Viral reactivation is one of the most serious complications for immunocompromised patients. Under immunosuppressive conditions, some viruses can be reactivated solely or simultaneously and may thus cause life-threatening infection. Therefore, the prompt and proper diagnosis of viral reactivation is important for the initiation of preemptive therapy. For this purpose, we recently developed a multiplex-virus polymerase chain reaction PCR) assay. The multiplex PCR assay is designed to qualitatively measure the genomic DN" of viruses at once: cytomegalovirus CMV), human herpesvirus type HHV-), HHV-, HHV-, Epstein-"arr virus E"V), varicella-zoster virus VZV), "K virus "KV), JC virus JCV), parvovirus " Parvo" ), herpes simplex virus type HSV-), HSV-, and hepatitis " virus H"V). When a speciic PCR signal is obtained, the viral load is determined by a quantitative real-time PCR. The qualitative multiplex and quantitative real-time PCR procedures take only hours to complete. With this assay system, we can identify viremia at the early stage and thereby prevent it from progressing to overt and symptomatic viral infection in immunocompromised patients, such as those receiving hematopoietic stem cell transplantation.
A diagnosis of acute monocytic leukemia (AML-M5) based on α-naphthyl butyrate esterase (α-NB) staining has some problems, because AML-M5 leukemic cells often show weak or faint positivity on α-NB staining. In these situations, some cases of AML-M5 tend to be misdiagnosed as AML-M0. Therefore, we evaluated the significance of weak or faint α-NB staining in AML-M5 diagnosed by flow cytometry (FCM). Nineteen AML cases in which leukemic cells were negative for naphthol AS-D chloroacetate esterase staining were studied. For FCM, we defined leukemic cells as having a monocytic nature when more than 10% of the leukemic cells were positive for at least one of the following antigens: CD4, CD11c, CD14, and CD64. The monocytic nature determined by FCM was consistent with positive or weak positivity on α-NB staining. Five of 6 cases in which leukemic cells exhibited faint positivity for α-NB staining could be diagnosed as AML-M5 by FCM, while negative α-NB staining was consistent with a diagnosis of AML-M0. These results suggest that AML-M5 should be taken into consideration even when leukemic cells are faintly positive for α-NB staining.
Gamma-heavy chain disease (γ-HCD) is a rare B-cell tumor producing truncated IgG lacking the light chain. The clinical features of γ-HCD are heterogeneous, similar to lymphoplasmacytic lymphoma, and most patients have generalized and progressive disease. In some γ-HCD patients, autoimmune diseases are associated. Thus, γ-HCD as a restricted or indolent disease is exceptional. A 66-year-old male was referred to our hospital because of subungual hemorrhage at the bilateral halluces. Physical and laboratory examination results were nonspecific, and the hemorrhage was revealed to be traumatic. However, serum electrophoresis demonstrated a small M-peak, which was monoclonal IgG-Fc without the corresponding light chain on immunofixation and immunoelectrophoresis. Bone marrow aspirate demonstrated a small number of lymphoplasmacytic cells that were positive for CD19, CD38, CD138, and cyIgG, but negative for cyκ- and -λ light chains on flow cytometry. A diagnosis of γ-HCD was made. Chest and abdominal CT demonstrated neither hepatosplenomegaly, lymphadenopathy, nor bone lytic lesions. The serum concentrations of IgG and M-peak configuration have remained relatively unchanged for nearly 3 years. Therefore, this γ-HCD may correspond to a rare form of monoclonal gammopathy with undetermined significance.
Background: Follicular lymphoma (FL), the most frequent type of indolent non Hodgkin lymphoma, exhibits a heterogeneous clinical behavior. Predictive biological variables are eagerly sought, in an effort to better anticipate outcomes for each individual patient. Cytokines are small proteins involved in cell signaling and immune regulation. The levels of soluble interleukin 2 receptor (sIL-2R), interleukin 6 (IL-6), and tumor necrosis factor (TNF) have been correlated with tumor burden and prognosis in solid tumors and some lymphomas. High sIL-2R has been associated with shorter progression-free survival (PFS) in FL, but the impact of the levels of IL-6 and TNF is not known in this disease specifically. Aims: To determine the prognostic significance of the serum levels of sIL-2R, IL-6 and TNF in patients with newly diagnosed FL. Methods: We identified 300 patients (132 males/168 females; median age: 60 years) diagnosed with FL at our institution between January 2002 and December 2017 who had available information about serum cytokine levels (sIL-2R, IL-6 and TNF), determined by ELISA, before the initiation of frontline treatment. Baseline patient and disease characteristics, type of frontline treatment, PFS and overall survival (OS) were assessed retrospectively and compared between patients with normal vs. elevated levels (above the upper normal limit) of each one of the three evaluated cytokines. Results: Baseline characteristics, treatment, response, PFS and OS data are detailed in the table. Patients with elevated IL-6 or TNF levels were older and those with elevated IL-6 had a worse performance status and higher rate of B symptoms. An advanced stage was more frequently seen in patients with any elevated cytokine, while secondary extranodal involvement, and specifically, bone marrow involvement, was more frequent if either sIL-2R or TNF were raised. Patients with any elevated cytokine were more likely to have elevated LDH or β 2-microglobulin (β 2 m) levels or a high-risk FLIPI score. A Ki67 index >30% was more frequently seen among patients with high TNF levels. Patients requiring frontline treatment with R-CHOP showed higher levels of any one of the 3 evaluated cytokines, while those who were not treated or received single-agent rituximab were more likely to have normal levels. The complete response (CR) rate was higher for patients with normal levels of sIL-2R and TNF. Median PFS was 10 years for treated patients in the entire series. 10-year PFS was significantly lower for patients with high levels of either sIL-2R, IL-6 or TNF. Similarly, patients who had elevated levels of any one of the 3 evaluated cytokines had a lower 10-year OS. However, in a multivariate analysis including FLIPI score, β 2 m and cytokine levels, only FLIPI and β 2 m retained statistical significance for PFS and OS.Summary/Conclusion: FL patients with elevated levels of cytokines are more symptomatic and have a higher tumor burden. Despite being treated more aggressively, they are less likely to achieve a CR after treatment or to mai...
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