Akinobu Matsuzaki

Kyushu University, Hukuoka, Fukuoka, Japan

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Publications (102)226.14 Total impact

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    ABSTRACT: Two consecutive treatment protocols, NHL-89 and NHL-96, for pediatric diffuse large cell lymphoma (DLC) and lymphoblastic lymphoma (LBL) were conducted between March 1989 and December 2004 by Kyushu-Yamaguchi Children's Cancer Study Group. Forty-two patients (DLC: 15, LBL: 27) and 34 patients (DLC: 8, LBL: 26) were enrolled in NHL-89 and NHL-96, respectively. DLC patients received induction therapy of high-dose methotrexate (MTX) followed by repeated administration of intermediate MTX. LBL patients received a 4-drug induction followed by intensification, consolidation with cranial radiotherapy (15 to 24Gy), and maintenance. The maintenance phase consisted of multiple drug treatment; including prednisolone, vincristine, cyclophosphamide, and 6-mercaptopurine. With a median follow-up of 150 months for NHL-89 and 90.5 months for NHL-96, the estimated event-free survival at 5 years are 76.2±6.6% and 67.7±8.0%, respectively. Both studies improved the prognosis of DLC and LBL over our previous study of NHL-858.
    [Rinshō ketsueki] The Japanese journal of clinical hematology 11/2012; 53(11):1898-905.
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    ABSTRACT: A total of 201 pediatric cases of acute lymphoblastic leukemia were treated with the ALL-96 protocol by the Kyushu-Yamaguchi Children's Cancer Study Group. Risk stratification was based on white cell counts, immunophenotype, the presence of central nervous system disease at diagnosis, organomegaly, and early treatment response (day 14 bone marrow status). All of the patients were classified into standard-risk (SR) or high-risk (HR) groups and were randomly assigned to receive maintenance therapy with either LSA2L2-type or 6-mercaptopurine (6-MP)/methotrexate (MTX) with vincristine (VCR) and dexamethasone (DEX) pulse in both risk groups. The 7-year event-free survival (EFS) and overall survival (OS) rates in the entire study population were 72.1% (95% CI: 68.0-76.2%) and 84.8% (95% CI: 79.7-89.9%), respectively, and the EFS of the SR patients (85.3% [95% CI: 78.2-92.4%]) was significantly better than HR patients (62.4% [95% CI: 52.2-72.6%]) (P = 0.0007). There were no differences in the EFS between the different maintenance therapies in each risk group; however, grade IV liver toxicity occurred more often in the patients receiving 6-MP/MTX with VCR and DEX therapy than in patients receiving LSA2L2.
    Pediatric Blood & Cancer 08/2010; 55(2):239-47. DOI:10.1002/pbc.22528 · 2.56 Impact Factor
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    ABSTRACT: This case study made use of semistructured interviews and a social network map to explore how adolescents with cancer develop resilience during the cancer experience. Seven adolescents with cancer aged 11 to 18 years and their mothers participated in this research. Pattern-matching logic using a 4-stage Self-Sustaining Process Model was applied to arrive at a comparative analysis. Findings indicated that initially, 5 adolescents who were told of their cancer diagnoses moved through the process during the cancer experience. Also, in newly diagnosed adolescents and in those who experienced relapse, a slight difference was noticed in terms of their response to studies and their hope levels. Second, 2 adolescents who were told of their diagnoses indirectly did not experience a complete passage through the phases comprising the process. Finally, the adolescents received social support from their families, friends, and relatives. This study suggests that an understanding of individual and cultural differences is important to improve resilience in adolescents with cancer. Because of the small sample surveyed by this research, further studies are needed to validate these conclusions and develop appropriate nursing intervention techniques.
