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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.
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Background: Melioidosis is a frequently fatal disease caused by an environmental bacterium Burkholderia pseudomallei. The disease is prevalent in northeast Thailand, particularly among rice field farmers who are at risk of bacterial exposure through contact with contaminated soil and water. However, not all exposure results in disease, and infection can manifest diverse outcomes. We postulate that genetic factors, whether from the bacterium, the host or the combination of both, may influence disease outcomes. To address this hypothesis, we aim to collect, sequence, and analyse genetic data from melioidosis patients and controls, along with isolates of B. pseudomallei obtained from patients. Additionally, we will study the metagenomics of the household water supply for both patients and controls, including the presence of B. pseudomallei. Methods: BurkHostGEN is an ongoing observational study being conducted at Sunpasitthiprasong Hospital, Ubon Ratchathani, Thailand. We are obtaining consent from 600 melioidosis patients and 700 controls, spanning both sexes, to collect 1 mL of blood for host DNA analysis, 3 mL of blood for RNA analysis, as well as 5 L of household water supply for metagenomic analysis. Additionally, we are isolating B. pseudomallei from the melioidosis patients to obtain bacterial DNA. This comprehensive approach will allow us to identify B. pseudomallei and their paired host genetic factors associated with disease acquisition and severity. Ethical approvals have been obtained for BurkHostGEN. Host and bacterial genetic data will be uploaded to European Genome-Phenome Archive (EGA) and European Nucleotide Archive (ENA), respectively. Conclusions: BurkHostGEN holds the potential to discover bacterial and host genetic factors associated with melioidosis infection and severity of illness. It can also support various study designs, including biomarker validation, disease pathogenesis, and epidemiological analysis not only for melioidosis but also for other infectious diseases.
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BACKGROUND: Management of unfit AML patients is a therapeutic challenge. Most hematologists tend to avoid aggressive treatment leaving patients with a choice of best supportive care. We hypothesized that metronomic chemotherapy could be an alternative treatment for unfit AML patients. METHODS: A multi-center randomized controlled trial was conducted in seven university-affiliated hospitals in Thailand. Unfit AML patients were recruited and followed up from December 2014 to December 2017. Patients were randomly assigned to receive either metronomic chemotherapy or palliative hydroxyurea. Overall survival rates were compared using Cox's proportional hazard survival analysis. RESULTS: A total of 81 eligible patients were randomly allocated and included for ITT analysis. The OS rate was higher in group receiving metronomic chemotherapy than in group receiving palliative treatment at 6 and 12 months with borderline significance (6 months HR 0.60; 95%CI 0.36, 1.02; p-value 0.060; 12 months: HR 0.66; 95%CI 0.41, 1.08; p-value 0.097). CONCLUSION: Metronomic chemotherapy could prolong survival time of unfit AML patients, especially in the first 12 months after diagnosis without increasing treatment-associated adverse events.
