1 Department of Internal Medicine and Clinical Immunology, Yokohama City University Graduate School of Medicine, Yokohama;
2 Department of Pathology, Tokai University School of Medicine, Kanagawa;
3 ...Department of Pathology, Cancer Institute, Japanese Foundation for Cancer Research, Tokyo;
4 Department of Pathology, St. Marianna University School of Medicine, Kawasaki;
5 Department of Chemotherapy, Kanagawa Cancer Center, Yokohama;
6 Division of Hemato-oncology, St. Marianna University School of Medicine, Yokohama City Seibu Hospital, Yokohama;
7 Department of Hematology, Tokai University School of Medicine, Kanagawa;
8 Department of Hematology, Yokohama City University Medical Center, Yokohama;
9 Cancer Center, Ehime University Graduate School of Medicine, Ehime;
10 Department of Hematology and Immunology, Kanazawa Medical University, Ishikawa;
11 Department of Internal Medicine, Okayama Red Cross General Hospital, Okayama;
12 Division of Hematology, Tenri Hospital, Nara and
13 Division of Hematology and Oncology, St. Marianna University School of Medicine, Kawasaki, Japan
Correspondence: Naoto Tomita, M.D., Department of Internal Medicine and Clinical Immunology, Yokohama City University Graduate School of Medicine, Yokohama, Japan E-mail: cavalier{at}ch-yamate.dlenet.com
Background: Lymphoid neoplasm with 18q21.3/ BCL2 and 8q24/ MYC translocation to immunoglobulin ( IG ) genes as dual-hit lymphoma/leukemia is very rare and known to have a poor clinical outcome.
Design and Methods: To clarify the clinicopathological characteristics of this malignancy, we analyzed 27 cases of cytogenetically proven dual-hit lymphoma/leukemia.
Results: Dual-hit lymphoma/leukemia was diagnosed at presentation in 22 cases and at relapse or disease progression in 5 cases. At the time of diagnosis of dual-hit lymphoma/leukemia, extranodal involvement was found in 25 cases (93%) and central nervous system involvement occurred in 15 cases (56%). The median survival and 1-year survival rate of the 27 cases were only 6 months and 22%, respectively, after diagnosis of the dual-hit lymphoma/leukemia. Seven cases of triple-hit lymphoma/leukemia (dual-hit lymphoma/leukemia with 3q27/ BCL6 translocation) were included; the median survival of these patients was only 4 months from the diagnosis of the dual-hit lymphoma/leukemia. The duration of survival of the patients with a triple-hit malignancy was shorter than that of the other 20 cases of dual-hit lymphoma/leukemia ( p =0.02). The translocation partner of MYC subdivided the dual-hit cases into two groups; 14 cases of IGH and 13 cases of IGK/L . The MIB-1 index was investigated in 14 cases with aggressive B-cell lymphoma, and was higher in the group with MYC-IGH translocation (n=7) than in the MYC-IGK/L group (n=7) ( p =0.02). Overall survival was not different between the MYC-IGH translocation group (n=14) and the MYC-IGK or MYC-IGL translocation group (n=13).
Conclusions: Dual-hit lymphoma/leukemia is a rare but distinct mature B-cell neoplasm with an extremely poor prognosis characterized by frequent extranodal involvement and central nervous system progression with either of the translocation partners of MYC .
Key words: BCL2 , MYC , dual-hit lymphoma/leukemia.
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No scoring system has ever been used to estimate the prognosis of individual tuberculosis (TB) patients.
To develop and validate a tuberculosis prognostic score.
This retrospective cohort study ...conducted in Japan comprised the development (n = 179; mean age 65.9 ± 18.8 years) and validation (n = 244; mean age 64.3 ± 20.1 years) of a tuberculosis prognostic score among patients with newly diagnosed smear-positive non-multidrug-resistant pulmonary tuberculosis without human immunodeficiency virus infection. The score (raw score) was defined by modifying a logistic regression formula using known risk factors as independent variables and in-patient death as a dependent variable.
The raw score was calculated as follows: age (years) + (oxygen requirement, 10 points) - 20 × albumin (g/dl) + (activity of daily living: independent, 0 point; semi-dependent, 5 points; totally dependent, 10 points). The raw scores were grouped into risk groups 1 (raw score < -30) to 5 (raw score ≥ 60) using 30-point intervals. Every increase in risk group was equivalent to a 7.3-fold increase in the odds ratio for in-hospital death (P < 0.001). The area under the receiver operating characteristics curve by risk group for in-patient death was 0.875 (P < 0.001).
In this study we were able to develop and validate a tuberculosis prognostic score.
We simultaneously assessed ultrasonography (US) and magnetic resonance imaging (MRI) in comparison with histopathological changes in the knee joints of long-lasting arthritis patients.
