Congenital dyserythropoietic anemia type I: First report from the Congenital Dyserythropoietic Anemia Registry of North America (CDAR).

Congenital dyserythropoietic anemias (CDAs) are characterized by ineffective erythropoiesis and distinctive erythroblast abnormalities; the diagnosis is often missed or delayed due to significant phenotypic heterogeneity. We established the CDA Registry of North America (CDAR) to study the natural history of CDA and create a biorepository to investigate the pathobiology of this heterogeneous disease. Seven of 47 patients enrolled so far in CDAR have CDA-I due to biallelic CDAN1 mutations. They all presented with perinatal anemia and required transfusions during infancy. Anemia spontaneously improved during infancy in three patients; two became transfusion-independent rapidly after starting interferon-α2; and two remain transfusion-dependent at last follow-up at ages 5 and 30 y.o. One of the transfusion-dependent patients underwent splenectomy at 11 y.o due to misdiagnosis and returned to medical attention at 27 y.o with severe hemolytic anemia and pulmonary hypertension. All patients developed iron overload even without transfusions; four were treated with chelation. Genetic testing allowed for more rapid and accurate diagnosis; the median age of confirmed diagnosis in our cohort was 3 y.o compared to 17.3 y.o historically. In conclusion, CDAR provides an organized research network for multidisciplinary clinical and research collaboration to conduct natural history and biologic studies in CDA.

Tolerance of dinutuximab therapy for treatment of high-risk neuroblastoma in two patients with end-stage renal disease on dialysis.

Autologous hematopoietic cell transplant (aHCT) has a significant survival advantage in patients with high-risk (HR) neuroblastoma. Transplant-associated thrombotic microangiopathy (TA-TMA) is a serious complication and may result in chronic renal disease leading to delay in subsequent posttransplant therapy and limitations of treatment options. Dinutuximab represents an important therapeutic advance in the treatment of pediatric HR neuroblastoma, but historically has not been administered in patients with GFR < 60 mL/m2 /min. Here, we present the safe outcome of dinutuximab administration while on renal replacement therapy in two cases of HR neuroblastoma with end-stage renal disease secondary to TA-TMA.

Rare Hereditary Hemolytic Anemias: Diagnostic Approach and Considerations in Management.

Hereditary hemolytic anemias (HHAs) comprise a heterogeneous group of anemias caused by mutations in genes coding the globins, red blood cell (RBC) membrane proteins, and RBC enzymes. Congenital dyserythropoietic anemias (CDAs) are rare disorders of erythropoiesis characterized by binucleated and multinucleated erythroblasts in bone marrow. CDAs typically present with a hemolytic phenotype, as the produced RBCs have structural defects and decreased survival and should be considered in the differential of HHAs. This article discusses the clinical presentation, laboratory findings, and management considerations for rare HHAs arising from unstable hemoglobins, RBC hydration defects, the less common RBC enzymopathies, and CDAs.

Abdominal Lymphoma Presenting as Terminal Ileitis: A Case Report.

BACKGROUND: Most pediatric patients with lymphoma do not have classic symptoms of fever, night sweats, and weight loss. Lymphoma can present as vague symptoms and may mimic common pediatric abdominal emergencies. In this case report, we present a child who presented with abdominal pain and who was initially misdiagnosed as having a surgical emergency. CASE REPORT: An 11-year-old previously healthy male was referred to the pediatric emergency department after he presented to an outside hospital with 3 days of right lower quadrant pain and 1 episode of diarrhea. The initial concern was appendicitis. He had a computed tomography scan of the abdomen and pelvis that showed thickening of the bowel wall, peritoneal thickening, and a right pleural effusion. His laboratory assessments were only notable for a mildly elevated lactate dehydrogenase level of 506 units/L. He had a colonoscopy, and biopsy specimens obtained from the terminal ileum and cecum were negative. He developed worsening symptoms, and subsequently underwent laparoscopic biopsy procedures of the omentum and terminal ileum, which were consistent with Burkitt lymphoma. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: We discuss the important oncologic findings of pediatric lymphoma, including oncologic emergencies and important laboratory and imaging tests that providers should consider while in the emergency department. This case highlights how pediatric lymphoma can mimic common pediatric pathologies providers often encounter in the emergency department.

MEF2B is a member of the BCL6 gene transcriptional complex and induces its expression in diffuse large B-cell lymphoma of the germinal center B-cell-like type.

Myocyte enhancer-binding factor 2B (MEF2B) has been implicated as a transcriptional regulator for BCL6. However, details about the interaction between MEF2B and BCL6 during expression, as well as the relationship of MEF2B to the expression of other germinal center (GC) markers, have not yet been fully explained. Using germinal center B-cell-like diffuse large B-cell lymphoma (GC-DLBCL) and activated B-cell diffuse large B-cell lymphoma (ABC-DLBCL) cell lines, we analyzed the expression of MEF2B and its associations with BCL6, CD10, and ERK. Furthermore, small interfering RNA (siRNA) was used to study the possible effects of MEF2B knockdown on these proteins and cell growth. Analysis of the BCL6 transcriptional complex was performed using electrophoretic mobility shift assay. The correlation between MEF2B expression and the genetic type of DLBCL was assessed using immunohistochemistry on 111 patient samples, and via in silico analysis of publicly available microarray (Gene Expression Omnibus (GEO)) datasets. Our results indicate that the expression of MEF2B protein is important for the growth of GC-DLBCL cells, as evidenced by MEF2B knockdown inhibition of cell growth and the subsequent suppression of BCL6, CD10, and ERK phosphorylation. Analysis of BCL6 transcription factors in nuclear extracts of MEF2-expressing DLBCL cells showed involvement of MEF2B with AP-2α and BCL6 proteins in the formation of the BCL6 gene transcriptional complex. Indeed, differential expression of MEF2B in the GC-DLBCL is statistically significant compared to the ABC-DLBCL in the GEO datasets, as well as in tissue microarray, as indicated via immunohistochemistry (Visco-Young algorithm). Our findings indicate that MEF2B is an essential component of the BCL6 gene transcriptional complex for the regulation of DLBCL growth via the promotion of BCL6 expression. Beyond its regulatory role in DLBCL growth, MEF2B expression correlated positively with BCL6 and CD10 expression, and was preferentially expressed in the GBC-DLBCL group.