Successful induction of immune tolerance in a patient with haemophilia B with inhibitor.

We describe successful induction of immune tolerance (IT) in a 10-month-old boy with severe haemophilia B. Urticaria developed soon after starting prophylactic treatment and was associated with an inhibitor at 7 Bethesda units mL(-1). Initially, we tried low dose factor IX therapy to induce IT with only a transient effect. The patient experienced an intracranial haemorrhage. A simple bolus dose of FIX eradicated the inhibitor. Thereafter he has been free from inhibitor and nephrotic syndrome for more than 5 years, although he receives FIX three times a week.

Successful unrelated cord blood transplantation in Philadelphia chromosome positive acute lymphoblastic leukemia during pulmonary aspergillosis treated by anti-fungal therapy, granulocyte colony-stimulating factor-mobilized granulocytes and surgical resection: case report.

A 3-year-old girl with Philadelphia chromosome positive acute lymphoblastic leukemia developed pulmonary aspergillosis during severe neutropenia by re-induction therapy. She was treated by intravenous fluconazole, oral itraconazole with plasma level monitoring and surgical resection of the focus for 3 months after clinical diagnosis of fungal infection was made. Once she had recovered from surgery we attempted to induce remission with anti-fungal treatment. She developed fever and neutropenia and appeared unlikely to remit with conventional chemotherapy. Unrelated one-antigen-mismatched cord blood (CB) transplantation was performed 2 months after the induction therapy. Her pulmonary aspergillosis was reactivated during subsequent conditioning. Anti-fungal drugs were switched to amphotericin B and granulocyte colony-stimulating factor-mobilized granulocyte concentrates were transfused. She obtained engraftment and has maintained complete hematological and molecular remission without signs of aspergillus infection for 13 months so far after transplantation. Even very high-risk transplantation in pediatric patients could be successfully supported by carefully designed intense comprehensive medical care.

Pneumomediastinum, subcutaneous emphysema, and pulmonary fibrosis in a patient with idiopathic pneumonia syndrome after bone marrow transplantation.

An adolescent female underwent bone marrow transplantation for relapsed leukemia and developed acute and chronic graft-versus-host disease and idiopathic pneumonia syndrome. Her lung disease responded to large doses of methylprednisolone but evolved to pulmonary fibrosis and pneumomediastinum and subcutaneous emphysema in the convalescent period. Pulmonary function tests revealed a restrictive pattern. Pneumomediastinum and subcutaneous emphysema are complications not only of obstructive but also of restrictive lung disease and vary with respect to time of onset.

[Unrelated bone marrow transplantation in two severe aplastic anemia patients preconditioned with a regimen of cyclophosphamide, antithymocyte globulin, and total body irradiation].

We report our experiences with HLA-matched unrelated bonemarrow transplantation combining a preconditioning regimen of cyclophosphamide, antithymocyte globulin (ATG), and total body irradiation for two patients with severe aplastic anemia (SAA) who had already undergone repeated blood transfusions. Short-term methotrexate and cyclosporine were administered for graft-versus-host disease (GVHD) prophylaxis. Both patients achieved rapid engraftment within 3 weeks, furthermore, neither acute nor chronic GVHD developed. Our conditioning regimen appeared to be well-suited for unrelated bone marrow transplantation in heavily transfused SAA patients. However, both patients experienced bouts of fever about 20-30 and 40-50 days after transplantation, and it was difficult to differentiate whether they were affected by acute GVHD, cytomegalovirus (CMV) infections, or serum sickness. Because weakly positive CMV antigenemia was detected, both patients were given ganciclovir. Although their fever did not respond initially, it gradually subsided following the combined administration of prednisolone. These outcomes suggest it is essential that attention be devoted to the potential for serum sickness and the high risk of herpes virus infections, particularly by CMV, following the use of intensive preconditioning regimens that include ATG.

CMV retinitis after cessation of ganciclovir therapy for CMV antigenemia in an unrelated BMT recipient.

An 11-year-old boy with severe aplastic anemia underwent unrelated BMT following TBI, antithymocyte globulin and CY. On day +23, CMV antigenemia was detected which resolved with ganciclovir. Eight days after discontinuing ganciclovir, he complained of impaired visual acuity. Ophthalmologic findings and a positive PCR study using anterior chamber fluid from the right eye confirmed the presumptive diagnosis of CMV retinitis, although CMV antigenemia and PCR studies using PBMC were then negative. He was successfully re-treated with ganciclovir. CMV retinitis should be considered even when CMV antigenemia is not present or PCR using PBMC is negative.

Respiratory syncytial virus infection of human alveolar epithelial cells enhances interferon regulatory factor 1 and interleukin-1beta-converting enzyme gene expression but does not cause apoptosis.

The induction kinetics of the transcriptional activities of interferon regulatory factor 1 (IRF-1), interleukin-1beta-converting enzyme (ICE), and CPP32 by respiratory syncytial virus (RSV) infection of human type II alveolar epithelial cells (A549 cells) were analyzed semiquantitatively by reverse transcriptase PCR. The appearance of ICE and CPP32 protein in cell lysate was examined by Western blotting analysis. The induction of apoptosis by RSV infection was examined by the appearance of DNA fragmentation detected by terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling. RSV moderately enhanced IRF-1 mRNA as early as 4 h after infection, and this enhancement lasted several hours. Following induction of the IRF-1 gene, ICE gene expression increased significantly, and an increase of ICE protein was observed in the RSV-infected cell lysate. These increments were observed in cells treated with live RSV but not in cells treated with inactivated RSV or control antigen. However, no infection-specific increase of CPP32 gene expression or the protein was observed. No nucleosomal fragmentation was observed in RSV-infected cells during the whole course of infection, despite the appearance of extensive cytopathic change and cell death. These observations suggest that RSV infection of human alveolar epithelial cells induces the ICE gene and its protein as a result of increased IRF-1 induction but that the increased ICE was insufficient to cause apoptosis in the RSV-infected cells. ICE might not be able to activate CPP32, which is thought to be the more important protease for apoptosis.