Nobuhiro Suzuki

Sapporo Medical University, Sapporo-shi, Hokkaido, Japan

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Publications (36)81.24 Total impact

  • Article: Multiple intracranial tumors in Philadelphia chromosome-positive acute lymphoblastic leukemia.
    International journal of hematology 03/2013; · 1.17 Impact Factor
  • Article: Epidemiology and treatment outcome of invasive fungal infections in patients with hematological malignancies.
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    ABSTRACT: Invasive fungal infection (IFI) causes morbidity and mortality among patients with hematological malignancies who receive cytotoxic chemotherapy or hematopoietic stem cell transplantation (HSCT). We evaluated the incidence and treatment outcomes of proven and probable IFI in 22 institutions between 2006 and 2008 following the recent European Organization for Research and Treatment of Cancer/Mycosis Study Group (EORTC/MSG) consensus criteria. We analyzed 2,821 patients with hematological malignancies, including 597 who had undergone HSCT; these included patients with acute leukemia (n = 697), myelodysplastic syndrome (n = 284), lymphoma (n = 1465), or multiple myeloma (n = 375). IFIs were diagnosed in 38 (1.3%) patients (18 proven and 20 probable), including 20 patients who underwent HSCT and 18 who received chemotherapy alone; these included patients with aspergillosis (n = 23), candidiasis (n = 6), mucormycosis (n = 6), trichosporonosis (n = 2), and geotrichosis (n = 1). The incidence of IFI was 5.4 % in allogeneic HSCT patients, 0.4 % in autologous HSCT patients, and 0.8 % in patients receiving chemotherapy alone. Eighteen patients with aspergillosis were diagnosed with probable pulmonary IFI as determined by computed tomography scan and positive galactomannan assay. Overall, antifungal targeted therapies resulted in successful outcomes in 60.0 % of patients. IFI-attributable mortality rate was higher in HSCT patients than in those receiving chemotherapy alone, but the difference was not statistically significant.
    International journal of hematology 10/2012; · 1.17 Impact Factor
  • Article: Reduced-intensity conditioning in unrelated donor cord blood transplantation for familial hemophagocytic lymphohistiocytosis.
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    ABSTRACT: Familial hemophagocytic lymphohistiocytosis (FHL) is a disorder of immune homeostasis characterized by fever, cytopenias, hepatosplenomegaly, and coagulopathy. We studied the outcomes of 13 FHL patients who underwent the first unrelated cord blood transplantation (UCBT) after non-myeloablative conditionings. The major regimen consisted of fludarabine (FLU; n = 12)+melphalan (MEL; n = 11)± low-dose total body irradiation (TBI 2-4 Gy; n = 6). The median age at presentation and period to UCBT were 6 and 5 months, respectively. Central nervous system (CNS) disease developed in one infant at diagnosis, and in two others until UCBT. HLH activity was controlled in all but one at the time of UCBT. Ten patients had early engraftment on median day 21 with no grade >2 treatment-related toxicity and two controllable grade >2 acute GVHD. Two patients with early rejection successfully underwent subsequent UCBT after myeloablative conditioning. Two others had late graft failure following mixed donor chimerism. Two deaths occurred from HLH; early liver failure and late CNS disease. Of 11 FLU+MEL-conditioned patients, the frequency of disease-free complete engraftment was higher for MEL (≥120 mg/m(2) )+TBI, or high-dose MEL (180 mg/m(2) ) than for others (83% vs. 25%, p = 0.036). The FLU+MEL-based non-myeloablative regimen was acceptable for FHL infants undergoing UCBT, although further studies will be needed for confirmation.
    American Journal of Hematology 03/2012; 87(6):637-9. · 4.67 Impact Factor
  • Article: Infantile acute promyelocytic leukemia without an RARα rearrangement.
    Pediatrics International 12/2011; 53(6):1070-3. · 0.63 Impact Factor
  • Article: Hemophagocytic lymphohistiocytosis after hematopoietic stem cell transplantation in children: a nationwide survey in Japan.
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    ABSTRACT: Hemophagocytic lymphohistiocytosis (HLH) is associated with hypercytokinemia in children. Although HLH can be also observed after hematopoietic stem cell transplantation (HSCT), the incidence and clinical features of HLH after HSCT remain obscure. The clinical features of HLH after HSCT (post-HSCT HLH) were investigated in children with malignancies, immune deficiencies, or aplastic anemia. The HLH/Langerhans Cell Histiocytosis (LCH) Committee of the Japanese Society of Pediatric Hematology (JSPH) sent questionnaires to hospitals with JPSH members asking for details of cases in which HLH occurred after HSCT between 1998 and 2008. Among 42 children who were diagnosed with post-HSCT HLH between 1998 and 2008 in Japan, 37 fulfilled our inclusion criteria; of these, 26 were classified as early-onset (onset <30 days after HSCT) and 11 were classified as late-onset (onset >30 days after HSCT). In the early-onset group, the presence of respiratory symptoms, high levels of total bilirubin, and triglycerides at onset and the lack of control of GVHD with tacrolimus were significantly associated with non-resolution of HLH (P < 0.05). The survival rate was significantly higher in patients with resolution of HLH than in those without resolution (59% vs. 14%, P < 0.05). These findings suggest that early-onset post-HSCT HLH is a specific entity of HLH, and appropriate diagnosis and prompt management need to be established.
