Effect of vasodilators in patient with pulmonary hypertension associated with hemolytic anemia

AbstractPulmonary arterial hypertension (PAH) has been described to associate with hemolytic anemia in updated clinical classification of pulmonary hypertension. A 56-year-old woman, diagnosed with warm antibody autoimmune hemolytic anemia (AIHA), was treated with oral corticosteroids at the Department of Hematology, Osaka University Hospital for 30 years. Her AIHA worsened 3 months before the admission, and she was treated with rituximab and cyclosporine in combination with prednisolone. Soon after she left the hospital, she developed dyspnea on effort and leg edema, therefore she was re-admitted to the Department of Cardiovascular Medicine. Echocardiogram and cardiac catheterization demonstrated PAH associated with AIHA. She was treated with three types of vasodilatory agents, resulting in an improvement in pulmonary arterial pressure and pulmonary vascular resistance after 6 weeks. A few weeks after she left the hospital, her hemolytic anemia became in remission without intensifying AIHA therapy, and did not worsen for a year of follow-up. Although corticosteroids are the first-line treatment for AIHA, medications for PAH should be considered when the first-line therapy for AIHA failed to improve PAH

The Density of CD10 Corresponds to Commitment and Progression in the Human B Lymphoid Lineage

Requirements for human B lymphopoiesis are still poorly understood, and that has hampered investigation of differentiation events. For example, there are few cell surface antigens that can be used as milestones of lineage progression. The CD10 ectoenzyme is one such marker and has been used to define CLP, but we found substantial tissue specific variations in CD10 levels, and there was no information about how that corresponded to differentiation options.The aim of the present study was to use recently developed culture methods to assess the nature and differentiation potential of progenitors sorted according to CD10 density from umbilical cord blood (CB), adult bone marrow (BM) or G-CSF mobilized peripheral blood (PB). Many CD34(+) cells in BM express high levels of CD10, while low or low/negative CD10 densities were found on CD34(+) cells in CB or G-CSF mobilized PB, respectively. The relative abundance of CD10(Lo) versus CD10(Hi) cells only accounts for some CB versus BM differences. Almost all of the CD34(+) CD10(Hi) cells expressed CD19 and lymphocyte transcription factors and corresponded to loss of myeloid potential. A high degree of immunoglobulin D(H)-J(H) gene rearrangements was characteristic only of the CD10(Hi) subset. In contrast, the CD34(+) CD10(Lo) progenitors efficiently produced plasmacytoid and conventional dendritic cells as well as myeloid cells. These findings suggest a positive correlation between CD10 density and degree of differentiation. Although freshly isolated CD34(+) CD10(Hi) cells were in cycle, those from CB or BM expanded poorly in culture, suggesting regulators of populations remain to be discovered.Steps in human B lymphopoiesis have not been sufficiently studied, and we now show that increased CD10 expression corresponds to differentiation potential and stage. CD34(+) CD10(Hi) progenitors are obviously in the B lineage but may have progressed beyond the point where they can be expanded in culture

Identification of a Cytokine-induced Antiapoptotic Molecule Anamorsin Essential for Definitive Hematopoiesis

Many growth factors and cytokines prevent apoptosis. Using an expression cloning method, we identified a novel antiapoptotic molecule named Anamorsin, which does not show any homology to known apoptosis regulatory molecules such as Bcl-2 family, caspase family, or signal transduction molecules. The expression of Anamorsin was completely dependent on stimulation with growth factors such as interleukin 3, stem cell factor, and thrombopoietin in factor-dependent hematopoietic cell lines, and forced expression of Anamorsin conferred resistance to apoptosis caused by growth factor deprivation in vitro. Furthermore, Anamorsin was found to act as an antiapoptotic molecule in vivo because Anamorsin−/− mice die in late gestation due to defective definitive hematopoiesis in the fetal liver (FL). Although the number of hematopoietic stem/progenitor cells in the FL did not decrease in these mice, myeloid, and particularly erythroid colony formation in response to cytokines, was severely disrupted. Also, Anamorsin−/− erythroid cells initiated apoptosis during terminal maturation. As for the mechanism of Anamorsin-mediated cell survival, a microarray analysis revealed that the expression of Bcl-xL and Jak2 was severely impaired in the FL of Anamorsin−/− mice. Thus, Anamorsin is considered to be a necessary molecule for hematopoiesis that mediates antiapoptotic effects of various cytokines

