Aberrant DNA methylation characterizes juvenile myelomonocytic leukemia with poor outcome.

Aberrant DNA methylation contributes to the malignant phenotype in virtually all types of cancer, including myeloid leukemia. We hypothesized that CpG island hypermethylation also occurs in juvenile myelomonocytic leukemia (JMML) and investigated whether it is associated with clinical, hematologic, or prognostic features. Based on quantitative measurements of DNA methylation in 127 JMML cases using mass spectrometry (MassARRAY), we identified 4 gene CpG islands with frequent hypermethylation: BMP4 (36% of patients), CALCA (54%), CDKN2B (22%), and RARB (13%).

Complex karyotype newly defined: the strongest prognostic factor in advanced childhood myelodysplastic syndrome.

To identify cytogenetic risk factors predicting outcome in children with advanced myelodysplastic syndrome, overall survival of 192 children prospectively enrolled in European Working Group of Myelodysplastic Syndrome in Childhood studies was evaluated with regard to karyotypic complexity. Structurally complex constitutes a new definition of complex karyotype characterized by more than or equal to 3 chromosomal aberrations, including at least one structural aberration. Five-year overall survival in patients with more than or equal to 3 clonal aberrations, which were not structurally complex, did not differ from that observed in patients with normal karyotype.

Subcutaneous anti-D globulin application is a safe treatment option of immune thrombocytopenia in children.

Subcutaneous (sc) administration of anti-D seems to offer the same efficacy as intravenous administration but with less side effects. Here we report our experience with sc anti-D for pediatric immune thrombocytopenia (ITP). A total of 12 children with a median age of 11.

Histiocytosis following T-acute lymphoblastic leukemia: a BFM study.

The coincidence of T-cell acute lymphoblastic leukemia (T-ALL) and histiocytic disorders, including hemophagocytic lymphohistiocytosis (T-ALL/HLH) and Langerhans cell histiocytosis (T-ALL/LCH), is very seldom and is usually associated with a dismal prognosis. Retrospective statistical analysis of all T-ALL patients, who have been registered in the BFM-ALL trials from 1981 - 2001 and who have subsequently developed a LCH/HLH, in order to identify any common risk factors pre-disposing to the synchronous occurrence of both disorders. Six out of 971 T-ALL patients had either HLH or LCH ( approximately 0.

Cutaneous Langerhans cell histiocytosis in children under one year.

Background: To evaluate the clinical course and outcome of infants with Langerhans cell histiocytosis (LCH) involving skin and to estimate the incidence of progression to multi-system (M-S) disease in those with isolated skin involvement.

Methods: A retrospective review was conducted on 22 LCH patients who were younger than 12 months at the onset of their skin eruption.

Results: Twelve patients had isolated skin involvement at diagnosis and 10 were evaluable for progression.

Extramedullary plasmacytoma of the adenoids.

Extramedullary plasmacytomas are extremely rarely diagnosed in children. We report two cases of extramedullary plasmacytoma detected coincidentally in the adenoidectomy specimens of children younger than 4 years. We show that these children are disease-free after local excision as the only treatment.

The mutational spectrum of PTPN11 in juvenile myelomonocytic leukemia and Noonan syndrome/myeloproliferative disease.

Germ line PTPN11 mutations cause 50% of cases of Noonan syndrome (NS). Somatic mutations in PTPN11 occur in 35% of patients with de novo, nonsyndromic juvenile myelomonocytic leukemia (JMML). Myeloproliferative disorders (MPDs), either transient or more fulminant forms, can also occur in infants with NS (NS/MPD).

Hematopoietic stem cell transplantation (HSCT) in children with juvenile myelomonocytic leukemia (JMML): results of the EWOG-MDS/EBMT trial.

Allogeneic hematopoietic stem cell transplantation (HSCT) is the only proven curative therapy for juvenile myelomonocytic leukemia (JMML). We, the European Working Group on Childhood MDS (EWOG-MDS) and the European Blood and Marrow Transplantation (EBMT) Group, report the outcome of 100 children (67 boys and 33 girls) with JMML given unmanipulated HSCT after a preparative regimen including busulfan, cyclophosphamide, and melphalan. Forty-eight and 52 children received transplants from an HLA-identical relative or an unrelated donor (UD), respectively.

High-risk neuroblastoma in Ontario: a report of experience from 1989 to 1995.

Purpose: We did a population-based study of children with high-risk neuroblastoma to determine their survival and look for factors that had an impact on survival.

Methods: We carried out a retrospective cohort study of patients diagnosed in Ontario from 1989 to 1995. 162 cases of neuroblastoma were diagnosed in the province with 70 (43%) considered high-risk: all were older than one year of age, with 15 patients classified as International Neuroblastoma Staging System (INSS) stage 3, and 55 INSS stage 4.

The role of surgery in the treatment of pediatric B-cell non-Hodgkin's lymphoma.

Background: Within the last 20 years, the role of surgery in the management of pediatric B-cell non-Hodgkin's lymphoma (B-NHL) has changed substantially. Along with the assignment of risk-adjusted therapy and specific treatment protocols, surgical procedures have been restricted to defined situations including abdominal emergencies, diagnostic biopsy, total tumor extirpation and second-look operations.

Methods: The authors retrospectively analyzed the effect of initial surgery and second-look operation on event-free survival (EFS) in 79 patients with B-NHL (abdominal primary, n = 57; head or neck tumor, n = 22).

Adverse outcomes in primary hemophagocytic lymphohistiocytosis.

Purpose: Hemophagocytic lymphohistiocytosis (HLH) is a rare condition characterized by abnormal proliferation of macrophages. Although the mortality rate in children diagnosed with primary HLH is high, little has been described about the nature of adverse events. This review evaluates unfavorable events in children with primary HLH to suggest methods of improving outcomes.

Philadelphia chromosome-positive mature B-cell (Burkitt cell) leukaemia.

Philadelphia chromosome-positive (Ph+) acute leukaemia usually shows lymphoblastic morphology and a B-precursor phenotype. The bone marrow aspirate of a 9-year-old boy showed a L3 blast cell morphology in 90% of cells; immunophenotyping revealed a mature B-blast population. The translocation t(9;22) (q34;q11) was seen in 45 out of 50 metaphases, and expression of the corresponding bcr1/abl fusion transcripts, but no IgH/myc co-localization or splitting of c-myc, was demonstrated.