Anemia In Pediatric Patients Research Articles

P451 Safety and efficacy of ferric carboxymaltose (FCM) for the treatment of iron deficiency anaemia in paediatric patients affected by inflammatory bowel disease (pIBD)

P451 Safety and efficacy of ferric carboxymaltose (FCM) for the treatment of iron deficiency anaemia in paediatric patients affected by inflammatory bowel disease (pIBD)

Efficacy of Eculizumab in Pediatric Patients with Paroxysmal Nocturnal Hemoglobinuria in the International PNH Registry

Background/Objective: Paroxysmal nocturnal hemoglobinuria (PNH) is an extremely rare disease and is even more rare in children; pediatric cases are estimated to account for <5% of all PNH cases (Ware RE, et al. N Engl J Med. 1991;325:991-996). There is a paucity of published data on outcomes in children with PNH treated with eculizumab. The International PNH Registry (NCT01374360) is a prospective, observational study of patients with PNH regardless of age, and represents the largest cohort of pediatric PNH patients. The objective of this analysis was to evaluate outcomes after initiation of eculizumab in pediatric patients and adult patients enrolled in the Registry.Methods: The analysis included eculizumab-treated patients enrolled in the Registry as of May 2017. Patients were stratified by age at baseline (defined as the date of eculizumab initiation; age categories, <18 and ≥18 years of age) and assessed at baseline and at last follow-up. Age at the time of disease onset, as defined by earliest reported PNH granulocyte clone, disease diagnosis, or PNH symptom, was also recorded. Patients needed ≥6 months of follow-up post-baseline to be eligible for analyses of change from baseline to last follow-up on eculizumab.Results: Of 4903 patients enrolled in the Registry as of May 1, 2017, 1725 had been treated with eculizumab and had data available on demographics and enrollment date (<18 years of age at baseline, n=47; ≥18 years of age at baseline, n=1678). In both age groups, the majority of patients were female (66.0%, pediatric cohort; 52.6%, adult cohort), and the majority were white (89.1% and 81.6%, respectively). Median (quartile [Q]1, Q3) age at disease onset was 14.7 (11.0, 15.8) in the pediatric cohort and 33.3 (23.7, 48.2) in the adult cohort; median (Q1, Q3) ages at baseline were 15.8 (14.9, 17.3) and 42.0 (30.8, 57.0), respectively. Fewer pediatric patients had history of thrombotic events (TEs) and other major adverse vascular events (MAVEs) at baseline compared with the adult cohort (Table), which is consistent with findings from a previous Registry analysis (Urbano-Ispizua A, et al. Haematologica. 2017;102:e76-e79). Most patients had ≥6 months of follow-up (n=44/47 [93.6%] and n=1532/1678 [91.3%], respectively) after baseline. Median (minimum, maximum) duration of time between baseline and last follow-up on eculizumab was 3.7 (0.1, 8.7) years in the pediatric cohort and 3.9 (0.0, 12.1) years in the adult cohort. Results for outcomes of interest are summarized in the Table. In both cohorts, mean lactate dehydrogenase ratio decreased from >5 times the upper limit of normal at baseline to normal or near normal range at last follow-up in both age cohorts. There were no TEs reported in the pediatric cohort after baseline, but 2/43 patients (4.7%) with no history of MAVEs at baseline experienced non-TE MAVEs after baseline. Among adult patients, 19/1497 (1.3%) with no history of TEs and 7/1497 (0.5%) with history of TEs experienced TEs after baseline. Non-TE MAVEs after baseline in patients with no history of MAVEs were experienced by 17/1492 patients (1.1%) and non-TE MAVEs after baseline in patients with history of MAVEs were experienced by 15/1492 patients (1.0%). The proportion of patients requiring transfusion was lower at last follow-up in both cohorts compared with baseline (23.0% at last follow-up vs 49.3% at baseline for adults and 32.3% at last follow-up vs 48.4% at baseline for pediatric patients). A similar proportion of patients became transfusion-independent after treatment with eculizumab in both age cohorts (32.3% [10/31] in the pediatric cohort compared with 33.8% [370/1095] in the adult cohort). The proportion of patients with PNH-related symptoms decreased after baseline in both cohorts for most of the symptoms assessed, although fewer than 10 pediatric patients had symptom data available at both baseline and last follow-up.Conclusions: The effectiveness of eculizumab for reducing intravascular hemolysis and transfusion requirements, and preventing MAVEs (including TEs) was similar in these large cohorts of pediatric patients with PNH and adults with PNH. The higher proportion of patients transfusion-dependent among the pediatric cohort may be associated with the higher likelihood of underlying aplastic anemia in pediatric patients with PNH. [Display omitted] DisclosuresUrbano-Ispizua:Alexion Pharmaceuticals, Inc.: Membership on an entity's Board of Directors or advisory committees. Kulasekararaj:Alexion Pharmaceuticals, Inc.: Consultancy, Honoraria, Other: Travel Support . Bartels:Alexion Pharmaceuticals, Inc.: Honoraria, Other: Travel Support and is site investigator for clinical trials with the company, Research Funding. Patriquin:Ra Pharmaceuticals: Consultancy, Research Funding; Octapharma: Honoraria; Alexion Pharmaceuticals, Inc.: Consultancy, Honoraria, Other: Travel Support and is site investigator for clinical trials with the company. Hoechsmann:Alexion Pharmaceuticals, Inc.: Consultancy, Honoraria, Research Funding. Wilson:Alexion Pharmaceuticals, Inc.: Employment, Equity Ownership. Gustovic:Alexion Pharma GmbH: Employment, Equity Ownership. Schrezenmeier:Alexion Pharmaceuticals, Inc.: Honoraria, Research Funding.

