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DOI： 10.1007/s12185-020-03048-9

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Familial Mediterranean fever (FMF) is a hereditary autoinflammatory disorder accompanied by periodic fever and sterile serositis. We report a 5-year-old boy with FMF, who underwent second unrelated cord blood transplantation (CBT) for recurrent familial hemophagocytic lymphohistiocytosis. Periodic attacks of fever and abdominal pain started 6 months after CBT. He was diagnosed with FMF according to the Tel-Hashomer criteria and treated successfully with colchicine. Genetic testing showed heterozygous p.E148Q mutation in the MEFV gene from both donor and recipient cells. Several CBT-related factors including use of an immunosuppressant can potentially be involved in the pathogenesis of FMF in our patient.

DOI： 10.1097/MPH.0000000000002081

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DOI： 10.1111/ped.14432

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Not available.

DOI： 10.3324/haematol.2020.266320

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An amendment to this paper has been published and can be accessed via a link at the top of the paper.

DOI： 10.1038/s41409-020-01076-x

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Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative therapy for the hematologic manifestations of Diamond-Blackfan anemia (DBA). However, data regarding the optimal conditioning regimen for DBA patients are limited. We retrospectively compared the outcomes of DBA patients who underwent HSCT using either myeloablative conditioning (MAC) or reduced-intensity conditioning (RIC) regimens. The patients belonged to a cohort treated at our hospitals between 2000 and 2018. HSCT was performed in 27 of 165 patients (16.4%). The median age at the time of HSCT was 3.6 years. Stem cell sources included bone marrow for 25 patients (HLA-matched sibling donors, n = 5; HLA-mismatched related donors, n = 2; HLA-matched/mismatched unrelated donors, n = 18) or cord blood for 2 patients. MAC or RIC regimens were used in 12 and 15 patients, respectively. Engraftment was successful in all 27 patients who underwent HSCT. Three patients who underwent HSCT using MAC regimens developed sinusoidal obstruction syndrome. The 3-year overall survival (OS) and failure-free survival rates (FFS) post-transplantations were 95.2% and 88.4%, respectively, with no significant differences between MAC and RIC regimens. Our data suggest that HSCTs using RIC regimens are effective and obtain engraftment with excellent OS and FFS for young DBA patients.

DOI： 10.1038/s41409-020-01056-1

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DOI： 10.1111/ped.14079

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Language：Japanese   Publisher：日本臨床外科学会  

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Background: Lymph node metastasis (LNM) is a relatively rare event in soft tissue sarcoma. An association between the timing of LNM detection and patient prognosis is presently unknown. Patients and Methods: We retrospectively analyzed the clinicopathological features of 33 patients with LNM between 2001 and 2015. Analysis of the timing of LNM diagnosis was grouped according to patients presenting LNM in either <8 months (the median time from primary tumor diagnosis to LNM) or ≥8 months after primary tumor diagnosis. Results: A relationship between the primary tumor size and the timing of the LNM was not significantly found (Rs = 0.0088, p=0.96). Sixteen patients had an LNM detection duration of <8 months, and 17 patients had a duration of ≥8 months. The 5-year survival for patients with an LNM detection duration of <8 months and ≥8 months was 19% and 71%, respectively (p=0.0016). There were 19 patients with pulmonary metastases. Among them, there were 13 patients with a duration of primary tumor diagnosis to LNM of <8 months and 6 with a duration of ≥8 months (p=0.01). Conclusion: Early LNM (<8 months) may predict poor prognosis in soft tissue sarcoma.

DOI： 10.1155/2019/6708474

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Kowsar Medical Publishing Company  

