 10 year increase (adjusted odds ratio [AOR] = 1.4, 95% CI: 1.0-2.0, p value 0.01) and Hb E/beta-thalassemia (AOR = 3.6, 95% CI: 1.3-10.3, p value 0.01) were statistically proven to be associated with renal tubular dysfunction. Hyperuricosuria was a significantly associated factor for microhematuria. (AOR = 2.9, 95% CI: 1.1-8.0, p value 0.03). CONCLUSIONS: Renal dysfunctions are prevalent in thalassemia patients, with older age and Hb E/beta-thalassemia genotype as significant risk factors for renal tubular dysfunction. Hyperuricosuria is a risk factor for microhematuria. Renal dysfunctions should be recognized and monitored in aging patients with Hb E/beta-thalassemia.

Characteristics and Outcomes of Secondary Acute Myeloid Leukemia and Acute Myeloid Leukemia With Myelodysplasia-Related Changes: Multicenter Study From the Thai Acute Leukemia Study Group.

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 × 109/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 × 109/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.

Comparison of Three Doses of Cytarabine Consolidation for Intermediate- and Adverse-risk Acute Myeloid Leukemia: Real World Evidence From Thai Acute Myeloid Leukemia Registry.

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/m2, high-dose cytarabine (HiDAC) 2 g/m2, and HiDAC 3 g/m2 were 12.6, 11.7, and 13 months, respectively. The median overall survival (OS) using IDAC 1.5 g/m2, HiDAC 2 g/m2, and HiDAC 3 g/m2 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 > 100×109/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/m2, and 78.1% of HiDAC 3 g/m2 without statistical significance. However, the incidence of septic shock was significantly higher after HiDAC 3 g/m2 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.

Clinical factors predictive of recurrent febrile neutropenia in adult patients with acute leukemia.

Febrile neutropenia (FN) is considered an oncologic emergency in acute leukemia. There were 250 FN events in 124 hospitalized patients with hematologic malignancy. These data imply that two FN events may occur per patient, yet data on the prevalence, risk factors, and outcomes of recurrent FN in adult patients with leukemia are limited. A retrospective cohort study was conducted that enrolled adult patients diagnosed with acute leukemia who developed FN. The eligible patients were categorized as with or without recurrent FN. A stepwise, multivariate logistic regression analysis was performed to identify predictors of recurrent FN. A total of 203 patients met the study criteria; of these, 46 (22.66%) had recurrent FN, and this group had a median of three recurrent FN emergencies. After adjusted, three independent factors remained in the final model including ALL, FN at admission, and treatment with idarubicin (3 days) and cytarabine (7 days). The three factors were positively associated with recurrent FN with adjusted odds ratios of 6.253, 4.068, and 10.757, respectively. No significant differences were found between the two groups in terms of other sources of infection, other pathogens, ICU stay, hospital stay, and mortality. ALL and FN at admission and treatment with idarubicin (3 days) and cytarabine (7 days) were associated with recurrent FN in acute leukemia patients with FN. Clinical outcomes for patients with or without recurrent FN were mostly comparable; however, due to its small sample size, further studies are required to confirm the results of this study.

Cognitive Impairment in Thalassemia and Associated Factors.

INTRODUCTION: Patients with thalassemia increase the risk of developing cognitive impairment. Chronic anemia, oxidative stress from excess iron, and hypercoagulable state were related to this condition. The study regarding its prevalence and the associated factor in Southeast Asia is limited. Therefore, the study aimed to investigate the prevalence of cognitive impairment and associated factors. METHODS: This was a cross-sectional study of thalassemic patients aged 18 years or more at the Hematology Clinic of Srinagarind Hospital, Khon Kaen University, Thailand, from January to May 2021. The Thai version of the Mini-Cog test was used to determine the presence of cognitive impairment. The clinical and laboratory parameters indicated as potential risk factors for dementia were evaluated in all patients. A stepwise logistic regression analysis was used to determine the associated risk factors for cognitive impairment. RESULTS: Among 150 patients, cognitive impairment was found in 40 patients (26.7%). Age per 10-year increase (adjusted odds ratio [AOR] of 1.6), no iron chelation therapy (AOR of 9.8), current smoking (AOR of 5.0), hemoglobin (Hb) (AOR of 0.63), and ferritin (AOR of 1.0001) were independent factors associated with cognitive impairment. CONCLUSIONS: The prevalence of cognitive impairment was high among thalassemic patients. Increasing age, low Hb, iron overload, and current smoking were significant associated factors with cognitive impairment. Screening for dementia in these patients is recommended, particularly in patients with high-risk factors.

