Multidrug-resistant (MDR)
spp. have been globally disseminated in association with the successful clonal lineage
international clone II (IC II). Because the prevalence of MDR
spp. in Japan remains ...very low, we characterized all
spp. (
= 866) from 76 hospitals between October 2012 and March 2013 to describe the entire molecular epidemiology of
spp. The most prevalent species was
(
= 645; 74.5%), with
IC II (
= 245) accounting for 28.3% of the total. Meropenem-resistant isolates accounted for 2.0% (
= 17) and carried IS
(
= 10),
(
= 4), or IS
(
= 3). Multilocus sequence typing of 110 representative
isolates revealed the considerable prevalence of domestic sequence types (STs).
IC II isolates were divided into the domestic sequence type 469 (ST469) (
= 18) and the globally disseminated STs ST208 (
= 14) and ST219 (
= 4). ST469 isolates were susceptible to more antimicrobial agents, while ST208 and ST219 overproduced the intrinsic AmpC β-lactamase.
IC II and some
non-IC II STs (e.g., ST149 and ST246) were associated with fluoroquinolone resistance. This study revealed that carbapenem-susceptible
IC II was moderately disseminated in Japan. The low prevalence of acquired carbapenemase genes and presence of domestic STs could contribute to the low prevalence of MDR
A similar epidemiology might have appeared before the global dissemination of MDR epidemic lineages. In addition, fluoroquinolone resistance associated with
IC II may provide insight into the significance of
epidemic clones.
Our previous phase II trial for treating human T-lymphotropic virus type I-associated adult T-cell leukemia-lymphoma (ATLL) with vincristine, cyclophosphamide, doxorubicin, and prednisone (VCAP), ...doxorubicin, ranimustine, and prednisone (AMP), and vindesine, etoposide, carboplatin, and prednisone (VECP) showed promising results. To test the superiority of VCAP-AMP-VECP over biweekly cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), we conducted a randomized controlled trial exclusively for ATLL.
Previously untreated patients with aggressive ATLL were assigned to receive either six courses of VCAP-AMP-VECP every 4 weeks or eight courses of biweekly CHOP. Both treatments were supported with granulocyte colony-stimulating factor and intrathecal prophylaxis.
A total of 118 patients were enrolled. The complete response (CR) rate was higher in the VCAP-AMP-VECP arm than in biweekly CHOP arm (40% v 25%, respectively; P = .020). Progression-free survival rate at 1 year was 28% in the VCAP-AMP-VECP arm compared with 16% in the CHOP arm (P = .100, two-sided P = .200). Overall survival (OS) at 3 years was 24% in the VCAP-AMP-VECP arm and 13% in the CHOP arm (P = .085, two-sided P = .169). For VCAP-AMP-VECP versus biweekly CHOP, grade 4 neutropenia, grade 4 thrombocytopenia, and grade 3 or 4 infection rates were 98% v 83%, 74% v 17%, and 32% v 15%, respectively. There were three toxic deaths in the VCAP-AMP-VECP arm.
The longer OS at 3 years and higher CR rate with VCAP-AMP-VECP compared with biweekly CHOP suggest that VCAP-AMP-VECP might be a more effective regimen at the expense of higher toxicities, providing the basis for future investigations in the treatment of ATLL.
