Umbilical Cord Blood as an Alternative Source of Reduced-Intensity Hematopoietic Stem Cell Transplantation for Chronic Epstein-Barr Virus–Associated T or Natural Killer Cell Lymphoproliferative Diseases

AbstractChronic Epstein-Barr virus–associated T/natural killer cell lymphoproliferative diseases represented by chronic active Epstein-Barr virus infection are lethal but are curable with several courses of chemotherapy and allogeneic hematopoietic stem cell transplantation (HSCT). Recently, we reported that reduced-intensity conditioning (RIC) provided better outcomes than myeloablative conditioning because RIC was less toxic. However, it was unclear whether cord blood transplantation (CBT) works in the context of RIC. We retrospectively analyzed 17 patients who underwent RIC followed by bone marrow transplantation (RIC-BMT) and 15 patients who underwent RIC followed by CBT (RIC-CBT). The representative regimen was fludarabine and melphalan based. The overall survival rates with RIC-BMT and RIC-CBT were 92.9% ± 6.9% and 93.3% ± 6.4%, respectively (P = .87). One patient died of lung graft-versus-host disease after RIC-BMT, and 1 patient died of multiple viral infections after RIC-CBT. Although cytotoxic chemotherapy was also immunosuppressive and might contribute to better donor cell engraftment after RIC-HSCT, the rate of engraftment failure after RIC-CBT was still higher than that after RIC-BMT (not significant); however, patients who had experienced graft failure were successfully rescued with a second HSCT. Unrelated cord blood can be an alternative source for RIC-HSCT if a patient has no family donor

Alveolar soft part sarcoma metastatic to the breast: a case report

Abstract Background Alveolar soft part sarcoma (ASPS) is an extremely rare neoplasm that tends to occur in the lower limbs of children and adolescents. Metastatic breast tumors constitute 0.5–2.0% of all malignant mammary neoplasms, and cases of ASPS with mammary metastases are very rare. Case presentation Three years ago, an 11-year-old girl presented to the hospital with pain in the right jaw after becoming aware of a mass in the right cheek. After detailed examination, the patient was diagnosed with ASPS with the primary tumor in the right cheek and multiple lung metastases, and chemotherapeutic treatment was initiated. One year later, accumulation of fluorodeoxyglucose (FDG) was observed in the right front of the skull (standardized uptake value (SUV)-max 2.8) and left breast (SUV-max 2.4) using FDG-positron emission tomography (PET) / computed tomography (CT). Ultrasonography revealed the mammary tumor as a hypoechoic, internally heterogeneous mass measuring 22.4 × 16.2 × 21.1 mm with a rich blood supply. Using pathological findings of core-needle biopsy, we diagnosed it as ASPS. Based on the above information, we made a diagnosis of ASPS with left mammary and cranial metastases. Due to chemoresistance, surgical excision was selected as the mode of treatment; resection of the metastatic cranial bone was performed first, and partial mastectomy of the left breast was performed in two stages. Postoperative conditions were good, and we are currently performing regular follow-ups (visual palpation every 3 months and semi-annual mammary gland ultrasonography). Conclusions We have reported an extremely rare case of ASPS with mammary metastasis with some reference-based discussion. In our case, disease control was obtained by a combination of drug therapy and surgical treatment

A congenital mutation of the novel gene LRRC8 causes agammaglobulinemia in humans

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 helixes 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