Nai-Wen Su

A case of tuberculosis-induced hemophagocytic lymphohistiocytosis in a patient under hemodialysis

The insidious onset, but rapid progression of hemophagocytic lymphohistiocytosis is always a diagnostic challenge. Herein, we report the case involving a 58-year-old man with diabetes-related nephropathy on dialysis who presented with fever of unknown origin, pancytopenia, and splenomegaly. A bone marrow smear showed extensive hemophagocytosis and the pathology disclosed granulomatous inflammation with caseous necrosis, suggestive of tuberculosis. Sputum culture and polymerase chain reaction confirmed tuberculosis. The patient exhibited signs of multiple-organ failure that were not reversed with anti-tuberculous medications and corticosteroids. The case reminds us that this is an uncommon clinical scenario, and only a timely diagnosis with prompt treatment results in a favorable outcome.

Germline variations at JAK2 , TERT , HBS1L - MYB and MECOM and the risk of myeloproliferative neoplasms in Taiwanese population

Germline variations at JAK2, TERT, HBS1L-MYB and MECOM have been found to associate with myeloproliferative neoplasms (MPNs) in European populations. Whether these germline variations are associated with MPNs in Taiwanese population is obscure. Here we aimed to evaluate the association of five germline variations (JAK2 46/1 haplotype tagged by rs12343867, JAK2 intron 8 rs12339666, TERT rs2736100, HBS1L-MYB rs9376092 and MECOM rs2201862) and the risk of MPNs in Taiwanese population. A total of 178 MPN patients (109 essential thrombocythemia, 54 polycythemia vera and 15 primary myelofibrosis) were enrolled into this study. The information of 17033 control subjects was obtained from Taiwan Biobank database. The JAK2 46/1 haplotype, JAK2 rs12339666 and TERT rs2736100 were significantly associated with Taiwanese MPNs (P = 3.6×10-19, 1.9×10-19 and 3.1×10-6, respectively), and JAK2V617F-positive MPNs (n=121) (P = 5.6×10-21, 4.4×10-21 and 8.6×10-7, respectively). In JAK2V617F-negative cases (n=55), only the JAK2 46/1 haplotype and JAK2 rs12339666 remained statistically significant (P= 0.009 and 0.007, respectively). When stratified by disease subtypes, the JAK2 46/1 haplotype and JAK2 rs12339666 were significantly associated with all three MPN subtypes, but TERT rs2736100 was only associated with essential thrombocythemia and polycythemia vera. We did not find any association of these five SNPs with CALR mutations in our cohort. Furthermore, the risk alleles of MECOM rs2201862 and HBS1L-MYB rs9376092 were demonstrated to be negatively associated with the risk of developing polycythemia vera. In conclusion, germline variations at JAK2 (both the 46/1 haplotype and rs12339666) and TERT rs2736100 were associated with MPNs in Taiwanese population.Germline variations at JAK2, TERT, HBS1L-MYB and MECOM have been found to associate with myeloproliferative neoplasms (MPNs) in European populations. Whether these germline variations are associated with MPNs in Taiwanese population is obscure. Here we aimed to evaluate the association of five germline variations (JAK2 46/1 haplotype tagged by rs12343867, JAK2 intron 8 rs12339666, TERT rs2736100, HBS1L-MYB rs9376092 and MECOM rs2201862) and the risk of MPNs in Taiwanese population. A total of 178 MPN patients (109 essential thrombocythemia, 54 polycythemia vera and 15 primary myelofibrosis) were enrolled into this study. The information of 17033 control subjects was obtained from Taiwan Biobank database. The JAK2 46/1 haplotype, JAK2 rs12339666 and TERT rs2736100 were significantly associated with Taiwanese MPNs (P = 3.6x10-19, 1.9x10-19 and 3.1x10-6, respectively), and JAK2V617F-positive MPNs (n=121) (P = 5.6x10-21, 4.4x10-21 and 8.6x10-7, respectively). In JAK2V617F-negative cases (n=55), only the JAK2 46/1 haplotype and JAK2 rs12339666 remained statistically significant (P= 0.009 and 0.007, respectively). When stratified by disease subtypes, the JAK2 46/1 haplotype and JAK2 rs12339666 were significantly associated with all three MPN subtypes, but TERT rs2736100 was only associated with essential thrombocythemia and polycythemia vera. We did not find any association of these five SNPs with CALR mutations in our cohort. Furthermore, the risk alleles of MECOM rs2201862 and HBS1L-MYB rs9376092 were demonstrated to be negatively associated with the risk of developing polycythemia vera. In conclusion, germline variations at JAK2 (both the 46/1 haplotype and rs12339666) and TERT rs2736100 were associated with MPNs in Taiwanese population.

