Clinical features of complex karyotype in newly diagnosed acute myeloid leukemia.

Complex karyotype acute myeloid leukemia (CK-AML) has been classified as an adverse-risk subtype. Although a few reports have further classified CK-AML as typical (including monosomy of chromosomes 5, 7 and 17 or deletion of 5q, 7q and/or 17p) or atypical, the clinical features of these subtypes in Japanese patients remain unclear. We retrospectively analyzed a total of 115 patients with CK-AML, including 77 with typical CK-AML and 38 with atypical CK-AML. Median overall survival (OS) was significantly shorter in patients with typical CK-AML than atypical CK-AML (143 days vs. 369 days, P = 0.009). Among patients with typical CK-AML, those with monosomy 17 or deletion of 17p had significantly shorter OS than patients without such abnormalities (105 days vs. 165 days, P = 0.033). TP53 mutations were more predominant in patients with typical CK-AML than in patients with atypical CK-AML (69.7% vs. 32.4%, P < 0.001). Patients with typical CK-AML had a poor prognosis regardless of TP53 mutation status. Among patients with atypical CK-AML, however, prognosis was worse for those with the TP53 mutation than those without the mutation. In conclusion, prognosis is extremely poor for both typical CK-AML and atypical CK-AML with TP53 mutation.

Positive Pattern Recognition System Using Alanine Aminotransferase, Type IV Collagen 7s, and E Value (Liver Stiffness) for the Diagnosis of Nonalcoholic Steatohepatitis Based on Natural History.

Introduction: The use of a simple diagnostic system for nonalcoholic fatty liver disease (NAFLD) instead of a biopsy is expected. We investigated a positive pattern recognition system for the evaluation of nonalcoholic fatty liver (NAFL) and the stages of nonalcoholic steatohepatitis (NASH). Methods: A total of 68 Japanese patients with biopsy-confirmed NAFLD were enrolled. Serological biomarkers and medical imaging markers were investigated to determine candidate markers. The markers were statistically evaluated, and the patients were distributed to pattern combinations. Results: We selected three markers based on natural history and set the critical values: alanine aminotransferase/ALT (persistent ≧ 44 IU/L) as a marker for hepatitis, type IV collagen 7S (≧5.1 ng/mL) for fibrosis, and E value (≧5.5 kPa) for stiffness. After evaluation of statistical accuracies, every patient was classified into their combination patterns. Comparing the relationships between histological classifications and positive patterns, the patients with NAFL were mainly distributed in pattern (ALT, type IV collagen, E value: -, -, -), those with NASH stage 0-1 in (+, -, +), those with NASH stage 2-3 in (+, +, +), and those with NASH stage 4 in (-, +, +). Conclusions: The positive patters changed with the NAFL and NASH conditions. Our results indicated a correlation between the positive patterns using three markers and the histological results. The positive pattern recognition system based on natural history is useful for the differential diagnosis of NAFLD and for the evaluation of the severity of fibrosis in patients with NASH.

[Primary diffuse large B-cell lymphoma of the breast in a male patient with Sjögren's syndrome].

When a 74-year-old male patient visited our hospital for the treatment of herpes zoster, his computed tomography (CT) revealed a mass in his right breast, axillary lymph node enlargement, and multiple lung nodules. A histological examination of the breast and lymph node biopsies revealed diffuse large B-cell lymphoma (DLBCL) while the bronchial and salivary gland biopsies showed secondary amyloidosis and Sjögren's syndrome (SjS). According to the Ann Arbor staging, the clinical stage of the lymphoma was evaluated as IIE. The patient achieved a complete remission after six cycles of rituximab, pirarubicin, cyclophosphamide, vincristine, and prednisolone (R-THP-COP) combined with intrathecal chemotherapy to prevent meningeal infiltration and irradiation after chemotherapy. Primary breast lymphoma was diagnosed within 2% of the breast tumor. Only sixteen male cases of breast lymphoma have been previously reported. In those reports, gynecomastia and hormonal therapy accounted for nine cases, but none of the cases coexisted with SjS. The present case is suggestive of the need to investigate possible autoimmune involvement in the development of lymphoma.

Aggressive variant of splenic marginal zone lymphoma characterized using a cancer panel test and treated with rituximab-containing chemotherapy: A case report.

RATIONALE: Aggressive variant of splenic marginal zone lymphoma (AV-SMZL) is a very rare disease that is often associated with TP53 mutations and has a poor prognosis. On the other hand, recent advances in genome sequencing techniques enable us to understand the molecular characteristics of rare cancers such as AV-SMZL. Here we present a case of AV-SMZL analyzed using a genetic test. PATIENT CONCERNS: A 66-year-old woman was admitted with splenomegaly and lymphocytosis. Computed tomography revealed marked splenomegaly without lymphadenopathy in any other areas. The serum soluble interleukin-2 receptor (sIL-2R) level was significantly elevated. Peripheral and bone marrow blood tests showed an increase in abnormal lymphocytes. DIAGNOSIS: A splenectomy revealed an SMZL pattern with increased numbers of large cells and mitotic cells and a high Ki-67 positivity rate, which led to a diagnosis of AV-SMZL. Although TP53 mutation was not detected, mutations in NOTCH2, NCOA4, PTEN, EPHA3, and KMT2D were identified. Among these, the mutations in NCOA4, PTEN, and EPHA3 were novel pathogenic mutations in SMZL, which suggests they may be related to the aggressiveness and persistence of the disease. INTERVENTIONS: The patient was administered a rituximab-containing regimen and rituximab-maintenance therapy. OUTCOMES: The patient continues to exhibit a complete response. LESSONS: This is a case of AV-SMZL in which a cancer panel test successfully detected genetic alterations that are potentially associated with its pathogenesis. These findings suggest that genetic analysis is useful for making diagnoses as well as for determining treatment strategies in AV-SMZL.