DOI： 10.5812/ijp.68869

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OBJECTIVE: This multicenter cooperative study aimed to analyze the adverse events (AEs) associated with tyrosine kinase inhibitors (TKIs) used as initial treatment for chronic-phase chronic myeloid leukemia (CML-CP) and their impact on outcome. METHODS: We retrospectively evaluated 450 patients with CML-CP who received TKIs between 2004 and 2014. RESULTS: The 5-year overall survival (OS) and event-free survival (EFS) rates were 95.1% and 89.0%, respectively. Patients with comorbidities (46.4%) and aged ≥60 years (50.4%) at diagnosis had significantly inferior OS to those without comorbidities and aged <60. Patients achieved higher rates of major molecular response (MMR) at 6 and 12 months after initial treatment with dasatinib or nilotinib compared to imatinib, but final MMR rates were almost the same. Sixty-six percent of patients required treatment modifications from first-line TKI therapy; the main reasons were AEs (48.4%) and failure (18%). Grade III-IV AEs in first-line TKI therapy were significantly correlated to inferior OS/EFS compared to grade 0-II AEs. CONCLUSION: Although long-term outcomes were similar in CML-CP patients treated with each TKI regardless of first-line TKI selection, severe AEs in first-line TKI therapy decreased their survival rates. Early change in TKIs is recommended, when faced with severe AEs of specific TKIs.

DOI： 10.1111/ejh.13081

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BACKGROUND: Patients undergoing hematopoietic stem cell transplantation (HSCT) frequently have HHV-6 reactivation typically during the early phase following HSCT. The long-term clinical complications and prognosis, however, remain unclear. METHODS: Between September 2010 and October 2012, whole blood samples from 105 patients collected weekly from prior to 6 weeks after HSCT underwent multiplex polymerase chain reaction (PCR) to screen for viral DNA, followed by real-time PCR for quantitative estimation. In 48 patients, only HHV-6 was detected in at least one sample. In 30 patients, no viral DNA was detected. Long-term clinical records were reviewed in March 2016. All 48 HHV-6-positive patients, and 24 patients in whom no viral DNA detected, were followed up. RESULTS: Median maximum HHV-6 DNA load in the blood of the HHV-6 reactivation group (n = 48) was 11 800 copies/μg peripheral blood leukocyte DNA (range, 52-310 000 000). Hemophagocytic syndrome (HPS) was diagnosed in two subjects with HHV-6 reactivation. Acute graft-versus-host disease (GVHD) developed more frequently in patients with HHV-6 reactivation than in patients without viral reactivation (P = 0.002), but there was no difference in incidence of chronic GVHD. There was no difference in engraftment of neutrophils and platelets between groups. There was also no difference in overall survival between groups. Onset of HPS, however, was associated with lower overall survival (P = 0.009). CONCLUSIONS: Human herpesvirus 6 reactivation was associated with acute GVHD, but not with chronic GVHD, engraftment or overall survival. Onset of HPS, however, predicts lower overall survival.

DOI： 10.1111/ped.13551

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DOI： 10.1007/s12185-017-2377-z

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BACKGROUND: Immune thrombocytopenic purpura (ITP) is commonly treated with i.v. immunoglobulin (IVIG). METHODS: We retrospectively evaluated whether pretreatment clinical and laboratory finding could predict the short- and long-term response to IVIG. RESULTS: Short-term response was estimated by platelet count 2 weeks after IVIG, and long-term response was assessed on thrombocytopenia-free survival (TFS). TFS was defined as the probability of survival without treatment failure after initial IVIG, such as relapse, requirement for additional therapeutic interventions, or progressing to chronic ITP. Seventy-six patients with newly diagnosed ITP who were initially treated with IVIG were evaluated. Fifty-three patients (69.7%) were determined as responders at 2 weeks after IVIG. On multivariate analysis, age ≥23 months (P = 0.020) and platelet count <9.0 × 109 /L (P = 0.018) were considered to be unfavorable factors for short-term response. Cumulative proportion of long-term (1 year) good prognosis was estimated at 53.0% (95%CI: 40.8-65.2). On multivariate analysis of unfavorable factors for long-term response, age ≥23 months (P = 0.020) was the only significant factor. CONCLUSIONS: For new-onset ITP in patients aged >2 years, corticosteroid therapy in addition to IVIG may be considered as the initial treatment.