    Pediatric Blood & Cancer 10/2011; 59(1):110-4. · 1.89 Impact Factor
  • Article: An evaluation of peripherally inserted central venous catheters for children with cancer requiring long-term venous access.
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    ABSTRACT: 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.
    International journal of hematology 09/2011; 94(4):372-7. · 1.17 Impact Factor
  • Article: Early expression of plasma CCL8 closely correlates with survival rate of acute graft-vs.-host disease in mice.
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    ABSTRACT: 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. 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. 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. 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.
    Experimental hematology 07/2011; 39(11):1101-12. · 3.11 Impact Factor
  • Article: Human cytomegalovirus UL97 D605E polymorphism has a high prevalence in immunocompetent Japanese infants and children.
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    ABSTRACT: 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.
    Microbiology and Immunology 03/2011; 55(5):328-30. · 1.30 Impact Factor
  • Article: Platelet transfusion refractoriness attributable to HLA antibodies produced by donor-derived cells after allogeneic bone marrow transplantation from one HLA-antigen-mismatched mother.
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    ABSTRACT: 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.
    Pediatric Transplantation 09/2010; 15(8):E177-82. · 1.48 Impact Factor
  • Article: Outcome of childhood acute lymphoblastic leukemia with induction failure treated by the Japan Association of Childhood Leukemia study (JACLS) ALL F-protocol.
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    ABSTRACT: Children with acute lymphoblastic leukemia (ALL) who fail to achieve complete remission (CR) after induction therapy (induction failure: IF) have a poor prognosis; however, there have been few prospective studies in patients with IF. Between April 1997 and March 2005, 27 of 1,237 leukemic patients (2.2%) failed to achieve CR after four- or five-drug induction therapy. Twenty-three of these patients entered the F-protocol study, which mainly consisted of acute-myeloid-leukemia-oriented chemotherapy followed by scheduled hematopoietic cell transplantation (HCT). Seventeen (73.9%) of the 23 patients responded to re-induction chemotherapy with CR. Of note, 15 (93.8%) of 16 patients with Philadelphia-chromosome-negative (non-Ph(+)) ALL achieved CR; in contrast, only 2 (28.6%) of 7 Ph(+) patients achieved CR. Fourteen (82.4%) of 17 patients remained in CR (CCR) until their scheduled HCT, 12 of the 14 with CCR underwent HCT as scheduled, and 6 patients remain in first CR after a median of 78 months (range, 49-107 months). The 5-year overall survival (OS) rates of 16 patients with non-Ph(+) and 7 patients with Ph(+) were 43.8 +/- 12.4% and 14.3 +/- 13.2%, respectively (P = 0.012). The 5-year OS rate of the 17 patients who obtained CR by re-induction therapy and the 6 who did not were 47.1 +/- 12.1% and 0%, respectively (P < 0.001). Acute-myeloid-leukemia-oriented chemotherapy followed by scheduled HCT is a promising treatment strategy for non-Ph(+) ALL patients with IF.
    Pediatric Blood & Cancer 10/2009; 54(1):71-8. · 1.89 Impact Factor
  • Article: Hematopoietic stem cell transplantation for familial hemophagocytic lymphohistiocytosis and Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis in Japan.
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    ABSTRACT: Post-transplant outcomes of hemophagocytic lymphohistiocytosis (HLH) patients were analyzed in Japan where Epstein-Barr virus (EBV)-associated severe forms are problematic. Fifty-seven patients (43 familial HLH [12 FHL2, 11 FHL3, 20 undefined], 14 EBV-HLH) who underwent stem cell transplantation (SCT) between 1995 and 2005 were enrolled based on the nationwide registration. Fifty-seven patients underwent 61 SCTs, including 4 consecutive SCTs. SCTs were employed using allogeneic donors in 93% of cases (allo 53, twin 1, auto 3). Unrelated donor cord blood transplantation (UCBT) was employed in half of cases (21 FHL, 7 EBV-HLH). Reduced intensity conditioning was used in 26% of cases. The 10-year overall survival rates (median +/- SE%) were 65.0 +/- 7.9% in FHL and 85.7 +/- 9.4% in EBV-HLH patients, respectively. The survival of UCBT recipients was >65% in both FHL and EBV-HLH patients. Three out of four patients were alive with successful engraftment after second UCBT. FHL patients showed a poorer outcome due to early treatment-related deaths (<100 days, seven patients) and a higher incidence of sequelae than EBV-HLH patients (P = 0.02). The risk of death for FHL patients having received an unrelated donor bone marrow transplant was marginally higher than that for a related donor SCT (P = 0.05) and that for UCBT (P = 0.07). EBV-HLH patients had a better prognosis after SCT than FHL patients. FHL patients showed either an equal or better outcome even after UCBT compared with the recent reports. UCB might therefore be acceptable as an alternate SCT source for HLH patients, although the optimal conditioning remains to be determined.