    Journal of Pediatric Oncology Nursing 02/2010; 27(2):73-93. DOI:10.1177/1043454209356786 · 0.87 Impact Factor
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    ABSTRACT: The mass screening (MS) for neuroblastoma (NB) at 6 months of age in Japan was discontinued in 2004. This study assessed the risks and benefits of MS based on an analysis of NB detected before or after discontinuation of MS in Japan. The clinical features and Brodeur's genetic type based on MYCN, DNA ploidy, and other genetic aberrations were assessed in 113 NB patients (20 cases after and 93 cases [55 MS cases] before the discontinuation of MS) older than 6 months treated at one institution since 1985. The 20 patients with NBs detected after MS was discontinued ranged in age from 7 to 67 months, 12 patients were stage 4, and 11 patients would have been detected at 6 months of age if they had undergone MS. The Brodeur's genetic type of these 20 patients showed that 30% (6/20) were type 1 (low risk), 55% (11/20) were type 2A (intermediate risk), and 15% (3/20) were type 2B (high risk). Of 93 patients with NB detected before MS was discontinued, 60% (56/93) were type 1, 18% (17/93) were type 2A, and 22% (20/93) were type 2B. Among the type 2A patients, 82% (9/11) of the patients detected after MS was discontinued showed stage 4, whereas only 50% (9/18) of those diagnosed before MS was discontinued were stage 4. The genetic analysis using single nucleotide polymorphism (SNP) array for type 2A showed that the pattern of genetic aberration was equivalent in those detected either before or after MS was discontinued. There was a decrease of type 1 and an increase of type 2A NB in patients after MS was discontinued in Japan. These results suggest that most of the type 1 detected by MS has regressed, and most of the type 2A detected by MS has appeared sporadically as advanced NB in patients older than 1 year.
    Journal of Pediatric Surgery 12/2009; 44(12):2253-7. DOI:10.1016/j.jpedsurg.2009.07.050 · 1.31 Impact Factor
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    ABSTRACT: A 5-month-old male with stage II malignant rhabdoid tumor of the kidney (MRTK) and a 24-month-old male with stage III MRTK were treated with surgical resection of tumors and chemotherapy of alternating ICE (ifosfamide, carboplatin, and etoposide) and VDC (vincristine, doxorubicin, and cyclophosphamide), followed by high-dose chemotherapy using etoposide, carboplatin, and melphalan with autologous hematopoietic stem cell transplantation (SCT). Two patients have been alive without any evidence of disease for 30 and 37 months after diagnosis, respectively, and require no medication. Consolidation with SCT should be further studies for selected patients with high-risk MRTK.
    Pediatric Blood & Cancer 07/2009; 52(7):888-90. DOI:10.1002/pbc.21958 · 2.56 Impact Factor
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    ABSTRACT: Immature DCs were generated from the peripheral blood monocytes from five children with refractory solid tumors (Ewing sarcoma, synovial sarcoma, neuroblastoma) using GM-CSF and IL-4. These DCs were then pulsed with tumor-specific synthetic peptides or tumor lysates in the presence of the immunogenic protein KLH for 12 h. Pulsed DCs were administered subcutaneously every one or two weeks in an outpatient setting without any toxicity. In one patient with Ewing sarcoma, the residual tumor disappeared following autologous PBSCT and DC therapy, and a complete remission has been maintained for 77 months. In two patients with synovial sarcoma or with neuroblastoma, growth of the tumors was temporally suppressed for one and 10 months, respectively, followed by their exacerbation. A DTH response was detected against KLH in all five patients and against the tumor lysate in one patient. In the patients with a possible DC-mediated anti-tumor effect, the number of CD8(+) HLA-DR(+) lymphocytes and INF-gamma(+)CD8(+) lymphocytes increased and an elevation of the NK cell cytotoxic activity was observed during and/or after DC therapy. DC-based immunotherapy may therefore be a feasible, well-tolerated and promising approach in the treatment of children with refractory malignant tumors.
    Pediatric Transplantation 12/2008; 13(6):746-53. DOI:10.1111/j.1399-3046.2008.01066.x · 1.63 Impact Factor
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    ABSTRACT: A 7-day-old Japanese female showed the absence of spontaneous movement in her both legs. MRI revealed tumors in the retroperitoneum invading into the spinal canal, the left cerebral hemisphere and the right eyeball. Histological examination of retroperitoneal tumor revealed the sheets of undifferentiated small round cells with hyperchromatic nuclei and scanty cytoplasm. EWS-FLI1 fusion gene was detected by RT-PCR, indicating Ewing sarcoma. She received chemo-radiotherapy and survived for 2 years and 10 months despite the multiple metastases at initial presentation.
