Treatment outcomes between cyclosporin and chemotherapy in adult subcutaneous panniculitis-like T-cell lymphoma: a report from nation-wide Thai lymphoma study group registry.

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare subtype of T-cell lymphomas with a characteristic feature of subcutaneous nodules associated with hemophagocytic lymphohistiocytosis (HLH). Treatment options for SPTCL are mainly chemotherapy (CMT) or immunosuppressive agents with selection currently dependent on physician decisions. Outcomes between the 2 treatment remedies have not yet been comprehensively compared. This study aimed to compare complete remission (CR) rates between SPTCL patients receiving cyclosporin (CSA)-based regimen (CSA +/- steroid) and CMT. The 5-year overall survival (OS) and 5-year progression free survival (PFS) were also analyzed. Clinical data from patients with SPTCL were drawn from the Thai Lymphoma Study Group registry who were newly diagnosed between 2007 and 2023. A total of 93 patients were selected with 45 cases having received CSA-based regimen and 48 cases having received CMT. There were more patients with limited stage at skin in the CSA group (63.8% vs. 36.2%, p = 0.003), while more patients with hepato- and/or splenomegaly were found in the CMT group (56.2% vs. 24.5%; p = 0.002). Germline HAVCR2 mutations were detected in 26/33 (78.8%) cases. The CR rate was significantly higher in patients treated with CSA (87% vs. 58.3%; OR = 6.5 [95%CI, 2.7-15.3]; p = 0.002). At a median follow-up of 87.8 months (range 0-185), the 5-year OS (98% vs. 87%, p = 0.19) and PFS (72.4% vs. 69.2%, p = 0.19) showed a trend favoring patients treated with CSA. Based on our study, CSA-based regimens are the preferred first-line treatment remedy for newly diagnosed SPTCL, especially in patients with limited cutaneous involvement.

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.

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.

Extracellular vesicles from thalassemia patients carry iron-containing ferritin and hemichrome that promote cardiac cell proliferation.

Extracellular vesicles (EVs) are bioactive, submicron-sized membrane vesicles released from all cell types upon activation or apoptosis. EVs including microparticles (MPs) and exosomes have emerged as important mediators of cell-to-cell communication in both normal and pathological states including thalassemia (thal). However, the role of EVs derived from ß-thal patients with iron overload (+ IO) and without iron overload (-IO) on cardiac cells is unclear. We hypothesized plasma EVs in thal patients containing ferritin (iron storage protein) and a denaturated hemoglobin-hemichrome that induce cardiac cell proliferation. The origins and numbers of EVs isolated from plasma of normal, thal (+ IO), and (- IO) patients were compared and determined for their iron and iron-containing proteins along with their effects on cardiac and endothelial cells. Data shows that MPs were originated from many cell sources with marked numbers of platelet origin. Only the number of RBC-derived MPs in thal (+ IO) patients was significantly high when compared to normal controls. Although MPs derived from both normal and thal patients promoted cardiac cell proliferation in a dose-dependent manner, only exosomes from thal patients promoted cardiac cell proliferation compared to the untreated. Moreover, the exosomes from thal (+ IO) potentially induce higher cardiac cell proliferation and angiogenesis in terms of tube number than thal (- IO) and normal controls. Interestingly, ferritin content in the exosomes isolated from thal (+ IO) was higher than that found in the MPs isolated from the same patient. The exosomes of thal patients with higher serum ferritin level also contained greater level of ferritin inside the exosomes. Apart from ferritin, there were trends of increasing hemichrome and iron presented in the plasma EVs and EV-treated H9C2 cells. Findings from this study support the hypothesis that EVs from ß-thal patients carry iron-load proteins that leads to the induction of cardiac cell proliferation.

Successful venous thromboprophylaxis in a patient with vaccine-induced immune thrombotic thrombocytopenia (VITT): a case report of the first reported case in Thailand.

BACKGROUND: Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare but fatal complication of the Coronavirus Disease 2019 vaccine. The many reports of VITT have mostly been in the Caucasian population. Here, we present the first reported case in an Asian population. CASE PRESENTATION: A 26-year-old female had severe headache and severe thrombocytopenia 8 days after administration of the ChAdOx1 nCoV-19 vaccine developed by AstraZeneca. Although no thrombosis was demonstrated by imaging studies, she had very highly elevated d-dimer levels during hospitalization. Serology for antibodies against platelet factor 4 was positive on several days with very high optical density readings. We found that the antibody could induce spontaneous platelet aggregation without the presence of heparin. We decided to treat her with intravenous immunoglobulin, high-dose dexamethasone, and a prophylactic dose of apixaban. She improved rapidly and was discharged from the hospital 6 days after admission. Neither thrombocytopenia nor thrombosis was subsequently detected at the three-week follow-up. CONCLUSIONS: Despite the lower rate of thrombosis, VITT can occur in the Asian population. Early detection and prompt treatment of VITT can improve the patient's clinical outcome. Thromboprophylaxis with nonheparin anticoagulants also prevents clot formation.

