[Usefulness of measuring serum procalcitonin levels by immunochromatographic assay in febrile neutropenia].

In order to clarify the usefulness of measuring procalcitonin (PCT) values under the extreme condition called febrile neutropenia (FN), PCT was measured with immunochromatographic assay (ICA) and electro-chemi-luminescence immunoassay (ECLIA) at two time points: upon FN occurrence and 12 to 24 hours after FN occurrence, and correlations and associations between the two methods were reviewed. A strong correlation between the ICA and ECLIA results was observed when Spearman's rank correlation coefficient was 0.878, and the association was also demonstrated by Fisher's direct test since P=4.68×10(-10). Special equipment is not required, the operations are simple, and the ICA method currently adopted by many facilities can be used as the standard method even for the clinical condition known as FN.

Dasatinib maintenance therapy after allogeneic hematopoietic stem cell transplantation for an isolated central nervous system blast crisis in chronic myelogenous leukemia.

A 22-year-old male with Ph-positive chronic myelogenous leukemia (CML) was started on treatment with imatinib. After 12 months of therapy, he achieved a complete cytogenetic response (CCyR). Although the CCyR persisted in his bone marrow, he developed an isolated CML blast crisis in his central nervous system (CNS) after 29 months of therapy. He underwent allogeneic hematopoietic stem cell transplantation (HSCT) following combination therapy with dasatinib, intrathecal chemotherapy and cranial irradiation. Subsequently, 168 days after allogeneic HSCT, he was started on dasatinib maintenance therapy to prevent a CNS relapse. Thirty-eight months after allogeneic HSCT, he has sustained a complete molecular response in both bone marrow and CNS. We believe dasatinib has the potential to prevent CNS relapse if used for maintenance therapy after allogeneic HSCT.

Intravascular large B-cell lymphoma diagnosed by FDG-PET/CT and endometrial biopsy.

Intravascular large B-cell lymphoma (IVLBCL) is a rare form of non-Hodgkin's lymphoma characterized by a proliferation of tumor cells within the lumina of small to medium-sized vessels. Because there are few or no concomitant solid lesions, a diagnosis of IVLBCL usually cannot be established by CT or MR imaging. Herein, we describe a case of IVLBCL involving the uterus, in which (18)F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) was useful for diagnosis. A 47-year-old woman was referred to our hospital because of fever and anemia. Laboratory examination demonstrated anemia and thrombocytopenia. Bone marrow aspiration and biopsy showed hemophagocytosis without involvement of lymphoma cells. Random skin biopsy did not demonstrate lymphoma involvement. FDG-PET/CT imaging showed FDG accumulation in the uterus. MR imaging demonstrated uterine leiomyoma only. Based on these findings, uterine endometrial biopsy was performed and histological diagnosis of IVLBCL involving the uterus was established. She received 6 courses of R-CHOP therapy and high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation. At present, she remains in complete remission after 33 months.

[Membranous nephropathy with nephrotic syndrome developed after allogeneic hematopoietic stem cell transplantation for acute lymphoblastic leukemia].

A 38-year-old man was diagnosed with acute lymphoblastic leukemia. We performed myeloablative bone marrow transplantation from an unrelated donor during the patient's first complete remission. After engraftment, he developed acute graft-versus-host disease involving the gastrointestinal tract on day 32. Steroids and mycophenolate mofetil were initiated from day 39. His symptoms improved and the dose of immunosuppressants was tapered and then discontinued on day 421. On day 491, he developed nephrotic syndrome (NS). Based on renal biopsy, membranous nephropathy was diagnosed. There were no apparent symptoms or abnormal laboratory data suggestive of chronic graft-versus-host disease (cGVHD). Steroid therapy was initiated from day 518 and proteinuria improved significantly. NS is very rare following allogeneic hematopoietic stem cell transplantation (allo-HSCT). When there is no concomitant cGVHD, as in this case, allo-HSCT-associated NS is difficult to distinguish from idiopathic NS.

[Epstein-Barr virus-associated post-transplant lymphoproliferative disorder diagnosed by the episode of intestinal perforation following allogeneic hematopoietic stem cell transplantation].

