Kazue Yasuda

Identification and immunohistochemical localization of macrophage migration inhibitory factor in human kidney

Macrophage migration inhibitory factor (MIF) was the first lymphokine identified in activated T‐lymphocytes. MIF can induce proinflammatory cytokines, such as interleukin‐1 and tumor necrosis factor‐α. In this study, we identified MIF expression in a tissue specimen of a normal portion of a nephrectomized human kidney by reverse transcription‐polymerase chain reaction (RT‐PCR) and Western blot analysis. Furthermore, immunohistochemical study using an anti‐human MIF polyclonal antibody demonstrated that MIF was mostly present in the renal tubule epithelial cells and, to a lesser extent, in Bowmans capsular epithelial cells. We also carried out immunohistochemistry on cultured human renal proximal tubule epithelial cells, which showed that MIF was present in the cytoplasm of the epithelial cells. These results suggest the possibility that MIF takes part in the mechanism of inflammation and immunological events in the human kidney.

Congenital dermatofibrosarcoma protuberans in a newborn infant with a massive back tumor: favorable effects of oral imatinib on the control of residual tumor growth.

Dermatofibrosarcoma protuberans (DFSP) is known as a very rare malignant tumor of the deep dermis and subcutaneous tissue. It typically develops during adolescence and adulthood, with pediatric and infantile cases, particularly congenital ones, being much less frequent. We report a neonate with congenital DFSP. A newborn girl presented with a massive back tumor at birth. The tumor was at first suspected to be infantile fibrosarcoma (IFS) after immunohistochemical analysis of biopsy material, although the results were not fully compatible with IFS. She received chemotherapy under a tentative diagnosis of IFS, but this was unsuccessful. Partial resection was therefore performed at the age of 8 months to reduce the tumor mass and to reexamine its immunohistochemical characteristics. Positive CD34 staining and Collagen &agr;1&agr;/platelet-derived growth factor beta chimera gene signals on analysis of the excised tumor tissues enabled a definitive diagnosis of DFSP. She then underwent local irradiation and was given a daily dose of oral tyrosine kinase inhibitor (imatinib). After almost 1 year, the patient is doing well without enlargement of the residual tumor.

Comparison between piperacillin/tazobactam and cefepime monotherapies as an empirical therapy for febrile neutropenia in children with hematological and malignant disorders: A prospective, randomized study

To evaluate the efficacy and safety of piperacillin/tazobactam (PIPC/TAZ) or cefepime (CFPM) monotherapy for febrile neutropenia (FN) in children, a total of 53 patients with 213 febrile episodes were randomly treated with either PIPC/TAZ 337.5 mg/kg/day, or CFPM 100 mg/kg/day. No significant differences were observed in the success rates of the PIPC/TAZ and CFPM treatments (62.1% vs. 59.1%, P = 0.650). Furthermore, no differences were noted in the rates of new infection and mortality, and no serious adverse effects occurred in either of groups. Both PIPC/TAZ and CFPM were effective and safe as an empirical therapy for FN in children. Pediatr Blood Cancer 2015;62:356–358.

Impact of folate therapy on combined immunodeficiency secondary to hereditary folate malabsorption.

Hereditary folate malabsorption (HFM) is a rare autosomal recessive disorder. Severe folate deficiency in HFM can result in immunodeficiency. We describe a female infant with HFM who acquired severe Pneumocystis pneumonia. The objective of the present study was to elucidate her immunological phenotype and to examine the time course of immune recovery following parenteral folate therapy. The patient demonstrated a combined immunodeficiency with an impaired T cell proliferation response, pan-hypogammaglobulinemia, and an imbalanced pro-inflammatory cytokine profile. She had normal white blood cell count, normal lymphocyte subsets, and normal complement levels. Two novel mutations were identified within the SLC46A1 gene to produce a compound heterozygote. We confirmed full recovery of her immunological and neurophysiological status with parenteral folate replacement. The time course of recovery of her immunological profile varied widely, however. HFM should be recognized as a unique form of immunodeficiency.

Itraconazole for invasive fungal infection with pediatric malignancies.