Nutritional support in allogeneic hematopoietic stem cell transplantation Asian perspective.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an integral part of the treatment strategy for patients with malignant or non-malignant hematological diseases. Clinical outcomes of patients undergoing allo-HSCT have significantly improved in recent decades. However, transplant-related morbidity and mortality remain major issues for allo-HSCT recipients. With regard to nutrition, patients undergoing allo-HSCT are at high risk for malnutrition. It is expected that clinical practice concerning nutritional support in allo-HSCT has been improving in recent decades; however, no data directly support this expectation. One major issue in managing nutritional support during allo-HSCT is the lack of large-scale randomized prospective studies, which leads to a lack of well-established strategies. Accordingly, we need to gather data from studies in non-HSCT and allo-HSCT settings. In some Asia-Pacific countries, a physician's lack of knowledge of nutritional support may impede the application of nutritional support practices recommended by existing guidelines. Another barrier may be the lack of access to an adequately qualified or trained registered dietitian (RD) at allo-HSCT units. Adequate training in the nutritional management of allo-HSCT patients should be provided to all RDs working with HSCT. Herein, we summarize the information on nutritional support in allo-HSCT, focusing on an Asian perspective.

Clinical factors predictive of mortality in acute leukemia patients with febrile neutropenia.

BACKGROUND: Acute leukemia is mainly treated with chemotherapy leading to febrile neutropenia (FN). There is limited data on clinical factors predictive of mortality in adults with acute leukemia and FN. METHODS: This was a retrospective cohort study and enrolled adult patients, diagnosed as acute leukemia, and developed FN. The eligible patients were admitted and followed up with mortality as the primary outcome. A stepwise, multivariate logistic regression analysis was used to find predictors for mortality. RESULTS: There were 203 patients met the study criteria. Of those, 14 patients died (6.89%). AML was the most common type of acute leukemia with FN (64.04%). There were five remaining factors in the final model: AML, FN at admission, prolong broad spectrum antibiotics, lower respiratory tract infection, and Aspergillosis. Only lower respiratory tract infection was significant with adjusted odds ratio of 7.794 (95% CI of 1.549, 39.212). The Hosmer-Lemeshow Chi square was 2.74 (p value 0.907). The lower respiratory tract infection group had higher proportions of Gram negative and fungus than the non-lower respiratory tract infection group; specifically E. coli (p 0.003), and Aspergillus (P < 0.001). CONCLUSIONS: There were two independent predictors of mortality in acute leukemia patients with FN: septic shock and lower respiratory tract infection regardless of leukemia type or pathogen. E. coli and Aspergillus were more common in those with lower respiratory tract infection than those without. No specific pathogens were found in cases of septic shock.

Types, Clinical Features, and Survival Outcomes of Patients with Acute Myeloid Leukemia in Thailand: A 3-Year Prospective Multicenter Study from the Thai Acute Leukemia Study Group (TALSG).

BACKGROUND: Acute myeloid leukemia (AML) is a common, challenging hematologic malignancy worldwide. Thai data on its characteristics and outcomes have never been systematically reported, to our knowledge. The objective of this study was to determine the clinical features and outcomes of Thai patients with AML. PATIENTS AND METHODS: This was a prospective observational study of nine academic hospitals. Patients with newly diagnosed AML were invited to register online. RESULTS: A total of 679 patients with AML were included. The presence of circulating peripheral blood blasts was correlated with a high white blood cell count. Acute promyelocytic leukemia (APL) had predominantly lower white blood cell counts and higher proportions without peripheral blood blasts compared with non-APL AML. Disseminated intravascular coagulation was commonly presented in APL (37.7%). Splenomegaly and normal platelet count were more frequently seen in patients with Philadelphia chromosome-positive AML. The median follow-up time for those who survived more than 1 year was 28.0 months. One-year overall survival rates for non-APL AML and APL were 31.9% and 88.2%, respectively; 2-year overall survival rates were 29.6% and 88.2%, respectively. Hematopoietic stem cell transplantation could improve survival in non-APL AML. CONCLUSION: APL should be considered despite absence of peripheral blood blast. This study demonstrates poor outcome of Thai AML and more research to improve outcomes are underway. Expanding access to hematopoietic stem cell transplantation should be considered in Thailand.