We evaluated the usefulness of prognostic markers in patients with diffuse large B‐cell lymphoma (DLBCL) treated with cyclophosphamide, vincristine, doxorubicin, and prednisolone (CHOP) ± rituximab ...(R‐CHOP) in Japan. We studied 730 patients with DLBCL; 451 received CHOP and 279 R‐CHOP. We analyzed biopsy samples immunohistochemically for markers of germinal center B cells (CD10, Bcl‐6), postgerminal center B cells (Multiple myeloma‐1), and apoptosis (Bcl‐2). The median follow‐up period for surviving patients was 56.4 months for the CHOP group and 25.2 months for the R‐CHOP group. DLBCL were categorized as germinal center B (GCB) subtype (352/730; 48.2%) or non‐GCB subtype (378/730; 51.8%). In the CHOP group, the high expression of CD10 (P = 0.022) or Bcl‐6 (P = 0.021), or GCB subtype (P = 0.05) was associated with better overall survival, whereas the high expression of Bcl‐2 (P = 0.001) or MUM1 (P = 0.011), or non‐GCB subtype (P = 0.05) was associated with worse overall survival. In the R‐CHOP group, however, these biomarkers except Bcl‐6 were not significant prognostic factors. The patients with non‐GCB subtype showed improved survival in the R‐CHOP group (P = 0.756). The International Prognostic Index was a useful clinical marker of survival in the CHOP group (P < 0.001) and also in the R‐CHOP group (P < 0.001). Results of improved survival with rituximab addition indicate that the relevance of previously recognized prognostic factors should be re‐evaluated. (Cancer Sci 2009; 100: 1842–1847)
NK cells represent a first line of immune defense, but are progressively dysregulated in multiple myeloma (MM) patients. To restore and facilitate their antitumor effect, NK cells are required in ...sufficient quantities and must be stimulated. We initially assessed the proportions of NKT and NK cells in 34 MM patients. The frequencies of both in PBMC populations correlated with those in BMMNCs irrespective of low BMMNC numbers. We then assessed the adjunctive effect of stimulating NKT cells with CD1d and α-GalCer complexes on the NK cells. The expression of NKG2D on CD56dimCD16+ NK cells and DNAM-1 on CD56brightCD16− NK cells increased after NKT cell activation. Apparently, NK cell-mediated anti-tumor effects were dependent on NKG2D and DNAM-1 ligands on myeloma cells. Thus, NK cell function in patients could be ameliorated, beyond the effect of immunosuppression, by NKT cell activation. This NKT-driven NK cell therapy could represent a potential new treatment modality.
•The frequencies of NKT and NK cells in PBMCs correlated with those in BMMNCs.•NKT cells of MM patients are functional after the stimulation with CD1d/Gal.•Activated NKT cells successfully induced NKG2D and DNAM-1 on NK cells of patients.•NK cell-mediated anti-tumor effects were dependent on NKG2D and DNAM-1 ligands.•NK cell function in MM patients could be ameliorated by NKT cell activation.
Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population with the ability to suppress immune responses and are currently classified into three distinct MDSC subsets: monocytic, ...granulocytic and non-monocytic, and non-granulocytic MDSCs. Although NK cells provide an important first-line defense against newly transformed cancer cells, it is unknown whether NK cells can regulate MDSC populations in the context of cancer. In this study, we initially found that the frequency of MDSCs in non-Hodgkin lymphoma (NHL) patients was increased and inversely correlated with that of NK cells, but not that of T cells. To investigate the regulation of MDSC subsets by NK cells, we used an EL4 murine lymphoma model and found the non-monocytic and non-granulocytic MDSC subset, i.e., Gr1
+
CD11b
+
Ly6G
med
Ly6C
med
MDSC, is increased after NK cell depletion. The MDSC population that expresses MHC class II, CD80, CD124, and CCR2 is regulated mainly by CD27
+
CD11b
+
NK cells. In addition, this MDSC subset produces some immunosuppressive cytokines, including IL-10 but not nitric oxide (NO) or arginase. We also examined two subsets of MDSCs (CD14
+
HLA-DR
−
and CD14
−
HLA-DR
−
MDSC) in NHL patients and found that higher IL-10-producing CD14
+
HLA-DR
−
MDSC subset can be seen in lymphoma patients with reduced NK cell frequency in peripheral blood. Our analyses of MDSCs in this study may enable a better understanding of how MDSCs manipulate the tumor microenvironment and are regulated by NK cells in patients with lymphoma.
