[Treatment outcome of non-Hodgkin lymphoma in childhood: KYCCSG NHL-89, 96].

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.

Randomized trial to compare LSA2L2-type maintenance therapy to daily 6-mercaptopurine and weekly methotrexate with vincristine and dexamethasone pulse for children with acute lymphoblastic leukemia.

Background: 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.

Procedure: 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.

How to improve resilience in adolescents with cancer in Japan.

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.

Graft-versus-lymphoma effect after reduced intensity allogeneic hematopoietic stem cell transplantation from HLA-two loci mismatched father in a patient with refractory non-Hodgkin lymphoma.

A 10-year-old female developed a mediastinal mass and was diagnosed as mixed lineage lymphoblastic lymphoma. The tumor was extremely refractory, and she never achieved remission despite intensive therapy using 12 anti-lymphoma agents and local irradiation. She received reduced-intensity allogeneic peripheral blood stem cell transplantation from her HLA-two loci mismatched father, and achieved complete remission.

Risks and benefits of ending of mass screening for neuroblastoma at 6 months of age in Japan.

Purpose: 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.

Methods: 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.

Langerhans cell histiocytosis with multifocal bone lesions: comparative clinical features between single and multi-systems.

Langerhans cell histiocytosis (LCH) can be a single system or multi-system disease. Both disease types can be associated with multi-focal bone lesions, but their bone involvement patterns have not been compared systematically. Of the new pediatric LCH cases enrolled into the JLSG-02 study during 2002-2007, 67 cases of single system multifocal bone (SMFB) LCH and 97 cases of multi-system bone (MSB) LCH were analyzed to determine if the bone involvement patterns differ in these two types, and whether these differences correlate with outcome.

Long-term survival after autologous peripheral blood stem cell transplantation in two patients with malignant rhabdoid tumor of the kidney.

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.

Immunotherapy with autologous dendritic cells and tumor antigens for children with refractory malignant solid tumors.

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.

Congenital Ewing sarcoma in retroperitoneum with multiple metastases.

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.

Fatal visceral varicella-zoster virus infection without skin involvement in a child with acute lymphoblastic leukemia.

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.

Expression of cytokine-associated genes in dendritic cells (DCs): comparison between adult peripheral blood- and umbilical cord blood-derived DCs by cDNA microarray.

Objective: 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.

Study Design: Immature DCs were obtained from UCB and APB of healthy human donors. Several cytokines were added to generate mature DCs.

Human herpesvirus 6 (HHV-6)-associated pleurisy after unrelated cord blood transplantation in children with chemotherapy-resistant malignant Lymphoma.

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.

Regulatory polymorphisms of multidrug resistance 1 (MDR1) gene are associated with the development of childhood acute lymphoblastic leukemia.

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.

Outcome of non-T-cell-depleted HLA-haploidentical hematopoietic stem cell transplantation from family donors in children and adolescents.

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.

Expression of matrix metalloproteinase (MMP) and tissue inhibitor of MMP (TIMP) genes in blasts of infant acute lymphoblastic leukemia with organ involvement.

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.

Identification of novel genes with prognostic value in childhood leukemia using cDNA microarray and quantitative RT-PCR.

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.

Immune response after influenza vaccination in children with cancer.

Purpose: To assess the immune response to inactivated trivalent split influenza vaccine in children with cancer.

Procedures: Forty-four children with various types of malignancies received two doses of influenza vaccine 2-4 weeks apart. Hemagglutinin-inhibition (HI) antibody titers were determined in paired sera obtained just before the first vaccination and 4 weeks after the second vaccination.

Long-term use of peripherally inserted central venous catheters for cancer chemotherapy in children.

Background: 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.

Prognostic factors for relapsed childhood acute lymphoblastic leukemia: impact of allogeneic stem cell transplantation--a report from the Kyushu-Yamaguchi Children's Cancer Study Group.

Background: The treatment results of childhood acute lymphoblastic leukemia (ALL) with a first relapse were retrospectively analyzed to determine prognostic factors. In particular, an attempt was made to clarify whether stem cell transplantation (SCT) had any advantages over chemotherapy.

Procedures: Of the 407 children with ALL diagnosed between 1984 and 1996, 117 suffered from a relapse before December 1999.

Differential mRNA expression of glucocorticoid receptor alpha and beta is associated with glucocorticoid sensitivity of acute lymphoblastic leukemia in children.

Background: Sensitivity of leukemic blasts to glucocorticoid is one of the important prognostic factors for pediatric acute lymphoblastic leukemia (ALL). Alternative splicing of the glucocorticoid receptor (GR) gene results in several isoforms. We examined an association of the expression pattern of GR isoforms in leukemic blasts with their sensitivity to glucocorticoid in childhood ALL.

Neutrophil-derived TNF-related apoptosis-inducing ligand (TRAIL): a novel mechanism of antitumor effect by neutrophils.

To detect the novel genes expressed uniquely in neutrophils and elucidate their function, the gene expression pattern was compared by using cDNA microarray containing 240 cytokine genes between the neutrophils and peripheral blood mononuclear cells (PBMCs) obtained from healthy human donors. Twenty-six genes, including tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), were expressed in neutrophils at a level >10 times higher than that seen in phytohemagglutinin-stimulated PBMCs. The amounts of mRNA and protein of TRAIL were quantified by real-time reverse transcription-PCR and ELISA, respectively.

Reversible posterior leukoencephalopathy syndrome in children with cancers.

We report three cases of reversible posterior leukoencephalopathy syndrome (RPLS) in children with cancers. All patients presented with sudden confusional state, visual disturbance, and transient mild hypertension under the treatment of childhood cancers. Magnetic resonance imaging of the brain demonstrated cortical and subcortical lesions predominantly in the occipital region, which showed high intensity signal on fluid-attenuated inversion recovery images.