[Primary biliary cholangitis complicated by primary hepatic extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue].

An 89-year-old woman was admitted to our hospital owing to liver dysfunction and ascites. Enhanced computed tomography (CT) revealed hepatomegaly and heterogeneous density in the liver. 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) /CT revealed diffuse accumulation of FDG throughout the liver. Histopathology of a biopsy specimen revealed hepatic mucosa-associated lymphoid tissue (MALT) lymphoma. Complete remission (CR) was achieved with two cycles of rituximab, pirarubicin, cyclophosphamide, vincristine, and prednisolone. Because a second CT demonstrated liver cirrhosis and a test for anti-mitochondrial antibody was positive, liver biopsy was repeated, and pathological examination confirmed primary biliary cholangitis (PBC). The lymphoma recurred after 18 months and was treated with rituximab, which again resulted in CR. Over the subsequent 7 years, the patient had no liver dysfunction or recurrent lymphoma. Interestingly, despite the underlying PBC, liver dysfunction in this case appeared only with the MALT lymphoma.

Molecular diagnostics of a single drug-resistant multiple myeloma case using targeted next-generation sequencing.

A 69-year-old man was diagnosed with IgG λ-type multiple myeloma (MM), Stage II in October 2010. He was treated with one cycle of high-dose dexamethasone. After three cycles of bortezomib, the patient exhibited slow elevations in the free light-chain levels and developed a significant new increase of serum M protein. Bone marrow cytogenetic analysis revealed a complex karyotype characteristic of malignant plasma cells. To better understand the molecular pathogenesis of this patient, we sequenced for mutations in the entire coding regions of 409 cancer-related genes using a semiconductor-based sequencing platform. Sequencing analysis revealed eight nonsynonymous somatic mutations in addition to several copy number variants, including CCND1 and RB1. These alterations may play roles in the pathobiology of this disease. This targeted next-generation sequencing can allow for the prediction of drug resistance and facilitate improvements in the treatment of MM patients.

Decrease of B-type natriuretic peptide to less than 200 pg/mL predicts longer survival in cardiac immunoglobulin light chain amyloidosis.

Immunoglobulin light chain (AL) amyloidosis is a systemic disorder caused by depositions of insoluble amyloid fibrils that are composed of fragments of monoclonal light chains produced by abnormal plasma cells. The prognosis is reported to be poor; median survival time (MST) is 1-2 years overall, and is 6 months in patients with cardiac involvement. We here report the treatment outcomes of 24 patients with AL amyloidosis at our hospital between January 2008 and December 2012, including 11 patients with cardiac involvement. MST from the diagnosis was significantly shorter (9.8 months) in patients with cardiac involvement. Of these, patients who achieved a decrease of B-type natriuretic peptide (BNP) to <200 pg/mL after treatment survived longer than patients who did not (MST: not reached vs. 6.1 months; p = 0.003, log-rank test). The median time to decrease BNP to <200 pg/mL was 6.3 months. The decline of BNP to 200 pg/mL or less during treatment predicts longer survival in patients with cardiac AL amyloidosis.

Autologous stem cell transplantation for AL amyloidosis: adjustment of melphalan dose by factors including BNP.

High-dose melphalan with autologous stem cell transplantation (HDM/ASCT) is a promising treatment option for eligible patients with systemic immunoglobulin light chain (AL) amyloidosis. We present the results of ASCT following risk-adapted melphalan conditioning on the basis of criteria proposed by our group, including B-type natriuretic peptide (BNP). Ten patients with primary systemic AL amyloidosis treated at our institute were evaluated. A full dose of melphalan (200 mg/m(2)) was administered to patients who met all the following: performance status, 0 or 1; number of organs involved, 2 or less; serum creatinine, 1.5 mg/dL or less; EF 50 % or more and BNP 200 pg/mL or less; otherwise 140 mg/m(2). The hematologic complete response was achieved in four and organ response was seen in two patients. The median event-free survival (EFS) of all patients was 21.5 months, and median overall survival (OS) was 47.0 months. EFS and OS were significantly longer for patients who received 200 mg/m(2) of melphalan than for those who received lower dose (EFS: not reached vs. 13.9 months, P = 0.0217; OS: not reached vs. 13.8 months, P = 0.0186). No treatment-related mortality within 100 days from ASCT was observed. Evaluation of cardiac diastolic function may contribute to safer HDM/ASCT and improve outcome of AL amyloidosis.

[Sustained complete molecular remission after cessation of imatinib mesylate treatment in a patient with relapsed chronic myelogenous leukemia after allogeneic stem cell transplantation].

We present a case with sustained complete molecular response (CMR) after cessation of two months of imatinib mesylate (IM) treatment for chronic myelogenous leukemia (CML) relapsed after allogeneic stem cell transplantation (Allo-SCT). A 30-year-old previously healthy woman was seen in a clinic because of left abdominal discomfort. Splenomegaly and increased leukocytes with Philadelphia chromosome led to the diagnosis of CML in the accelerated phase. She received four months of IM treatment followed by allo-SCT from her HLA-matched sibling. She achieved and maintained CMR without developing acute GVHD for six months, when hematologic relapse occurred. While reducing the immunosuppressant, she received IM; however, it was discontinued two months later due to myelosuppression. Even after the termination of IM, the positivity of chimeric BCR-ABL gene detected by FISH analysis in peripheral blood continued to decrease. The molecular analysis of bone marrow one year after allo-PBSCT revealed CMR lasting for more than two years after cessation of IM. IM may possibly enhance the graft-versus-leukemia effects by reducing tumor burden in cases relapsed after allo-SCT.