Tamoxifen enhances romidepsin-induced apoptosis in T-cell malignant cells via activation of FOXO1 signaling pathway.

Although romidepsin as monotherapy appears to be useful for treating T-cell lymphoma, combined chemotherapy with other therapeutic agents is required for improvement of the treatment outcome. To establish safer and more effective regimens, systematic screening was conducted to identify suitable drugs to be used in combination with romidepsin for T-cell malignancies, and the underlying molecular mechanisms were examined. The most effective agent was tamoxifen. The combination of romidepsin and tamoxifen had a significant synergistic effect in inducing apoptosis. The growth-inhibitory effects of the combined treatment were reversed by α-tocopherol. FOXO1 expression was greatly upregulated in MOLT-4 cells treated with romidepsin plus tamoxifen. Knockdown of FOXO1 expression by siRNA significantly reduced the cell death induced by romidepsin plus tamoxifen. The combination of romidepsin and tamoxifen might be considered for the treatment of T-cell lymphoma patients.

Intramedullary Conus Medullaris Tuberculoma: A Case Report and Review of the Literature.

Intramedullary tuberculoma (IMT) of the conus medullaris is extremely rare. We present a case of intramedullary conus medullaris tuberculoma in which the diagnosis was based on there being very high levels of adenosine deaminase (ADA) in the patient's cerebrospinal fluid (CSF) and improvement with antituberculous therapy. A 78-year-old man presented after having had a dull ache in both thighs and progressive paraparesis. The patient's medical history included diffuse large B-cell lymphoma, which had undergone remission due to chemotherapy two years earlier, and long-term, well-controlled diabetes. A chest X-ray showed no evidence of tuberculosis. The results of CSF analysis were compatible with Froin's syndrome. An initial diagnosis was made of an intramedullary tumor of the conus medullaris, based on magnetic resonance imaging (MRI). A myelotomy and multiple punch out biopsy were performed, and histopathology of the tissues revealed mild reactive gliosis. Due to the patient having high levels of CSF-ADA, IMT of the conus medullaris was suspected. The patient was treated with an 18-month course of antituberculous therapy. The dull ache gradually disappeared, and motor power improved slightly. A follow-up MRI of the lumbosacral (LS) spine revealed that the lesion had completely disappeared. Intramedullary tuberculoma of the conus medullaris should be considered in patients with underlying malignancy and no symptoms of systemic tuberculosis. CSF adenosine deaminase levels can be helpful in determining the presence of central nervous system tuberculosis when other systemic signs of disease are lacking.

Abnormally Prolonged Bleeding After an Arthroscopic Knee Reconstruction Because of an Inherited Factor XIII Deficiency: A Case Report.

CASE: An 18-year-old man developed ecchymosis after arthroscopic anterior cruciate ligament reconstruction with semitendinosus graft and meniscal repair. The results of routine coagulation studies were normal, but factor assays showed a reduction in factor XIII levels. The bleeding symptoms were dramatically improved after administration of cryoprecipitate. CONCLUSION: Factor XIII deficiency is one of the rare clotting factor deficiencies that can be present at birth or be manifested later in life. Clinical awareness of factor XIII deficiency is essential so that appropriate testing and treatment can be achieved.

Better survivals in adolescent and Young adults, compared to adults with acute lymphoblastic leukemia - A multicenter prospective registry in Thai population.

