Nobuo Mizue

Treatment of McLeod phenotype chronic granulomatous disease with reduced-intensity conditioning and unrelated-donor umbilical cord blood transplantation

Patients with chronic granulomatous disease (CGD) complicated by antimycotics-refractory invasive aspergillosis have an extremely poor prognosis if they cannot undergo allogeneic hematopoietic stem cell transplantation from a suitable related donor while in good clinical condition.We successfully treated a 20-year-old man with very rare McLeod phenotype CGD with reduced-intensity conditioning and unrelated-donor umbilical cord blood transplantation.We postulate that reduced-intensity conditioning—allogeneic hematopoietic stem cell transplantation is a promising therapeutic strategy for patients with CGD even if only unrelated-donor umbilical cord blood is available.

An evaluation of peripherally inserted central venous catheters for children with cancer requiring long-term venous access

Long-term venous access is essential when treating malignant diseases. We reviewed our experience with peripherally inserted central venous catheters (PICC) in children suffering from various malignancies with regard to catheter life, reasons for removal, and complications. Ninety-three PICCs were inserted in 78 children. Median catheter life was 162 days (range 6–575 days) with a total of 16,266 catheter days. Seventy-five PICCs (80.6%) had been placed until the elective removal or patients’ death, whereas 18 PICCs (19.4%) were removed due to PICC-related complications; a rate of 1.11 per 1,000 catheter days. Complications requiring removal of PICCs included infection (n = 12), occlusion (n = 3), dislodgement (n = 2), and phlebitis (n = 1) with rates of 0.74, 0.18, 0.12 and 0.06 per 1,000 catheter days, respectively. We conclude that PICC provides reliable long-term intravenous access in children suffering from malignancies.

Detection of BK virus and adenovirus in the urine from children after allogeneic stem cell transplantation.

The development of hemorrhagic cystitis (HC) and urinary excretion of polyoma BK virus (BKV) and adenovirus (ADV) was investigated by polymerase chain reaction in 20 children undergoing allogeneic stem cell transplantation. Five children developed HC, and all of them excreted BKV; however, only 1 excreted ADV, suggesting that BKV is more significant cause of HC than ADV in children undergoing stem cell transplantation.

Gastric antral vascular ectasia in 2‐yr‐old girl undergoing unrelated cord blood stem cell transplantation

Abstract:  Gastrointestinal bleeding is a common complication after hematopoietic stem cell transplantation (HSCT) and is often related to acute graft‐vs.‐host disease (aGVHD). Gastric antral vascular ectasia (GAVE), recently recognized as a complication after HSCT, is a rare cause of severe gastrointestinal bleeding, which has only been reported in adult patients so far. We report a 2‐yr‐old girl who developed GAVE after unrelated cord blood stem cell transplantation (CBSCT) as treatment of intractable Epstein–Barr virus‐associated hemophagocytic lymphohistiocytosis (EBV‐HLH). Her conditioning regimen for CBSCT consisted of etoposide, busulfan, and cyclophosphamide. She was doing well after CBSCT without recurrence and developed only grade I aGVHD. She suddenly developed coffee ground emesis, tarry stools and severe anemia 76 days after CBSCT. As antacids were ineffective, esophagogastroduodenoscopy was performed and revealed GAVE on day 97. Endoscopic coagulation therapy was performed twice; subsequently, she needed no further transfusions and there was no clinical recurrence of GAVE.

Relapse of T-cell all after stem cell transplant presenting as hypertrophic cardiomyopathy: the value of non-invasive diagnostic imaging in detecting cardiac leukemia.

We describe a 14‐year‐old female with acute lymphoblastic leukemia (ALL) with a mediastinal mass at diagnosis who developed hypertrophic cardiomyopathy (HC) after stem cell transplantation (SCT). During refractory relapse after SCT using bone marrow from her HLA‐matched sibling, she underwent whole thorax irradiation because of pleural effusion and a recurrent mediastinal mass. After a second SCT using peripheral blood from the same donor, she developed HC suspected to be related to tacrolimus. However, isolated cardiac relapse was finally diagnosed by several non‐invasive imaging techniques. Cardiac irradiation resolved her cardiac failure, though she eventually developed progressive and fatal hematological disease.

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.

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.

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.

Primary central nervous system lymphoma in an immunocompetent 12-year-old boy

An immunocompetent 12-year-old Japanese boy complained of headache followed by nausea, vomiting, and hemiparesis. Computed tomography (CT) of his head showed an intracranial mass, which was mainly located in his left corona radiata and nearly isodense to cortex. Its density was slightly increased by contrast-enhanced CT (Fig. 1a, b). In magnetic resonance images (MRI) of his head, the intracranial mass showed low intensity on T1weighted images and high intensity on T2-weighted images (Fig. 1c, d). The mass had spread to left thalamus and basal ganglion. At first, some brain tumor or inflammatory demyelinating disease was considered in the differential diagnosis. An open biopsy was thus performed for definitive diagnosis. The patient was diagnosed with malignant lymphoma of the central nervous system in our institution. No other mass other than the intracranial mass was detected by gallium scintigraphy or whole-body CT. A bone marrow examination from the bilateral iliac crest was performed and showed no infiltration of lymphoma cells. He was therefore diagnosed with primary central nervous system lymphoma (PCNSL). PCNSL has been reported to be extremely rare in childhood. Our patient’s diagnosis was confirmed by a central pathology review system of childhood lymphoma in Japan. Lymphoid cells with irregular nuclear contours highly infiltrated through the perivascular space into the brain parenchyma (Fig. 2a). These cells were immunostained positively with CD 20, 79a, and bcl2, and negatively with cCD 3, CD 10, CD 5, CD 33, CD 45RO, and cyclin D1 (Fig. 2b). The patient was treated with chemotherapy following the NHL-B02p group 4 protocol of the Japan Association of Childhood Leukemia Study. This protocol includes high-dose methotrexate (HD-MTX) and high-dose cytarabine. He received triple intrathecal therapy; a simultaneous CSF examination showed no lymphoma cells. After three courses of chemotherapy, his intracranial mass became