Manjusha Kumar

Esthesioneuroblastoma in children

Esthesioneuroblastoma (olfactory neuroblastoma) is a rare tumor of the olfactory epithelium. Approximately 1,000 cases have been described in the literature since the original description in 1924. It occurs in older individuals and is rare in children. The authors describe the clinicopathologic presentation in a series of five children treated with neoadjuvant/adjuvant chemotherapy and review the English literature for previously described patients younger than 18 years to assess clinical presentation, mode of treatment, and outcome in this age group.

Griscelli syndrome : Rare neonatal syndrome of recurrent hemophagocytosis

Griscelli syndrome (GS) is a rare inherited disease characterized by immunodeficiency and partial albinism. The microscopic findings of the skin and hair are highly suggestive of the disease. The GS locus colocalizes on chromosome 15q21 with the myosin-Va gene (MYO5a), and mutations have been identified in few patients. We describe a 2-month-old Hispanic girl with severe pancytopenia secondary to hemophagocytosis. Even though a mutation at the Griscelli locus had not been identified, her clinical features and outcome were typical of GS. The purpose of this article is to alert physicians to the association between GS and hemophagocytosis. We suggest that GS should be considered in infants with hemophagocytosis because the features of partial albinism can be subtle. The relevant literature is summarized.

Clinical course of postthrombotic syndrome in children with history of venous thromboembolism.

Postthrombotic syndrome (PTS) is a chronic morbidity of venous thromboembolism (VTE) in children. Information about the evolution of PTS is lacking in children. Present study was aimed to evaluate the time-course of extremity PTS in children who were serially followed in a hematology clinic. This retrospective cohort study included 69 consecutive children with documented VTEs that presented with symptoms of extremity VTE: 67 extremity VTEs with or without extension to vena cava, 2 inferior vena cava VTEs. Severity of PTS was assessed using modified Villalta scale. Median age of the cohort was 12.6 years (interquartile range 1.6–15 years) while median follow-up was 28.7 months (interquartile range 13.3–33.4 months. PTS prevalence was 46.8% [95% confidence interval (CI) 37.9–57.7%]. Lower extremity VTE was associated with development of PTS compared to upper extremity VTE regardless of catheter use (P = 0.002). The time-course of PTS fluctuated in 11 of 33 children (33%; 95% CI 20–47%) at a median interval of 12 months from diagnosis of VTE (range 4–14 months): three progressed from mild/moderate to severe, one improved from moderate to mild, seven fluctuated between mild and moderate. Recurrence and incomplete resolution of VTE were associated with variability in PTS severity (P < 0.05). In summary, this study suggested that almost 50% of study cohort developed PTS, and the time-course of PTS was not static in one third of children. Future research should focus on identifying the predictors contributing to the worsening of PTS and developing risk-stratified treatment interventions so as to improve the outcome of children with VTE.

Kidney function in long-term pediatric survivors of acute lymphoblastic leukemia following allogeneic bone marrow transplantation.

Renal dysfunction may occur in survivors of bone marrow transplantation (BMT). The renal function of children who have survived 5 to 10 years after BMT has not been reported. Bone marrow transplantation was performed in 55 children with acute lymphoblastic leukemia less than 18 years of age at the University of Florida between September 1983 and October 1992. All received a uniform conditioning regimen of high-dose cystosine arabinoside and fractionated total body irradiation. Twenty-three are currently surviving. The survival average period following transplantation is 79 +/- 6.6 (SD) months. The longest survival is 129 months after BMT. We retrospectively examined data evaluating kidney function prior to transplantation, within 150 days after transplantation, and at each childs most recent clinic visit (1.7 to 10 years after transplantation). We were able to collect follow-up data regarding renal function for 17 survivors. Two children (11%) have renal dysfunction in the form of hypertension, glucosuria, and hematuria. One of them had acute renal insufficiency during the first 100 days following BMT. An unexpected finding was the presence of hyperfiltration in 10 patients. In conclusion, in this homogeneous group of children, allogenic BMT did not lead to significant long-term renal dysfunction.

Pregnancy in bone marrow failure syndromes: Diamond-Blackfan anaemia and Shwachman-Diamond syndrome.

Pregnancy in bone marrow failure syndromes has risk to mother and fetus. There are fewer than 30 reports of cases with Diamond‐Blackfan anaemia (DBA), and none with Shwachman‐Diamond syndrome (SD). We report two DBA and one SD cases. One DBA mother received transfusions intra‐partum, and the other only post‐partum. Both required caesarean sections (C‐sections) for failure of labour to progress and severe pre‐eclampsia respectively. Both subsequently resumed pre‐pregnancy steroid‐induced control of anaemia. ~40% of DBA pregnancies required maternal transfusions; 25% delivered by C‐section. The SD patient also had Ehlers‐Danlos (ED) syndrome and urticaria pigmentosa (UP). Her blood counts were adequate until week 38, when the platelet count dropped and a C‐section was performed. Pregnancy management in marrow failure disorders requires obstetricians with expertise in high‐risk pregnancies, and haematologists with experience with marrow failure syndromes.

