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Objective: Acute graft‐versus‐host disease (aGVHD) is a major cause of treatment‐related mortality after allogeneic hematopoietic stem cell transplantation. Endothelial cell damage may trigger the initiation of aGVHD. Methods: Endothelial damage and repair were evaluated by counting circulating endothelial cells (CECs) and endothelial progenitor cells (EPCs) in 17 allogeneic hematopoietic stem cell transplantation patients at pre‐conditioning, day 0, day 7, day 14, day 30, and day 60 by multicolor flow cytometry. Von Willebrand factor activity was simultaneously measured. Results: Eight patients developed aGVHD and were compared to non‐aGVHD patients. Patients' characteristics were not different, except for previous treatment courses. There was no difference in von Willebrand factor activity between the two groups. Both CEC and EPC counts were decreased on day 7 and day 14 and then increased thereafter. The CEC count on day 7 was significantly lower in the aGVHD group than in the non‐aGVHD group (p =.0401). Restoration of the EPC count on day 60 was significantly suppressed in the aGVHD group (p =.0464). The CEC count on day 7 could predict aGVHD development (AUC 0.8214, p =.0372). Conclusion: The present results showed that CEC count on day 7 could be a predictor of aGVHD. [ABSTRACT FROM AUTHOR]

Sinusitis is a serious infectious complication of allogeneic hematopoietic stem cell transplantation. Schizophyllum commune (S commune) is a common basidiomycete fungus that is rarely involved in human disease. We report herein a case of S commune sinusitis after allogeneic bone marrow transplantation. A 66‐year‐old man with myelodysplastic syndrome underwent allogeneic bone marrow transplantation and developed maxillary and ethmoid sinusitis. The sinusitis did not improve with liposomal amphotericin B after neutrophil engraftment, so we considered that surgical intervention was needed for the recovery of sinusitis. Endoscopic sinus surgery was performed. In the debridement tissue of paranasal mucosa, filamentous fungal elements were observed. Moreover, genetic analysis of the tissue revealed the presence of S commune. Schizophyllum commune should be recognized as a fungal pathogen that causes sinusitis after allogeneic hematopoietic stem cell transplantation. This case suggests the effectiveness of prompt surgical intervention with liposomal amphotericin B treatment for S commune sinusitis and the usefulness of genetic diagnosis for cases under antifungal treatment. (160 words) [ABSTRACT FROM AUTHOR]

Behçet's disease (BD) is a disorder characterized by systemic inflammation of multiple organs, including the intestines. Several studies have reported a relationship between myelodysplastic syndrome and BD, and trisomy 8 was frequently seen, especially in intestinal BD. However, the association of BD with primary myelofibrosis (PMF) has not been well documented. A 58-year-old Japanese female was diagnosed with PMF in 2014. The symptoms of PMF resolved with ruxolitinib. However, she developed fever and intestinal perforation due to multiple ulcers in the terminal ileum in 2017. Intestinal perforation recurred 1 month later, and the dose of ruxolitinib was tapered. After discontinuation of ruxolitinib, she presented with recurrent oral aphthous ulcers and uveitis. Subsequently, intestinal perforation recurred, and she was diagnosed with intestinal BD. Trisomy 8 was identified in her peripheral blood. She underwent steroid therapy, azathioprine, and infliximab. This case suggests relationships between PMF, trisomy 8, and BD. [ABSTRACT FROM AUTHOR]

Primary adrenal lymphoma (PAL) is a rare subtype of all non-Hodgkin lymphomas in several literature reviews [[1]]. The following definition of PAL as used: (1) histologically proven lymphoma that involves one or both adrenal glands; (2) no prior history of lymphoma elsewhere; and (3) lymph nodes or other organ involvement allowed, but the adrenal lesion should be unequivocally dominant [[3]]. One patient (14.3%) received adrenalectomy for diagnosis and therapeutic purposes and did not receive chemotherapy because of renal failure and the patient's choice. Although upfront ASCT is not routinely recommended for DLBCL in first CR, some studies reported the efficacy of upfront ASCT in limited patients as high-risk DLBCL and primary central nervous system lymphoma [[11]]. [Extracted from the article]

