The duration of functioning of a subcutaneous implantable port for the treatment of hematological tumors: a single institution-based study.

BACKGROUND: Although subcutaneous implantable ports have been indicated as venous access for chemotherapy, these devices have not been used routinely for hematological tumors. METHODS: Between May 2006 and April 2009, 39 ports were implanted in 37 patients with hematological tumors and 16 ports were implanted in 14 patients with nonhematological tumors. The patients were treated with standard/first-line and/or salvage/second-line or greater chemotherapy, and were prospectively followed until port removal, death, or the end of the study. RESULTS: Thirty-five (96%) patients with hematological tumors developed grade 4 hematological toxicity, while 1 (7%) patient with nonhematological tumors showed grade 4 neutropenia. The actual duration of the port in situ ranged from 14 to 719 days (mean, 271.4 days) in the hematology group, and from 50 to 955 days (mean, 419.5 days) in the nonhematology group (P = 0.039). The Kaplan-Meier-estimated median duration of port in situ in the hematology group was 364 days, which was significantly shorter than that in the nonhematology group (P = 0.009). When patient death and port removal for the end of treatment were censored, the rate of port functioning at 1 year was estimated to be 83% in the hematology group. Bloodstream infection (BSI) occurred in 7 patients with hematological tumors and in 1 patient with metastatic colorectal cancer; however, microbiological confirmation that the implantable port was the source of the BSI was inconclusive. CONCLUSION: The duration of port functioning in patients with hematological tumors was comparable to that in patients with nonhematological tumors. The higher rate of BSI in the hematology group was primarily attributable to profound neutropenia.

Persistent elevation of plasma osteopontin levels in HIV patients despite highly active antiretroviral therapy.

In human immunodeficiency virus (HIV) infection, not only HIV itself but also systemic immune activation plays a role in the disease progression to acquired immune deficiency syndrome (AIDS). The systemic immune activation may be present even during highly active antiretroviral therapy (HAART). An increased expression of osteopontin, a proinflammatory cytokine, during HAART was reported in lymph nodes of HIV infected individuals. Osteopontin is also known to be involved in the pathogenesis of various HAART-induced diseases. Here, we measured osteopontin and other inflammatory markers such as neopterin and galectin-9 using serially collected plasma from patients with HIV/AIDS to find novel markers for immune activation. Four AIDS patients complicated with various opportunistic infections and one acute HIV patient were studied. Osteopontin levels (normal levels: < 820 ng/ml) were elevated in all the patients (1,178-2,450 ng/ml). Likewise, galectin-9 levels (normal levels: < 46 pg/ml) were elevated in all patients (> 130 pg/ml), with the exceptionally high level in the acute HIV patient (4,196 pg/ml). Neopterin levels (normal ranges: 2-8 pmol/L) were elevated in four patients (21-99 pmol/L). After HAART, the levels of galectin-9 and neopterin apparently decreased, whereas the levels of osteopontin did not decrease. Thus, the high levels of osteopontin were sustained despite the clinical improvement. Fisher exact probability test showed that the mode of the changes was different between osteopontin and galectin-9, and between osteopontin and neopterin (p = 0.024). We therefore propose that the plasma osteopontin is a useful marker of immune activation during HAART and HAART-induced side effects.

Co-occurrence of monoclonal gammopathy and myelodysplasia: a retrospective study of fourteen cases.

We report a series of 14 patients with myelodysplastic syndrome (MDS) accompanied by a monoclonal gammopathy unrelated to therapy. Twelve of these had monoclonal gammopathy of undermined significance (MGUS) and two had smoldering multiple myeloma. These cases represent 10.2 % of all MDS cases seen at our institution over a 14-year period (January 2000 to December 2013). The incidence of MGUS was determined to be significantly higher in MDS than in age-matched concurrent controls by χ(2) test. Absence of prior chemotherapy and simultaneous presentation of MDS and MGUS in most cases suggest true co-occurrence of the two disorders. MGUS was found in all WHO subtypes of MDS with a wide range of risk factors. However, 11 out of the 12 MDS cases accompanied with MGUS had relatively low karyotypic risks. In addition, serum M protein levels remained largely unchanged in 4 cases of MGUS for which serial determinations were performed. These findings indicate that MGUS may not affect the prognosis of MDS.

Elevated levels of full-length and thrombin-cleaved osteopontin during acute dengue virus infection are associated with coagulation abnormalities.

INTRODUCTION: Dengue virus (DENV) is transmitted by the mosquito vector, and causes a wide range of symptoms that lead to dengue fever (DF) or life-threatening dengue hemorrhagic fever (DHF). The host and viral correlates that contribute to DF and DHF are complex and poorly understood, but appear to be linked to inflammation and impaired coagulation. Full-length osteopontin (FL-OPN), a glycoprotein, and its activated thrombin-cleaved product, trOPN, integrate multiple immunological signals through the induction of pro-inflammatory cytokines. MATERIALS AND METHOD: To understand the role of OPN in DENV-infection, we assessed circulating levels of FL-OPN, trOPN, and several coagulation markers (D-dimer, thrombin-antithrombin complex [TAT], thrombomodulin [TM], and ferritin in blood obtained from 65 DENV infected patients in the critical and recovery phases of DF and DHF during a dengue virus epidemic in the Philippines in 2010. RESULTS: Levels of FL-OPN, trOPN, D-dimer, TAT, and TM were significantly elevated in the critical phase in both the DF and DHF groups, as compared with healthy controls. During the recovery phase, FL-OPN levels declined while trOPN levels increased dramatically in both the DF and DHF groups. FL-OPN levels were directly correlated with D-dimer and ferritin levels, while the generation of trOPN was associated with TAT levels, platelet counts, and viral RNA load. CONCLUSION: Our study demonstrated the marked elevation of plasma levels of FL-OPN and thrombin-cleaved OPN product, trOPN, in DENV-infection for the first time. Further studies on the biological functions of these matricellular proteins in DENV-infection would clarify its pathogenesis.

