Myelodysplastic syndrome in children and adolescents

Myelodysplastic syndromes (MDS) are clonal disorders characterized by ineffective hematopoiesis and subsequent frequent development of acute myeloid leukemia (AML). In children and adolescents, MDS are uncommon disorders, accounting for less than 5% of hematopoietic malignancy, with great heterogeneity in presentation and clinical course. The genetic changes predisposing children to MDS are largely obscure. Monosomy 7 is the most common chromosomal abnormality, often occurring as a sole abnormality. The recent pediatric modification of the World Health Organization (WHO) classification has greatly facilitated the diagnostic process. Refractory cytopenia (RC) is the most common MDS subtype in children, occurring in about half of all MDS cases. There is consensus that the relationship between MDS with increased blast count and de novo AML is better defined by biological and clinical features than by blast count. Because monosomy 7 is the only chromosomal abnormality strongly suggestive of MDS, children presenting with a low blast count and other chromosomal aberrations or normal karyotype must be closely observed before a diagnosis of MDS can be established. With an increasing number of children surviving primary cancer with chemotherapy or radiation therapy, the incidence of secondary therapy-related MDS is rising. The MDS risk is also increased in patients with inherited bone marrow failure disorders; this relationship provides valuable insights into MDS biology. Allogeneic hematopoietic stem cell transplantation (HSCT) from a matched related or suitable unrelated donor is the choice for most children with MDS and can rescue a large proportion of patients.     

Multiple hypoechoic hepatic lesions in a patient with Gaucher disease.

The most common symptoms of Gaucher disease include hepatosplenomegaly and anemia and thrombocytopenia due to hypersplenism. We describe the case of a patient with Gaucher disease who had cachexia, massive hepatomegaly, and multiple focal hepatic lesions. The clinical and radiologic findings suggested malignancy. A biopsy specimen was taken from a hepatic lesion and revealed infiltration by Gaucher cells. We discuss our findings in light of the putative increased incidence of hematologic malignancies in patients with Gaucher disease.     

Morphological differentiation of severe aplastic anaemia from hypocellular refractory cytopenia of childhood: reproducibility of histopathological diagnostic criteria

Baumann I, Führer M, Behrendt S, Campr V, Csomor J, Furlan I, de Haas V, Kerndrup G, Leguit R J, De Paepe P, Noellke P, Niemeyer C & Schwarz S
(2012) Histopathology  61, 10–17 Morphological differentiation of severe aplastic anaemia from hypocellular refractory cytopenia of childhood: reproducibility of histopathological diagnostic criteria Aims: To evaluate the reproducibility and reliability of the histomorphological criteria differentiating severe aplastic anaemia (SAA) and hypoplastic refractory cytopenia of childhood (RCC), the most frequently acquired hypocellular bone marrow conditions of childhood. Methods and results: We performed a double‐blind interobserver study of 100 different cases of SAA and RCC among seven haematopathologists of the European Working Group of MDS in Childhood (EWOG‐MDS) and the German SAA study. Cases with foci of typical myelodysplastic syndrome (MDS) morphology, such as patchy erythropoiesis with defective maturation, in an otherwise highly hypocellular or adipocytic bone marrow were classified as having RCC. Bone marrow samples without a patchy distribution, few scattered myeloid cells or haematopoietic aplasia were diagnosed as SAA. In only four of 100 cases did the reference pathologists not reach agreement regarding classification as SAA or RCC. The kappa index was 0.79. Conclusions: Our results show that the vast majority of SAA and RCC cases can be reliably differentiated by morphological means alone. A clear differentiation between SAA and RCC at presentation is mandatory for optimizing therapy strategies, and might be responsible for the fact that, in the German childhood SAA study, the probability of developing clonal disease after immunosuppressive therapy has dropped to 3%.     

