Late effects and quality of life of childhood cancer survivors: Part 2. Impact of radiotherapy.

To examine the late effects and health-related quality of life of childhood cancer survivors (CCS) after radiotherapy (RT), we performed a cross-sectional survey using self-rating questionnaires. The subjects were divided into 3 groups: CCS treated with or without RT, and a general population matched for age, gender, residential area, and work status. The numbers in each group were 113, 72, and 1,000, respectively.

Prognostic significance of the BAALC isoform pattern and CEBPA mutations in pediatric acute myeloid leukemia with normal karyotype: a study by the Japanese Childhood AML Cooperative Study Group.

High BAALC (brain and acute leukemia, cytoplasmic) gene expression may indicate an adverse prognosis for adults who have acute myeloid leukemia (AML) and a normal karyotype, but its prognostic significance for pediatric AML cases is unclear. Whether different BAALC isoform patterns are of prognostic significance is also unclear. Newly diagnosed AML patients with normal karyotype who were treated by the Japanese Childhood AML Cooperative Treatment Protocol AML 99 were analyzed in terms of their BAALC expression levels (n = 29), BAALC isoforms (n = 29), and CEBPA mutations (n = 49).

Late effects and quality of life of childhood cancer survivors: part 1. Impact of stem cell transplantation.

To examine the late effects and health-related quality of life among childhood cancer survivors (CCS) after stem cell transplantation (SCT), we performed a cross-sectional survey using self-rating questionnaires. The subjects were divided into 3 groups: SCT-treated CCS, CCS treated without SCT, and the general population who matched for age, gender, residential area, and work status with the CCS. We analyzed the questionnaires of 185 CCS and 1,000 control participants.

Survey of childhood cancer survivors who stopped follow-up physician visits.

Background: Childhood cancer cure rates have increased remarkably; however, survivors face an increased risk of morbidity and mortality. Survivors may benefit from anticipatory guidance and periodic surveillance to minimize morbidity and mortality.

Methods: Subjects included 114 5-year survivors of childhood cancer who were diagnosed and treated in three hospitals in Nagoya between 1975 and 2001 and who stopped follow-up physician visits during the preceding 2 years.

Mental health among young adult survivors of childhood cancer and their siblings including posttraumatic growth.

Background: Few studies have addressed the mental health status of young adult childhood cancer survivors (CCSs) and their siblings (SIBs). This paper focuses on depression, anxiety, posttraumatic stress symptoms (PTSS), and posttraumatic growth (PTG) among Japanese CCSs and their SIBs.

Methods: Adolescent and young adult CCSs (n=185), in remission for more than 1 year, their SIBs (n=72), and general controls (CONTs) (n=1,000) completed anonymous self-report questionnaires for depression, anxiety, PTSS, and PTG.

[Effectiveness of remission induction with high-dose cytarabine for relapsed or refractory pediatric acute leukemia].

We conducted a multicenter postmarketing study to investigate the efficacy and safety of reinduction therapy with a high-dose cytarabine-containing regimen for pediatric patients with relapsed or refractory acute leukemia. Seven of 13 patients (53.8%) with ALL achieved complete or partial remission, and only 1 of 6 patients (16.

Comparison of matched-sibling donor BMT and unrelated donor BMT in children and adolescent with acquired severe aplastic anemia.

From January 1991 to March 2007, 61 children and adolescent with acquired severe aplastic anemia received BMT in our institutions. We retrospectively compared the outcome of 30 cases of matched-sibling donor BMT (MSD-BMT) and 31 cases of unrelated donor BMT (URD-BMT). We observed one graft failure among MSD-BMT recipients and three graft failures among URD-BMT recipients, respectively.

Relationship between tacrolimus blood concentrations and clinical outcome during the first 4 weeks after SCT in children.

The relationship between tacrolimus concentration and acute GVHD is not well known, with few published data available for lower target levels. We hypothesized that lower levels of tacrolimus would correlate with higher incidence of acute GVHD and poorer prognosis. Receiver operator characteristic curves (ROC) were used to quantify tacrolimus blood levels as predictors of grade II-IV acute GVHD.

Outcome of childhood acute lymphoblastic leukemia with induction failure treated by the Japan Association of Childhood Leukemia study (JACLS) ALL F-protocol.

Background: 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.

Patients And Methods: 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.

Late occurrence of severe hyponatremia followed by extrapontine osmotic demyelination syndrome after successful conservative management of postpartum hemorrhage due to placenta accreta by uterine artery embolization.