Adult acute lymphoblastic leukemia (ALL) is an uncommon hematologic malignancy with high relapse and mortality rate. This study aimed to describe characteristics and outcomes of Thai ALL patients, and to determine the differences between adolescent and young adult (AYA) and adult ALL. ALL patients aged > 15 years were prospectively enrolled from 2015 to 2017. AYA patients were defined as age ≤ 39 years. Out of the 188 enrolled ALL patients, 9 were excluded due to changes in diagnosis or incomplete data. From the remaining 179 patients, 103 (57.5%) were AYA and 76 (42.5%) were adult. AYA ALL patients were predominantly male, had higher T-cell phenotype, higher white blood cells and hemoglobin, with lower frequency of Philadelphia chromosome or BCR-ABL1 mutation. All patients received treatment by adult hematologist, however 40.8% of AYA ALL patients were treated with pediatric adapted protocol. The effects of stem cell transplantation (SCT) and age were determined by stratified patients as: AYA - no SCT 91 (51.1%), AYA - SCT 12 (6.7%), adult - no SCT 64 (36.0%) and adult - SCT 11 (6.2%). The 2-year overall survival were: 53.9%, 60.6%, 39.2% and 70.1%, respectively. The 2-year event-free survival were: 45.0%, 54.0%, 21.0% and 49.9%, respectively. This is a large multicenter ALL cohort study conducted in Thailand. Patients who underwent SCT showed significantly improved OS and EFS, confirming the benefit of graft-versus-leukemia effect in ALL. However, further studies with longer follow-up, expanded use of SCT, use of molecular data, and minimal residual disease status are warranted.

Improved Survival of Elderly-fit Patients With Acute Myeloid Leukemia Requiring Intensive Therapy: 3-Year Multicenter Analysis From TALWG.

BACKGROUND: Elderly patients with acute myeloid leukemia (AML) have a poorer prognosis than younger ones. Several factors contribute to the poor outcomes for this patient group. PATIENTS AND METHODS: This study investigated the epidemiology, clinical characteristics, treatment, and clinical outcomes of elderly Thai patients with AML. This 3-year, prospective, multicenter study was focused on Thai patients with AML aged over 60 years who were diagnosed between 2014 and 2016. RESULTS: Of 680 patients with AML, 235 elderly patients with AML (34.6%) were identified, with a mean age of 70 ± 8 years. Using a 3-group cytogenetic risk classification (favorable, intermediate, and adverse risk), the proportions of patients in each category were 3.6%, 73.8%, and 22.6%, respectively. The median follow-up time for surviving patients was 846 days. The median overall survival (OS) of the patients was 128.2 days (range, 0-1205 days), with a 1-year OS of 13%. From a multivariate analysis, the significant factors associated with an improved long-term OS were patients with an Eastern Cooperative Oncology Group performance status 0 to 2 and those receiving intensive therapy. CONCLUSION: Our study confirms the high prevalence of AML in elderly patients with generally poor outcomes. Selected patients with a good performance status and those who received intensive induction treatment could have a long-term survival.

Epidemiologic study of major complications in adolescent and adult patients with thalassemia in Northeastern Thailand: the E-SAAN study phase I.

INTRODUCTION: Thalassemia-related complications are one of the main factors that increase morbidity and mortality in aging patients with thalassemia. This study was aimed to report the prevalence and clinical risk factors for the complications in thalassemia. METHODS: A multi-center prospective cohort study was conducted in patients with thalassemia aged ≥10 years old. Thalassemia-related complications were heart failure, pulmonary hypertension, extramedullary hematopoiesis, endocrine disorders, infections, thrombosis and leg ulcers. The clinical parameters significantly associated with the complications were analyzed by logistic regression methods. RESULTS: The prevalence of thalassemia-related complications was 60.5% in patients with transfusion-dependent thalassemia (TDT) and 43% in patients with non-transfusion-dependent thalassemia (NTDT). Splenectomy was statistically associated with complications in both TDT and NTDT patients (adjusted odds ratio (AOR) = 7.4, p-value = 0.0001 and AOR = 2.6, p-value = 0.001). Age ≥50 years old (AOR = 2.9, p-value = 0.04) and female gender (AOR = 0.5, p-value = 0.03) were statistically associated with the complications in patients with NTDT. CONCLUSION: Nearly half of the patients in this cohort had disease-related complications. Splenectomy and advanced age were important factors for complication involvement. Early screening for the complications may reduce the morbidity and mortality in patients with thalassemia.