Increased B cell activation is present in JAK2 V617F-mutated, CALR -mutated and triple-negative essential thrombocythemia

Essential thrombocythemia (ET) is a BCL-ABL1-negative myeloproliferative neoplasm. We have reported that increased activated B cells can facilitate platelet production mediated by cytokines regardless JAK2 mutational status in ET. Recently, calreticulin (CALR) mutations were discovered in ~30% JAK2/MPL-unmutated ET and primary myelofibrosis. Here we sought to screen for CALR mutations and to evaluate B cell immune profiles in a cohort of adult Taiwanese ET patients. B cell populations, granulocytes/monocytes membrane-bound B cell-activating factor (mBAFF) levels, B cells toll-like receptor 4 (TLR4) expression and intracellular levels of interleukin (IL)-1β/IL-6 and the expression of CD69, CD80, and CD86 were quantified by flow cytometry. Serum BAFF concentration was measured by ELISA. 48 healthy adults were used for comparison. 19 (35.2%) of 54 ET patients harbored 8 types of CALR exon 9 mutations including 4 (7.4%) patients with concomitant JAK2V617F mutations. Compared to JAK2V617F mutation, CALR mutations correlated with younger age at diagnosis (p=0.04), higher platelet count (p=0.004), lower hemoglobin level (p=0.013) and lower leukocyte count (p=0.013). Multivariate analysis adjusted for age, sex, follow-up period and hematological parameters confirmed that increased activated B cells were universally present in JAK2-mutated, CALR-mutated and triple-negative ET patients when compared to healthy adults. JAK2- and CALR-mutated ET have significantly higher fraction of B cells with TLR4 expression when compared to triple-negative ET (p=0.019 and 0.02, respectively). CALR-mutated ET had significantly higher number of CD69-positive activated B cells when compared to triple-negative ET (p=0.035). In conclusion, increased B cell activation is present in ET patients across different mutational subgroups.

Chemotherapy Combination with Bevacizumab for the Treatment of Vascular Sarcoma

Vascular sarcoma is a rare tumor associated with high mortality because of rapid local relapse and a high incidence of metastasis. A combination of surgery, radiotherapy and chemotherapy is commonly suggested, but this gives formidable insult to the patient, and yet, the prognosis remains poor. The angiogenesis inhibitor bevacizumab has been shown to have significant antitumor activity when used to treat various cancers and it is proposed that this is due, at least in part, to its anti-angiogenic effect. Here we present four cases of vascular sarcoma that treated with bevacizumab plus chemotherapy and retrospective review. The results are partial response in one case, stable disease in two cases, and disease progression in one case.

CHOP plus L-asparaginase for Patients with Peripheral T-cell Lymphoma

Background: Our aim here was to contribute toward development of a broadly accepted treatment regimen for peripheral T-cell lymphoma.Methods: Seven patients were diagnosed as peripheral T cell lymphoma in our institution from July 2008 to December 2010. They received first-line chemotherapy with CHOP plus L-asparaginase. Chemotherapy protocol was L-asparaginase (L-ASP) at 6000 IU/m2 D1~5 i.m. concomitant with standard CHOP every three weeks.Results: Patients had good tolerance to combination therapy of CHOP with L-asparaginase (A-CHOP). Two of our patients had stable disease, another five achieved complete remission, but two patients relapsed after five months and one year later, respectively. The response rate was 71% for A-CHOP treatment. No coagulation defect or bleeding tendency was found in each cycle of chemotherapy.Conclusions: All patients were well-tolerated to the A-CHOP regimen. But the additional effect of L-asparaginase in peripheral T-cell lymphoma treatment needs more studies to confirm it.