    Pediatric Blood & Cancer 11/2008; 51(5):698-701. DOI:10.1002/pbc.21678 · 2.56 Impact Factor
  • Pediatric Blood & Cancer 10/2008; 51(4):567. DOI:10.1002/pbc.21647 · 2.56 Impact Factor
  • Molecular Immunology 10/2008; 45(16):4176-4176. DOI:10.1016/j.molimm.2008.08.243 · 3.00 Impact Factor
  • Pediatric Blood & Cancer 04/2008; 50(4):943-4. DOI:10.1002/pbc.21309 · 2.56 Impact Factor
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    ABSTRACT: The expression of cytokine-associated genes in dendritic cells (DCs) derived from umbilical cord blood (UCB) and adult peripheral blood (APB) was comprehensively compared in order to elucidate the difference in DC function between newborns and adults. Immature DCs were obtained from UCB and APB of healthy human donors. Several cytokines were added to generate mature DCs. Gene expression was compared using cDNA microarray containing 553 cytokine-associated genes. Eleven genes with differential expression were selected and determined their expression levels in DCs by quantitative real-time RT-PCR. The expression of the Th1 response-related genes (IL-12B and IL-18) and chemokine genes (CXCL9, CXCL13, CCL18 and CCL24) was significantly lower in UCB-DCs than in APB-DC in both maturation states. On the other hand, calgranulins A and B, which are speculated to induce immune tolerance, showed higher expression in UCB-DCs. The expression of cell cycle-related genes (CDC2 and cyclin B1) was significantly higher in UCB-DCs than in APB-DCs, and immature UCB-DCs proliferated more rapidly than immature APB-DCs. The expression of genes related to immune responses was significantly different between UCB- and APB-DCs, which may cause a decreased DC-mediated immunity and an increased susceptibility to infection in newborns.
    Immunology Letters 03/2008; 116(1):55-63. DOI:10.1016/j.imlet.2007.11.006 · 2.37 Impact Factor
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    ABSTRACT: A 5-year-old girl with acute lymphoblastic leukemia in remission suffered from fatal visceral varicella-zoster virus (VZV) infection after the oral administration of a high-dose dexamethasone. She abruptly developed fulminant hepatitis and disseminated intravascular coagulation, and died 3 days later. VZV DNA and antigens were detected in the peripheral blood (6 x 10(8) copies/mL) and a postmortem liver specimen, respectively. The exposure to VZV was not confirmed and no skin lesions were observed. VZV infection should be considered in patients with unexplained liver dysfunction under severe immunosuppressive condition, even in the absence of viral exposure and skin involvement.
    Pediatric Hematology and Oncology 01/2008; 25(3):237-42. DOI:10.1080/08880010801938215 · 0.96 Impact Factor
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    ABSTRACT: The aim of this study is to determine whether the polymorphisms of the MDR1 gene are associated with the development of childhood acute lymphoblastic leukemia (ALL). The MDR1 gene polymorphisms, -2352 G>A, -934A>G, -692T>C (5' regulatory region) and 3435C>T (exon 26), were examined in 157 ALL patients and 96 healthy children. The amounts of MDR1 mRNA were quantified in 54 healthy individuals using normal peripheral blood mononuclear cells to evaluate the effect of each polymorphism on the gene expression. The frequency of the G/G genotype of the -2352 G>A was significantly higher in ALL than in controls (74/109 versus 52/96, p=0.04). The frequency of the T/T genotype of the 3435C>T was also significantly higher in ALL (29/118 versus 10/96, p=0.006). In a haplotype analysis using the 5' regulatory sites, the frequency of a certain haplotype was higher in ALL than in controls (59/90 versus 42/88, p=0.048). When the -2352G>A was examined in different age groups, patients aged six or older were found to have the G/G genotype more frequently than the controls (42/51 versus 52/96, p=0.0014), while no difference was observed in the younger age group. The amounts of MDR1 mRNA were significantly higher in either G/G or G/A genotype of the -2352 G>A than in A/A genotype (p=0.04). The present study suggests that the genetic background of MDR1 may be associated with the development of childhood ALL, possibly due to a quantitative change in the MDR1 gene resulting from genetic polymorphisms.
