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In pediatric cancer patients, the estimated glomerular filtration rate based on serum cystatin C (CysC) was reported to be suitable for estimating kidney function because of low serum creatinine (Cr) and high serum βWe describe two pediatric cases of JMML with an elevated serum CysC level. Urinalysis tests showed no abnormalities and no evidence of nephritis or nephropathy, and there were no findings indicating abnormal kidney function, such as Cr clearance in one case or the estimated glomerular filtration rate based on serum Cr in both cases, except for the serum CysC levels. There were no other causes of a high serum CysC level, including hyperthyroidism and steroid administration. The patients were treated with a conventional dosage of drugs, and their serum CysC levels decreased to the normal range when they were in complete remission after treatment.An elevated serum CysC level may reflect tumor burden independent of kidney function in JMML patients. Therefore, creatinine or inulin clearance should be determined to more accurately estimate kidney function for administering an optimal dose of anticancer drugs. In addition, a high serum CysC level may be a potential biomarker of cancer progression.

Background The prognosis of high-risk osteosarcoma, defined by the presence of chemo-resistance, metastatic disease at diagnosis, and relapse, remains poor. The efficacy of high-dose chemotherapy (HDC) and autologous stem-cell transplantation (ASCT) for high-risk osteosarcoma is still unclear. Methods We retrospectively reviewed pediatric patients with high-risk osteosarcoma who underwent HDC and ASCT at our institution between 2002 and 2018 and performed a review of the literature regarding the efficacy of HDC and ASCT for high-risk osteosarcoma. Results Six patients with high-risk osteosarcoma underwent high-dose melphalan (180 mg/m2)-based chemotherapy followed by ASCT. Two patients received HDC consisting of ifosfamide and melphalan. Three patients received HDC consisting of etoposide, carboplatin, and melphalan. One patient underwent tandem HDC consisting of thiotepa and etoposide followed by melphalan, thiotepa, and etoposide. Non-hematological toxicities presented mainly as mucositis and diarrhea. Two patients developed grade 3 mucositis. No life-threatening toxicities were observed in any of the six patients. One patient with disease progression before HDC died of multiple metastases, while five patients, with no evidence of disease in the peri-transplant periods, were alive at the time of publication; there was no disease recurrence at a median follow-up period of 144 months (range, 24–215 months). Our review of the literature supports the use of HDC with a higher dose of melphalan (180–280 mg/m2) for high-risk osteosarcoma. Conclusions Melphalan-based HDC and ASCT can be a promising treatment for high-risk osteosarcoma. Additionally, surgical removal of macroscopic residual lesions may be essential in peri-transplant periods.

Poor graft function (PGF) is a major obstacle to successful allogeneic stem cell transplantation after achieving normal bone marrow function. We report a successful treatment of domino DLI for poor graft function in younger brother with hyper IgM syndrome from HLA-identical elder brother with the same disorder with a history of HLA-mismatched unrelated bone marrow transplantation using same donor. Immunological profiling revealed that DLI-induced T-regulatory cells could correct skewed immune responses in the BM microenvironment due to secondary PGF pathogenesis. Immunological tolerized domino DLI can be a new therapeutic option for secondary PGF in HLA-identical sibling pairs with congenital immunodeficiency.

Poor graft function (PGF) is a major obstacle to successful allogeneic stem cell transplantation after achieving normal bone marrow function. We report a successful treatment of domino DLI for poor graft function in younger brother with hyper IgM syndrome from HLA-identical elder brother with the same disorder with a history of HLA-mismatched unrelated bone marrow transplantation using same donor. Immunological profiling revealed that DLI-induced T-regulatory cells could correct skewed immune responses in the BM microenvironment due to secondary PGF pathogenesis. Immunological tolerized domino DLI can be a new therapeutic option for secondary PGF in HLA-identical sibling pairs with congenital immunodeficiency.

Purpose Pericardial effusion (PE) is a potentially life-threatening complication following hematopoietic stem cell transplantation (HCT). A higher incidence of early-onset PE, unrelated to graft-versus-host disease, before day 100 after HCT has been reported in pediatric patients, but the pathogenic mechanism is poorly understood. Aiming to determine the pathogenesis of early-onset PE in pediatric patients, we analyzed the cytokine concentration and cell population in the pericardial fluid of four pediatric patients with PE. Methods Between January 2009 and December 2015, four patients requiring pericardiocentesis for clinically significant PE were identified in 60 patients. We evaluated the interleukin-6 (IL-6), interferon-γ, IL-1β, and tumor necrosis factor-α levels in PE. Two patients were available for analysis with intracellular cytokine flow cytometry and a chimerism assay. Results All patients showed the accumulation of pericardial macrophages and high concentrations of IL-6 in PE. Notably, the accumulated pericardial macrophages were CD163+ CD15+ CD14+ cells of host origin that produced IL-6. Conclusion These IL-6-producing tissue-resident macrophages may be key players in the pathogenesis of early-onset PE.