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Common variable immunodeficiency (CVID) is a primary B cell immunodeficiency disorder. Symptoms do not develop immediately after birth, and patients are often diagnosed in childhood and adulthood. These patients often develop autoimmune diseases and malignant tumors. We herein report a 50-year-old woman with severe hypogammaglobulinemia and recurrent respiratory tract infections who was diagnosed with CVID. Target sequencing showed a TNFRSF13B heterozygous frameshift variant. The patient had many comorbidities, probably caused by a CVID-induced immune imbalance. Physicians who treat adult patients are often unaware of CVID. CVID should be recognized as a differential diagnosis in hypogammaglobulinemia and recurrent infections.

A 61-year-old man was admitted to our hospital with fever and massive leukocytosis. A bone marrow smear revealed an increased density of myeloid cells in various stages of maturation as well as dysplasia in the neutrophils. There was no proliferation of blasts, eosinophils, or basophils. Genomic analysis of the bone marrow cells revealed no detectable abnormalities associated with myeloproliferative neoplasms, including BCR-ABL1. Therefore, the patient was diagnosed with atypical chronic myeloid leukemia (aCML). Chromosomal analysis revealed the presence of 1-17 double minute chromosomes (dmin) in 20 of 20 tumor cells examined. Multiple MYC signals were detected via interphase fluorescence in situ hybridization, indicating MYC gene amplification in the dmins. Three months after the oral administration of hydroxyurea, leukocytosis reoccurred. Therefore, induction therapy followed with umbilical cord blood transplantation was performed. However, MYC signals remained detectable in the bone marrow sample obtained immediately after neutrophil engraftment, indicating the presence of residual tumor cells. To the best of our knowledge, this is the first case report of aCML with dmin gene amplification, suggesting that the dmin MYC amplification exacerbated the patient's disease.

In 2003, a 60-year-old man presenting with thrombocytosis was referred to our hospital. Laboratory tests revealed normal white blood cell count and hemoglobin level. Bone marrow examination showed an increased number of megakaryocytes with dysplasia. G-banded karyotype analysis revealed del (5q). Initially, the patient was diagnosed with myelodysplastic/myeloproliferative neoplasm (MDS/MPN), and it was treated with aspirin and hydroxyurea. During the treatment course, fluorescence in situ hybridization for CSF1R and EGR1 was performed to detect del (5q), which showed negative results. In 2017, the patient had increased platelet count despite receiving treatment. A comprehensive genomic profiling revealed that the deleted region in this case was present in 5q14-5q23, which was different from the common deleted region of 5q- syndrome (5q32-5q33, where CSF1R was present) and that of high-risk MDS or acute myeloid leukemia (5q31, where EGR1 was present). Moreover, a CALR mutation was also detected. This case met the diagnostic criteria of essential thrombocythemia. The platelet count decreased with the administration of anagrelide. In conclusion, comprehensive genetic profiling is very important, and it leads to accurate diagnosis and therapy.

A 27-year-old man visited our hospital with painless swelling of the left scrotum. Hematologic studies showed the following levels of lactate dehydrogenase, 3,171 IU/l ; alpha-fetoprotein, 2.2 ng/ml ; and β- human chorionic gonadotropin, 0.4 ng/ml, and abdominal computed tomography revealed a mass of 10×8 ×4 cm in the left testis, and that of 3.5×3.0×5.0 cm in the left renal hilar lymph node, without any other metastasis. Left high inguinal orchiectomy was performed, and histopathological examination revealed mixed form with seminoma and teratoma. He was diagnosed to have a left germ cell tumor with left renal hilar lymph node metastases, pT1, N3, M0, stage II C, indicating poor prognosis with IGCCC. The patient received four cycles of chemotherapy, COMPE regimen (CDDP, VCR, MTX, PEP, VP-16 [etoposide]). After lactate dehydrogenase, alpha-fetoprotein, and β -human chorionic gonadotropin all normalized, retroperitoneal lymph node dissection was performed. Histopathological examination revealed only a mature teratoma. Two and half years later, hematologic studies showed blast transformation. Bone marrow biopsy revealed acute myeloblastic lymphoma (M2). The patient received one cycle of AraC and daunorubicin, one cycle of high dose AraC, and three cycles of AraC and mitoxantrone. After chemotherapy, he has maintained a disease-free status for 11 years. In this case, etoposide, a topoisomerase II inhibitor, was the presumed cause of therapy-related acute myeloid leukemia. After administering chemotherapeutic agents especially etoposide, it is important to check blood count periodically for a long time.

The use of mesenchymal stem cells (MSC) for tissue and organ regeneration offers advantages because the MSC contain multipotent progenitor cells and reported to be immunoprivileged as well as immunosuppressive. Therefore, cell therapy with allogeneic MSC has been reported as a promising treatment for severe acute graft versus host disease (GVHD). We reported a pilot study for GVHD treatments using a small number of allogeneic MSC. We also reported that MSC can show osteogenic differentiation capability when implanted in vivo as well as cultured in vitro. Based on these findings, we attempted to use allogeneic MSC for the treatment of genetic disorder of hypophosphatasia patient. Present paper summarizes our clinical experiences of allogeneic MSC for the purpose of regenerative medicine.