DOI： 10.1111/ped.13505

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DOI： 10.1111/ped.13437

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We present a 4-yr-old boy with adrenocortical carcinoma (ACC), diagnosed due to the appearance of gynecomastia as the presenting symptom. Six months prior to admission, an acute growth spurt along with the development of bilateral breast swelling was observed. He did not present any features of virilization, including enlargement of the testes, increase in testis volume, and penis size. Laboratory investigations showed gonadotropin-independent hypergonadism, with low LH/ FSH levels and elevated estradiol/testosterone levels. Abdominal computed tomography revealed a large heterogeneous mass adjacent to the right kidney and below the liver. Pathological investigations of the biopsy specimen demonstrated that the tumor was an ACC. Pre- and post-operative combination chemotherapy with mitotane was administered and surgical resection was carried out. Post-surgery, the elevated estradiol/testosterone concentrations reverted to within the reference range. Urinary steroid profile and tissue concentration analysis of estradiol and testosterone indicated the presence of estrogen in the ACC tissue. An investigation for TP53 gene aberrations revealed the presence of a germline point mutation in exon 4 (c.215C>G (p.Pro72Arg)). In ACC, the most common symptom is virilization, and feminization, characterized by gynecomastia, is very rare. However, a diagnostic possibility of ACC should be considered when we encounter patients who have developed gynecomastia without the influence of causative factors such as obesity or puberty, and do not present with the typical signs of virilization.

DOI： 10.1297/cpe.27.9

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Several studies have indicated that viral reactivations following allogeneic hematopoietic stem cell transplantation (allo-HSCT) are frequent, but viral reactivations after autologous HSCT (auto-HSCT) have not been investigated in detail. We performed multiplex polymerase chain reaction (PCR) assay to examine multiple viral reactivations simultaneously in 24 patients undergoing auto-HSCT between September 2010 and December 2012. Weekly whole blood samples were collected from pre- to 42 days post-HSCT, and tested for the following 13 viruses; herpes simplex virus 1 (HSV-1), HSV-2, varicella-zoster virus (VZV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), human herpesvirus 6 (HHV-6), HHV-7, HHV-8, adeno virus (ADV), BK virus (BKV), JC virus (JCV), parvovirus B19 (B19V), and hepatitis B virus (HBV).  Fifteen (63%) patients had at least one type of viral reactivation. HHV6 (n = 10; 41.7%) was most frequently detected followed by EBV (n = 7; 29.2%). HHV-6 peaked on day 21 after HSCT and promptly declined. In addition, HBV, CMV, HHV7, and B19V were each detected in one patient. HHV6 reactivation was detected in almost half the auto-HSCT patients, which was similar to the incidence in allo-HSCT patients. The incidence of EBV was unexpectedly high. Viral infections in patients undergoing auto-HSCT were higher than previously reported in other studies. Although there were no particular complications of viral infection, we should pay attention to possible viral reactivations in auto-HSCT patients. J. Med. Virol. 89:358-362, 2017. © 2016 Wiley Periodicals, Inc.

DOI： 10.1002/jmv.24621

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Viral reactivation following hematopoietic stem cell transplantation (HSCT) can cause various complications especially viral encephalitis. In this prospective study, we investigated the correlation of post-HSCT viral reactivation in blood with CNS dysfunction. We employed a multiplex PCR that detects 13 kinds of viruses as a first-line screening test and real-time PCR for subsequent quantitative evaluation. Five hundred ninety-one whole blood samples were collected from 105 patients from before until 42 days after HSCT. Seven patients developed CNS dysfunction such as altered consciousness. In six of the seven, the multiplex PCR test detected HHV-6 DNA in at least one sample. In contrast, DNA from other viruses, such as CMV, EBV, HHV-7, adenovirus, and HBV was never detected in any of the seven patients throughout the study period. Quantitative measurement of whole blood HHV-6 DNA levels demonstrated four of the six HHV-6 DNA loads were elevated at successive time points during the CNS dysfunction. In addition, the virus DNA peaks were temporally associated with the development of CNS dysfunction. CSF was tested in two of the four patients and high HHV-6 DNA levels comparable to those in whole blood were confirmed in both. These four patients were, thus, suspected to have developed HHV-6 encephalitis, a rate of 3.8% in the study population. Our results suggest that early diagnosis of probable HHV-6 encephalitis can be improved by confirming high HHV-6 DNA load in blood.