Background:  Invasive fungal infection (IFI) is an increasingly common and often fatal infection in children with hematological malignancies and solid tumor. Prophylactic therapy with anti‐fungal agents is very important for these patients, because the early diagnosis of IFI is very difficult.

Stem cell transplantation for acute myeloid leukemia with pulmonary and cerebral mucormycosis.

Mucormycosis is one of the most refractory invasive fungal infections and often causes fatal infection in immunocompromised patients, such as those with severe diabetes mellitus and hematologic malignancies.

Refractory sacrococcygeal germ cell tumor in Schinzel-Giedion syndrome.

We describe a boy with Schinzel-Giedion syndrome who developed refractory sacrococcygeal germ cell tumor with elements of embryonal carcinoma and immature teratoma. He developed local recurrence soon after tumor resection. The tumor was highly resistant to platinum-based combination chemotherapy, local irradiation, and salvage chemotherapy. Frequent infections resulted in a delay in treatment, although apparent fragility had not been observed clinically. He died from tumor progression at 32 months of age. Intensification of chemotherapy does not seem to be feasible for tumors in patients with Schinzel-Giedion syndrome.

Successful treatment of immune tolerance induction with rituximab in a patient with severe hemophilia B and inhibitor.

Inhibitor development is one of the major problems in hemophilia patients. Whereas the inhibitor incidence in hemophilia A is estimated to be as high as 25-30%, it appears to be less frequent in hemophilia B, occurring in about 1-3% of hemophilia B patients. There are only a few case reports about immune tolerance induction (ITI) for hemophilia B patients. The present report describes ITI with rituximab in a patient with severe hemophilia B and inhibitor. The patient was diagnosed with severe hemophilia B at 9 months. He received prophylactic replacement therapy with plasma-derived factor IX (pd FIX). After 19 exposure days, inhibitor of factor IX was detected in his plasma, and replacement therapy was stopped. However, as he suffered from intracranial hemorrhage at the age of 1 year, he underwent first ITI at the age of 1 year. Unfortunately, this failed to reduce the level of the inhibitor, and this strategy was stopped after 2 years. Second ITI with pd FIX also failed. At the age of 14 years, ITI with rituximab was performed after obtaining informed consent. The patient received rituximab 375 mg/m once a week for four doses and received 40 u/kg of pd FIX every day. At 4 weeks after the start of ITI with rituximab, the level of the inhibitor of factor IX was diminished and was undetectable for 1 year after therapy. In this patient, ITI with rituximab was well tolerated and effective. This method should be considered for patients with hemophilia B and inhibitor.

Precursor-T lymphoblastic lymphoma after unrelated bone marrow transplantation in a patient with Fanconi anemia.

Lymphoid malignancies are rare in patients with Fanconi anemia (FA), particularly after bone marrow transplantation. A boy, who was diagnosed with FA at the age of 5; underwent successful bone marrow transplantation at the age of 11. One year later, he presented with fever and dry cough, and was found to have an anterior mediastinal tumor. Biopsy of the tumor revealed precursor-T cell lymphoblastic lymphoma. Human leukocyte antigen analysis confirmed that the tumor cells were derived from the patients own cells. He received mild chemotherapy for lymphoma, but his condition deteriorated rapidly and he died from excessive chemotherapy-related toxicity. The literature contains no reports of successful chemotherapy for lymphoid tumors in patients with FA, and therefore, alternatives to chemotherapy should be considered in the treatment of such patients.

Effect of meropenem with or without immunoglobulin as second-line therapy for pediatric febrile neutropenia

Meropenem (MEPM) is widely used for treatment of febrile neutropenia. There have been many reports on MEPM for pediatric febrile neutropenia showing success rates of approximately 50–75%. Although i.v. immunoglobulin (IVIG) is widely used for treatment of infection with antibiotics, there has been no report on the efficacy of IVIG for pediatric febrile neutropenia. This prospective randomized study was therefore carried out to clarify the usefulness of MEPM with or without IVIG as second line‐therapy for pediatric febrile neutropenia.