We report a case of haemophagocytic syndrome (HPS) occurring after allogeneic bone marrow transplantation (BMT) for acute promyelocytic leukaemia (APL) in a patient in fourth complete remission (CR). Anti-cytomegalovirus (CMV) antibody (Ab) was negative in this patient before BMT. BMT was performed from an HLA-identical unrelated donor who was positive for CMV Ab. After bone marrow engraftment and haematological recovery, severe acute graft-versus-host disease (GVHD) developed. This patient was treated with methylprednisolone in addition to cyclosporin A (CsA). Acute GVHD showed partial improvement, but CMV antigenaemia was observed. Despite administration of gancyclovir and immunoglobulin, CMV antigenaemia showed no improvement and HPS developed. As no other infections or malignancies were observed, we suspect that CMV infection was the trigger for development of HPS.

We describe a rare case of a primary primitive neuroectodermal tumor (PNET) in the lung of a 17-year-old girl. Grossly, the tumor, located in the right lower lobe, was relatively well-circumscribed and whitish to yellowish in color with scattered hemorrhagic necrosis. Microscopically, the tumor was composed of ovoid to polygonal cells with a high nuclear to cytoplasmic ratio and relatively scant cytoplasm, arranged in solid sheets with intervening fine fibrovascular stroma. Immunohistochemically, the tumor was positive for the MIC2 gene product, whereas AE1/AE3, CAM5.2, and a variety of neuroendocrine markers such as chromogranin A, synaptophysin, and ProGRP, were negative. Three months after the lobectomy, recurrent tumors were noted in the mediastinum and right thoracic wall, and she died despite combined chemotherapy and radiation therapy. In this case cytogenetic analysis showed a hypertriploid karyotype with multiple numerical and structural chromosomal aberrations, but failed to disclose distinct evidence of translocation between chromosome 11 and 22. However, the reverse transcriptase-polymerase chain reaction (RT-PCR) demonstrated EWS/FLI-1 fusion transcripts, confirming the histopathologic diagnosis of PNET. This case indicates that the primary pulmonary PNET is a highly aggressive neoplasm occurring at a young age, and should prompt combined systemic chemotherapy, even though it is organ-confined.

Aberrant methylation of tumor suppressor genes (TSG) has been studied in multiple myeloma (MM). We determined the methylation status of the FHIT (fragile histidine triad) gene, a putative TSG, in 48 patients with MM. Clinical association with its methylation status was then analyzed. The FHIT gene methylation was observed in 21 of the 48 patients (44%). No association between FHIT gene methylation and clinical variables such as age, gender and clinical stage was found. However, the estimated 50% survival time of the methylated group was significantly shorter than that of the unmethylated group (18.2 vs. 45.1 months, P < 0.05). Univariate analysis revealed adverse prognostic factors: FHIT gene methylation (P = 0.028), poor performance status (I to IV, P = 0.002), anemia (< or =8.5 g/dL, P = 0.007), hypoalbuminemia (< or =3.5 g/dL, P < 0.002), high serum C-reactive protein levels (>0.5 mg/dL, P = 0.002), elevated beta-2-microglobulin serum levels (>6.5 mg/L, P < 0.001), and treatments not including autologous peripheral blood stem cell transplantation (auto-PBSCT) (P = 0.007). Multivariate analysis identified FHIT gene methylation [hazard ratio (HR) 1.722, 95% confidence interval (CI) 1.150-2.603, P = 0.009], elevated beta-2-microglobulin serum levels (>6.5 mg/L, HR 2.005, 95% CI 1.035-3.937, P = 0.004), and treatments not including auto-PBSCT are independent predictive variables. These findings indicate that aberrant methylation of the FHIT gene is an independent adverse prognostic factor in MM.

No abstract

IntroductionRecently, more patients desire to preserve the uterus when treating uterine adenomyosis. Gonadotropin-releasing hormone agonist (GnRHa) therapy is highly effective for adenomyosis, but it can only be administered for a limited duration and is associated with high recurrence rates [1]. Draw-back therapy, in which side effects are suppressed and the effect is extended by lowering the GnRHa dose, has been proposed and reported to be effective for adenomyosis [2][3][4]. Previously, the authors reported on the effectiveness of draw-back therapy for a patient with deep thrombosis of the lower limb associated with adenomyosis [5]. However, the safety and efficacy of draw-back therapy for adenomyosis with thrombosis caused by low-dose oral contraceptives (OCs) have not been reported. Here, they describe their experience with a case of cerebral venous and sinus thrombosis (CVST) that occurred during low-dose OC therapy for adenomyosis for which long-term GnRHa draw-back therapy was possible. Case ReportThe patient was a 38-year-old married nulligravida with a body mass index of 22.5 and a history of smoking. Her history was also significant for adenomyosis, which was diagnosed at age 34 years at another hospital and which receded after six months on lowdose OCs. She presented to this hospital with menstrual pain and postmenstrual lower abdominal pain. Adenomyosis was diagnosed using ultrasound examination and magnetic resonance imaging (MRI). After diagnosis at this hospital, regular GnRHa therapy (leuprorelin acetate 1.88 mg, six months) was administered twice in two years. The patient's adenomyosis receded after administration, but both times it worsened again and the symptoms reappeared, so she was instructed to stop smoking and was administered low-dose OCs.The patient complained of headaches after 18 months on lowdose OCs and was examined by the neurosurgery department at another general hospital. CVST was diagnosed using imaging studies (Figures 1a, b). Laboratory tests revealed a high D-dimer level at 3.0 µg/ml, but no other abnormalities were observed, including thrombotic factors such as antithrombin, protein C, protein S, and antiphospholipid antibodies. Low-dose OC therapy was halted, and antiplatelet therapy was administered for the CVST. The patient's dysmenorrhea and postmenstrual lower abdominal pain from adenomyosis were treated only symptomatically.After six months, the adenomyosis symptoms reappeared and intensified, therefore GnRHa draw-back therapy was initiated after obtaining sufficiently informed consent and the approval of