Although gamma heavy chain disease (γ-HCD) lesions occasionally morphologically resemble angioimmunoblastic T-cell lymphoma (AITL), no association has been described in detail due to the rarity of the disease. In this report, we present a rare manifestation of methotrexate (MTX)-associated lymphoproliferative disorders (LPDs) with AITL-like features accompanied by γ-HCD in a 75-year-old man with rheumatoid arthritis (RA). A biopsy specimen was evaluated using immunohistochemistry, clonal analyses of immunoglobulin VH and T-cell receptor γ gene rearrangements by polymerase chain reaction, and Sanger sequencing for confirmation of the structure of deleted γ-HCD clones. The histological features characterized by proliferation of CD4- and PD-1-positive medium-sized T cells and arborizing high endothelial venules together with numbers of small lymphocytes, eosinophils, plasma cells, and histiocytes in the background mimicked those of AITL, but did not completely fulfill the diagnostic criteria. Clonal analysis demonstrated that the specimen contained multiple LPDs of both B-cell and T-cell lineages. Sequence analysis confirmed the co-existence of a clone responsible for production of the abnormal heavy chain. This report provides new insights into the pathology of γ-HCD. Multiple host-derived factors (e.g., RA and/or use of MTX) may be responsible for the occurrence of LPDs of multiple lineages within a single lymph node. [ABSTRACT FROM AUTHOR]

Perforin-2 is constitutively expressed in macrophages that are required for bacterial control. In this study, we found that perforin-2 is expressed in human macrophages with two isoforms: full-length perforin-2a and a splice variant, perforin-2b. Two isoforms show different subcellular distributions. Perforin-2a was predominantly localized to the membrane of endosome-like vesicles by a C-terminal transmembrane domain. In contrast, the short isoform perforin-2b lacking the transmembrane domain failed to localize to the membrane of vesicles. Furthermore, we determined that the pro-inflammatory stimuli LPS and TNF-α induced perforin-2a expression via the NF-κB pathway and triggered perforin-2a vesicles fusion with lysosomes. On the other hand, we detected the secretion of perforin-2b in response to LPS stimulation. Taken together, our data provide the evidence that membrane-bound and secretory isoforms of perforin-2 are present in human macrophages and may play important roles in immune defense. [ABSTRACT FROM AUTHOR]

Abstract Upshaw-Schulman syndrome (USS) is an inherited type of thrombotic thrombocytopenic purpura (TTP) that is extremely rare, but often diagnosed during pregnancy. Reversible cerebral vasoconstriction syndrome (RCVS) is the transient stenosis of several cerebral arteries that is frequently diagnosed post-partum. We describe a 28-year-old woman with USS complicated by RCVS after delivery that was treated by plasma exchange with a good outcome. She was referred to our hospital with thunderclap headache, anemia and thrombocytopenia that occurred immediately postpartum. She was diagnosed with TTP and multiple cerebral infarctions. Plasma exchange promptly improved her symptoms on hospital day 3. Moreover, multiple stenoses of cerebral arteries indicating RCVS were resolved. Since her sister also had an episode of thrombocytopenia during pregnancy, inherited TTP was suspected and genetic analyses confirmed USS. Pregnancy is a risk for not only TTP, but also RCVS. Endothelial damage might be an underlining cause and vasospasm after delivery is a trigger of RCVS. Plasma exchange was effective against both TTP and RCVS. [ABSTRACT FROM AUTHOR]

