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Unrelated cord blood transplantation (CBT) has been worldwide for bone marrow reconstitution. CBT is associated with a high frequency of engraftment failure and rejection due to a small dose of graft cells. In cases of engraftment failure or rejection following unrelated CBT, retransplantation from the original donors is impossible. We report a successful transplantation with CD34p+ blood cells selected from a 2-loci HLA-mismatched mother to a child with acute monocytic leukemia after engraftment failure of the primary CBT. Selected CD34p+ blood cell transplantation is a useful approach for retransplantation in the setting of engraftment failure.

Epstein-Barr virus (EBV) occasionally infects T and NK cells and causes EBV-infected T/NK-cell lymphoproliferative disease (LPD), which comprises chronic active EBV infection, EBV-associated hemophagocytic syndrome, mosquito allergy, hydroa vacciniforme, aggressive NK-cell leukemia, and NK/T-cell lymphoma. The diagnosis is proven by the monoclonal proliferation of EBV-infected T or NK cells, which is a time-consuming and complicated method. T-cell monoclonality is helpful for the screening of EBV-infected T-cell LPD in patients with EBV-genome burden and is easily shown with T-cell-receptor rearrangement or the T-cell repertoire, whereas NK-cell monoclonality is difficult to prove due to its lacking such rearranged receptors. We investigated a set of killer immunoglobulin-like receptors (KIRs) and also CD94-NKG2 heterodimers on NK cells, namely the NK-cell repertoire. Skewed repertoires were seen in all patients with EBV-infected NK-cell LPD, but not in any patients with EBV-infected T-cell LPD and were restored only after successful treatment. The normal KIR repertoire is variable for each individual and it seems difficult to detect minimal residual EBV-infected lymphocytes. However, the NK-cell repertoire is feasible for identifying EBV-infected NK-cell LPD and evaluating the treatment effect.

A girl with congenital agammaglobulinemia and minor facial anomalies lacked B cells in peripheral blood: karyotypic analysis of white blood cells showed balanced translocation, t(9;20)(q33.2;q12). In the current study, we isolated a novel gene, leucine-rich repeat-containing 8 (LRRC8), at the translocation site on chromosome 9. It has four transmembrane helices with one isolated and eight sequentially located leucine-rich repeats (LRRs) and constitutes a new protein family. It is expressed on T cells as well as on B-lineage cells. Translocation truncates the LRRC8 gene, resulting in deletion of the eighth, ninth, and half of the seventh LRR domains located close to the C-terminal. The truncated form of the LRRC8 gene is transcribed with sequences from the noncoding region adjacent to the truncated seventh LRR. Protein products derived from the truncated gene are coexpressed on white blood cells with the intact LRRC8 protein from the untranslocated allele. Transplantation experiments with murine bone marrow cells that were forced to express the truncated LRRC8 show that expression of the truncated protein inhibited B cell development. These results indicate that LRRC8 is responsible for the B cell deficiency in this patient and is required for B cell development.

A monosomy 7 leukemia cell line, designated MONO-7, was established from the peripheral blood of a patient with monosomy 7 acute myelocytic leukemia (French-American-British classification M0). The cells were cultured continuously for more than 24 months in RPMI-1640 medium supplemented with 10% heat-inactivated fetal calf serum. The cell line exhibits an unclassified appearance. Cytochemically, alpha-naphthol-acetate esterase and myeloperoxidase are negative. Immunophenotypically, the cell line expresses CD33, CD13, CD56, CD34, CD38, HLA-DR, and CD45, but lacks T and B cell-associated antigens. Karyotypic analysis of the cell line showed only 45,XY,-7. Analysis of the N-ras gene mutation demonstrated identical mutations in fresh leukemic cells and the MONO-7 cell line. Clonal rearrangements of the immunoglobulin heavy-chain gene, T-cell receptor beta-chain gene, or T-cell receptor gamma-chain gene were not found in DNA extracted from MONO-7 cells. The growth of MONO-7 cells in vitro was stimulated by recombinant human granulocyte-macrophage colony-stimulating factor or interleukin 3. To our knowledge, this is the first report of the establishment of a cell line with the karyotype 45,XY,-7 without any other abnormality and with a ras gene mutation.

We report three pediatric patients with ganciclovir-resistant cytomegalovirus (CMV) retinitis who were successfully treated with foscarnet. The patients were recipients of hematopoietic stem cell transplantation (SCT) from HLA-mismatched donors. Because these patients had developed or experienced progressive CMV retinitis during ganciclovir therapy, they received foscarnet therapy at 60 mg/kg every 8 h. Their retinitis resolved promptly after initiating foscarnet therapy, suggesting foscarnet's effectiveness in treating ganciclovir-resistant CMV infection. The amount of CMV mRNA was quantitatively measured using an NASBA technique, which amplified the β2.7 transcripts specific for CMV replication. This technique was useful for monitoring disease activity in a more rapid and sensitive manner than the PCR assay for CMV DNA. Bone Marrow Transplantation (2001) 27, 1141–1145.

Human herpesvirus 6 (HHV-6) infection and disease are serious complications of allogeneic hematopoietic stem cell transplantation (allo-SCT). Ganciclovir (GCV) is effective against HHV-6 in vitro but the antiviral susceptibility of HHV-6 has not been well characterized in vivo. We retrospectively compared the HHV-6 reactivation rate in pediatric allo-SCT recipients with and without GCV prophylaxis. The HHV-6 reactivation rate at 3 weeks after allo-SCT in patients without prophylactic GCV administration was significantly higher than that in those receiving prophylactic GCV (11/28 vs 0/13, P < 0.01). Five of 36 patients without prophylactic GCV showed clinical manifestations including skin rash, interstitial pneumonitis, persistent thrombocytopenia, enterocolitis and thrombotic microangiopathy, respectively. HHV-6-associated symptoms were observed in one of the 13 patients receiving prophylactic GCV. This patient showed fever, diarrhea and graft rejection concomitantly with a sudden increase of HHV-6 DNA copy number. Patients who received GCV for treatment of HHV-6 infection showed an improvement in symptoms and/or decrease of HHV-6 copy number. Thus, GCV is effective for treating HHV-6 disease after allo-SCT in vivo.