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ABSTRACTObjective Patients living with myeloproliferative neoplasms (MPNs) suffer from symptom burden that affect quality of life. Due to the differences in cultures, climates, and genetic background, we aimed to investigate the symptom burden of Thai MPN patients Methods A comprehensive survey using the MPN-10 questionnaire was carried out between September 1, 2014, and September 30, 2017. The scores obtained were then correlated with clinical outcomes.. Results A total of 145 patients were enrolled. Nearly 90% of patients reported being symptomatic. The mean MPN-10 score was 13.6 (SD = 11). The mean MPN-10 score was highest in PMF, whereas the mean score and intensity of individual items were surprisingly low in ET and PV. Notably, the mean MPN-10 score was significantly higher in patients with documented splenomegaly compared to those with a normal-sized spleen. However, there were no correlations between MPN-10 scores and the mutation status, disease complications such as thrombosis and hemorrhage, progression to myelofibrosis or leukemia, and mortality. Patients who needed regular transfusions reported a higher MPN-10 score compared to those who did not. Conclusion The MPN-10 score did not predict survival outcomes among Thai MPN patients. Higher MPN-10 was associated with more transfusion. Thai MPN patients reported lower MPN-10 compared to western population especially PV and ET.

Fertility is a concern in young female survivors of hematological malignancies. We evaluated post-treatment ovarian function in patients by measuring anti-Müllerian hormone (AMH) and conventional hormone levels to correlate with menstruation and fertility. The prospective cohort study included 29 reproductive-aged women diagnosed with Hodgkin lymphoma (n = 11), non-Hodgkin lymphoma (n = 9) or acute myeloid leukemia (n = 9). Hormone assays were measured after treatment was completed and compared to age-matched healthy controls. Menstrual changes and postmenopausal symptoms were assessed annually. Serum AMH levels were significantly lower compared to controls at 12 months after treatment [1.0 (0.18–1.8) vs. 2.2 (1.8–4.8) ng/mL; P

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

Germline HAVCR2 mutations are frequently detected in subcutaneous panniculitis-like T-cell lymphoma (SPTCL) patients with/without hemophagocytic lymphohistiocytosis (HLH) but factors associated with variable manifestations remain undetermined. To evaluate clinical variations and associated factors in SPTCL and/or HLH with/without HAVCR2 mutations, we performed direct sequencing of HAVCR2 exon 2 using DNA from patients with SPTCL or idiopathic HLH/HLH-like systemic illnesses, defined by HLH alone without secondary causes. The systematic review and individual patient data (IPD) level meta-analysis which included the present and previously published studies reporting HAVCR2 mutations in SPTCL with/without HLH populations was subsequently conducted using random-effects meta-analysis and multivariate logistic regression. Among 34 patients enrolled, ten of 28 SPTCL patients developed HLH/HLH-like systemic illnesses. Six cases with HAVCR2Y82C mutation manifested with HLH without panniculitis. Male sex (P=0.03) and age

Eltrombopag, an FDA-approved non-peptidyl thrombopoietin receptor agonist, is clinically used for the treatment of aplastic anemia, a disease characterized by hematopoietic stem cell failure and pancytopenia, to improve platelet counts and stem cell function. Eltrombopag treatment results in a durable trilineage hematopoietic expansion in patients. Some of the eltrombopag hematopoietic activity has been attributed to its off-target effects, including iron chelation properties. However, the mechanism of action for its full spectrum of clinical effects is still poorly understood. Here, we report that eltrombopag bound to the TET2 catalytic domain and inhibited its dioxygenase activity, which was independent of its role as an iron chelator. The DNA demethylating enzyme TET2, essential for hematopoietic stem cell differentiation and lineage commitment, is frequently mutated in myeloid malignancies. Eltrombopag treatment expanded TET2-proficient normal hematopoietic stem and progenitor cells, in part because of its ability to mimic loss of TET2 with simultaneous thrombopoietin receptor activation. On the contrary, TET inhibition in TET2 mutant malignant myeloid cells prevented neoplastic clonal evolution in vitro and in vivo. This mechanism of action may offer a restorative therapeutic index and provide a scientific rationale to treat selected patients with TET2 mutant–associated or TET deficiency–associated myeloid malignancies.

TCR repertoire diversification constitutes a foundation for successful immune reconstitution after allogeneic hematopoietic cell transplantation (allo-HCT). Deep TCR Vβ sequencing of 135 serial specimens from a cohort of 35 allo-HCT recipients/donors was performed to dissect posttransplant TCR architecture and dynamics. Paired analysis of clonotypic repertoires showed a minimal overlap with donor expansions. Rarefied and hyperexpanded clonotypic patterns were hallmarks of T cell reconstitution and influenced clinical outcomes. Donor and pretransplant TCR diversity as well as divergence of class I human leukocyte antigen genotypes were major predictors of recipient TCR repertoire recovery. Complementary determining region 3–based specificity spectrum analysis indicated a predominant expansion of pathogen- and tumor-associated clonotypes in the late post–allo-HCT phase, while autoreactive clones were more expanded in the case of graft-versus-host disease occurrence. These findings shed light on post–allo-HCT adaptive immune reconstitution processes and possibly help in tracking alloreactive responses.