Multiple myeloma (MM) is refractory to conventional chemotherapy. To achieve a sustained complete remission, we performed planned non-myeloablative allogeneic stem cell transplantation (NST) after autologous hematopoietic stem cell transplantation (HSCT) in a patient with stage III MM. Autologous HSCT was performed using high-dose melphalan after conventional chemotherapy, followed by NST from an HLA-identical sibling using low-dose total body irradiation (200  cGy) for conditioning. Cyclosporine and mycophenolate mofetil were used for graft-vs-host disease (GVHD) prophylaxis. Acute GVHD was transiently seen in the skin and intestine, while, in addition, mild chronic GVHD was seen in the oral mucosa and skin. Complete donor chimerism was achieved and the disappearance of tumor-derived monoclonal B cells was confirmed based on an analysis of immunoglobulin light chain messenger signals on day 156 when chronic GVHD occurred. The clinical course in this case strongly suggested the existence of a graft-vs-myeloma effect. [ABSTRACT FROM AUTHOR]

Kunishima S, Matsushita T, Shiratsuchi M, Ikuta T, Nishimura J, Hamaguchi M, Naoe T, Saito H. Detection of unique neutrophil non-muscle myosin heavy chain-A localization by immunofluorescence analysis inMYH9disorder presented with macrothrombocytopenia without leukocyte inclusions and deafness.Eur J Haematol 2005: 74: 1–5.© Blackwell Munksgaard 2005.MYH9disorders are autosomal-dominant macrothrombocytopenias with leukocyte inclusions caused by mutations in theMYH9gene, which encodes the non-muscle myosin heavy chain-A (NMMHCA). We report a patient with anMYH9disorder who presented with macrothrombocytopenia without leukocyte inclusions and severe bilateral sensory deafness. Conventional May–Grünwald–Giemsa staining failed to detect granulocyte cytoplasmic inclusions, whereas immunofluorescence analysis clearly demonstrated abnormal neutrophil NMMHCA localization. Genetic analyses revealed a novel heterozygous 18 base deletion inMYH9, leading to a six-amino acid in-frame deletion (N76_S81del) in NMMHCA. These results further support the usefulness of immunofluorescence analysis in differential diagnosis ofMYH9disorders. [ABSTRACT FROM AUTHOR]

The BCR-ABL fusion gene is important for the leukemogenesis of chronic myeloid leukemia (CML). A relationship between types of BCR-ABL transcripts in CML and clinical features has been proposed. We present here a patient with CML who carried an aberrant BCR-ABL transcript with an intronic sequence insert. A 26-year-old woman was diagnosed as having Philadelphia chromosome (Ph) positive CML. Reverse transcription polymerase chain reaction detected an atypically large BCR-ABL mRNA transcript. Sequencing revealed a 589bp insertion consisting of a 5' portion of BCR intron b2 and a 3' portion of ABL intron 1b between BCR exon b2 and ABL exon a2. Although the typical b2a2 transcript was undetectable initially, it appeared after intensive chemotherapy. The aberrant transcript presumably arose as a result of a lack of splicing, and chemotherapy might modify the disease course by selecting the subpopulation of the CML clone expressing typical BCR-ABL mRNA dominantly. [ABSTRACT FROM AUTHOR]

Investigates the correlation between the telomerase activity in myeloma cells and cell cycle status. Role of telomerase in indefinite proliferation; Independence of telomerase regulation from apoptotic signals induced by interferon-alpha.

The article presents a case study of a 40-year-old man who was admitted to the hospital to undergo evaluation of thrombocytopenia in January 2011. Peripheral blood analysis and bone marrow aspiration revealed a mature B-cell leukemia with MYC and BCL2 translocation, known as double-hit lymphoma. The article discusses treatment with allogeneic hematopoietic stem cell transplant, graft-versus-host disease (GVHD) risks, and the clinical characteristics of double-hit leukemia.

Examines the apoptosis resistance of mature neutrophils in a case of chronic neutrophilic leukemia. Implication of the absence of Philadelphia chromosome; Usability of granulocyte macrophage colony-stimulating factor; Susceptibility of spontaneous apoptosis.