Severe bacterial infections in patients with non-transfusion-dependent thalassemia: prevalence and clinical risk factors.

INTRODUCTION: Bacterial infection is one of the major causes of death in patients with thalassemia. Clinical predictive factors for severe bacterial infection were evaluated in patients with non-transfusion-dependent thalassemia (NTDT). METHODS: A retrospective study was conducted of patients with NTDT aged ≥ 10 years at Srinagarind Hospital, Khon Kaen University, Thailand. Clinical characteristics and potential clinical risk factors for bacterial infection were collected. Risk factors for bacterial infection were evaluated by multivariate logistic regression analysis. RESULTS: A severe bacterial infection was found in 11 of the total 211 patients with NTDT (5.2%). None of the clinical factors assessed was shown to be statistically associated with severe bacterial infection in patients with NTDT. However, three factors were demonstrated to be potential predictive factors for severe bacterial infection: time after splenectomy >10 years, deferoxamine therapy, and serum ferritin >1000 ng/ml. None of the patients died from infection. CONCLUSION: The prevalence of bacterial infection in patients with NTDT was found to be moderate. Time after splenectomy >10 years, deferoxamine therapy, and iron overload may be clinical risk factors for severe bacterial infection in patients with NTDT. Bacterial infection should be recognized in splenectomized patients with NTDT, particularly those who have an iron overload.

A risk score for predicting pulmonary hypertension in patients with non-transfusion-dependent thalassemia in northeastern Thailand: The E-SAAN score.

INTRODUCTION: Pulmonary hypertension (PH) is a major complication in patients with non-transfusion-dependent thalassemia (NTDT). The risk score was developed to be a screening test for PH risk in these patients. METHODS: A multi-center study was conducted in patients with NTDT aged ≥10 years old. PH risk was defined as tricuspid regurgitation velocity >2.9 m/s by echocardiography. The clinical parameters significantly associated with PH were entered into the logistic regression model. RESULTS: The E-SAAN score included (1) age >35 years (2.5 points), (2) time after splenectomy >5 years (2.5 points), and (3) ß-thalassemia/hemoglobin E (2 points). Using the cut-off point of 4.5 points, the score showed a good discrimination in the validating group with an area under receiver-operating characteristics curve of 0.88 (95% CI 0.8-0.95). CONCLUSION: The E-SAAN score is a simple and practical score which can be used as a screening test for PH risk in patients with NTDT.

Effect of genotype on pulmonary hypertension risk in patients with thalassemia.

INTRODUCTION: Pulmonary hypertension is one of the major complications in patients with non-transfusion-dependent thalassemia (NTDT). Patients with NTDT have distinct genetic subgroups. Therefore, the effects of different genotype groups on pulmonary hypertension risk in patients with NTDT were assessed. METHODS: A cross-sectional study was conducted in patients with NTDT aged ≥ 10 yr old at Srinagarind University Hospital and Udonthani Hospital, Thailand. Pulmonary hypertension risk was defined as peak tricuspid regurgitation velocity > 2.9 m/s by trans-thoracic echocardiography. Clinical characteristics and laboratory data that literature has indicated as risk factors for pulmonary hypertension were collected. The effect of genotype group on pulmonary hypertension risk was evaluated by using multivariate logistic regression analysis. RESULTS: Of 219 patients, pulmonary hypertension risk was found in 24 patients (10.96%). All patients were categorized into two groups according to genetic data that included: (i) ß-thalassemia (139, 63.5%), (ii) α-thalassemia and combined α and ß-thalassemia (80, 36.5%). Genotype groups were statistically and significantly associated with pulmonary hypertension risk based on the adjusted odds ratios after adjustment for other factors. Patients with ß-thalassemia had a statistically significant higher risk for pulmonary hypertension risk (odds ratio = 9.47, P = 0.036) compared to patients with α-thalassemia and patients with combined α and ß-thalassemia. CONCLUSION: The genotype group is an independent risk factor for pulmonary hypertension in patients with NTDT. Echocardiography should be routinely recommended for all patients with ß-thalassemia. Routine screening in patients with α-thalassemia and combined α and ß-thalassemia, however, may not be necessary or should focus on the older population.