DOI： 10.1002/jmv.24340

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Viral reactivations following hematopoietic stem cell transplantation are thought to result from the breakdown of both cell-mediated and humoral immunity. As a result, many viruses could be reactivated individually or simultaneously. Using a multiplex polymerase chain reaction (PCR), we prospectively examined many kinds of viral DNAs at a time in 105 patients who underwent allogeneic hematopoietic stem cell transplantation. In total, 591 whole blood samples were collected weekly from pre- to 42 days post-transplantation and the following 13 viruses were tested; herpes simplex virus 1 (HSV-1), HSV-2, varicella-zoster virus (VZV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), human herpes virus 6 (HHV-6), HHV-7, HHV-8, adenovirus, BK virus (BKV), JC virus (JCV), parvovirus B19, and hepatitis B virus (HBV). Several viral DNAs were detected in 12 patients before hematopoietic stem cell transplantation. The detection rate gradually increased after transplantation and peaked at 21 days. The most frequently detected virus was HHV-6 (n = 63; 60.0%), followed by EBV (n = 11; 10.5%), CMV (n = 11; 10.5%), and HHV-7 (n = 9; 8.6%). Adenovirus and HBV were each detected in one patient (1.0%). Detection of HHV-6 DNA was significantly more common among patients undergoing cord blood transplantation or with steroid treatment. EBV DNA tended to be more common in patients treated with anti-thymocyte globulin. Multiplex PCR was useful for detecting many viral reactivations after hematopoietic stem cell transplantation, simultaneously. Cord blood transplantation, steroid treatment, or anti-thymocyte globulin use was confirmed to be risk factors after transplantation.

DOI： 10.1002/jmv.24161

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In childhood acute myelogenous leukemia, extramedullary tumor is an occasional clinical symptom. However, extramedullary acute megakaryocytic leukemia is extremely rare. Here, we report an extremely rare case of acute megakaryocytic leukemia in a patient who presented with extramedullary tumor of cerebral falx as a first manifestation before the diagnosis of systemic bone marrow leukemia.

DOI： 10.1097/MPH.0000000000000153

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Hemophagocytic lymphohistiocytosis (HLH) is frequently lethal in its early phase due to complicating disseminated intravascular coagulation (DIC). The authors report a 14-mo-old girl with severe DIC complicating Epstein-Barr virus associated HLH. She was successfully treated with immunochemotherapy consisting mainly of etoposide and additional recombinant thrombomodulin (r-TM), a newly developed anticoagulant. Although the efficacy of r-TM cannot be proven in a single case report, additional anticoagulation therapy with r-TM is safe and may reduce early deaths in patients with DIC-complicated severe HLH. More clinical experience is required, although r-TM is currently licensed only in Japan.

DOI： 10.1007/s12098-013-1145-1

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Neuroblastoma is a malignant tumor predominantly occurring in children and usually arising from the adrenal gland or sympathetic ganglia. We describe a neuroblastoma in a 1-month-old boy arising from his left orbital cavity. This tumor was refractory to chemotherapy or radiotherapy, requiring enucleation of the left eye for complete removal of the intraorbital tumor. Thereafter, he received high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation, and has been in complete remission for 3 years. Unlike neuroblastomas arising from the adrenal gland or sympathetic ganglia, primary orbital neuroblastoma may be refractory even in early infancy.

DOI： 10.1111/ped.12239

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DOI： 10.1007/s12185-013-1285-0

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Hypocellular acute myeloid leukemia (AML) is extremely rare in childhood. We report on a 7-year-old girl with hypocellular AML who was treated successfully with granulocyte-colony stimulating factor (G-CSF) and combined chemotherapy. High-dose G-CSF induced complete remission and she subsequently received reduced intensity conditioning and unrelated cord blood transplantation; however, this resulted in early rejection. After a complete hematological recovery, she received 3 courses of combination chemotherapy oriented toward AML. She has remained in complete remission for over 1 year after the completion of the therapy. G-CSF effectively induced remission, and combination chemotherapy has been proven to be feasible for patients with childhood hypocellular AML.