A 64-year-old man was diagnosed as having acute myeloid leukemia. We performed sequential treatment with chemotherapy and reduced-intensity stem cell transplantation from an unrelated donor while the patient was in partial remission. After engraftment, he developed acute graft-versus-host disease of the gut on day 42 and steroid therapy was started. Despite transient aggravation of diarrhea, his symptoms slowly improved and the dose of steroid was tapered. On day 159, he complained of acute left lower abdominal pain. A CT scan showed perforation of the digestive tract and ileectomy was performed. At surgery, multiple ulcers of the intestine were found and one of the ulcers was perforated. Pathologically, transmural and diffuse proliferation of atypical cells in the ulcer were confirmed. Since these cells were positive for CD20 and Epstein-Barr-virus (EBV) encoded RNA, we made a diagnosis of EBV-associated post-transplant lymphoproliferative disorder (PTLD). Reduction in the dose of immunosuppressive agents and rituximab led to complete remission of PTLD. PTLD after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is relatively rare, and the development of gastrointestinal perforation after allo-HSCT is very rare.

Ethinylestradiol 20 µg/drospirenone 3 mg in a flexible extended regimen for the management of endometriosis-associated pelvic pain: a randomized controlled trial.

OBJECTIVE: To investigate the efficacy and safety of ethinylestradiol 20 µg/drospirenone 3 mg in a flexible extended regimen (FlexibleMIB) compared with placebo to treat endometriosis-associated pelvic pain (EAPP). DESIGN: A phase 3, randomized, double-blind, placebo-controlled, parallel-group study, consisting of a 24-week double-blind treatment phase followed by a 28-week open-label extension phase with an unblinded reference arm. SETTING: Thirty-two centers. PATIENT(S): A total of 312 patients with endometriosis. INTERVENTION(S): Patients were randomized to FlexibleMIB, placebo, or dienogest. The FlexibleMIB and placebo arms received 1 tablet per day continuously for 120 days, with a 4-day tablet-free interval either after 120 days or after ≥3 consecutive days of spotting and/or bleeding on days 25-120. After 24 weeks, placebo recipients were changed to FlexibleMIB. Patients randomized to dienogest received 2 mg/d for 52 weeks in an unblinded reference arm. MAIN OUTCOME MEASURE(S): Absolute change in the most severe EAPP based on visual analog scale scores from the baseline observation phase to the end of the double-blind treatment phase. RESULT(S): Compared with placebo, FlexibleMIB significantly reduced the most severe EAPP (mean difference in visual analog scale score: -26.3 mm). FlexibleMIB also improved other endometriosis-associated pain and gynecologic findings and reduced the size of endometriomas. CONCLUSION(S): FlexibleMIB improved EAPP and was well tolerated, suggesting it may be a new alternative for managing endometriosis. CLINICAL TRIALS REGISTRATION NUMBER: NCT01697111.

[Autologous hematopoietic stem cell transplantation for aggressive B-cell non-Hodgkin's lymphoma].

To evaluate the results of high-dose chemotherapy (HDT) and autologous hematopoietic stem cell transplantation (ASCT) in patients with diffuse B-cell aggressive non-Hodgkin's lymphoma(NHL). Between 1991 and 2004, 25 patients who did not achieve complete remission and 26 in complete remission from conventional chemotherapy received HDC-ASCT. Of 25 patients with refractory NHL,14 were chemotherapy-sensitive before HDT-ASCT and 11 were chemotherapy-resistant. CR was achieved after HDC-ASCT in 50% of 14 chemotherapy sensitive patients and in none of 11 chemotherapy-resistant patients. The 5-year probability of event-free survival for chemotherapy-sensitive and chemotherapy-resistant patients was 51.3% and 20.8%, respectively (p<0.05, log-rank test). Moreover, the 5-year probability of event-free survival for patients in the low-risk group with International Prognostic Index (IPI) and in the high-risk group with IPI was 75.0% and 16.3%, respectively (p<0.05, log-rank test). HDT-ASCT should be considered for patients with refractory aggressive NHL who are chemotherapy-sensitive rather than chemotherapy-resistant. Twenty-six patients in complete remission received consolidation therapy with HDT-ASCT. The 5-year probability of disease-free survival for patients in the low-risk group and in the high-risk group was 68.8% and 60.0%,respectively (p = 0.9 6). HDT-ASCT should be considered for patients at high risk who achieve complete remission after induction treatment. In future, HDT-ASCT combined with rituximab as induction therapy or as consolidation therapy is needed for patients with aggressive NHL in the high-risk group.

