Red-cell aplasia due to persistent human parvovirus B19 infection three years after umbilical cord blood transplantation-a case study

　造血幹細胞移植後に生じる貧血は，骨髄の造血能低下やウイルス感染症等の様々な背景が原因となることがあり，診断が困難であることが多い．ヒトパルボウイルス B19（human parvovirus B19：PVB19）は伝染性紅斑の原因ウイルスであり，遺伝性球状赤血球症等の赤血球寿命が短縮している溶血性貧血患者では，急性赤芽球癆を呈することが知られている．PVB19は移植患者を含む免疫不全状態の患者で慢性貧血を引き起こすことがあり，腎移植患者などでの報告例は多く存在するが，臍帯血移植後における PVB19感染による後天性赤芽球癆の症例の報告はほとんどない．今回我々は，臍帯血移植が成功したのち３年を経て発症した PVB19が４か月以上持続感染している症例を経験したので報告する．　Onset of anemia after hematopoietic stem cell transplantation can be caused by various background factors such as reduced hematopoiesis of the bone marrow and viral infection. Therefore, diagnosis is often difficult. Human parvovirus B19 (PVB19) due to acquired pure red-cell aplasia is the causative virus of erythema infectiosum, and it is well known that patients with hemolytic anemia with a short erythrocyte life span such as in the case of hereditary spherocytosis present with acute red-cell aplasia. PVB19 can cause chronic anemia in immunocompromised patients, including transplantation patients, and while there are many reported cases in kidney transplant patients, etc., there are few reported cases of cord blood transplantation. Here, we report a case of onset of PVB19 that occurred three years after successful umbilical cord blood transplantation and caused persistent infection for over a period of four months

リツキシマブ併用ベンダムスチン療法が奏効した腸管monomorphic PTLD

　移植後リンパ増殖性疾患（PTLD）は，造血幹細胞移植後に免疫抑制剤を使用した結果として，Ｔ細胞機能が低下して生じる異常なリンパ球，または形質細胞の増殖で，移植領域において最も致死的で注意を要する合併症の一つである．PTLD は４つのカテゴリーに分類され，その中のmonomorphic PTLD は、悪性リンパ腫の形態を呈する．Monomorphic PTLD の治療には，免疫抑制剤減量，リツキシマブ（Ｒ）単独療法やR-CHOP 療法があるが，予後は不良である．今回，難治性PTLD に対してリツキシマブ併用ベンダムスチン療法が奏効し寛解をえることができた症例を経験したので報告する．症例は50歳代男性で、骨髄異形成症候群に対して臍帯血移植を施行し，GVHD 予防にタクロリムスを使用した．移植後，消化管GVHD を発症し，プレドニゾロンで治療中，monomorphic PTLD（びまん性大細胞型Ｂ細胞リンパ腫）を発症した．免疫抑制剤中止後，リツキシマブ（Ｒ）単独療法，R-CHOP like 療法を施行したが効果不良であった．リツキシマブ併用ベンダムスチン療法に変更し４コース施行後，消化管内視鏡検査で病変は消失し，CT 検査で完全奏効を確認した．治療終了し約１年経過しているが，現在も症状増悪なく経過できており，難治性monomorphic PTLD に対してリツキシマブ併用ベンダムスチン療法が有効であった．Post-transplantation lymphoproliferative disorder (PTLD) occurs as a result of the use of immunosuppressants following hematopoietic stem cell transplantation, which causes the emergence of abnormal lymphocytes owing to the decline in T-cell function and the proliferation of plasma cells. It is thus one of the most fatal complications and the biggest concern for transplantation cases. PTLD is classified into 4 categories, and monomorphic PTLD takes the form of a malignant lymphoma. Immunosuppressant dose reduction, rituximab (R) monotherapy, and R-CHOP therapy are used to treat monomorphic PTLD, but the prognosis is poor for these forms of treatment. This report describes the experience of a patient with refractory PTLD who went into remission after responding to combination therapy with rituximab and bendamustine. A 50-year-old man underwent cord blood transplantation because of a myelodysplastic syndrome. Tacrolimus was used for GVHD prevention. After transplantation, symptoms of GVHD of the gastrointestinal tract developed, and during treatment using prednisolone, symptoms of monomorphic PTLD (diffuse large B-cell lymphoma) emerged. Once immunosuppressant use was discontinued, the patient underwent R monotherapy and R-CHOPlike treatment, but the response was poor. The treatment was then changed to combination therapy with rituximab and bendamustine; after 4 courses of treatment, gastrointestinal endoscopy revealed that the pathological abnormality had disappeared, and a complete response was confirmed. One year has passed since the completion of treatment, and at present, the patient’s symptoms have not worsened, suggesting that combination therapy with rituximab and bendamustine is effective for treating monomorphic PTLD

