Takanori Oda

Incidence of human parvovirus B19 DNA detection in blood donors.

Summary. 1000 serum samples from blood donors were tested for human parvovirus B19 (B19) DNA by a nested PCR assay: six samples were positive for B19 DNA. The frequency was 1/167 (0‐6%), considerably higher than previous surveys (0‐004‐0‐03%). Five of the six samples were also positive for anti‐B19 IgM, indicating an acute phase of infection. It is recommended to screen for B19 DNA in blood products to prevent transfusion mediated viral infection for those susceptible such as immunocompromised patients and pregnant women.

Risk-directed treatment of infant acute lymphoblastic leukaemia based on early assessment of MLL gene status: results of the Japan Infant Leukaemia Study (MLL96).

Summary.  We studied the effectiveness of risk‐directed therapy for infants younger than 13 months of age with acute lymphoblastic leukaemia (ALL). Fifty‐five infants were assigned to different treatment programs (from December 1995 to December 1998) on the basis of their MLL gene status at diagnosis. Forty‐two cases (76·3%) had a rearranged MLL gene (MLL+) and were treated with remission induction therapy followed by sequential intensive chemotherapy, including multiple genotoxic agents (MLL9601 protocol). Haematopoietic stem cell transplantation (HSCT) was attempted if suitable donors were available. Thirteen infants (23·7%) were classified as MLL– and treated for 2·5 years with intensive chemotherapy for high‐risk B‐ALL (MLL9602 protocol). Complete remission was induced in 38 of the 42 infants (90·5%) with MLL+ ALL and in all 13 patients (100%) with MLL– disease. In the MLL+ subgroup, the estimated event‐free survival (EFS) rate at 3 years post diagnosis was 34·0% ± 7·5%, compared with 92·3% ± 7·4% in the MLL– subgroup (overall comparison, P = 0·001 by log‐rank analysis). Both age less than 6 months (hazard ratio = 6·87, 95% CI = 0·91–52·3; P = 0·013) and central nervous system (CNS) involvement at diagnosis (hazard ratio = 2·92 95% CI = 1·29–6·63; P = 0·015) were significant independent predictors of an inferior outcome. These findings indicate a strategic advantage in classifying infant ALL as either MLL+ or MLL– early in the clinical course and selecting therapy accordingly. Standard chemotherapy for high‐risk B‐lineage ALL appeared adequate for MLL– cases. Novel therapeutic initiatives are warranted for infants with MLL+ disease, particularly those with initial CNS leukaemic involvement or age less than 6 months, or both.

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.

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.

Human parvovirus B19‐induced aplastic crisis in iron deficiency anemia

Human parvovirus B19 (HPVB19) infects and replicates in erythroid progenitor cells. Its specific cytotoxic effect on these cells results in aplastic crises in patients with congenital hemolytic anemias. Aplastic crisis due to HPVB19 infection in a healthy girl revealed occult iron deficiency anemia. The condition is characterized by a high serum iron level in the aplastic phase and rapid recovery after administration of iron. Temporary HPVB19‐induced red blood cell aplasia could occur in patients with other anemias, particularly those with non‐inherited form of hemolysis.

TRANSPLANTED PERIPHERAL BLOOD STEM CELLS, MOBILIZED BY CHEMOTHERAPY ALONE, CAN INDUCE PERSISTENT HEMATOPOIESIS IN CHILDREN WITH ACUTE LEUKEMIA

Three patients with leukemia were transplanted with peripheral blood stem cells mobilized by in tensification or maintenance chemotherapy alone. They maintained persistent reconstituted hematopoiesis for at least 9 years. The experience provides evidence that long-term marrow repopulating cells can be mobilized into the blood to an adequate repopulating extent by chemotherapy alone.

Adrenocortical carcinoma characterized by gynecomastia: A case report

Abstract. We present a 4-yr-old boy with adrenocortical carcinoma (ACC), diagnosed due to the appearance of gynecomastia as the presenting symptom. Six months prior to admission, an acute growth spurt along with the development of bilateral breast swelling was observed. He did not present any features of virilization, including enlargement of the testes, increase in testis volume, and penis size. Laboratory investigations showed gonadotropin-independent hypergonadism, with low LH/ FSH levels and elevated estradiol/testosterone levels. Abdominal computed tomography revealed a large heterogeneous mass adjacent to the right kidney and below the liver. Pathological investigations of the biopsy specimen demonstrated that the tumor was an ACC. Pre- and post-operative combination chemotherapy with mitotane was administered and surgical resection was carried out. Post-surgery, the elevated estradiol/testosterone concentrations reverted to within the reference range. Urinary steroid profile and tissue concentration analysis of estradiol and testosterone indicated the presence of estrogen in the ACC tissue. An investigation for TP53 gene aberrations revealed the presence of a germline point mutation in exon 4 (c.215C>G (p.Pro72Arg)). In ACC, the most common symptom is virilization, and feminization, characterized by gynecomastia, is very rare. However, a diagnostic possibility of ACC should be considered when we encounter patients who have developed gynecomastia without the influence of causative factors such as obesity or puberty, and do not present with the typical signs of virilization.