Internalization of cell-derived microparticles triggers endothelial pro-inflammatory responses.

BACKGROUND: Increased numbers of circulating microparticles (MPs) have long been documented in thalassemia and are considered as a contributing factor in developing the thromboembolic events (TEEs), which are associated with endothelial dysfunction. Indeed, the cellular and molecular mechanisms by which MPs and endothelial cells interact and their consequences remain poorly investigated. OBJECTIVE: The present study aims to compare the biological effects of MPs obtained from healthy subjects and ß-thalassemia/HbE patients on endothelial pro-inflammatory responses. METHODS: MPs isolated from plasma by two-step centrifugation from 10 healthy donors, 19 splenectomized and 30 non-splenectomized ß-thalassemia/HbE patients were first characterized for their cellular origins, then counted and incubated with primary human umbilical vein endothelial cells (HUVECs). Internalization of MPs into HUVECs and their induction on endothelial cell activation and pro-inflammatory responses were determined. RESULTS: MPs either from healthy or ß-thalassemia/HbE patients could become internalized into endothelial cells, but unlike MPs from healthy donors and non-splenectomized patients, MPs from splenectomized patients were the most active and induced the 2-fold up-regulation of pro-inflammatory genes, IL1B, CXCL8, and CCL2 and 4-fold increase in interleukin-1ß. In addition, MPs from both healthy subjects and splenectomized patients at 106/ml failed to trigger the secretion of endothelial IL-6 and IL-8 while higher MP concentration at 5 × 106/ml significantly induced this secretion. CONCLUSIONS: Plasma MPs isolated from splenectomized ß-thalassemia/HbE patients are capable of triggering pro-inflammatory responses from endothelial cells reflected at both gene and protein levels.

Killer cell immunoglobulin-like receptors in Thai patients with multiple myeloma.

BACKGROUND: Natural killer (NK) cells have been implicated in the immune response against multiple myeloma (MM) cells. Killer cell immunoglobulin-like receptors (KIRs) regulate NK cell activity by recognizing specific human leukocyte antigen (HLA) class I as ligands. OBJECTIVE: To investigate the association of KIR genes and ligands with MM in the Thai population. METHODS: KIR gene polymorphisms and their HLA ligands were investigated in 66 Thai patients with MM and 200 healthy controls. RESULTS: The frequencies of KIR3DL1 and 2DS4 were significantly lower in myeloma patients than in controls (P = 0.02). The frequencies of KIR3DL1, 2DS4, 2DL1 with C2, and 3DL1 with Bw4 were significantly higher in the patients achieving > very good partial response (VGPR) than those achieving ≤ VGPR after treatment with bortezomib (P = 0.009, 0.009, 0.01, and 0.02, respectively). CONCLUSIONS: This study suggests the association of KIR genes with the protection against MM and the association of inhibitory KIR and ligands with the response to treatment in MM.

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.

Microparticles from splenectomized ß-thalassemia/HbE patients play roles on procoagulant activities with thrombotic potential.

Thromboembolic events including cerebral thrombosis, deep vein thrombosis, and pulmonary embolism are major complications in ß-thalassemia. Damaged red blood cells and chronic platelet activation in splenectomized ß-thalassemia/HbE patients were associated with increased microparticles (MPs) releases into blood circulation. MPs are small membrane vesicles, which play important roles on coagulation. However, the role of MP in thalassemia is poorly understood. In this study, the effects of splenectomized-MPs on platelet activation and aggregation were investigated. The results showed that isolated MPs from fresh platelet-free plasma of patients and normal subjects directly induce platelet activation, platelet aggregation, and platelet-neutrophil aggregation in a dose-dependent manner. Interestingly, MPs obtained from splenectomized patients are more efficient in induction of platelet activation (P-selectin+) when compared to MPs from normal subjects (P < 0.05), tenfold lower than pathophysiological level, at 1:0.1 platelet MP ratio. Co-incubation of splenectomized-MPs with either normal-, non-splenectomized- or splenectomized-platelets at 1:10 platelet MP ratio increased platelet activation up to 5.1 ± 2.2, 5.6 ± 3.7, and 9.5 ± 3.0%, respectively, when normalized with individual baseline. These findings suggest that splenectomized patients were proned to be activated by MPs, and splenectomized-MPs could play an important role on chronic platelet activation and aggregation, leading to thrombus formation in ß-thalassemia/HbE patients.

