A high survival rate, 75.6% at 5 years, was achieved for childhood with de novo AML in the AML99 trial. The treatment strategy was well tolerated with only 1.7% induction death rate and 3.5% remission death rate. Low-risk children were successfully treated with chemotherapy alone.

The purpose of this review is to provide an updated overview of the pathogenesis and treatment of Langerhans cell histiocytosis (LCH). The pathogenesis of LCH remains obscure and the optimal treatment for LCH has not been established, although incremental progress has been made. Proinflammatory cytokines and chemokines are known to play a role in LCH, which suggests that LCH is an immune disorder. However, the oncogenic BRAF mutation is also detected in more than half of LCH patients, which suggests that LCH is a neoplastic disorder. Remaining major issues in the treatment of LCH are how to rescue patients who have risk-organ involvement but do not respond to first-line therapy, the optimal treatment for the orphan disease of multifocal adult LCH, and how to reduce and treat central nervous system-related consequences, such as central diabetes insipidus and neurodegeneration. More research is needed to better understand the pathogenesis of this disease and to resolve the treatment issues.

Human herpesvirus 6 (HHV-6) infection was studied in 82 bone marrow transplant (BMT) recipients (72 allogeneic, 10 autologous). All recipients and 30 donors were seropositive for HHV-6 antibody at the time of bone marrow transplantation. Thirty-one recipients (37.8%) had HHV-6 viremia 2-4 weeks after transplantation. The incidence of HHV-6 viremia was significantly higher among allogeneic BMT recipients than in autologous BMT recipients (P=.011). Therefore, the following analyses of allogeneic BMT recipients were carried out (n=72). Geometric mean antibody titers (log(10)) were significantly higher in recipients without viremia than in those with viremia (1.84+/-0.39 vs. 1.61+/-0.42; P=.022). Logistic regression analysis demonstrated that leukemia or lymphoma is an independent risk factor (P=.031) for HHV-6 viremia. Rash occurring within 1 month after transplantation was observed in 17 (54.8%) of 31 recipients with HHV-6 viremia but in only 8 (19.5%) of 41 recipients without HHV-6 viremia (P=.001).

ABSTRACThad a high risk of bias due to their study design and were conducted more than 10 years ago and may not be applicable to the standard of care of today.11 Updated evidence to aid treatment decisions in pediatric SAA is, therefore, required.In children, the choice of an appropriate treatment is particularly influenced by the long-term sequelae of the disease and its therapy. Thus, failure-free survival is much more important than survival alone when analyzing the long-term outcomes of children with aplastic anemia. Lack of response, relapse, and clonal evolution are problematic in the IST setting, whereas graft failure, acute and chronic graft-versus-host disease (GVHD), and infectious complications limit the success of BMT. In the present study, we compared the outcomes of children with SAA who received IST or BMT from an MFD as first-line treatment using data from nationwide IST and BMT registries. Methods PatientsBetween 1992 and 2009, a total of 599 consecutive children (younger than 17 years) with acquired SAA underwent BMT from an MFD or received IST as first-line treatment in Japan; 213 patients with an MFD underwent BMT and were registered in the Transplant Registry Unified Management Program (TRUMP) conducted by the Japanese Society for Hematopoietic Cell Transplantation, and 386 patients without an MFD were enrolled in two consecutive prospective multicenter trials (AA-92/97) conducted by the Japanese Childhood Aplastic Anemia Study Group and were initially treated with IST (Table 1). The disease severities were defined as previously reported.12,13 Underlying inherited marrow failure disorders were excluded clinically and by chromosome fragility testing. Marrow cytogenetic studies were performed for all patients, and patients with clonal cytogenetic abnormalities were excluded from this study. Patients with paroxysmal nocturnal hemoglobinuria with clinical symptoms and positive findings on the Ham test/sucrose test were also excluded from this analysis. All treatments were performed after obtaining written informed consent from patients or their parents in accordance with the Declaration of Helsinki. Immunosuppressive therapy and bone marrow transplantation proceduresThe characteristics of the treatment procedures are detailed in Table 2. Three hundred and eighty-six patients were enrolled in the AA-92 (n=84) and AA-97 (n=302) trials, and all the patients were initially treated with a combination of antithymocyte globulin and cyclosporine A. Response to IST and disease relapse were evaluated as previously reported.12 Transplantation data were collected with the use of standardized forms provided by the TRUMP. A total of 213 patients underwent BMT from an MFD as first-line treatment following the local protocols for conditioning regimens and GVHD prophylaxis. Patients who did not reach neutrophil counts >0.5×10 9 /L for 3 consecutive days after transplantation were considered to have had primary graft failure. Patients with initial engraftment in whom absolute neutrophil counts subsequently declin...