We studied 15 ...patients with rheumatoid arthritis and 5 patients with osteoarthritis, who underwent total knee arthroplasty. On the day before surgery, the joints were examined by US and contrast-enhanced MRI. In US, synovitis was graded with 0-3 grey scale (GSUS) and power Doppler (PDUS). In MRI, synovitis was graded according to OMERACT-RAMRIS (grade 0-3). Synovial tissue samples were obtained during arthroplasty and evaluated on the basis of inflammatory cell infiltrates (grade 0-3), synovial lining layer thickness (grade 0-3) and vascularity (grade 0-3).
Positive findings of PDUS and contrast-enhanced MRI were 45% and 85% of 20 operated joints, respectively. GSUS, PDUS and MRI synovitis were well correlated with overall histopathological grades of synovitis (Spearman correlation coefficients 0.48, 0.84 and 0.48, p<0.05, p<0.01 and p<0.05, respectively). Moreover, positive PDUS findings were closely associated with all pathological comportments of synovitis including inflammatory cell infiltrates, synovial lining layer thickness and vascularity.
The present study revealed that positive PDUS findings more faithfully illustrated active synovitis than MRI, whereas contrast-enhanced MRI was more sensitive in detecting synovitis in patients with long-lasting arthritis. It is important to understand distinct features of the both modalities for clinical assessment of chronic joint diseases.
We previously showed that bacterial DNA contains immunostimulatory motifs consisting of unmethylated CpG dinucleotides flanked by two 5' purines and two 3' pyrimidines. These motifs rapidly trigger ...an innate immune response, characterized by the production of IL-6, IL-12, and IFN-gamma. Since DNA vaccines are constructed from plasmids of bacterial DNA, we examined whether CpG motifs present in these plasmids contributed to the immunogenicity of DNA vaccines. In vitro experiments showed that DNA plasmids induced production of the same cytokines stimulated by bacterial DNA, an effect eliminated by DNase treatment. In vivo experiments showed that the immunogenicity of a DNA vaccine was significantly reduced by methylating its CpG motifs and was significantly increased by coadministering exogenous CpG-containing DNA. These findings support the conclusion that CpG motifs in the plasmid backbone of DNA vaccines play an important role in the induction of Ag-specific immunity.
Summary
Introduction
The management of pregnant women with acute leukemia is usually challenging. We collected data concerning pregnant women with acute leukemia in the Kanagawa area in Japan.
...Methods
A questionnaire was sent to 24 institutions in the Kanagawa area.
Results
Data were obtained for 11 patients, median age of 31 years (range, 20–36). Eight patients had acute myeloid leukemia and three had acute lymphoblastic leukemia. Six patients were diagnosed in the first trimester of pregnancy, one in the second trimester, and four in the third trimester. Five of six patients diagnosed in the first trimester had abortions before chemotherapy, and one had an elective abortion after receiving chemotherapy. All patients diagnosed in the second or third trimester delivered live infants. Of the six patients diagnosed in the first trimester, two died of recurrent leukemia, and four remained in remission. Of the five patients diagnosed in the second or third trimester, four achieved complete remission and remained in remission. One patient died of sepsis 4 days after cesarean section.
Conclusions
Careful surveillance and monitoring of the fetus and close co‐operation among hematologists, gynecologists, and pediatricians are essential to successfully treat pregnant women with acute leukemia.
The real cumulative persistence probabilities with bisphosphonates after 5 years was 51.7%. Prescriptions by specialists other than gynecologists and rheumatologists (p < 0.001), male sex (p < ...0.001), older age (> or =65 years) (p = 0.001), and cyclical etidronate (p < 0.001) were significantly associated with low persistence. Success rates of switching bisphosphonate were 75.6%.
Many patients discontinue daily bisphosphonate therapy prematurely due to the stringent dosing procedures and adverse events. Consequently, some patients are receiving two or more sequential bisphosphonates in daily practice. Our objective was to study factors associated with the real cumulative persistence with bisphosphonate therapy including treatment courses with multiple sequential drugs in the real world setting.
We retrospectively analyzed 1,307 patients (male 197, female 1110) newly prescribed with bisphosphonates between January 1, 2000, and June 30, 2005.
The real cumulative persistence probabilities with bisphosphonates after 1, 3, and 5 years were 74.8%, 60.6%, and 51.7%, respectively. Switching of bisphosphonates was observed 168 times in 146 patients. Adverse events occurred 126 times in 124 patients including 86 events with gastrointestinal complaints. Univariate analysis showed that prescriptions by specialists other than gynecologists and rheumatologists (p < 0.001), male sex (p < 0.001), older age (> or =65 years) (p = 0.001), and cyclical etidronate (p < 0.001) were significantly associated with low persistence. Success rates of switching bisphosphonate were 75.6%.
Switching of bisphosphonates was not uncommon. Despite switching bisphosphonates to improve persistence, the real cumulative persistence with bisphosphonate was suboptimal, especially among patients of certain physician specialties and male sex.
Mucormycosis in immunocompromised patients is often reported. We report a patient who developed non‐thrombotic pulmonary embolism due to Cunninghamella bertholletiae after allogeneic stem cell ...transplantation.
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