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.

Clinical Significance of Bone Marrow Involvement as Confirmed by Bone Marrow Aspiration vs. Bone Marrow Biopsy in Diffuse Large B-cell Lymphoma.

BACKGROUND: In diffuse large B-cell lymphoma (DLBCL), bone marrow (BM) involvement confirmed by BM biopsy confers a poor prognosis. However, in clinical practice, there may be disagreement in results between BM biopsy and BM aspiration in determination of BM involvement. It is unknown which of BM biopsy or BM aspiration better correlates with clinical outcome. OBJECTIVE: To evaluate clinical outcome of BM involvement as confirmed by BM aspiration vs. confirmation by BM biopsy in patients with DLBCL. MATERIAL AND METHOD: Clinical data, treatment, and outcome of 126 DLBCL patients with available BM aspirate slides who attended the Hematology Clinic at Siriraj Hospital between January 1, 2007 and December 31, 2009 were reviewed. BM aspirate slides were revised and interpreted by hematologists. RESULTS: BM involvement was found in 12.7% (16/126) by BM biopsy and 24.6% (31/126) by BM aspiration. Regarding BM biopsy results, rates of complete remission (CR) among patients with unequivocal involvement, equivocal involvement, and without involvement were 75.0%, 57.1%, and 77.7%, respectively (p = 0.464). Two-year overall survival (OS) rates among the three groups were not significantly different (p = 0.663). Regarding BM aspiration results, CR rates among patients with unequivocal involvement, equivocal involvement, and without involvement were 80.6%, 75.8%, and 72.7% (p = 0.755). Two-year OS rates among the three groups were not significantly different (p = 0.118). In multivariate analysis, BM involvement as determined by either BM biopsy or BM aspiration was not associated with CR rate or 2-year OS rates. However, the International Prognostic Index (PI) and use of rituximab were found to be signifcantly associated with CR rate and OS. CONCLUSION: In patients with DLBCL, BM involvement confirmed by either BM biopsy or BM aspiration appears not to influence the rate of complete remission or 2-year overall survival.

Platelet activation and platelet-leukocyte interaction in ß-thalassemia/hemoglobin E patients with marked nucleated erythrocytosis.

Patients with thalassemia, an inherited hemolytic anemia, have increased risk of hypercoagulable complications. A whole blood flow cytometric (FCM) method has been used for studies of platelet activation and platelet-leukocyte aggregation in these patients. However, this FCM method presents technical difficulties because of the high proportion of immature red blood cells (RBCs) in these patients. A protocol for the simultaneous measurement of platelet activation and their aggregation with leukocyte populations in whole blood using four-color FCM which excluded immature RBC was devised, and evaluated for the evaluation of platelet function in patients with ß-thalassemia/hemoglobin E (HbE). Whole blood from these patients and from healthy volunteers was stained for platelet activation and platelet-leukocyte aggregates using anti-CD42a, anti-CD62P, anti-CD45 and glycophorin A (GPA) conjugated with different fluorochromes. Our FCM method is simple, effective and based on the assumption that GPA is present on all immature RBCs, but is not expressed on CD45⁺ leukocytes. Results from the studies showed that blood samples from these patients contained a high frequency of circulating activated platelets (CD42a⁺/CD62P⁺) when compared to samples from healthy individuals. The percentage of platelet-neutrophil, platelet-monocyte-but not platelet-lymphocyte-aggregates were also elevated in both thalassemia genotypes with marked increase in patients who had undergone splenectomy. These findings suggest that platelets adhere to neutrophils and monocytes are activated which support the clinical observation that splenectomized thalassemia patients have an increased risk of arterial or venous thrombotic manifestations.

Cutaneous Involvement of Extranodal NK/T Cell Lymphoma, Nasal Type, a Clinical and Histopathological Mimicker of Various Skin Diseases.