    Pediatric Blood & Cancer 10/2009; 54(2):299-306. · 1.89 Impact Factor
  • Article: Nationwide survey of single-system single site Langerhans cell histiocytosis in Japan.
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    ABSTRACT: Since neither a standard treatment nor a protocol study for single-system single site (SS-s)-type Langerhans cell histiocytosis (LCH) exists, we conducted a nationwide survey in Japan to clarify the epidemiology and clinical outcome of this subtype. Questionnaires regarding the clinical course of children with SS-s-type LCH diagnosed between 1995 and 2006 were sent to all members of the Japanese Society of Pediatric Hematology. One hundred forty-six children with histologically proven SS-s LCH were evaluable. The most frequently affected organ was bone (82%), followed by skin (12%). Few patients (14%) had a CNS-RISK lesion defined by the Histiocyte Society. Patients with a skin lesion were diagnosed at a significantly younger age than patients with a bone lesion (median: 6 months vs. 5 years 11 months, P < 0.001). The treatment regimen varied, but one-third of the patients in total and 71% of patients with a CNS-RISK lesion received chemotherapy that did not include etoposide. All but one patient attained remission. Ten patients (7%) showed reactivation. Of these, all eight with an initial bone lesion only exhibited reactivation in the bone(s). One patient with an initial skin lesion exhibited reactivation in the thymus. None of the patients died from disease progression or treatment complications. Our retrospective study, in which a relatively large proportion of the patients received chemotherapy, reveals that patients with SS-s LCH have a good prognosis. A prospective study should be conducted to confirm this and to identify the most effective and least toxic therapy for SS-s LCH.
    Pediatric Blood & Cancer 09/2009; 54(1):98-102. · 1.89 Impact Factor
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    Article: Incidence and risk of postherpetic neuralgia after varicella zoster virus infection in hematopoietic cell transplantation recipients: Hokkaido Hematology Study Group.
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    ABSTRACT: To assess the incidence of and risk factors associated with postherpetic neuralgia (PHN) after hematopoietic cell transplantation (HCT) varicella zoster virus (VZV) infection, we conducted a retrospective chart review of 418 consecutive patients who underwent HCT between April 2005 and March 2007. The male/female ratio was 221/197, median age at HCT was 47 years (range: 0-69 years), and autologous/allogeneic/syngeneic HCT ratio was 154/263/1. Seventy-eight patients developed VZV infection after HCT. Sixty-two patients had localized zoster, 11 patients had disseminated zoster (rash like chicken pox), and 4 patients had visceral zoster. All cases were treated with acyclovir (ACV) or valacyclovir (VACV), and there was no VZV infection-related death. Twenty-seven (35%) of the 78 patients with VZV infection suffered PHN after resolution of VZV infection. Multivariate analysis showed that advanced age is the only risk factor in autologous HCT (P = .0075; odds ratio [OR] = 1.14; 95% confidence interval [CI], 0.97-1.33). On the other hand, advanced age (P = .0097; OR = 1.06; 95% CI, 1.01-1.12), male gender (P = .0055; OR = 12.7; 95% CI, 1.61-100.1), and graft-versus-host disease (GVHD) prophylaxis with a tacrolimus-based regimen (P = .0092; OR = 9.56; 95% CI, 1.44-63.3) were associated with increased risk of PHN in allogeneic HCT. This study for the first time clarified the risk of PHN in HCT recipients.
    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 07/2009; 15(6):724-9. · 3.15 Impact Factor
  • Article: Occurrence of the African subgroup (Ia) of BK polyomavirus in younger Japanese children.