Development of severe hyponatremia followed by extrapontine osmotic demyelination syndrome was reported as a significant late complication after successful conservative management of postpartum hemorrhage due to placenta accreta by uterine artery embolization.

A study of rasburicase for the management of hyperuricemia in pediatric patients with newly diagnosed hematologic malignancies at high risk for tumor lysis syndrome.

Tumor lysis syndrome (TLS), including hyperuricemia, is a frequent serious complication in patients with hematologic malignancies. This study in Japanese patients evaluated the efficacy, safety, and pharmacokinetic profile of rasburicase in pediatric patients with hematologic malignancies. Patients aged <18 years at high risk for TLS, with newly diagnosed hematologic malignancies, were randomized to intravenous rasburicase 0.

Risk-stratified therapy and the intensive use of cytarabine improves the outcome in childhood acute myeloid leukemia: the AML99 trial from the Japanese Childhood AML Cooperative Study Group.

Purpose: To improve the prognosis in children with newly diagnosed acute myeloid leukemia (AML) by introducing a dose-dense intensive chemotherapy regimen and an appropriate risk stratification system.

Patients And Methods: Two hundred forty children with de novo AML were treated with continuous cytarabine-based induction therapy and stratified to three risk groups based on the initial treatment response, age, and WBC at diagnosis and cytogenetics. All of the patients were treated with intensive consolidation chemotherapy including three or four courses of high-dose cytarabine.

FBXW7 and NOTCH1 mutations in childhood T cell acute lymphoblastic leukaemia and T cell non-Hodgkin lymphoma.

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.

Retrospective analysis of relapsed or primary refractory childhood lymphoblastic lymphoma in Japan.

Background And Procedure: To assess the clinical course with response to second-line treatment and to evaluate the role of hematopoietic stem cell transplantation (SCT) in children with relapsed or primary refractory lymphoblastic lymphoma (LBL), we analyzed data of 48 patients with relapsed/primary refractory diseases among 260 LBL patients identified in a national survey of 1996-2004.

Results: Twenty-six patients achieved second complete remission; 9 achieved partial remission. Of 13 patients who showed progression despite first and second line therapy, only one patient was alive on the second relapse after unrelated cord blood transplantation.

Impact of the methotrexate administration dose on the need for intrathecal treatment in children and adolescents with anaplastic large-cell lymphoma: results of a randomized trial of the EICNHL Group.

Purpose: To compare the efficacy and safety of two methotrexate doses and administration schedules in children with anaplastic large-cell lymphoma (ALCL).

Patients And Methods: This randomized trial for children with ALCL was based on the Non-Hodgkin's Lymphoma-Berlin-Frankfurt-Muenster 90 (NHL-BFM90) study protocol and compared six courses of methotrexate 1 g/m2 over 24 hours and an intrathecal injection (IT) followed by folinic acid rescue at 42 hours (MTX1 arm) with six courses of methotrexate 3 g/m2 over 3 hours followed by folinic acid rescue at 24 hours without IT (MTX3 arm). This trial involved most European pediatric/lymphoma study groups and a Japanese group.

Outcome of bone marrow transplantation from HLA-identical sibling donor in children with hematological malignancies using methotrexate alone as prophylaxis for graft-versus-host disease.

Most previous studies of graft-versus-host disease (GVHD) prophylaxis with methotrexate (MTX) alone in patients undergoing HLA-identical sibling donor bone marrow transplantation were performed in adults. With this background, we attempted to analyze the incidence and risk factors of GVHD in bone marrow transplantation (BMT) from an HLA-identical sibling donor in children with hematological malignancies using MTX alone as a prophylaxis for GVHD. Ninety-four patients received MTX by intravenous bolus injection, with a dose of 15 mg/m(2) on day +1, followed by 10 mg/m(2) on days +3, +6, and +11, and then weekly until day +60.

Remission induction therapy containing rituximab markedly improved the outcome of untreated mature B cell lymphoma.

Many controlled clinical trials have proven that rituximab improves the clinical outcome of patients with mature B cell lymphoma. This study was conducted to assess the contribution of rituximab in the actual clinical practice. Patients with newly diagnosed mature B cell lymphoma treated at 20 National Hospital Organization hospitals from January 2000 to December 2004 were consecutively registered.