    Leukemia Research 12/2007; 31(12):1633-40. DOI:10.1016/j.leukres.2007.04.009 · 2.69 Impact Factor
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    ABSTRACT: Two children, 5 and 10 years of age, received unrelated cord blood transplantation (CBT) for malignant lymphoma. Both of them suffered from pleurisy with and without interstitial pneumonitis after transplantation. By the quantitative real-time polymerase chain reaction, human herpesvirus 6 (HHV-6) variant B DNA was detected in pleural effusion. This is the first report of HHV-6-associated pleurisy after hematopoietic stem cell transplantation. HHV-6-associated pleurisy should be considered as a complication after hematopoietic stem cell transplantation even in the absence of pneumonitis. Quantitative polymerase chain reaction is a useful tool for rapid detection of viral DNA, which may facilitate precise diagnosis and appropriate treatment.
    Journal of Pediatric Hematology/Oncology 11/2007; 29(10):709-12. DOI:10.1097/MPH.0b013e318142b50d · 0.96 Impact Factor
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    ABSTRACT: The mRNA contents of matrix metalloproteinase (MMP)-2, MMP-9, tissue inhibitor of MMP (TIMP)-1 and TIMP-2 in leukemia cells from 33 infants with acute lymphoblastic leukemia (ALL) were quantified at initial presentation, and the correlation between their expression and patient clinical characteristics was examined. The mRNA contents of MMP-2 and MMP-9 were not associated with any patient characteristics. Positive correlation was found between hepatosplenomegaly and the MMP-2/TIMP-1 and MMP-2/TIMP-2 ratios (p=0.005 and 0.009) and between CNS involvement and the MMP-2/TIMP-2 ratio (p=0.012). The results suggest that MMP/TIMP balance is closely related to the infiltration of leukemia cells into extramedullary organs.
    Leukemia Research 11/2007; 31(10):1437-40. DOI:10.1016/j.leukres.2007.01.015 · 2.69 Impact Factor
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    ABSTRACT: Non-T-cell-depleted HLA-haploidentical hematopoietic stem cell transplantation (SCT) from family members has been reported, but its effectiveness and safety are not fully known. In this study, we examined the outcomes of 83 children and adolescents with nonmalignant (n = 11) or malignant (n = 72) disorders who underwent SCT mismatched at 2 or 3 HLA loci, either from the mother (n = 56), a noninherited maternal antigen (NIMA)-mismatched sibling (n = 14), or the father/a noninherited paternal antigen (NIPA)-mismatched sibling (n = 13). Engraftment was satisfactory. Severe (grade III-IV) acute graft-versushost disease (GVHD) was noted only in malignant disease, with an incidence of 21 of 64 evaluable patients. GVHD prophylaxis with a combination of tacrolimus and methotrexate was significantly associated with a lower risk of severe acute GVHD, compared with other types of prophylaxis (P = .04). Nine of 11 patients with nonmalignant disease and 29 of 72 patients with malignant disease were alive at a median follow-up of 26 months (range, 4-57 months). Outcomes were not significantly different among the 3 donor groups (mother versus NIMA-mismatched sibling versus father/NIPA-mismatched sibling) for the malignancy disorders. Our results indicate that non-T-cell-depleted HLA-haploidentical SCT may be feasible, with appropriate GVHD prophylaxis, for young recipients who lack immediate access to a conventional stem cell source.
    International Journal of Hematology 05/2007; 85(3):246-55. DOI:10.1532/IJH97.06185 · 1.68 Impact Factor
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    ABSTRACT: A 14-year-old boy presented with a short history of general fatigue. Laboratory examination of the peripheral blood revealed white blood cells 11,300/microl, hemoglobin 10.4 g/dl, platelets 45,000/microl, fibrinogen < 50 mg/dl, fibrin/fibrinogen degradation products 536 microg/ml and lactate dehydrogenase 1,684 U/l. A bone marrow aspirate contained 89.6% of undifferentiated tumor cells. A hematological malignancy was suspected and the patient was treated with idarubicin and cytarabine. However, further examination revealed that tumor cells were positive for CD56 and lacked lineage markers of lymphoid or myeloid cells. They were positive for PAS, HHF35 and desmin, and negative for MPO. Reverse transcriptase polymerase chain reaction demonstrated PAX3/FKHR fusion transcripts, confirming the diagnosis of alveolar rhabdomyosarcoma. Radiological examination revealed only one enlarged lymph node being 1.5 cm in diameter at the paraaortic region in the abdomen, and failed to find a primary tumor. After three courses of chemotherapy containing etoposide, cyclophosphamide, pirarubicin, cisplatin and vincristine, tumor cells were eradicated from the bone marrow. The patient received an allogeneic bone marrow transplantation eight months after diagnosis, although he died of hepatic veno-occlusive disease on day 21. Alveolar rhabdomyosarcoma often develops in older children and younger adults, and its bone marrow infiltration may mimic acute leukemia.