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    ABSTRACT: BK polyomavirus (BKV) is ubiquitous among humans, usually infecting them asymptomatically during childhood. BKV persists in renal tissue of individuals and their progeny are excreted in urine, particularly in immunocompromised patients. JC virus, another human polyomavirus, has been considered to be transmitted from parents to children during prolonged cohabitation. However, BKV has been supposed to be transmitted not only within but also outside the family. In the present study, to clarify this possibility, we analyzed phylogenetically 35 BKV which were excreted in the urine by Japanese children and adults undergoing stem cell transplantation. Subtypes I, III and IV were detected in 15, two and one children and in 15, one and one adults, respectively. Among 15 subtype I isolates from children, three, four and eight belonged to subgroups Ia, Ib-1 and Ic, respectively. All the three children from whom Ia was detected were less than 9 years old. In contrast in the adults, three subtype I belonged to Ib-1 and the other 12 to Ic. These findings may reflect the recent transmission of BKV Ia strains to Japanese children.
    Microbiology and Immunology 07/2009; 53(6):319-22. · 1.30 Impact Factor
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    Article: Characteristics of hemophagocytic lymphohistiocytosis in neonates: a nationwide survey in Japan.
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    ABSTRACT: To assess the etiology, prognosis, and appropriate treatment of hemophagocytic lymphohistiocytosis (HLH) in neonates. We collected information on neonates in whom HLH was diagnosed between 1997 and 2007 from participating members of the Japanese Society of Pediatric Hematology. HLH was diagnosed in 20 patients within 4 weeks after birth. Of the diagnostic criteria for HLH-2004, the incidence of fever was quite low in preterm infants, and hypertriglyceridemia and neutropenia were uncommon. Familial HLH (n = 6) or severe combined immunodeficiency-associated HLH (n = 1) was diagnosed in 7 patients, and 2 of them have survived. Herpes simplex virus-associated HLH was diagnosed in 6 patients, and 2 of them have survived. The overall survival rate for the 20 patients was 40%. HLH is rare in neonates and has a poor prognosis. Early diagnosis and immediate treatment are required when considering the possibility of herpes simplex virus-associated or familial HLH.
    The Journal of pediatrics 06/2009; 155(2):235-8.e1. · 4.02 Impact Factor
  • Article: An infant with self-healing cutaneous Langerhans cell histiocytosis followed by isolated thymic relapse.
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    ABSTRACT: 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.
    Pediatric Blood & Cancer 05/2009; 53(2):229-31. · 1.89 Impact Factor
  • Article: Treatment of an infant with severe acute refractory immune thrombocytopenic purpura using combination therapy including rituximab.
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    ABSTRACT: 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.
    Pediatric Blood & Cancer 04/2009; 53(2):203-5. · 1.89 Impact Factor
  • Article: FBXW7 and NOTCH1 mutations in childhood T cell acute lymphoblastic leukaemia and T cell non-Hodgkin lymphoma.
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    ABSTRACT: Mutation analysis of FBXW7 and NOTCH1 genes was performed in 55 T cell acute lymphoblastic leukaemia (T-ALL) and 14 T cell non-Hodgkin lymphoma (T-NHL) patients who were treated on the Japan Association of Childhood Leukaemia Study (JACLS) protocols ALL-97 and NHL-98. FBXW7 and/or NOTCH1 mutations were found in 22 (40.0%) of 55 T-ALL and 7 (50.0%) of 14 T-NHL patients. FBXW7 mutations were found in 8 (14.6%) of 55 T-ALL and 3 (21.4%) of 14 T-NHL patients, and NOTCH1 mutations in 17 (30.9%) of 55 T-ALL and 6 (42.9%) of 14 T-NHL patients. Three (5.4%) T-ALL and two (1.4%) T-NHL patients had mutations in both FBXW7 and NOTCH1. FBXW7 mutations included one insertion, one deletion, one deletion/insertion and nine missense mutations. NOTCH1 mutations were detected in the heterodimerization domain (HD) in 15 cases, in the PEST domain in seven cases, and in both the HD and PEST domains in one case. Five-year event-free survival and overall survival for patients with FBXW7 and/or NOTCH1 mutations were 95.5% (95% CI, 71.9-99.4%) and 100% respectively, suggesting that T-ALL patients with FBXW7 and/or NOTCH1 mutation represent a good prognosis compared to those without FBXW7 and/or NOTCH1 mutations (63.6%, P = 0.007 and 78.8%, P = 0.023, respectively).
    British Journal of Haematology 03/2009; 145(2):198-206. · 4.94 Impact Factor
  • Article: Successful treatment of refractory Langerhans cell histiocytosis with pulmonary aspergillosis by reduced-intensity conditioning cord blood transplantation.
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    ABSTRACT: 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.
    Pediatric Transplantation 02/2009; 14(3):E4-10. · 1.48 Impact Factor
  • Article: Quantification of BK polyoma viruria in Japanese children and adults with hemorrhagic cystitis complicating stem cell transplantation.
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    ABSTRACT: 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.
    Journal of Medical Virology 01/2009; 80(12):2108-12. · 2.82 Impact Factor