BACKGROUND: Extranodal NK/T cell lymphoma, nasal type (ENK/T) with cutaneous involvement has various histopathological findings and diverse clinical manifestations. METHODS: A retrospective study of cutaneous involvement of ENK/T lymphoma between 2006 and 2018 was conducted. RESULTS: Twenty-two cases were eligible for this study. Twelve cases could be proven as secondary cutaneous involvement by ENK/T lymphoma, while the remaining could not be confirmed as primary cutaneous ENK/T lymphoma. The histopathological patterns included dermal and subcutaneous nodular infiltration pattern in 11/22 cases (50%), lobular panniculitis pattern in 6/22 cases (27.3%), interface dermatitis pattern in 4/22 cases (18.2%), and granulomatous dermatitis pattern in 1/22 case (4.5%). The median follow-up was 18.3 months. Overall, the one-year and five-year survival rates were 31.3% and 13.3%, respectively. CONCLUSIONS: A variety of histopathological patterns of cutaneous involvement by ENK/T lymphoma should be differentiated from other cutaneous lymphomas, dermatitis, and infection. When atypical medium or large-sized lymphoid cells are encountered within skin lesions, pathologists should realize these lesions can be ENK/T lymphoma, especially in cases with coexisting tumor necrosis or angioinvasion. A complete evaluation of the upper aerodigestive tract is mandatory to identify the occult primary site of ENK/T lymphoma before establishing primary cutaneous ENK/T lymphoma.

Comparison of the region-based and pixel-wise methods for cardiac T2* analysis in 50 transfusion-dependent Thai thalassemia patients.

PURPOSE: To compare the observer variability of the conventional region-based (RB) to the typical and proposed pixel-wise (PW) methods for cardiac T2* analysis in thalassemia patients. DESIGN AND METHODS: Fifty thalassemia major patients were enrolled for the study. Short-axis bright- and black-blood sequences were acquired and analyzed using the RB and PW methods. Regions were defined using the whole septum (WS) or partial septum (PS). From the same PS region, results were reported by mean (PS-PW) and median (MPS-PW). Intraobserver and interobserver variabilities were investigated on all data set by 2 independent observers blinded to the result. RESULTS: The T2* values from the PS-PW and MPS-PW methods were comparable to the conventional WS-RB method on both scanning techniques. When comparing the interobserver variability from the WS-RB to the PS-PW method, the coefficient of variation of the PS-PW method was equivalent (4.5% vs 4.7%, P = NS) for the bright-blood technique but 31% lower (4.0% vs 2.8%, P = 0.21) for the black-blood technique. The proposed MPS-PW method performed even better with respect to the conventional WS-RB method, decreasing interobserver coefficient of variation by 24% (4.5% vs 3.5%, P = 0.08) and 42% (4.0% vs 2.4%, P = 0.02), respectively. Intraobserver reproducibility followed the same trend. CONCLUSIONS: The proposed PW method using the median of T2* values calculated from partial interventricular septum region provided lower intraobserver and interobserver variabilities compared with the conventional RB or typical PW methods.

A five-year retrospective study of treatment outcomes using the L-asparaginase-based regimen as a first-line chemotherapy protocol for patients diagnosed with extranodal NK/T-cell lymphoma, nasal-type, in Thailand.

OBJECTIVE: To assess clinical outcomes of newly diagnosed extranodal NK/T-cell lymphoma nasal-type (ENKTL) patients treated with L-asparaginase-containing chemotherapy as first-line chemotherapy. MATERIALS AND METHODS: We retrospectively reviewed data of new ENKTL patients in Siriraj Hospital, Thailand during 2012-2016. RESULTS: Among 27 patients, 16 were men and 11 were women, and their median age was 52 (range, 25-83) years. The primary sites were the aero-nasal area (23) and skin (4). Clinical stages of ENKTL were I, II, III and IV in 10, 8, 1 and 8 patients, respectively. Patients classified according to the NK cell-lymphoma prognostic index with PINK (27) and PINK-E (19) as low, intermediate, and high were 14, 8, 5, respectively and 11, 4, and 4, respectively. Chemotherapy regimens used were SMILE (24) and AspaMetDex (3). Fourteen patients received post- chemotherapy local radiation. The overall response rate for 26 assessable patients was 69%, with complete response in 14 patients (52%). Median progression-free and overall survival were 32 and 33 months, respectively. The most common L-asparaginase regimen related complications were hypofibrinogenemia (24) and hypersensitivity (9). The overall mortality at follow-up was 14/27 (52%) owing to sepsis (11) and disease progression (3). DISCUSSION: L-asparaginase-based regimens showed similar results as other study results. including those in which hematopoietic stem cell transplantation was performed, suggesting that transplantation can be avoided if it is unaffordable. Thrombosis or bleeding, the regimen side effects, should be carefully monitored during treatment. CONCLUSIONS: L-asparaginase-based regimens offer a good outcome as a front-line treatment for ENKTL.

