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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.
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Inmunoconjugados , Linfoma de Células B Grandes Difuso , Linfoma no Hodgkin , Humanos , Pueblos del Sudeste Asiático , Tailandia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma no Hodgkin/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Inmunoconjugados/uso terapéutico , RituximabRESUMEN
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.
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Disfunción Cognitiva , Demencia , Talasemia , Disfunción Cognitiva/epidemiología , Estudios Transversales , Humanos , Tailandia/epidemiología , Talasemia/complicaciones , Talasemia/tratamiento farmacológico , Talasemia/epidemiologíaRESUMEN
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.
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Enfermedades Renales , Insuficiencia Renal , Talasemia , Talasemia beta , Adulto , Humanos , Talasemia beta/complicaciones , Talasemia beta/epidemiología , Estudios Transversales , Tailandia/epidemiología , Enfermedades Renales/complicaciones , Talasemia/complicaciones , Talasemia/epidemiología , Factores de Riesgo , Insuficiencia Renal/complicacionesRESUMEN
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.
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Osteoporosis , Talasemia , Adulto , Humanos , Absorciometría de Fotón/efectos adversos , Densidad Ósea , Estudios Transversales , Factor 15 de Diferenciación de Crecimiento , Hemoglobinas , Vértebras Lumbares , Osteoporosis/epidemiología , Osteoporosis/etiología , Talasemia/complicacionesRESUMEN
INTRODUCTION: Risk stratification is essential for treatment decision in myelodysplastic neoplasms (MDS). Molecular international prognostic scoring system (M-IPSS) has been recently developed combining somatic mutations and clinical information being used in the revised international prognostic scoring system (R-IPSS). OBJECTIVE: We aimed to explore the performances of M-IPSS and R-IPSS in Thai patients with MDS. METHOD: MDS patients were stratified into risk categories using R-IPSS and M-IPSS scores. The performance of both models were evaluated for prognostic prediction. RESULTS: One hundred and sixty-two MDS patients were recruited from the multicenter study. Survival analysis revealed that both R-IPSS and M-IPSS were good prediction models with the Concordance Index (C-index) of 0.71 (95% Confidence interval [CI] 0.64-0.78) and 0.75 (95% CI 0.69-0.80), respectively (p = 0.22). Comparing the two, 13 of 162 (8%) cases were re-staged between lower and higher risks which would have affected treatment decisions. CONCLUSION: Our study showed that R-IPSS score can be used for risk stratification in most Thai patients. A prediction model using somatic mutations specifically in Asian patients should be formulated in the future.
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Síndromes Mielodisplásicos , Neoplasias , Humanos , Pronóstico , Estudios Retrospectivos , Pueblos del Sudeste Asiático , Síndromes Mielodisplásicos/diagnóstico , Síndromes Mielodisplásicos/genéticaRESUMEN
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.
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BACKGROUND: Unexplained cytopenia (UC) and low-risk myelodysplastic syndrome (MDS) are distinguished mainly by morphologic dysplasia, which sometimes shows inter-observer discrepancy. We hypothesized that gene mutations are strong prognostic factors for these low-risk patients. MATERIALS AND METHODS: We enrolled patients from 4 medical centers with unexplained cytopenia of at least 1 lineage. Diagnosis of low-risk MDS was made according to WHO 2016 classification and a revised international prognostic scoring system (R-IPSS) score of ≤ 3.5. DNA was extracted from bone marrow or blood and sequenced by targeted next generation sequencing (NGS). RESULTS: One hundred twenty-one patients were recruited: 25% with UC and 75% with low-risk MDS. Complete blood counts were similar, but low-risk MDS patients carried higher numbers of mutations (1 vs. 0; P = .04) than UC patients. Overall, the most frequent mutated genes were TET2 (14.6%), SF3B1 (12.2%), and ASXL1 (9.7%). Survival rates of low-risk MDS patients versus UC patients were not significantly different. UC patients and low-risk MDS patients without genetic abnormalities showed superior 5-year progression free survival compared to MDS patients with mutations (100% vs. 76.0%; P = .005). Overall, ASXL1 mutations were associated with decreased 4-year overall survival compared to wild-type (59% vs. 31%; P = .01). In a multivariate analysis, ASXL1 and DNMT3A mutations in low-risk MDS patients were associated with a higher risk of disease progression with hazard ratios of 7.88 (95% CI 1.76-35.32, P = .01) and 7.45 (95% CI 1.61-34.46, P = .01), respectively. CONCLUSION: Mutation detection is important for proper risk stratification of patients presenting with idiopathic cytopenia.
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Leucemia Mieloide Aguda , Síndromes Mielodisplásicos , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Leucemia Mieloide Aguda/complicaciones , Mutación , Síndromes Mielodisplásicos/complicaciones , Síndromes Mielodisplásicos/diagnóstico , Síndromes Mielodisplásicos/genética , PronósticoRESUMEN
INTRODUCTION: Myelodysplastic syndromes (MDS) predominantly present with varying degrees of cytopenia, while myelodysplastic syndromes/myeloproliferative neoplasms (MDS/MPN) exhibit proliferative features. Genetic defects underlying different complete blood count (CBC) alterations remain to be defined. OBJECTIVE: We aimed to evaluate mutations and impacts on abnormal blood counts in MDS and MDS/MPN. METHOD: MDS and MDS/MPN patients were recruited and sequenced by targeted next-generation sequencing. Clinical parameters, especially CBC, were evaluated for the association with genetic abnormalities and clinical outcomes. RESULTS: A total of 168 patients with myeloid neoplasms were recruited (92 cases of low-risk MDS, 57 cases of high-risk MDS and 19 cases of MDS/MPN). Compared to low-risk MDS and MDS/MPN, patients with high-risk MDS were presented with more severe neutropenia with 17.5% showing absolute neutrophil counts (ANC) lower than 0.5 × 109/L. Patients with MDS/MPN more commonly harboured mutations and had a higher number of mutations per case than low-risk MDS (94.7% vs. 56.5%; p < 0.001 and 3 vs. 1; p < 0.001, respectively). Patients with SF3B1 mutations showed lower haemoglobin levels than wild-type (7.9 vs. 8.4â g/dL, p = 0.02), but were associated with normal platelet counts (286 vs. 93 × 109/L; p < 0.001). Patients with U2AF1 mutations were associated with more severe leukopenia than wild-type (3 vs. 4.18 × 109/L; p = 0.02). KRAS mutations were associated with monocytosis (p < 0.001). Multivariate analysis revealed high-risk MDS, MDS/MPN, severe neutropenia (ANC < 0.5 × 109/L), and mutations in ASXL1 and SETBP1 were associated with inferior survival outcomes. CONCLUSION: Certain mutations were related to more severe anaemia, lower white blood cell count or monocytosis in Asian MDS and MDS/MPN patients.
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Síndromes Mielodisplásicos , Enfermedades Mielodisplásicas-Mieloproliferativas , Trastornos Mieloproliferativos , Neoplasias , Neutropenia , Humanos , Mutación , Síndromes Mielodisplásicos/genética , Enfermedades Mielodisplásicas-Mieloproliferativas/genética , Trastornos Mieloproliferativos/genéticaRESUMEN
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.