The role of neurotrophins and insulin on tau pathology in Alzheimer's disease

Alterations in the structure and function of tau protein is the primary pathology of a variety of neurodegenerative diseases, including Alzheimer's disease (AD). In these diseases, hyperphosphorylated tau protein forms aggregates which are deposited in the somadendritic regions of the neurons in the central nervous system. This series of events is toxic to neurons, and plays a crucial role in disease development. However, the events leading to the deregulation of tau protein in AD are not clear. Recently, there has been much research into the possible roles of neurotrophic factors in AD. AD brain exhibits changes in levels of different neurotrophic factors, including brain-derived neurotrophic factor and nerve growth factor. These neurotrophic factors are known to be important for the proper functioning of neurons, and their deregulation may play an important role in AD disease progression. Of particular interest, these neurotrophic factors may play a role in the regulation and proper function of tau protein. In this review, the roles of neurotrophic factors in AD and in the regulation of tau protein are discussed.     

Case Study: Biopercular lesions and acquired mutism in a young patient

A 13-year-old patient developed complete mutism and buccofacial apraxia following toxic vasculitis due to a yellow scorpion sting. Language functions were preserved. A CT scan disclosed mainly biopercular infarcts. It is suggested that the lost control of vocalization and speech is associated with biopercular lesions and that a preserved right opercular region can take over this function in the presence of damage to homologous left opercular region.     

Refractory anemia in childhood: a retrospective analysis of 67 patients with particular reference to monosomy 7

Primary myelodysplasia (MDS) without an increased number of blasts is a rare finding in childhood. We performed a retrospective analysis of 67 children with a diagnosis of primary MDS to determine the clinical and hematologic course of the disease. The median age at diagnosis was 8.3 years (range, 0.3-18.1 years). In contrast to refractory anemia in adults, 44% of patients had hemoglobin levels greater than 10 g/100 mL. The median white blood cell count and the absolute neutrophil count were 3.6 x 109/L and 0.9 x 109/L, respectively. Seventy-five percent of patients had thrombocytopenia. Bone marrow was hypocellular in 43% of the patients. Results of cytogenetic analysis showed monosomy 7 in 49%, trisomy 8 in 9%, and other abnormalities in 9% of the patients. The probability of survival 10 years after diagnosis was 0.48 (standard error [SE] = 0.10). Patients with monosomy 7 had significantly higher estimated probabilities of progression to advanced MDS than did patients with other chromosomal anomalies or normal karyotype. Of the 67 children, 41 underwent allogeneic stem cell transplantation (SCT). Patients whose disease did not progress to advanced MDS before SCT had significantly greater probability of survival than patients who experienced progression (0.76 [SE = 0.09] vs 0.36 [SE = 0.16]). SCT improved the outcomes for patients with monosomy 7 and should be offered early in the course of the disease. Recommendations for best treatment options for children with other chromosomal abnormalities or normal karyotype may have to await results of prospective clinical trials.     

Immunosuppressive therapy for aplastic anemia in children: a more severe disease predicts better survival

Severe acquired aplastic anaemia (SAA) is a life-threatening disease characterized by pancytopenia and hypoplastic bone marrow. Autologous T lymphocytes are thought to cause bone marrow failure by immune-mediated excessive apoptosis of stem and progenitor cells. The disease is subclassified into a severe (neutrophil count, > 0.2 x 10(9)/L [> 200/microL]) and a very severe (< 0.2 x 10(9)/L [< 200/microL]) (vSAA) form. We report the results of a prospective multicenter trial with a combined immunosuppressive regimen of cyclosporin A (CSA), anti-thymocyte globulin (ATG) and, in cases with neutrophil counts fewer than 0.5 x 10(9)/L (< 500/microL), granulocyte colony-stimulating factor (G-CSF) for treatment of SAA in children. Children with vSAA showed a higher rate of complete response than did children with SAA (68% versus 45%; P = .009), as well as better survival (93% versus 81%; P < .001). Thus, in children with SAA a more severe disease stage at diagnosis indicates a favorable outcome with immunosuppressive therapy.