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Shwachman-Diamond syndrome (SDS) is an autosomal recessive inherited disorder characterized by bone marrow failure, exocrine pancreatic dysfunction, and skeletal abnormalities. SDS is typically caused by a pathogenic mutation in the Shwachman-Bodian-Diamond Syndrome (SBDS) gene. Patients with SDS have an increased risk of developing acute myeloid leukemia (AML) and myelodysplastic syndromes. We identified germline biallelic SBDS mutations (p.K62X and p.I167M) in a 50-year-old AML patient who had never experienced the typical symptoms of SDS. The K62X mutation is one of the most common pathogenic mutations, whereas the significance of the I167M mutation was unclear. Based on cellular experiments, we concluded that the I167M mutation contributed to the development of AML, and chemotherapy including topoisomerase inhibitors, which induce DNA double-strand breaks, may have been toxic to this patient. Our experience indicates that some asymptomatic Shwachman-Bodian-Diamond syndrome mutations contribute to the development of leukemia, and that careful treatment selection may be warranted for patients harboring these mutations.

Chronic active Epstein-Barr virus infection (CAEBV) is a systemic T- or NK-lymphoproliferative disorder (LPD) caused by EBV. Allogenic hematopoietic stem cell transplantation (HSCT) is the only curative therapy for CAEBV, but relapse sometimes occurs. Relapse is generally attributed to proliferation of recipient-derived CAEBV cells. We herein report a case of donor-derived CAEBV-like NK-cell post-transplant lymphoproliferative disease (PTLD) in a 41-year-old female after the first allogenic HSCT for CAEBV from an HLA-matched sibling donor. A second HSCT from an HLA-matched unrelated donor successfully controlled the disease, but EBV infection of cells derived from the second donor continued to be detected. Although the mechanisms underlying CAEBV and CAEBV-like NK-cell PTLD have not yet been elucidated in detail, the findings of the present case imply that host genetic factors, including familial factors, may be important in disease development.

Shwachman-Diamond syndrome (SDS) is an autosomal recessive inherited disorder characterized by bone marrow failure, exocrine pancreatic dysfunction, and skeletal abnormalities. SDS is typically caused by a pathogenic mutation in the Shwachman-Bodian-Diamond Syndrome (SBDS) gene. Patients with SDS have an increased risk of developing acute myeloid leukemia (AML) and myelodysplastic syndromes. We identified germline biallelic SBDS mutations (p.K62X and p.I167M) in a 50-year-old AML patient who had never experienced the typical symptoms of SDS. The K62X mutation is one of the most common pathogenic mutations, whereas the significance of the I167M mutation was unclear. Based on cellular experiments, we concluded that the I167M mutation contributed to the development of AML, and chemotherapy including topoisomerase inhibitors, which induce DNA double-strand breaks, may have been toxic to this patient. Our experience indicates that some asymptomatic Shwachman-Bodian-Diamond syndrome mutations contribute to the development of leukemia, and that careful treatment selection may be warranted for patients harboring these mutations.

We report a case of acquired hypofibrinogenemia with multiple myeloma presenting λ-type IgG monoclonal protein. The patient had anemia and renal deficiency, and also developed bleeding tendency due to severe coagulopathy. Her fibrinogen level was under the detectable limits in a functional assay. Enzyme-linked immunosorbent assay (ELISA) and immunoblotting analysis results were consistent with functional assay results, and deficiency patterns observed in cross-mixing tests for PT and aPTT confirmed the diagnosis of hypofibrinogenemia. To determine the cause of hypofibrinogenemia, we purified the patient’s immunoglobulin via protein A agarose, and confirmed that fibrinogen was included in the bound fraction, strongly indicating paraprotein interference with fibrinogen. As accelerated removal of fibrinogen was indicated, we incubated the patient’s plasma up to 48 h, but did not observe significant loss of fibrinogen. In sharp contrast, fibrinogen returned to below the detection level 12 h after infusion of fresh frozen plasma. These findings support leukocyte-mediated fibrinogen removal, rather than paraprotein-triggered fibrinogen instability. Surprisingly, the patient’s paraprotein was IgG2, but we speculate the amount of paraprotein (IgG 5346 mg/dL) compensated for lower affinity to Fcγ receptors.

Angioimmunoblastic T-cell lymphoma (AITL) is a common subtype of peripheral T-cell lymphoma with an aggressive clinical course and poor prognosis after conventional chemotherapy, for which there is no current standard of care. We describe here an 87-year-old woman with AITL, whose clinical diagnosis was complicated by the presence of B immunoblasts positive for Epstein–Barr virus in the lymph nodes and monoclonal plasma cells in the bone marrow at initial presentation. Rebiopsy of the lymph node led to the correct diagnosis of AITL with concurrent smoldering plasma cell myeloma. She was treated with several courses of conventional chemotherapy, resulting in progressive disease, and then switched to the immunomodulatory drug lenalidomide, which used in Japan for the treatment of multiple myeloma. Lenalidomide was effective in controlling both AITL and plasma cell myeloma.

Pulmonary alveolar proteinosis (PAP) is a rare disorder characterized by the abnormal accumulation of alveolar surfactant protein in alveolar spaces. We report herein a rare case of myelodysplastic syndrome (MDS-RAEB) complicated by severe PAP, and successful allogeneic bone marrow transplantation (BMT) for both disorders. An unrelated BMT was planned for a 48-year-old male with advanced MDS-RAEB. Just before the initiation of the conditioning regimen for unrelated BMT in March 2007, he developed dyspnea. A diagnosis of PAP was made based on findings of chest X-ray, CT scanning, and the fluid obtained by bronchoalveolar lavage. To improve his dyspnea and improve BMT safety, whole lung lavage (WLL) was performed twice, with the partial improvement of PAP. Unrelated allogeneic BMT was performed in September 2007. We had to perform a third WLL because of the worsening of PAP on day 26 after BMT. Despite many infectious complications after BMT, GVHD was relatively mild. PAP had almost disappeared 6 months after BMT. He was well with favorable hematopoiesis 20 months after the BMT without any specific treatment. There has been no report of an MDS patient with PAP in whom 3 WLL procedures were performed before and after allogeneic BMT.