Cytomegalovirus Infection and Treatment in Allogeneic Hematopoietic Stem Cell Transplantation: A Retrospective Study from a Single Institution in an Endemic Area.

OBJECTIVE: Although Cytomegalovirus (CMV) infection is a major complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT), the risk factors for CMV reactivation and treatment failure in CMV endemic areas have remained unclear. This study investigated the risk factors for CMV reactivation among allo-HSCT recipients in an area where CMV is highly endemic. MATERIALS AND METHODS: Medical records of 82 allo-HSCT recipients from a CMV endemic area were retrospectively reviewed. The patients were stratified into two groups: those with CMV reactivation (n=32) and those without CMV reactivation (n=50). We investigated possible variables associated with CMV reactivation and treatment failure. RESULTS: Univariate analyses showed that non-remission disease status [hazard ratio (HR): 2.15; p=0.032] and ≥grade III acute graft-versus-host disease (GVHD) (HR: 3.07; p=0.002) were associated with CMV reactivation. Multivariate analysis further demonstrated that older age (HR: 1.03; p=0.029) and ≥grade III acute GVHD (HR: 2.98; p=0.012) were associated with CMV reactivation. Overall survival time seemed lower among patients with CMV reactivation than among patients without CMV reactivation, although the difference was not statistically significant (p=0.165). The absence of ≥grade III acute GVHD was associated with successful CMV treatment in the current study (odds ratio: 4.40; p=0.008). CONCLUSION: Prophylactic anti-CMV therapy might need to be considered for allo-HSCT recipients who have ≥grade III GVHD.

Early mortality in multiple myeloma: Experiences from a single institution.

OBJECTIVE: Multiple myeloma (MM) is a hematological malignancy that presents with infection, anemia, bone lesions, renal function impairment, and hypercalcemia. The survival of MM patients has improved in recent decades; however, early mortality remains a critical problem. The aim of this study was to identify the etiologies and clinical variables associated with early mortality in MM. In addition, the effects of bortezomib on reducing early mortality incidence were investigated. METHOD AND MATERIALS: Medical records from 122 MM patients diagnosed between November 2007 and December 2013 were retrospectively reviewed. Early mortality was defined as death by any cause within the first 180 days after pathological diagnosis. RESULTS: In newly diagnosed MM patients, early mortality occurred in 22.95% of patients. Infection accounted for 67.86% of early deaths. Multivariate analyses by Cox proportional-hazards regression showed that higher ß2-microglobulin (P < 0.001) and serum lactate dehydrogenase (P < 0.001) levels, and lower serum albumin levels (P < 0.001) were associated with early mortality. Both first-line and greater than or equal to second-line bortezomib treatments were not associated with superior 180-day overall survival (P = 0.546 for first-line bortezomib treatment; P = 0.066 for greater than or equal to second-line bortezomib treatment). CONCLUSION: Our results suggest that infection is the leading cause of early death in MM. High ß2-microglobulin, high serum lactate dehydrogenase, and low serum albumin levels are poor prognostic factors for early mortality. Bortezomib therapy does not appear to reduce the incidence of early mortality in MM patients.

Thalassemia Phenotypes and Genotypes in Taiwan: A Retrospective Study Based on Thalassemia Screening of Young Men for Military Conscription.

Prenatal thalassemia studies from Taiwan show that one-third of fetuses with genetic abnormalities have ß-thalassemia major (ß-TM). However, the phenotypes and genotypes of adult thalassemia warrant further investigation. From September 2006 to April 2014, 741 male candidates drafted for military service with mean corpuscular volume (MCV) <80 fL and serum ferritin >20 µg/L were analyzed. The results showed that the detection rates of α- and ß-thalassemia (α- an ß-thal) were 50.20% (372/741) and 49.12% (364/741), respectively. Only five patients (0.67%) were diagnosed with both α- and ß-thal. The - -(SEA)/αα mutation was found in 76.88% (286/372) of α-thal patients. Heterozygous mutations in IVS-II-654 (C > T) and codons 41/42 (-TCTT) accounted for 55.77% (203/364) of ß-thal cases. The leukocyte counts for α- and ß-thal were 6241.74 ± 1552.99 and 6622.87 ± 1814.41 × 10(9)/L, respectively (p = 0.007). The α-thal patients had lower red blood cell (RBC) mass (5.85 ± 0.44 × 10(12)/L vs. 6.09 ± 0.45 × 10(12)/L; p < 0.001) and higher hemoglobin (Hb) (12.82 ± 0.72 vs. 12.35 ± 0.71 g/dL; p < 0.001) than ß-thal patients. Mean serum ferritin values were 169.67 and 241.36 µg/L, respectively, in α- and ß-thal patients (p < 0.001), indicating more profound ineffective erythropoiesis in ß-thal. Only four of the 741 patients underwent further hematological follow-up. Our study suggests that iron overload might be a potential problem in ß-thal patients; therefore, regular follow-up is highly recommended.

Basic fibroblast growth factor induces VEGF expression in chondrosarcoma cells and subsequently promotes endothelial progenitor cell-primed angiogenesis.