A B S T R A C T PurposeTo 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 MethodsSeventy-two patients with AML-DS were treated with remission induction chemotherapy consisting of pirarubicin (25 mg/m 2 /d for 2 days), cytarabine (100 mg/m 2 /d for 7 days), and etoposide (150 mg/m 2 /d for 3 days). Patients received four courses of intensification therapy of the same regimen. Prophylaxis for CNS leukemia was not included. ResultsAll but two patients were younger than 4 years, and 67 of the 72 patients (93%) were diagnosed as acute megakaryoblastic leukemia (AMKL). Seventy of the 72 patients (97.2%) achieved a complete remission (CR), and the estimated 4-year event-free survival (EFS) rate was 83% Ϯ 9%. Nine patients relapsed, and one died as a result of pneumonia during CR. Multivariate analysis revealed that the presence of monosomy 7 was a greater risk factor of adverse outcome (odds ratio ϭ 5.67; P ϭ .027). ConclusionA less intensive chemotherapeutic regimen produces excellent outcomes in standard-risk AML-DS patient. Risk-oriented therapy should be considered for future trials in AML-DS.We would like to emphasize that the TRM in the current study was only 1.4% (one of 72 patients) which is much lower than those of previous reports. 7-9,16 On the other hand, relapse and induction failure were found in 11 of 72 patients (14%), which is more frequent than in other reports with intensive regimens. 6,8,13 On the basis of the results of the present study, we have designed a risk-oriented therapy protocol for our next trial with AML-DS. The patients with M1 marrow after induction therapy should be classified into a standard-risk group and receive the same dose of pirarubicin and cytarabine regimen. In POG 8498, daunorubicin was used only in induction, with a total dose of 135 mg/m 2 , and high-dose cytarabine in consolidation. Although this study included only small cohort of 14 DS patients, all were alive as last updated in 2005. 31 We will include high-dose cytarabine for patients with M2 or M3 marrow after induction therapy, classified into a high-risk group, who might have adverse prognostic factors such as age older than 3 and the presence of monosomy 7. AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTERESTThe author(s) indicated no potential conflicts of interest.

A novel MEF2D-BCL9 fusion we identified characterizes a novel subset of pediatric ALL, predicts poor prognosis, and may be a candidate for novel molecular targeting.

SummaryTo 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). The morphology of blast cells was categorized into three groups according to the stage of megakaryocyte maturation. The blast cells were more immature in DS-AMKL than in non-DS-AMKL in terms of morphology and immunophenotyping. Cytogenetic abnormalities of leukaemic cells were classified into seven categories: normal karyotype including constitutional trisomy 21 in DS-AMKL; numerical abnormalities only; t(1;22)(p13;q13); 3q21q26 abnormalities; t(16;21)(p11;q22); )5/del(5q) and/or )7/del(7q); and other structural changes. The outcome of children with either DS-AMKL or non-DS-AMKL is excellent. The 10-year overall survival estimate was 79% [95% confidence interval (CI): 54-90] for DS-AMKL and 76% (95% CI: 58-91) for non-DS-AMKL (P = 0AE81) with a median follow-up of 78 months (range, 20-243 months). Our study shows the diverse heterogeneity of childhood AMKL and the need for subclassification according to cytogenetic and morphological features.

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.