The long-term immunosuppressive effects of disulfide-linked HLA-G dimer in mice with collagen-induced arthritis

HLA-G, a natural immunosuppressant present in the human placenta during pregnancy, prevents fetal destruction by the maternal immune system. The immunosuppressive effect of HLA-G is mediated by the immune cell inhibitory receptors, LILRB1 and LILRB2. HLA-G forms disulfide-linked dimers by natural oxidation, and the dimer associates with LILRB1/B2 much more strongly than the monomer. Furthermore, the dimer formation remarkably enhanced the LILRB-mediated signaling. In this report, we studied the in vivo immunosuppressive effect of the HLA-G dimer, using the collagen-induced arthritis model mouse. Mice were treated with the HLA-G monomer or dimer intracutaneously at the left foot joint, once or for 5 days, and the clinical severity was evaluated daily in a double-blind study. The HLA-G monomer and dimer both produced excellent anti-inflammatory effects with a single, local administration. Notably, as compared to the monomer, the dimer exhibited significant immunosuppressive effects at lower concentrations, which persisted for about two months. In accordance with this result, a binding study revealed that the HLA-G dimer binds PIR-B, the mouse homolog of the LILRBs, with higher affinity and avidity than the monomer. The HLA-G dimer is expected to be quite useful as an anti-rheumatoid arthritis agent, in small amounts with minimal side effects. (C) 2012 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved

Successful treatment with ABL tyrosine kinase inhibitor for patients with acute myeloid leukemia with BCR-ABL1

Acute myeloid leukemia (AML) with BCR-ABL1 is rare and has a poor prognosis with conventional chemotherapy or ABL tyrosine kinase inhibitors (TKIs) alone. We reported a case of AML with BCR-ABL1 patient who was successfully treated with dasatinib alone; additionally, we previously reported another case of long-term remission maintained with imatinib monotherapy. These results suggested that a treatment with a novel and significantly potent TKI may be effective in AML with BCR-ABL1 patients with low tumor burden and without additional chromosome aberrations and ABL kinase domain mutations

Perinatal Exposure to Insecticide Methamidophos Suppressed Production of Proinflammatory Cytokines Responding to Virus Infection in Lung Tissues in Mice

Methamidophos, a representative organophosphate insecticide, is regulated because of its severe neurotoxicity, but it is suspected of contaminating agricultural foods in many countries due to illicit use. To reveal unknown effects of methamidophos on human health, we evaluated the developmental immunotoxicity of methamidophos using a respiratory syncytial virus (RSV) infection mouse model. Pregnant mice were exposed to methamidophos (10 or 20 ppm) in their drinking water from gestation day 10 to weaning on postnatal day 21. Offsprings born to these dams were intranasally infected with RSV. The levels of interleukin-6 (IL-6) and interferon-gamma in the bronchoalveolar lavage fluids after infection were significantly decreased in offspring mice exposed to methamidophos. Treatment with methamidophos did not affect the pulmonary viral titers but suppressed moderately the inflammation of lung tissues of RSV-infected offspring, histopathologically. DNA microarray analysis revealed that gene expression of the cytokines in the lungs of offspring mice exposed to 20 ppm of methamidophos was apparently suppressed compared with the control. Methamidophos did not suppress IL-6 production in RSV-infected J774.1 cell cultures. Thus, exposure of the mother to methamidophos during pregnancy and nursing was suggested to cause an irregular immune response in the lung tissues in the offspring mice