Response to steroids predicts response to rituximab in pediatric chronic immune thrombocytopenia.

Treatment choice in pediatric immune thrombocytopenia (ITP) is arbitrary, because few studies are powered to identify predictors of therapy response. Increasingly, rituximab is becoming a treatment of choice in those refractory to other therapies.

Hematopoietic growth factors for the treatment of aplastic anemia.

The use of hematopoietic growth factors, although well established for the management of chemotherapy-induced neutropenia, remains controversial for the treatment of aplastic anemia and inherited bone marrow failure syndromes. The most commonly used factors are granulocyte colony-stimulating factor, granulocyte macrophage colony-stimulating factor, and erythropoietin. Newer growth factors such as stem cell factor, thrombopoietin, Flt3 ligand, and interleukins have shown promising results in the laboratory, and some have been used in clinical trials. This article reviews the clinical use of old and new hematopoietic growth factors in acquired and inherited bone marrow failure, and discusses emerging concerns about long term toxicity of these factors.

Clinical outcomes of splenectomy in children: Report of the splenectomy in congenital hemolytic anemia registry

The outcomes of children with congenital hemolytic anemia (CHA) undergoing total splenectomy (TS) or partial splenectomy (PS) remain unclear. In this study, we collected data from 100 children with CHA who underwent TS or PS from 2005 to 2013 at 16 sites in the Splenectomy in Congenital Hemolytic Anemia (SICHA) consortium using a patient registry. We analyzed demographics and baseline clinical status, operative details, and outcomes at 4, 24, and 52 weeks after surgery. Results were summarized as hematologic outcomes, short‐term adverse events (AEs) (≤30 days after surgery), and long‐term AEs (31–365 days after surgery). For children with hereditary spherocytosis, after surgery there was an increase in hemoglobin (baseline 10.1 ± 1.8 g/dl, 52 week 12.8 ± 1.6 g/dl; mean ± SD), decrease in reticulocyte and bilirubin as well as control of symptoms. Children with sickle cell disease had control of clinical symptoms after surgery, but had no change in hematologic parameters. There was an 11% rate of short‐term AEs and 11% rate of long‐term AEs. As we accumulate more subjects and longer follow‐up, use of a patient registry should enhance our capacity for clinical trials and engage all stakeholders in the decision‐making process. Am. J. Hematol. 90:187–192, 2015.

Hematologic outcomes after total splenectomy and partial splenectomy for congenital hemolytic anemia.

PURPOSE The purpose of this study was to define the hematologic response to total splenectomy (TS) or partial splenectomy (PS) in children with hereditary spherocytosis (HS) or sickle cell disease (SCD). METHODS The Splenectomy in Congenital Hemolytic Anemia (SICHA) consortium registry collected hematologic outcomes of children with CHA undergoing TS or PS to 1 year after surgery. Using random effects mixed modeling, we evaluated the association of operative type with change in hemoglobin, reticulocyte counts, and bilirubin. We also compared laparoscopic to open splenectomy. RESULTS The analysis included 130 children, with 62.3% (n=81) undergoing TS. For children with HS, all hematologic measures improved after TS, including a 4.1g/dl increase in hemoglobin. Hematologic parameters also improved after PS, although the response was less robust (hemoglobin increase 2.4 g/dl, p<0.001). For children with SCD, there was no change in hemoglobin. Laparoscopy was not associated with differences in hematologic outcomes compared to open. TS and laparoscopy were associated with shorter length of stay. CONCLUSION Children with HS have an excellent hematologic response after TS or PS, although the hematologic response is more robust following TS. Children with SCD have smaller changes in their hematologic parameters. These data offer guidance to families and clinicians considering TS or PS.

Severe aplastic anaemia and Grave's disease in a paediatric patient

Summary.  Severe aplastic anaemia (SAA) is considered to be an autoimmune disorder affecting the haematopoietic cells and most often is idiopathic. An association between SAA and other autoimmune diseases is rare and has been described in adults for eosinophilic fasciitis, thymomas, systemic lupus erythematosus and thyroid disorders. We describe the first paediatric patient with chronic relapsing SAA and Graves disease. We discuss the difficulty in diagnosis of Graves disease, the possibility of its manifestation due to withdrawal of immunosuppressants, and issues to consider in the treatment of this disease in the setting of bone marrow failure.