Clinical features and outcome of MLL gene rearranged acute lymphoblastic leukemia in infants with additional chromosomal abnormalities other than 11q23 translocation.

The treatment outcome for infant acute lymphoblastic leukemia (ALL) with positive MLL gene rearrangements remains poor. We analyzed whether additional chromosomal abnormalities (ACA) other than 11q23 translocation could affect the disease behavior and its prognosis. Eighteen of seventy-four patients with infant acute lymphoblastic leukemia showed ACA, including three-way translocations in four, other novel translocations in four, and complex structural chromosomal changes in four.

The role of hematopoietic stem cell transplantation with relapsed or primary refractory childhood B-cell non-Hodgkin lymphoma and mature B-cell leukemia: a retrospective analysis of enrolled cases in Japan.

Background: There have been excellent treatment results for children with B-cell non-Hodgkin lymphoma (B-NHL) and mature B-cell leukemia (B-ALL) in the last few decades. However, a small subset of relapsed or refractory patients, after first-line therapy, still have a poor prognosis.

Procedure: Thirty-three patients with relapsed or primary refractory B-NHL/B-ALL among 327 newly diagnosed patients between 1996 and 2004 were analyzed retrospectively.

Acute megakaryoblastic leukaemia (AMKL) in children: a comparison of AMKL with and without Down syndrome.

To characterize childhood acute megakaryoblastic leukaemia (AMKL), we reviewed 45 children with AMKL diagnosed between 1986 and 2005 at Nagoya University Hospital and Japanese Red Cross Nagoya First Hospital. Twenty-four patients (53%) had AMKL associated with Down syndrome (DS-AMKL) and 21 (47%) had non-DS-AMKL. The median age of the DS-AMKL patients was 21 months (range, 8-38 months) and that of non-DS-AMKL patients was 15 months (range, 2-185 months).

Prospective study of a pirarubicin, intermediate-dose cytarabine, and etoposide regimen in children with Down syndrome and acute myeloid leukemia: the Japanese Childhood AML Cooperative Study Group.

Purpose: To evaluate a less intensive chemotherapeutic regimen specifically designed for patients with Down syndrome (DS) and acute myeloid leukemia (AML), and to determine the prognostic factors for event-free survival.

Patients And Methods: Seventy-two patients with AML-DS were treated with remission induction chemotherapy consisting of pirarubicin (25 mg/m2/d for 2 days), cytarabine (100 mg/m2/d for 7 days), and etoposide (150 mg/m2/d for 3 days). Patients received four courses of intensification therapy of the same regimen.

Tandem duplications of MLL and FLT3 are correlated with poor prognoses in pediatric acute myeloid leukemia: a study of the Japanese childhood AML Cooperative Study Group.

Background: Mixed-lineage leukemia (MLL)-partial tandem duplication (PTD) is associated with poor prognosis in adult acute myeloid leukemia (AML), but its relationship to pediatric AML is unknown.

Procedure: One hundred fifty-eight newly diagnosed AML patients, including 13 FAB-M3 and 10 Down syndrome (DS) patients, who were treated on the Japanese Childhood AML Cooperative Treatment Protocol AML 99 were analyzed for MLL-PTD, as well as internal tandem duplication (ITD) and the kinase domain mutation (D835Mt) in the FLT3 gene.

Results: We found MLL-PTD in 21 (13.

A novel epsilon gamma delta beta thalassemia of 1.4 Mb deletion found in a Japanese patient.

A novel large deletion, causing epsilon gamma delta beta thalassemia (here called, epsilon gamma delta beta thalassemia Jpn-I) was discovered in a 6-year-old Japanese boy. He was born uneventfully, but revealed thalassemia minor after birth. The mutation was inherited from his mother.

Outcome of risk-based therapy for infant acute lymphoblastic leukemia with or without an MLL gene rearrangement, with emphasis on late effects: a final report of two consecutive studies, MLL96 and MLL98, of the Japan Infant Leukemia Study Group.

We evaluated the efficacy of a treatment strategy in which infants with acute lymphoblastic leukemia (ALL) were stratified by their MLL gene status and then assigned to different risk-based therapies. A total of 102 patients were registered on two consecutive multicenter trials, designated MLL96 and MLL98, between 1995 and 2001. Those with a rearranged MLL gene (MLL-R, n=80) were assigned to receive intensive chemotherapy followed by hematopoietic stem cell transplantation (HSCT), while those with germline MLL (MLL-G, n=22) were treated with chemotherapy alone.