Thymoma-associated pure red cell aplasia (PRCA) accounts for a significant proportion of cases of secondary PRCA and immunosuppressive therapy has been reported to be useful in this condition. ...However, because of its rarity, the long-term response and relapse rates after immunosuppressive therapy are largely unknown, and optimal management of this disorder remains unclear. The aim of this study was to collect more information on the outcome of patients with thymoma-associated PRCA.
We conducted a nationwide survey in Japan. From a total of 185 patients, comprising 73 with idiopathic and 112 with secondary PRCA, 41 patients with thymoma were evaluated for this report. End-points of this study were the response rate, duration of the response after immunosuppressive therapy and overall survival.
Surgical removal of thymoma was reported in 36 patients, 16 of whom developed PRCA at a median of 80 months post-thymectomy. First remission induction therapy was effective in 19 of 20 patients treated with cyclosporine, 6 of 13 patients treated with corticosteroids and 1 of 1 treated with cyclophosphamide. No cyclosporine-responders relapsed within a median observation period of 18 months (range; 1 to 118 months). Relapse of anemia was observed in three corticosteroid-responders who did not receive additional cyclosporine. Only two patients were in remission after stopping therapy for 19 and 67 months. The estimated median overall survival time of all patients was 142 months.
Thymoma-associated PRCA showed an excellent response to cyclosporine and cyclosporine-containing regimens were effective in preventing relapse of anemia. It does, however, remain uncertain whether cyclosporine can induce a maintenance-free hematologic response.
This study investigated endogenous factors that may increase the elimination of vancomycin (VCM) in adult methicillin-resistant Staphylococcus aureus (MRSA) patients with pneumonia.
48 patients (32 ...men and 16 women) admitted to the National Hospital Organization Kumamoto Medical Center for pneumonia due to MRSA were evaluated. VCM (500 - 2,000 mg/dose) was administered intravenously for 60 - 120 min at 8- - 12-h intervals. The dose of VCM prescribed was determined based on the treatment guidelines of the Infectious Diseases Society of America and was dependent on a patient's creatinine clearance.
Univariate analysis identified that potassium value (K) (p = 0.081) and urinary pH (p = 0.026) were possibly associated with decreased VCM concentration. Multivariate analysis confirmed that urinary pH was an independent risk factor for VCM clearance (p = 0.029). VCM clearance in patients with a urine pH of 8 was significantly higher (p = 0.032) than in patients with a urinary pH of 5. As urinary pH increased in alkalinity, a greater decrease in VCM concentrations was observed.
Elevation of urinary pH promotes the urinary excretion of VCM, likely by promoting the dissociation of the carboxyl group of VCM. Thus, in the clinical setting, urinary pH should be measured and considered when determining dosage, as it may affect the VCM blood concentration.
Mature T cell lymphoma has been noted for poor prognosis when compared with B cell lymphoma, even in the pre-rituximab era. To confirm this difference, a retrospective cohort study was conducted. One ...hundred-and nineteen patients with mature T cell lymphoma and 568 patients with diffuse large B cell lymphoma (DLBCL) who did not receive rituximab as first induction were studied. Overall survival (OS) was worse for patients with international prognostic index (IPI) scores indicating low-risk mature T cell lymphoma than for those with DLBCL (3-year OS 87 % vs. 58 %,
P
= 0.001), but not in other risk groups. Prognosis of mature T cell lymphoma was significantly poorer in the IPI low-risk group, as compared with DLBCL.
Granulocytic sarcoma is a rare disease that is rarely curable with conventional chemotherapy. This report describes a case of a patient with bulky granulocytic sarcoma of the retroperitoneum who was ...treated with high-dose chemotherapy and autologous peripheral blood stem cell transplantation without administering granulocyte colony-stimulating factor before stem cell collection. According to bone marrow assessment and imaging studies, the patient remained in complete remission at 5 years after transplantation. This case suggests that high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation is a therapeutic option for granulocytic sarcoma. J Clin Exp Hematop 53(3) : 235-239, 2013
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