DOI： 10.1097/MPH.0b013e3182388966

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Language：Japanese   Publishing type：Research paper (scientific journal)  

A girl, 7 years of age, was reported who had been suffered from migratory arthralgia, bone pain and erythematous rash. She had increased inflammatory markers such as C-reactive protein, erythrocyte sedimentation rate, and mild anemia for more than 6 months. In the beginning, she was suspected of having either juvenile idiopathic arthritis or chronic recurrent multifocal osteomyelitis. However, after about 6 months, there were abrupt increases of LDH in serum titers and blast cells were also revealed by bone marrow examination. Upon these findings, she was diagnosed with acute lymphocytic leukemia. Since bone pain and arthralgia bone pain and arthralgia are both indicative of numerous inflammatory disorders such as infectious myelitis, juvenile chronic arthritis, childhood leukemia and malignancies, and auto-inflammatory bone diseases, especially chronic recurrent multifocal osteomyelitis, it is difficult to accurately diagnose right away. For now, these aforementioned inflammatory responses are the sole key findings for clinical investigations. Other than that, there are not enough reports yet to help diagnose incases similar to this. Therefore, it is difficult to differentiate between the disorders above even after blood tests, Ga-scincigraphy, and imaging examinations. Moreover, in the case of childhood leukemia, it was difficult to differentiate these diseases by routine X-ray surveys in the general pediatric fields. The reasons are because there are only a few descriptions on X-ray bone examinations on findings of X-ray bone investigations, and both are usually non-specific. However, according to the pediatric radiology specialists, of which there are only a few in Japan, the imaging results show somewhat abnormal findings could be spotted from the early stage. Through this present case, it is suggested to us that it is important to consult the pediatric radiology specialists in order to speed up the diagnostic process. Furthermore, the accumulation of radiological findings of leukemia in children with bone pain and arthralgia will attribute to an early diagnosis and lead to the resolution of pathogenesis of leukemia.

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PTR is a serious problem in patients being treated for hematologic disorders. Two patients with acute leukemia developed PTR after allogeneic BMT from one HLA-antigen-mismatched mother attributable to HLA antibodies, which could not be detected in their serum before BMT. HLA antibodies, whose specificity resembled that of each patient, were detected in each donor's serum. Each donor had probably been immunized during pregnancy by their partner's HLA antigens expressed by the fetus, consequently, transplanted donor-derived cells provoked HLA antibodies in each recipient early after BMT, and those HLA antibodies induced PTR. If the mothers are selected as donors for their children, they should be tested for the presence of HLA antibodies.

DOI： 10.1111/j.1399-3046.2010.01365.x

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DOI： 10.1111/j.1442-200X.2011.03364.x

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OBJECTIVE: To elucidate the significance of early expression of CC-chemokine ligand motif 8 (CCL8) in mice with graft-vs.-host disease (GVHD), we investigated its induction mechanisms and correlation with overall survival rate in GVHD mice. Plasma CCL8 increases on day 5 of allogeneic transplantation, when signs of GVHD are barely detectable. Increase of allogeneic splenocytes in grafts exacerbates GVHD and leads to upregulation of plasma CCL8 on day 5. Overall survival is the gold standard in determining the severity of acute GVHD in mice, but the absence of clinical and/or pathological manifestations in the early phase make it difficult to estimate vital outcomes at this stage of allogeneic marrow transplantation. MATERIALS AND METHODS: After lethal irradiation, BALB/c mice received bone marrow transplantation from C57BL/6 mice. Survival rate was monitored and clinical and pathological scores of GVHD were examined. Coculture of BALB/c-derived dendritic cells and C57BL/6-derived splenocytes was performed. CCL8 was measured by immunoassay. RESULTS: The plasma CCL8 level at day 5 of transplantation was closely correlated with survival rate and clinical/pathological scores on day 14. In vitro study revealed that the BALB/c-derived dendritic cells expressed CCL8 upon stimulation of C57BL/6 CD4(+) T cells by cell interactions through major histocompatibility complex class II molecules. CONCLUSIONS: These investigations indicate that early and preclinical expression of CCL8 in plasma predicts overall survival of GVHD mice. Together with an involvement of allo-recognition in CCL8 expression, it suggests that CCL8 plays an important role in GVHD pathology.