Acute Promyelocytic Leukemia Presenting with Central Nervous System Involvement: A Report of 2 Cases

Central nervous system (CNS) involvement in acute promyelocytic leukemia (APL) is rare, and the presence of CNS symptoms at the time of diagnosis of APL is even rarer. We report 2 cases of APL presenting with CNS involvement. A 43-yr-old woman presented with easy bruising and stuporous mentality. Her complete blood count (CBC) revealed leukocytosis with increased blasts. Bone marrow (BM) analysis was carried out, and the diagnosis of APL was confirmed. This was done by cytogenetic analysis and demonstration of PML-RARα rearrangement by reverse transcriptase PCR in the BM cells. A lumbar puncture was performed to investigate the cause of her stuporous mentality, and her cerebrospinal fluid (CSF) analysis revealed 97% leukemic promyelocytes. Despite systemic and CNS therapy, she died due to septic shock by infection and rapid disease progression only 3 days after her admission. Another patient, a 3-yr-old girl, presented with easy bruising and epistaxis, and her CBC showed pancytopenia with increased blasts. BM studies confirmed APL. Quantitative PCR for PML-RARα in the BM cells revealed a PML-RARα/ABL ratio of 0.33 and CSF analysis revealed 9.5% leukemic promyelocytes (2 of 21 cells). She received induction chemotherapy and intrathecal therapy and achieved complete remission (CR) in the BM and CNS. She has been maintained in the CR status for the past 31 months. Thus, patients with APL must be evaluated for CNS involvement if any neurological symptoms are present at the time of diagnosis

Change of CD20 Expression in Diffuse Large B-Cell Lymphoma Treated with Rituximab, an Anti-CD20 Monoclonal Antibody: A Study of the Osaka Lymphoma Study Group

Change of CD20 expression was examined in cases of diffuse large B-cell lymphoma (DLBCL). CD20 expression after treatment with anti-CD20 antibody (rituximab, Rx) for DLBCL was examined in 23 cases who received serial biopsy by immunohistochemistry (IHC) and flow cytometry (FCM). CD20– by IHC and/or FCM was defined as CD20–. Four cases were CD20– at initial biopsy but became CD20+ after chemotherapy with Rx (CH-R) (group A). Recurrent tumors in three group A cases became resistant to CH-R. Initial and recurrent tumors were CD20+ before and after CH-R in 17 cases (group B). Tumors before CH-R were CD20– in two cases (group C) and continued to be CD20– in one and turned CD20+ in the other with survival time after the relapse of 8 and 23 months, respectively. Evaluation of CD20 expression with immunohistochemical and flow cytometric methods is used for the prediction of responsiveness of relapsed DLBCL for CH-R

Baseline characteristics and disease burden in patients in the International Paroxysmal Nocturnal Hemoglobinuria Registry

Paroxysmal nocturnal hemoglobinuria is a rare, acquired disease associated with hemolytic anemia, bone marrow failure, thrombosis, and, frequently, poor quality of life. The International PNH Registry is a worldwide, observational, non-interventional study collecting safety, effectiveness, and quality-of-life data from patients with a confirmed paroxysmal nocturnal hemoglobinuria diagnosis or detectable paroxysmal nocturnal hemoglobinuria clone, irrespective of treatment. In addition to evaluating the long-term safety and effectiveness of eculizumab in a global population, the registry aims to improve diagnosis, optimize patient management and outcomes, and enhance the understanding of the natural history of paroxysmal nocturnal hemoglobinuria. Here we report the characteristics of the first 1610 patients enrolled. Median disease duration was 4.6 years. Median granulocyte paroxysmal nocturnal hemoglobinuria clone size was 68.1% (range 0.01-100%). Overall, 16% of patients had a history of thrombotic events and 14% a history of impaired renal function. Therapies included anticoagulation (31%), immunosuppression (19%), and eculizumab (25%). Frequently reported symptoms included fatigue (80%), dyspnea (64%), hemoglobinuria (62%), abdominal pain (44%), and chest pain (33%). Patients suffered from poor quality of life; 23% of patients had been hospitalized due to paroxysmal nocturnal hemoglobinuria-related complications and 17% stated that paroxysmal nocturnal hemoglobinuria was the reason they were not working or were working less. This international registry will provide an ongoing, valuable resource to further the clinical understanding of paroxysmal nocturnal hemoglobinuria