Absent or extremely low neutrophil alkaline phosphatase activity levels in patients with myelodysplastic syndromes.

Three patients with myelodysplastic syndrome (MDS) had absent or extremely low levels of neutrophil alkaline phosphatase (NAP) activity (arbitrarily defined as an NAP score <10). All patients showed varying degrees of hypogranulation in neutrophil morphology. The NAP activity levels transiently normalized following the administration of granulocyte colony-stimulating factor (G-CSF) in two cases. No patients experienced any severe infectious episodes. These results suggest that NAP activity is not central to the neutrophil function.

Galectin-9 plasma levels reflect adverse hematological and immunological features in acute dengue virus infection.

BACKGROUND: Dengue virus (DENV) infection remains a major public health burden worldwide. Soluble mediators may play a critical role in the pathogenesis of acute DENV infection. Galectin-9 (Gal-9) is a soluble ß-galactoside-binding lectin, with multiple immunoregulatory and inflammatory properties. OBJECTIVE: To investigate plasma Gal-9 levels as a biomarker for DENV infection. STUDY DESIGN: We enrolled 65 DENV infected patients during the 2010 epidemic in the Philippines and measured their plasma Gal-9 and cytokine/chemokine levels, DENV genotypes, and copy number during the critical and recovery phases of illness. RESULTS: During the critical phase, Gal-9 levels were significantly higher in DENV infected patients compared to healthy or those with non-dengue febrile illness. The highest Gal-9 levels were observed in dengue hemorrhagic fever (DHF) patients (DHF: 2464 pg/ml; dengue fever patients (DF): 1407 pg/ml; non-dengue febrile illness: 616 pg/ml; healthy: 196 pg/ml). In the recovery phase, Gal-9 levels significantly declined from peak levels in DF and DHF patients. Gal-9 levels tracked viral load, and were associated with multiple cytokines and chemokines (IL-1α, IL-8, IP-10, and VEGF), including monocyte frequencies and hematologic variables of coagulation. Further discriminant analyses showed that eotaxin, Gal-9, IFN-α2, and MCP-1 could detect 92% of DHF and 79.3% of DF, specifically (P<0.01). CONCLUSION: Gal-9 appears to track DENV inflammatory responses, and therefore, it could serve as an important novel biomarker of acute DENV infection and disease severity.

Immune pancytopenia associated with a leukemic B-cell tumor carrying t(14;18)(q32;q21) translocation.

We report a 75-year-old man who was initially suggested to have acute leukemia. The hemoglobin level was 3.8 g/dL, white cell count was 7,700/µL with an absence of mature neutrophils and 69.0% leukemic cells, and platelet was 0.4 × 10(4)/µL. Coombs' antiglobulin test was positive. Leukemic cells were CD5(-), CD10(+), CD20(+), CD23(-), and IgG/λ(dim+). The bone marrow consisted of normal hematopoietic precursors, whereas fluorescence in situ hybridization detected the BCL2/IgH fusion gene. He was treated with rituximab-containing chemotherapy, resulting in the resolution of pancytopenia. The underlying disease was a leukemic B-cell tumor with t(14;18)(q32;q21), and the pancytopenia was mainly caused by autoimmune mechanisms.

Involvement of osteopontin and its signaling molecule CD44 in clinicopathological features of adult T cell leukemia.

We previously reported that the osteopontin (OPN) gene as well as CD44 is trans-activated by the Tax protein of HTLV-1, however the synthesis of both in adult T cell leukemia (ATL) has not been described yet. Here we showed the expression of these molecules in plasma and tissue of ATL. Significant differences were found among the normal and four subtypes of 27 ATL patients in plasma levels of OPN (p=3.6×10(-6)) and soluble CD44 (p<0.001) and they were significantly related to each other (p<0.002). Also they were significantly associated with the performance status, total number of involved lesions, and lactic dehydrogenase, and inversely with lymphocyte count (p<0.01). Immunohistochemical staining of lymph-nodes and skin from 7 ATL patients using anti-OPN and anti-CD44 antibodies demonstrated that both expressions were weak/moderate in ATL cells but moderate/strong in infiltrated macrophages in 6 patients. These results demonstrate that OPN and CD44 play important roles in tumor formations and their products in plasma could be markers of the severity in ATL.

John Auer and Auer rods; controversies revisited.

John Auer first described needle or rod-shaped intracytoplasmic inclusion bodies in leukemia cells in 1906. Auer rods can be seen in myeloid neoplasms ranging from acute myeloid leukemias (AML) to myelodysplasia, but not in normal or non-neoplastic reactive states. This article briefly describes John Auer's experience and discusses debates on Auer rods, and criticizes their place in the definition of refractory anemia with excess of blasts-2 (RAEB-2) in the WHO classification of the myelodysplastic syndromes (MDS).