Efficacy and safety of intravenous itraconazole as empirical antifungal therapy for persistent fever in neutropenic patients with hematological malignancies in Japan.

Recently, empirical antifungal therapy with intravenous itraconazole (ITCZ) for neutropenic patients with antibiotics-resistant fever has been approved by Japanese Ministry of Health, Labour and Welfare on the bases of previous multicenter trials of foreign countries. In this study, we conducted a single-arm, multicenter, prospective study in order to evaluate the efficacy of empirical ITCZ injection on Japanese patients. Sixty-eight patients with hematological diseases who underwent anticancer chemotherapy or stem cell transplantation were enrolled. In this study, we found that the overall clinical response rate to ITCZ injection was 67.6% and success rate of achieving composite endpoints including survival, defervescence during neutropenia, no breakthrough fungal infections, and no premature discontinuation of drug was 50.0%. Mild adverse reactions were observed in 6 patients (8.8%). Further analysis revealed that possible/probable deep fungal infection according to the 2002 and 2008 criteria defined by EORTC/MSG were found in 19.1 and 7.5% of the patients, respectively. Interestingly, response rate to ITCZ injection of possible/probable cases according to the 2002 and 2008 criteria was 61.5% (8/13) and 100% (5/5), respectively. These results not only proved the good efficacy and safety of empirical ITCZ injection for Japanese patients, but also indicated a utility of the drug on future "presumptive" approach.

Usefulness of transesophageal echocardiographic observation during chemotherapy for cardiac metastasis of non-Hodgkin lymphoma complicated with left ventricular diastolic collapse.

A 53-year-old man, who had been treated for penile origin diffuse large B cell type non-Hodgkin lymphoma (NHL), suffered from right femoral pain and dyspnea. Positron emission tomography (PET) revealed abnormal accumulation in his right femur and cardiac segments. Transthoracic echocardiography revealed massive localized pericardial effusion with the collapse of both ventricles and the mass-like echo in the left atrium. We performed emergent pericardiocentesis and diagnosed this case as a recurrence of NHL with cardiac metastasis. With the use of transesophageal echocardiography (TEE), we confirmed the mass-like echo around the inter-atrial septum, which directly invaded to the aortic ring and the right atrial wall. In order to evaluate the effect of chemotherapy, we performed TEE and observed the precise changes of intra-cardiac tumor size. With the use of TEE monitoring, we could select the appropriate chemotherapeutic regimen, and the tumor became smaller and finally diminished. The femoral accumulation detected by PET also disappeared. We experienced a case of cardiac metastasis of NHL complicated with left ventricular diastolic collapse due to the massive localized pericardial effusion. TEE is a useful tool to evaluate precisely the efficacy of chemotherapy for intra-cardiac tumors.

Thiopurine S-methyltransferase gene polymorphism in Japanese patients with autoimmune liver diseases.

BACKGROUND AND AIM: Thiopurine S-methyltransferase (TPMT) genotypes or phenotypes may be a predictive factor for azathioprine-induced toxicities. We investigated the genotypic status of TPMT to evaluate the risk of azathioprine-related adverse effects in Japanese patients with different liver diseases, including autoimmune hepatitis (AIH). METHODS: 49 patients with AIH, 67 with primary biliary cirrhosis (PBC), and 120 with hepatitis C virus (HCV) were examined. TPMT genotypes were determined by PCR-restriction fragment length polymorphism-based assays. RESULTS: The distribution of TPMT genotypes was 90% TPMT*1/TPMT*1, 8% TPMT*1/TPMT*3C, and 2% TPMT*3C/TPMT*3C in AIH, and 94% TPMT*1/TPMT*1, 4.5% TPMT*1/TPMT*3C, and 1.5% TPMT*3C/TPMT*3C in PBC. All except 1 patient with HCV had the TPMT*1/TPMT*1 genotype. Severe myelosuppression occurred in two of nine patients with AIH who received azathioprine, one of whom was homozygous for TPMT*3C. CONCLUSIONS: TPMT*3C variants are more frequent in patients with AIH or PBC than in patients with viral hepatitis or healthy volunteers in Japan. Pharmacogenetic screening for TPMT polymorphisms before commencing azathioprine therapy may help to prevent severe hematotoxicity in patients with TPMT deficiency.