Extranodal Natural Killer/T-cell Lymphoma, Nasal Type:Diagnosis and Treatment

The aggressive lymphoma, extranodal natural killer/T-cell lymphoma-nasal type, is strongly associated with Epstein-Barr virus (EBV) and is most common in Asia and in South and Central America. By contrast, incidence is low in the United States and Europe, where extranodal natural killer/T-cell lymphoma represents only 0.2%-0.4% of all newly diagnosed non-Hodgkin lymphomas. At diagnosis, it is important to test for EBV DNA in plasma by polymerase chain reaction and to carry out positron emission tomography/computer tomography and magnetic resonance imaging of the nasopharynx. In stage I/II disease, radiotherapy is the most important treatment modality, but in high-risk stage I/II disease (stage II, age > 60 y, elevated lactate dehydrogenase, Eastern Cooperative Oncology Group performance score ≥2, primary tumor invasion), it should be combined with chemotherapy. The most optimal responses are reached with nonmultidrug resistance-based therapy (eg, asparaginase- or platinum-based therapy). Therapeutic approaches consist of either platinum-based concurrent chemoradiotherapy or sequential chemoradiotherapy. The minimum dose of radiotherapy should be 50-56 Gy. Treatment of stage III/IV disease consists of 3 cycles of chemotherapy followed by autologous hematopoietic cell transplantation. Allogeneic hematopoietic cell transplantation should only be considered in case of relapsed disease or after difficulty reaching complete remission. During treatment and follow-up, plasma EBV levels should be monitored as a marker of tumor load

Concanavalin A staining: a potential biomarker to predict cytarabine sensitivity in acute myeloid leukemia

Acute myeloid leukemia (AML) is a cancer of the myeloid lineage of blood cells, with an overall 5-year survival rate of 25%, mainly due to therapy-resistant relapses in > 50% of patients. The standard treatment for AML comprises cytarabine (AraC) with anthracyclines. Biomarkers to determine AraC sensitivity are currently lacking, thus hampering the rational choice of optimal treatment protocols, which would be especially warranted in the case of primary refractory disease. In the current study, we hypothesized that AraC-resistant AML cells harbor a different “sugar decoration”, i.e., glycosylation profile, compared with sensitive cells, which could be used as biomarker for AraC sensitivity. Therefore, we analyzed the expression of glycosylation-related genes in publicly available AML datasets, whereby the high expression of mannosylation-related genes (6 out of 13) was significantly associated with a worse survival in patients treated with AraC-based intensive chemotherapy protocols. In line with these data, the AraC-resistant AML cells expressed higher levels of high mannose N-glycans, as detected by mass spectrometry-based glycomics. Concanavalin A (ConA), a lectin that specifically recognizes α-mannoses in N-glycans, bound more strongly to AraC-resistant cells, and the extent of the ConA binding was correlated with AraC sensitivity in a panel of AML cell lines. Furthermore, the ConA staining could discriminate AraC sensitivity in vitro between two patient-derived AML samples taken at diagnosis. Therefore, the ConA staining may be a potential novel biomarker to predict AraC sensitivity in AML

Transcription factor 4 (TCF4) expression predicts clinical outcome in RUNX1 mutated and translocated acute myeloid leukemia

Contains fulltext : 229528.pdf (publisher's version ) (Open Access

Erythrocytosis in the general population:clinical characteristics and association with clonal hematopoiesis

Erythrocytosis is a common reason for referral to hematology services and is usually secondary in origin. The aim of this study was to assess clinical characteristics and clonal hematopoiesis (CH) in individuals with erythrocytosis in the population-based Lifelines cohort (n 5 147 167). Erythrocytosis was defined using strict (World Health Organization [WHO] 2008/British Committee for Standards in Hematology) and wide (WHO 2016) criteria. Individuals with erythrocytosis (strict criteria) and concurrent leukocytosis and/or thrombocytosis were 1:2 matched with individuals with isolated erythrocytosis and analyzed for somatic mutations indicative of CH ($5% variant allele frequency). One hundred eighty five males (0.3%) and 223 females (0.3%) met the strict criteria, whereas 4868 males (7.6%) and 309 females (0.4%) met the wide criteria. Erythrocytosis, only when defined using strict criteria, was associated with cardiovascular morbidity (odds ratio [OR], 1.8; 95% confidence interval [CI], 1.2-2.6), cardiovascular mortality (hazard ratio [HR], 2.2; 95% CI, 1.0-4.6), and all-cause mortality (HR, 1.7; 95% CI, 1.2-2.6), independent of conventional risk factors. Mutations were detected in 51 of 133 (38%) evaluable individuals, with comparable frequencies between individuals with and without concurrent cytosis. The JAK2 V617F mutation was observed in 7 of 133 (5.3%) individuals, all having concurrent cytosis. The prevalence of mutations in BCOR/BCORL1 (16%) was high, suggesting aberrant epigenetic regulation. Erythrocytosis with CH was associated with cardiovascular morbidity (OR, 9.1; 95% CI, 1.2-68.4) in a multivariable model. Our data indicate that only when defined using strict criteria erythrocytosis is associated with cardiovascular morbidity (especially in the presence of CH), cardiovascular mortality, and all-cause mortality

Peripheral blood cytopenias in the aging general population and risk of incident hematological disease and mortality

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Anti-thymocyte globulin with CsA and MMF as GVHD prophylaxis in nonmyeloablative HLA-mismatched allogeneic HCT

Nonmyeloablative regimens are used for allogeneic hematopoietic cell transplantation (HCT) of older or medically unfit patients, but successful outcome is still hindered by graft-versus-host disease (GVHD), especially in the setting of HLA-mismatched HCT. New GVHD prophylaxis strategies are emerging, including the triple drug strategy, that improve the GVHD-free and relapse-free survival (GRFS). Because the impact of ATG in HLA-mismatched Flu-TBI-based nonmyeloablative HCT has not been investigated, we did a retrospective analysis in three Dutch centers. 67 patients were evaluable, with a median age of 56 years. Overall survival, relapse-free survival and GRFS at 4 years were 52%, 43%, and 38%, respectively. NRM findings and cumulative incidence of relapse at 4 years were 26% and 31%, respectively. At 1-year grade II-IV had occurred in 40% of the patients, and the incidence of moderate-severe chronic GVHD incidence was 16%. Acknowledging the limitations of retrospective analyses, we conclude that the use of ATG for HLA-mismatched truly nonmyeloablative Flu-TBI HCT is feasible and results in acceptable long term outcomes, especially with regards to GRFS. We consider ATG in combination with cyclosporin and mycophenolate mofetil as an alternative for the triple drug strategy that uses sirolimus for GVHD prophylaxis in this particular setting