Chondrosarcoma, a common malignant tumour, develops in bone. Effective adjuvant therapy remains inadequate for treatment, meaning poor prognosis. It is imperative to explore novel remedies. Angiogenesis is a rate-limiting step in progression that explains neovessel formation for blood supply in the tumour microenvironment. Numerous studies indicate that EPCs (endothelial progenitor cells) promote angiogenesis and contribute to tumour growth. bFGF (basic fibroblast growth factor), a secreted cytokine, regulates biological activity, including angiogenesis, and correlates with tumorigenesis. However, the role of bFGF in angiogenesis-related tumour progression by recruiting EPCs in human chondrosarcoma is rarely discussed. In the present study, we found that bFGF induced VEGF (vascular endothelial growth factor) expression via the FGFR1 (fibroblast growth factor receptor 1)/c-Src/p38/NF-κB (nuclear factor κB) signalling pathway in chondrosarcoma cells, thereby triggering angiogenesis of endothelial progenitor cells. Our in vivo data revealed that tumour-secreted bFGF promotes angiogenesis in both mouse plug and chick CAM (chorioallantoic membrane) assays. Xenograft mouse model data, due to bFGF-regulated angiogenesis, showed the bFGF regulates angiogenesis-linked tumour growth. Finally, bFGF was highly expressed in chondrosarcoma patients compared with normal cartilage, positively correlating with VEGF expression and tumour stage. The present study reveals a novel therapeutic target for chondrosarcoma progression.

Mechanistic aspects of lauryl gallate-induced differentiation and apoptosis in human acute myeloid leukemia cells.

Lauryl gallate (LG) is a gallic acid derivative that has been widely used as an antioxidant food additive. In this study, we examined the anticancer effects of LG on the human acute myeloid leukemia (AML) HL60 and KG-1 cells. Our results showed that LG inhibited cell proliferation in a concentration- and time-dependent manner in both HL60 and KG-1 cells. The IC50s of LG in HL60 and KG-1 cells were 3.5 and 8.0 µM, respectively. Treatment with LG increased the proportions of annexin V-stained and sub-G1-phase HL60 and KG-1 cells. Moreover, activation of both extrinsic and intrinsic apoptotic pathways was involved in LG-induced AML cell apoptosis, accompanied by dissipation of mitochondrial membrane potential, downregulation of anti-apoptotic proteins (Bcl-2, Mcl-1, and Bcl-xL), upregulation of pro-apoptotic proteins (Bak, PUMA, DR4, and DR5), and increased caspase-2, -3, -8, and -9 activation. Our results also indicated that LG could induce monocytic differentiation in both HL60 and KG-1 cells, confirmed by morphological changes, nitroblue tetrazolium reduction assays, nonspecific esterase assays, and increased CD14 expression. After blocking LG-induced ERK and Sp1 expression using the ERK-specific inhibitor PD98059, monocytic differentiation in both HL60 and KG-1 cells decreased, suggesting that LG-induced differentiation proceeded through an ERK/Sp1 signaling axis.

Venous outflow reconstruction using an expanded polytetrafluoroethylene vascular graft in living-donor liver transplant: a single-center experience.

OBJECTIVES: Limited studies have focused on the feasibility and technical requirements of using expanded polytetrafluoroethylene vessel grafts for venous outflow reconstruction in a living-donor liver transplant using right liver grafts without the middle hepatic vein. MATERIALS AND METHODS: Between August 2007 and December 2012, thirty-two patients who had received an expanded polytetrafluoroethylene vascular graft for outflow reconstruction during a living-donor liver transplant using a right liver graft without the middle hepatic vein were retrospectively reviewed. Preoperative and operative data, complications, and mortality were compared among patients who received the expanded polytetrafluoroethylene grafts with individual anastomoses (n = 18) or confluent anastomoses (n =14). RESULTS: For patients who had received an individual and a confluent anastomosis, graft reconstruction time was 25.8 and 14.9 minutes (P = .000). No cases of graft occlusion occurred during first 72 hours after surgery. Although 5 patients (15.6%) died within 90 days, none of the deaths were associated with the vascular grafts. Operative mortality was not statistically different between patients who had received an individual anastomosis (3/18, 16.7%) and those who had received a confluent anastomosis (2/14, 14.3%) (P = 1.000). CONCLUSIONS: Individual and confluent anastomoses using an expanded polytetrafluoroethylene vascular graft is a feasible approach to venous outflow reconstruction in a living-donor liver transplant using right liver grafts without the middle hepatic vein.

Macrohematuria as initial presentation in a girl with factor VIII and factor IX inhibitors associated with systemic lupus erythematosus.

Acquired hemophilia is rarely observed in a pediatric population. We report a case of a 14-year-old girl presented with ecchymoses and macrohematuria. She developed factor VIII and factor IX inhibitors, and was diagnosed with simultaneous acquired hemophilia and systemic lupus erythematosus (SLE). Recombinant-activated FVII and corticosteroid were prescribed due to macrohematuria-related hypovolemia and anemia, which resolved satisfactorily. This case is a reminder that the rare concurrent presence of factor VIII and factor IX inhibitors could be associated with SLE in a pediatric population. Children with SLE-associated-acquired hemophilia may develop macrohematuria as well.

Primary splenic lymphoma associated with hemophagocytic lymphohistiocytosis complicated with splenic rupture.

Primary splenic lymphoma (PSL) is a rare disease with ambiguous definition, comprising less than 1% of non-Hodgkin's lymphoma. Even rarer is PSL combined with hemophagocytic lymphohistiocytosis (HLH), which has presentations of fever, cytopenia, hepatosplenomegaly, hyperferritinemia, and phagocytosis of hematopoietic cells in the reticuloendothelial system. We report the case of a 77-year-old man who presented with HLH initially. Refusing diagnostic splenectomy, he received chemotherapy. Spontaneous splenic rupture occurred after chemotherapy. In the following emergency operation, PSL was diagnosed. He received another 5 courses of chemotherapy with the R-CNOP regimen (rituximab, cyclophosphamide, mitoxantrone, vincristine, prednisolone). Now he has no residual or relapsed disease. Diagnostic splenectomy for adult HLH patients without definite etiologies may play an important role.