DOI： 10.1016/j.exphem.2011.07.006

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Long-term venous access is essential when treating malignant diseases. We reviewed our experience with peripherally inserted central venous catheters (PICC) in children suffering from various malignancies with regard to catheter life, reasons for removal, and complications. Ninety-three PICCs were inserted in 78 children. Median catheter life was 162 days (range 6-575 days) with a total of 16,266 catheter days. Seventy-five PICCs (80.6%) had been placed until the elective removal or patients' death, whereas 18 PICCs (19.4%) were removed due to PICC-related complications; a rate of 1.11 per 1,000 catheter days. Complications requiring removal of PICCs included infection (n = 12), occlusion (n = 3), dislodgement (n = 2), and phlebitis (n = 1) with rates of 0.74, 0.18, 0.12 and 0.06 per 1,000 catheter days, respectively. We conclude that PICC provides reliable long-term intravenous access in children suffering from malignancies.

DOI： 10.1007/s12185-011-0928-2

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There is no existing data on UL97 mutation in human cytomegalovirus (HCMV) isolates obtained from individuals who have never been exposed to ganciclovir (GCV). UL97 codons 439 to 645 from 61 CMV isolates from 61 immunocompetent Japanese infants and children were sequenced directly. No known GCV resistance mutations were found, meaning that the UL97 mutation had resulted from the use of GCV. On the other hand, a mutation at codon 605 (D to E) was frequently identified (56/61: 91.8%). This could be a genetic marker for HCMV in East Asian counties, because of its low prevalence in the strains of HCMV circulating in Western countries.

DOI： 10.1111/j.1348-0421.2011.00327.x

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The prognosis of multisystem LCH in children with risk organ involvement is extremely poor when they fail to respond to conventional chemotherapy. In such patients, allogeneic SCT may produce complete and sustained remission; however, high-dose myeloablative regimens are frequently associated with treatment-related morbidity and mortality. More recently, allogeneic SCT following an RIC regimen has been performed as an alternative salvage approach. We describe a nine-month-old boy with refractory multisystem LCH with pulmonary aspergillosis who was successfully treated with reduced-intensity cord blood transplantation.

DOI： 10.1111/j.1399-3046.2008.01124.x

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Thymic involvement with Langerhans cell histiocytosis (LCH) typically occurs in children as part of multi-system (M-S) LCH. Patients who develop skin-only LCH during infancy may either follow a self-healing course with spontaneous regression or may progress to M-S involvement. We describe a male infant who developed isolated thymic LCH after spontaneous complete regression of isolated cutaneous lesions. His erythrocyte sedimentation rate and C-reactive protein increased temporarily during the skin-only stage of LCH, and increased again considerably during the thymic relapse. Even for patients with skin-only LCH, these laboratory data might indicate possible relapse or late progression of the disease.

DOI： 10.1002/pbc.22026

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Some infants with acute immune thrombocytopenic purpura (ITP) do not respond to first-line therapy, and currently there is no consensus on therapy for these refractory cases. We describe a 12-week-old infant with acute ITP who was unresponsive to intravenous immunoglobulin and corticosteroid, and developed gastrointestinal bleeding. Several combination therapies were unsuccessful. After four doses of rituximab followed by intravenous immunoglobulin and corticosteroid, his platelet counts gradually increased. Combined therapy which includes rituximab may be a promising treatment for severe acute refractory ITP.

DOI： 10.1002/pbc.22036

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DOI： 10.1111/j.1348-0421.2009.00129.x

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OBJECTIVE: Using a proteomic approach, we recently identified plasma CCL8 as a potential biomarker for diagnosis of graft-vs-host-disease (GVHD) in mice as well as humans. Because mass spectrometric analysis is only semi-quantitative, a quantitative method of measuring plasma CCL8 levels in mice is needed. MATERIALS AND METHODS: We established an enzyme-linked immunosorbent assay for the quantitative measurement of CCL8 concentrations in mouse plasma. RESULTS: Our newly established enzyme-linked immunosorbent assay revealed that the plasma CCL8 concentrations (mean +/- standard error; n=12) were 1287+/-55.7 ng/mL and 1604+/-110.8 ng/mL on days 7 and 14 after allogeneic bone marrow transplantation (BMT), respectively, while the plasma concentrations was 316.6+/-16.3 ng/mL on day 7 after syngeneic BMT. A Western blotting analysis also showed a difference in the plasma CCL8 levels between the allogeneic and syngeneic BMT groups, as did clinical GVHD scores. Neither lipopolysaccharide nor poly(I:C) elevated the plasma CCL8 concentrations, although a dramatic increase in interleukin-6 was detected after both treatments. CONCLUSION: An elevated plasma CCL8 concentration may be a promising plasma marker for GVHD in mouse models.

