Successful High-dose Chemotherapy in Combination With Autologous Peripheral Blood Stem Cell Transplantation in an Anuric Child With Neuroblastoma.

No reports describe high-dose chemotherapy (HDCT) with autologous peripheral blood stem cell transplantation (auto-PBSCT) in pediatric patients with neuroblastoma and end-stage renal disease. Here, we report the case of a patient with high-risk neuroblastoma who developed anuria during treatment. HDCT with auto-PBSCT under hemodialysis, with strict attention to the ultrafiltration volume and dose modification of alkylating agents, was performed. Although the first auto-PBSCT led to engraftment failure, the second auto-PBSCT resulted in successful myeloid engraftment 8 months after anuria. This case demonstrated that HDCT with auto-PBSCT can be safely performed in children with renal failure under hemodialysis.

Kidney-protective Effect of Magnesium Supplementation in Cisplatin-containing Chemotherapy for Pediatric Cancer: A Retrospective Study.

In total, 158 chemotherapy courses containing cisplatin for 37 pediatric cases of newly diagnosed cancer were divided into 2 groups depending on whether magnesium (Mg) supplementation was administered (Mg+: 92 courses) or not (Mg-: 66 courses). Renal impairment was defined as grade 2 or higher creatinine elevation (CE) after each chemotherapy course. The incidence of CE in the Mg+ was significantly lower than in the Mg- (9.8% vs. 22.7%; P=0.025). Multivariate analysis revealed that Mg supplementation significantly reduced the incidence of CE (odds ratio, 0.36; confidence interval, 0.13-0.99). In pediatric patients, Mg supplementation during cisplatin-containing chemotherapy was associated with less cisplatin-induced nephrotoxicity to prevent cisplatin-induced nephrotoxicity.

First report of an Asian family with hemoglobin Evans [α2 62 (E11) Val → Met].

Hemoglobin Evans is an unstable variant caused by a single nucleotide mutation that produces a valine-to-methionine substitution at residue 62 of the α-globin chain. It has not been reported in the Asian population and only three cases have been reported worldwide. We diagnosed a Japanese boy with chronic hemolytic anemia with hemoglobin Evans after genetic testing. This is the first familial case of hemoglobin Evans in an Asian population.

Unique clonal relationship between T-cell acute lymphoblastic leukemia and subsequent Langerhans cell histiocytosis with TCR rearrangement and NOTCH1 mutation.

Acute lymphoblastic leukemia (ALL) occasionally develops before or after the onset of Langerhans cell histiocytosis (LCH). The mechanism of LCH developing after ALL remains unclear; thus the clonality of LCH developing during maintenance chemotherapy for T-cell ALL (T-ALL) was investigated. The T-ALL and LCH cells tested had the same T-cell receptor (TCR) gamma rearrangement. Mutation analysis of the NOTCH1 gene revealed 7213C>T (Q2405X) in exon 34 in T-ALL and LCH cells, but 5156T>C (I1719T) in exon 27 only in T-ALL. Polymerase chain reaction-restriction fragment length polymorphism analysis revealed three patterns of NOTCH1 mutations in T-ALL cells. The results suggest that the T-ALL and LCH cells were derived from a common precursor with TCR rearrangement and a single NOTCH1 mutation, rather than LCH cells developing from a minor clone of T-ALL with single NOTCH1 mutation.

Differences in CTG triplet repeat expansion in leukemic cells and normal lymphocytes from a 14-year-old female with congenital myotonic dystrophy.

We describe a rare case of acute lymphoblastic leukemia in a 14-year-old female with congenital myotonic dystrophy manifested as mental retardation, extensive contractures of multiple joints of the lower extremities, and severe scoliosis. Because of the potential toxicity of chemotherapy and the patient's poor performance status, a modified chemotherapy regimen was administered. Analysis of the greatly expanded number of CTG repeats at the 3' untranslated region of DMPK gene showed that the number of repeats was 233 greater in leukemic cells than in normal lymphocytes; this elongation may have occurred during the cellular proliferation of leukemic clones.

Identification of novel fusion genes with 28S ribosomal DNA in hematologic malignancies.

Fusion genes are frequently observed in hematologic malignancies and soft tissue sarcomas, and are usually associated with chromosome abnormalities. Many of these fusion genes create in-frame fusion transcripts that result in the production of fusion proteins, and some of which aid tumorigenesis. These fusion proteins are often associated with disease phenotype and clinical outcome, and act as markers for minimal residual disease and indicators of therapeutic targets. Here, we identified the 28S ribosomal DNA (RN28S1) gene as a novel fusion partner of the B-cell leukemia/lymphoma 11B gene (BCL11B), the immunoglobulin κ variable 3-20 gene (IGKV3-20) and the component of oligomeric Golgi complex 1 gene (COG1) in hematologic malignancies. The RN28S1-BCL11B fusion transcript was identified in a case with mixed-lineage (T/myeloid) acute leukemia having t(6;14)(q25;q32) by cDNA bubble PCR using BCL11B primers; however, the gene fused to BCL11B on 14q32 was not on 6q25. IGKV3-20-RN28S1 and COG1-RN28S1 fusion transcripts were identified in the Burkitt lymphoma cell line HBL-5, and the multiple myeloma cell line KMS-18. RN28S1 would not translate, and the breakpoints in partner genes of RN28S1 were within the coding exons, suggesting that disruption of fusion partners by fusion to RN28S1 is the possible mechanism of tumorigenesis. Although further analysis is needed to elucidate the mechanism(s) through which these RN28S1-related fusions play roles in tumorigenesis, our findings provide important insights into the role of rDNA function in human genomic architecture and tumorigenesis.

Multidisciplinary therapy including proton beam radiotherapy for a Ewing sarcoma family tumor of maxillary sinus in a 4-year-old girl.

BACKGROUND: Although complete resection offers the best chance for controlling head and neck Ewing sarcoma family tumors (ESFTs), it is occasionally unfeasible because of possible functional and cosmetic side effects. Planning multidisciplinary treatment for head and neck ESFT is challenging. METHODS AND RESULTS: A 4-year-old girl had left-sided excessive tearing, nasal obstruction, and exophthalmos for 4 months. A CT scan showed a mass filling the left maxillary sinus and extending to the left orbital wall. After a diagnosis of ESFT was established with biopsy, the patient was treated with vincristine, doxorubicin, cyclophosphamide/ifosfamide etoposide (VDC/IE) regimen over 50 weeks; partial maxillectomy was performed at week 15 and was followed by proton radiotherapy. The patient has remained tumor-free for 16 months, with preservation of facial form and function. CONCLUSION: Partial resection combined with proton radiotherapy may enable maximal tumor control and minimal functional and cosmetic side effects in children with head and neck ESFT.

Sequential analysis of cadherin expression in a 4-year-old girl with intracranial ependymoma.

INTRODUCTION: Cadherins are Ca(2+)-dependent cell-to-cell adhesion molecules that play an important role in tissue construction and morphogenesis in multicellular organisms. Cadherin involvement in tumor metastasis has recently been reported. CASE REPORT: We investigated the expression of E-cadherin and N-cadherin in paraffin-embedded sequential surgical specimens and autopsy specimens from a 4-year-old girl with recurrent ependymoma, subsequent to cerebrospinal fluid (CSF) dissemination. We observed low expression of E-cadherin in all surgical specimens and autopsy specimens. In contrast, expression of N-cadherin was high in all surgical specimens, but was decreased in autopsy specimens. CONCLUSION: Decreased expression of N-cadherin may be associated with CSF dissemination and may serve as a useful marker for CSF dissemination in patients with intracranial ependymoma.