    [Rinshō ketsueki] The Japanese journal of clinical hematology 04/2007; 48(4):315-20.
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    ABSTRACT: Summary We investigated PAX5 expression in childhood B-lineage acute lymphoblastic leukaemia (ALL). Seven of 21 children with B-lineage ALL had multiple PAX5 variants, while 14 children and healthy controls showed full-length (FL) and one variant PAX5. By Western blotting, healthy controls displayed Pax5-FL, while one short Pax5, derived from the deletion of exon 8 (Pax5-DeltaE8) was produced in 90% of ALL samples, as well as in ALL cell lines. PAX5-DeltaE8 lacked more than 50% of the transactivation domain, indicating that aberrant Pax5 production might lead to the arrest of B-cell differentiation, contributing to the pathogenesis of B-lineage ALL.
    British Journal of Haematology 02/2007; 136(2):297-300. DOI:10.1111/j.1365-2141.2006.06425.x · 4.96 Impact Factor
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    ABSTRACT: The aim of this study was to identify genes distinctively expressed or suppressed in childhood leukemia with different prognoses, using cDNA microarray and quantitative reverse transcription-polymerase chain reaction (RT-PCR). The expression levels of the selected genes by cDNA microarray were quantified in primary leukemic blasts from 44 patients (acute lymphoblastic leukemia, 28; acute myelogenous leukemia (AML), 13; transient myeloproliferative disorder, 3). The expression levels of CDKN2C, CRADD, and IGFBP-2 genes were significantly associated with the event-free survival of the patients in AML. The present results suggest that a combination of cDNA microarray and quantitative RT-PCR may be useful to identify novel genes with prognostic value in childhood AML.
    Pediatric Hematology and Oncology 04/2006; 23(2):115-27. DOI:10.1080/08880010500457780 · 0.96 Impact Factor
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    ABSTRACT: Peripherally inserted central venous catheters (PICCs) have been increasingly used in pediatric patients. However, little is known about the incidence and risk of complications when using this device in children with cancer. The purposes of this study are to assess the feasibility of PICCs and to determine the risk factors for PICC-related complications in pediatric patients with various types of malignancies. We attempted to place PICCs in 53 patients with a median age of 5 years ranging from 2 months to 20 years. PICCs were used to administer fluid, parenteral nutrition, anticancer agents, antibiotics, and blood products and also for the through-line blood sampling. The duration of catheterization and the incidence of PICC-related complications requiring removal were retrospectively evaluated in association with the diagnosis, sex, age and body weight of the patients, size, insertion site and tip location of the catheters, type of treatment, and duration of leukopenia. PICCs were successfully placed in 109 of 112 attempts (97.3%) in 53 patients, and they were followed for a total of 11,797 catheter days (median placement, 87 days; range, 3 to 512 days). Fifty five PICCs (50.5%) were removed as a result of PICC-related complications with a rate of 4.66 per 1,000 catheter days. The most common reasons for catheter removal were occlusion (n=18), breakage/leakage (15), and infection (10). More than 70% of such complications occurred more than 30 days after placement. The catheter tip location in the superior vena cava or the right atrium might decrease the risk of complications. Other parameters did not influence the incidence of complications. PICCs were found to provide a reliable access for prolonged intravenous administration and blood sampling in children intensively treated for hematologic and solid malignancies, thus leading to a reduction of physical pain and psychological stress in such patients. However, the long-term placement of PICCs may also be related to an increased risk of complications.
    Supportive Care Cancer 03/2006; 14(2):153-60. DOI:10.1007/s00520-005-0848-x · 2.50 Impact Factor

Publication Stats

1k Citations
226.14 Total Impact Points

Institutions

  • 1985–2010
    • Kyushu University
      • • Department of Pediatrics
      • • Medical Institute of Bioregulation - MIB Hospital
      Hukuoka, Fukuoka, Japan
  • 2002
    • St.Mary's Hospital (Fukuoka - Japan)
      Hukuoka, Fukuoka, Japan
  • 1999–2001
    • Kurume University
      • Department of Pediatrics
      Куруме, Fukuoka, Japan