DOI： 10.1016/j.exphem.2008.12.006

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Polyoma BK virus (BKV) is frequently found in the urine of stem cell transplantation (SCT) patients with hemorrhagic cystitis (HC), but also occurs in SCT patients without HC. How BK viruria relates to the development of HC in SCT patients, especially in children, has not yet been fully evaluated. In the present study, we analyzed the relationship of several factors including urinary BKV load to HC development in children and adults undergoing SCT. We employed a quantitative PCR assay and evaluated 37 patients (aged 9 months-62 years) of whom 12 developed HC and 25 did not. Older age was a risk factor for the development of HC; however, other factors such as sex, primary disease, type of SCT, conditioning regimen and aGVHD were not. Peak urinary BKV values in HC patients were not higher than those in non-HC patients. Severity of HC also did not correlate with urinary BKV loads. However, in some patients who secreted higher urinary BKV loads, the peak loads were closely related with the onset of HC. Higher BKV loads may be a risk factor for the development of HC in conjunction with other coexisting factors.

DOI： 10.1002/jmv.21328

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Although graft-versus-host disease (GVHD) is a life-threatening complication of hematopoietic stem-cell transplantation (HSCT), its current diagnosis depends mainly on clinical manifestations and invasive biopsies. Specific biomarkers for GVHD would facilitate early and accurate recognition of this grave condition. Using proteomics, we screened for plasma proteins specific for GVHD in a mouse model. One peak with 8972-Da molecular mass (m/z) retained a discriminatory value in 2 diagnostic groups (GVHD and normal controls) with increased expression in the disease and decreased expression during cyclosporin A treatment, and was barely detectable in syngeneic transplantation. Purification and mass analysis identified this molecule as CCL8, a member of a large chemokine family. In human samples, the serum concentration of CCL8 correlated closely with GVHD severity. All non-GVHD samples contained less than 48 pg/mL (mean +/- SE: 22.5 +/- 5.5 pg/mL, range: 12.6-48.0 pg/mL, n = 7). In sharp contrast, CCL8 was highly up-regulated in GVHD sera ranging from 52.0 to 333.6 pg/mL (mean +/- SE: 165.0 +/- 39.8 pg/mL, n = 7). Strikingly, 2 patients with severe fatal GVHD had extremely high levels of CCL8 (333.6 and 290.4 pg/mL. CCL8 is a promising specific serum marker for the early and accurate diagnosis of GVHD.

DOI： 10.1182/blood-2007-06-097287

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Although pure red cell aplasia is a well-known side effect of carbamazepine treatment, intravascular hemolytic anemia is rare. We describe a 5-year-old boy who developed concurrent intravascular hemolytic anemia and erythroblastopenia, probably due to carbamazepine. Carbamazepine treatment was subsequently discontinued, and the patient was treated with red blood cell transfusions, haptoglobin, and methylprednisolone. His hematologic abnormalities were almost fully recovered within 2 weeks. Examination of the patient's and mother's erythrocyte enzyme activities revealed mildly decreased erythrocyte glutathione peroxidase (GSH-Px) activity. We speculate that patients with reduced GSH-Px activity are at a high risk of developing carbamazepine-induced hemolytic crisis and/or aplastic crisis.

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Adenovirus infection during stem cell transplantation is associated with high morbidity and mortality. Adenovirus species B and C have been the main causes for these infections; however, epidemiological details about the species are still unclear. To clarify the contributions of species B and C adenovirus, the DNA was tested serially by quantitative real-time PCR in peripheral blood, stool and urine of 32 patients (16 adults and 16 children) undergoing stem cell transplantation. Adenovirus species B viremia was detected in 10 of 16 adult and 6 of 16 pediatric transplant recipients. Adenovirus species C viremia was also detected simultaneously in five adult and three pediatric recipients. The stool and urine of patients with adenovirus viremia were also positive for the same adenovirus species as in blood. In contrast, in none of 50 healthy adult controls was adenovirus species B or C viremia detected. Among patients who developed adenovirus viremia, one adult recipient developed disseminated disease and died from multiple organ failure. The remaining patients experienced fever of several degrees and/or diarrhea during the period of adenovirus viremia; however, they all recovered without antiviral therapy. The results indicated that stem cell transplantation was frequently associated with adenovirus species B or C viremia, although it did not always cause serious infectious complications.