An urgent need for improving thalassemia care due to the wide gap in current real-life practice and clinical practice guidelines.

Based on Thalassemia International Federation clinical practice guidelines (CPG) for non-transfusion dependent and transfusion dependent thalassemia, several measures should be routinely implemented such as monitoring and surveillance of thalassemia related complications for early detection and proper clinical management. To evaluate the prevalence and the performance of routine surveillance for thalassemia related complications during 2 periods; before and after published CPGs (2012-2014 vs 2015-2017), data from 524 adult thalassemia patients attended at Siriraj hospital were compared among different treating physician groups; thalassemia, private hematology, and internal medicine clinics. Three most common complications were osteopenia/osteoporosis (69.8%), gallstones (67.6%) and abnormal vitamin D level (67.6%). Iron overload has been widely evaluated (93.1%) followed by liver function test (82.3%). However, the rate of evaluation for other complications were significantly reduced and < 25% of patients were evaluated in several complications. Comparing among clinics, the surveillance rate has increased significantly for several endocrine complications only in patients treated at thalassemia clinic but not in others. This study was the first study that evaluated real-world practical management of thalassemia patient in terms of complication surveillance. This different clinical practice has called for an immediate policy change to improve and standardize a care for thalassemia patients in Thailand.

MTAP-related increased erythroblast proliferation as a mechanism of polycythaemia vera.

Polycythaemia vera (PV) is a haematological disorder caused by an overproduction of erythroid cells. To date, the molecular mechanisms involved in the disease pathogenesis are still ambiguous. This study aims to identify aberrantly expressed proteins in erythroblasts of PV patients by utilizing mass spectrometry-based proteomic analysis. Haematopoietic stem cells (HSCs) were isolated from newly-diagnosed PV patients, PV patients who have received cytoreductive therapy, and healthy subjects. In vitro erythroblast expansion confirmed that the isolated HSCs recapitulated the disease phenotype as the number of erythroblasts from newly-diagnosed PV patients was significantly higher than those from the other groups. Proteomic comparison revealed 17 proteins that were differentially expressed in the erythroblasts from the newly-diagnosed PV patients compared to those from healthy subjects, but which were restored to normal levels in the patients who had received cytoreductive therapy. One of these proteins was S-methyl-5'-thioadenosine phosphorylase (MTAP), which had reduced expression in PV patients' erythroblasts. Furthermore, MTAP knockdown in normal erythroblasts was shown to enhance their proliferative capacity. Together, this study identifies differentially expressed proteins in erythroblasts of healthy subjects and those of PV patients, indicating that an alteration of protein expression in erythroblasts may be crucial to the pathology of PV.

A rare occurrence of hairy cell leukemia in the Thai population: a case report.

Hairy cell leukemia (HCL) has been mainly reported from the Western countries. Herein we describe a case of HCL diagnosed in a Thai patient. A 36-year-old man presented with abdominal discomfort, frequent gum bleeding and significant weight loss for 2 months. Physical examination revealed moderate anemia, petechial hemorrhage on the extremities and an enlarged spleen down to the umbilicus. No hepatomegaly or lymphadenopathy was detected. Complete blood counts revealed a hemoglobin (Hb) of 6.6 g/dL, a white blood cell (WBC) count of 1.6 x 10(9)/L (neutrophil 16%, lymphocyte 71%, monocyte 11%, atypical lymphocyte 1%), and a platelet (PLT) count of 17 x 10(9)/L. Abnormal large mononuclear cells with villous projections were seen in the blood smear. Although bone marrow (BM) aspiration resulted in a dry tap, abnormal lymphocytes with villous projections could again be identified in the touch preparation. Flow cytometric analysis showed a distinct population above the normal lymphocyte region on CD45/SSC gates with a strong expression of CD19, CD20, CD22, CD25, CD11c, and kappa. CD5, CD23, CD10, CD4, and CD8 were all negative. BM biopsy was consistent with HCL. The patient was treated with splenectomy followed by 8 cycles of fludarabine and cyclophosphamide chemotherapy. At 21 months after diagnosis, the patient was doing well with a Hb of 16.9 g/dl, a WBC count of 6.8 x 10(9)/L, neutrophil 49.9%, lymphocyte 39.6%, monocyte 8.6%, and a PLT count of 329 x 10(9)/L). No abnormal lymphoid cells were detected in the blood smear. This present report represents the first Thai HCL case that was immunophenotypically confirmed by flow cytometry and successfully treated at Siriraj Hospital.