Tsuchiya S

Epstein-Barr Virus-Associated Lymphoproliferative Disorder after Unrelated Bone Marrow Transplantation in a Young Child with Wiskott-Aldrich Syndrome

We report a case of a 16-month-old Wiskott-Aldrich syndrome (WAS) patient with a WASP gene mutation who received human leukocyte antigen (HLA)-matched, unrelated allogeneic bone marrow transplantation (BMT) followed by an Epstein-Barr virus-associated lymphoproliferative disorder (EB-LPD), diagnosed by clinical findings, polymerase chain reaction detection of the EB virus genome, and spontaneous lymphocyte proliferation of donor cell origin. EB-LPD is one of frequent lethal complications in HLA-mismatched or unrelated BMT in this syndrome. Adoptive immunotherapy with donor leukocyte transfusion, including appropriate numbers of CD3-positive T cells, was effective for the EB-LPD, achieving almost complete recovery 1 year later without any findings of graft-versus-host disease.

Successful treatment of steroid-resistant severe acute GVHD with 24-h continuous infusion of FK506.

We report our findings in two cases of steroid-resistant severe acute GVHD after allogeneic BMT successfully treated with FK506 (tacrolimus). An 18-year-old female (patient 1) who underwent BMT from an HLA-identical sibling for ALL in first CR, developed generalized erythema and profuse watery diarrhea, which progressed to acute GVHD of grade III severity, resistant to steroid control. After continuous 24-h administration of FK506, the diarrhea improved within 10 days. Patient 2, a 9-year-old girl with AML who underwent unrelated BMT, had skin, gut and liver lesions of acute GVHD grade IV, which did not respond to high-dose steroid therapy. They were controlled, however, by continuous intravenous infusion of FK506. Both patients are still surviving after more than 1 year without any acute GVHD sequelae or signs of chronic illness. The adverse effects of FK506 were mild and tolerable in both cases. Comparison of our findings with those in the literature suggests that it is important to give FK506 at plasma concentrations as high as 25–35 ng/ml by continuous intravenous infusion for extended periods to control steroid-resistant severe acute GVHD.

Mutations of the Epstein‐Barr virus LMP‐1 oncogene in a 10‐year‐old Japanese girl with nasopharyngeal carcinoma

A 10‐year‐old patient with nasopharyngeal carcinoma (NPC) was studied for mutations within the carboxy‐terminal portion of the Epstein‐Barr virus (EBV) latent membrane protein (LMP)‐1 gene. The EBV genome, defined as type A, was detected in biopsied tumor specimens by Southern hybridization with specific probes. Sequence analysis of the carboxy‐terminal part of the LMP‐1 gene revealed no deletions but seven single‐base substitutions, four of which were found to be identical to those previously detected in codons for amino acids 322 to 366 in the Chinese NPC CAO. Although yet unresolved, the observed mutations may be associated with the pathogenesis of NPC.