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Patients with chronic granulomatous disease (CGD) complicated by antimycotics-refractory invasive aspergillosis have an extremely poor prognosis if they cannot undergo allogeneic hematopoietic stem cell transplantation from a suitable related donor while in good clinical condition. We successfully treated a 20-year-old man with very rare McLeod phenotype CGD with reduced-intensity conditioning and unrelated-donor umbilical cord blood transplantation. We postulate that reduced-intensity conditioning-allogeneic hematopoietic stem cell transplantation is a promising therapeutic strategy for patients with CGD even if only unrelated-donor umbilical cord blood is available.

PubMed

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Language：English   Publishing type：Research paper (scientific journal)  

The prognosis of stage IV malignant rhabdoid tumor of the kidney (MRTK) has been extremely poor. However, a combination of ICE (ifosfamide, carboplatin, and etoposide) and VDCy (vincristine, doxorubicin, and cyclophosphamide) was recently reported to be effective for metastatic MRTK. We describe a 21-month-old girl with stage IV MRTK who was successfully treated with ICE, VDCy, and radiotherapy. She remained well, without recurrence, 24 months after diagnosis. Alternating therapy with ICE and VDCy might become a standard regimen for stage IV MRTK, although further study is required to confirm its effectiveness.

PubMed

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Language：English   Publishing type：Research paper (scientific journal)  

The development of hemorrhagic cystitis (HC) and urinary excretion of polyoma BK virus (BKV) and adenovirus (ADV) was investigated by polymerase chain reaction in 20 children undergoing allogeneic stem cell transplantation. Five children developed HC, and all of them excreted BKV; however, only 1 excreted ADV, suggesting that BKV is more significant cause of HC than ADV in children undergoing stem cell transplantation.

PubMed

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Language：English   Publishing type：Research paper (scientific journal)  

PubMed

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Language：Japanese  

Other Link:： http://search.jamas.or.jp/link/ui/2007347952

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Language：Japanese  

Other Link:： http://search.jamas.or.jp/link/ui/2007347948

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Language：Japanese  

Other Link:： http://search.jamas.or.jp/link/ui/2007312847

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Language：Japanese   Publisher：小児愛育協会  

Other Link:： http://search.jamas.or.jp/link/ui/2006221972

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Language：Japanese   Publisher：がんの子供を守る会  

Other Link:： https://projects.repo.nii.ac.jp/?action=repository_uri&item_id=262368

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Language：Japanese   Publisher：The Japanese Society of Hematology  

Transient abnormal myelopoiesis (TAM) is usually a self-limiting myeloproliferative disorder observed in approximately 10% of newborn infants with Down syndrome. However, progressive liver fibrosis may occur in patients with TAM and is often lethal. We investigated the utility of the serum levels of hyaluronic acid (HA) and N-terminal peptide of III procollagen (P-III-P) as markers of liver fibrosis and indication for chemotherapy. We reviewed 4 cases of TAM retrospectively. HA levels were more than one hundred times as high as the upper limit of the normal range in 2 patients, one of whom died from gastrointestinal bleeding. His HA and P-III-P had increased up to 18,800 U/m<i>l</i> and 26.2 ng/m<i>l</i>, respectively, just before he died. Another patient's serum HA and P-III-P increased to 6,100 U/m<i>l</i> and 12.8 ng/m<i>l</i>, respectively, however his liver fibrosis resolved with low-dose cytosine arabinoside treatment after exchange transfusion during his clinical course. We suggest that serum HA is useful as a marker of liver fibrosis and a prognostic indicator for chemotherapy in patients with TAM. Early treatment including both exchange transfusion and chemotherapy should be considered for patients presenting with extremely high or an elevating tendency of their HA serum levels.

Other Link:： http://search.jamas.or.jp/link/ui/2006091515

DOI： 10.11406/rinketsu.46.1179

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