We investigated the hematopoietic status of aplastic anemia with FDG-PET before and after immunosuppressive therapy. FDG-PET showed a patchy uptake pattern before treatment, indicating residual compensatory hypercellular marrow. Three years after successful treatment with ATG plus CsA, the heterogeneity of bone marrow uptake persisted, suggesting that expanded reconstitution of hematopoiesis may require a long time even after the achievement of hematological remission.

We describe a patient that developed Epstein-Barr virus (EBV)-associated post-transplant lymphoproliferative disorders (PTLD), which presented as interstitial pneumonia. He had received allogeneic bone marrow transplantation for the treatment of acute myeloid leukemia 17 months before, when he developed hypoxemia requiring emergent admission. Chest computed tomography revealed pulmonary interstitial shadows, but neither hepatomegaly nor lymphadenopathy were detected. Bronchoscopy with lung biopsy revealed a lymphomatous proliferation of EBV-infected B cells. The interstitial pneumonia rapidly deteriorated, but improved dramatically after treatment with anti-CD20 monoclonal antibody (rituximab). This is the first report of a patient with lung EBV-PTLD that presented as interstitial pneumonia and was successfully treated with rituximab.

This is a preliminary feasibility study to assess the pharmacokinetics and efficacy of pentostatin in a patient undergoing dialysis. Pentostatin is a safe and well-tolerated medication, but a dose reduction is required for patients with renal insufficiency. We present a patient with chronic adult T-cell leukemia, whose white blood cell count exceeded 100 X 10(9)/l, and end-stage renal disease, receiving long-term thrice-weekly dialysis. The initial treatment with oral cyclophosphamide or with oral etoposide resulted in no response. After informed consent was obtained, pentostatin (1, 2, or 3mg/m2) was administered. 1 or 2 hours after injection, the patient received hemodialysis over 4 hours to remove any of the drug remaining in his system. Plasma concentrations of pentostatin were calculated with the known pharmacokinetics parameters. The differential equations describing a 2-compartment open-infusion pharmacokinetic model were fitted to the measured concentration-time data. Tumor lysis syndrome occurred 4 days after the course of the highest dose (3mg/m2), and the patient achieved complete remission. Anorexia, graded as 2 according to the NCI-CTC classification system, occurred and continued for four weeks. Pentostatin therapy consisting of the decreased dose (2mg/m2) was then administered every other week and provided a transient partial response with mild anorexia. Consequently, pentostatin can be considered as one of the chemotherapeutic regimens available for a patient undergoing dialysis.

We report a 67-year-old man who developed pure red cell aplasia (PRCA) during therapy for epilepsy with sodium valproate since April 2004. He was admitted to our hospital because of severe anemia (Hb 5.0g/dl, reticulocyte 0.1%) in August 2004. A bone marrow examination showed marked erythroid hypoplasia and a diagnosis of drug-induced PRCA was made. Because the discontinuation of valproate for one month failed to increase the number of reticulocytes and frequent blood transfusions were necessary, cyclosporine therapy was initiated. Within a week, substantial recovery of the numbers of reticulocytes was obtained, the cyclosporine had, however, to be changed to prednisolone due to the refusal of the patient to continue with it, resulting in the exacerbation of his anemia. After three weeks, cyclosporine therapy was resumed, which achieved rapid and remarkable recovery of red blood cells (Hb 8.9g/dl, reticulocyte 4.9%) within one month. Sixteen cases of valproate-induced PRCA have been reported in the literature and all cases except one recovered only by discontinuing or reducing the administration of valproate. However, our case required cyclosporine therapy in addition to the discontinuation of valproate. These results suggest that not only the direct toxic effect on erythropoiesis but also T lymphocyte-mediated immunological mechanism was involved in the pathogenesis of valproate-induced PRCA.

A multi-center series of 117 patients with malignant lymphoma were analyzed to evaluate the clinical significance of soluble interleukin-2 receptor alpha chain (sIL-2R alpha). The initial levels of sIL-2R alpha ranged from 277 U/ml to 22,800 U/ml with a mean level of 3,451 +/- 4,268 U/ml and a median level of 1,600 U/ml. The sIL-2R alpha levels of the diffuse lymphoma/intermediate-grade subtypes defined by the LSG classification/Working Formulation were higher than those of the follicular lymphoma/low-grade subtypes. There was a tendency for B-cell lymphomas to show higher sIL-2R alpha levels than T-cell lymphomas. The sIL-2R alpha level was correlated with the Ann Arbor clinical stage (I, II versus III, IV), presence or absence of B symptoms, and performance status (0, 1 versus 2, 3, 4) of the patients. The sIL-2R alpha levels were in good accordance with the four risk groups defined by the International Prognostic Indices. Of 21 patients whose tumor burden was serially measured, the coefficients of correlation between sIL-2R alpha and tumor mass were > 0.6 in 18 cases. Sixty-two patients achieved complete remission (CR) during the study; the initial and minimum sIL-2R alpha levels were lower than those of the non-CR patients. This study confirmed that sIL-2R alpha is a convenient and useful marker in the management of malignant lymphoma.