Anemia in Pediatric Inflammatory Bowel Disease.

Anemia is the most frequent extra-intestinal finding in inflammatory bowel disease (IBD). The aim of this study is to determine the prevalence and types of anemia in pediatric patients with IBD at diagnosis and at approximately 1 year follow-up. This is a retrospective chart review of patients diagnosed with IBD from 2005 to 2012, ages 1 to 18 years. Patients who had hemoglobin, hematocrit, mean corpuscular volume, and iron indices obtained at the time of diagnosis and at approximately 1 year follow-up were included in the study. The prevalence of anemia at the beginning and the end of the study was recorded. Using the soluble transferrin receptor index the type of anemia was determined. At diagnosis, 67.31% of patients were anemic. Overall, 28.85% of patients had either iron deficiency anemia (IDA) or a combination of IDA and anemia of chronic disease (ACD), whereas 38.46% had ACD alone. At follow-up, 20.51% were anemic. 15.38% had either IDA or a combination of IDA and ACD; 5.13% had ACD alone. The pattern of anemia and response to therapy differed among the IBD phenotypes CONCLUSIONS:: Anemia is frequent in inflammatory bowel disease. The prevalence was higher in Crohn disease (CD). At 1 year, the prevalence of anemia decreased significantly, but persisted. Anemia of chronic disease predominated in CD. Iron deficiency anemia continued to be present in CD and ulcerative colitis.

Pharmacokinetics of ferric pyrophosphate citrate administered via dialysate and intravenously to pediatric patients on chronic hemodialysis

BackgroundIron deficiency is a common cause of anemia in pediatric patients with hemodialysis-dependent chronic kidney disease (CKD-5HD). Ferric pyrophosphate citrate (FPC, Triferic®) donates iron directly to transferrin, bypassing the reticuloendothelial system and avoiding iron sequestration. Administration of FPC via dialysate or intravenously (IV) may provide a suitable therapeutic option to current IV iron preparations for these patients.MethodsThe pharmacokinetics and safety of FPC administered via dialysate and IV to patients aged < 6 years (n = 3), 6 to < 12 years (n = 4), and 12 to <18 years (n = 15) were investigated in a multicenter, open-label, two-period, single-dose study. FPC (0.07 mg iron/kg) was infused IV into the venous blood return line during hemodialysis session no. 1. FPC iron was added to bicarbonate concentrate to deliver 2 μM (110 μg/L) iron via dialysate during hemodialysis session no. 2.ResultsMean serum total iron concentrations peaked 3 to 4 h after administration via dialysate and 2 to 4 h after IV administration and returned to baseline by 10 h after the start of hemodialysis for both routes. Iron exposure was greater after administration via dialysate than after IV administration. The absolute amount of absorbed iron after administration via dialysate roughly doubled with increasing age, but the weight-normalized amount of absorbed iron was relatively constant across age groups (~ 0.06–0.10 mg/kg). FPC was well tolerated in the small number of patients studied.ConclusionsFPC iron can be administered to pediatric patients with CKD-5HD via dialysate or by the IV route. Further study of FPC administered to maintain hemoglobin concentration is indicated.

Outcome of hematopoietic stem cell transplantation in severe aplastic anemia in pediatric patients

Outcome of hematopoietic stem cell transplantation in severe aplastic anemia in pediatric patients

Anemia in pediatric patients under five years old: A cross-sectional study

Anemia is considered the most prevalent nutritional deficiency globally, affecting about a quarter of the world population, especially children. This study was done to study the prevalence of anemia in child under five years of age. This cross-sectional study was carried out including of preschool children aged from 6 months to 5 years. Hemoglobin levels were measured to diagnose anemia (hemoglobin <11.0 g/dL) and data were collected on independent variables such as age, sex, area of residence (urban or rural), daycare center enrollment, birth weight, breastfeeding history, and maternal anemia during pregnancy. Anemia in the particular region was ranges from 29.7% to 25.9 % in 3 consecutive years. No significant differences were found in anemia prevalence between boys and girls. Prevalence of anemia was higher in rural areas than in urban areas. Because of the severity of the public-health problem and the potential threat to health, survival and development of present and future generations, the prevention and the control of anemia should be given immediate priority in the health and nutrition sectors. Keywords Anemia, Health, Children

The hematological effects of nitrous oxide anesthesia in pediatric patients.

Prolonged administration of nitrous oxide causes an increase in plasma homocysteine in children via vitamin B12 inactivation. However, it is unclear whether nitrous oxide doses used in clinical practice cause adverse hematological effects in pediatric patients. This retrospective study included 54 pediatric patients undergoing elective spinal surgery: 41 received nitrous oxide throughout anesthesia (maintenance group), 9 received nitrous oxide for induction and/or emergence (induction/emergence group), and 4 did not receive nitrous oxide (nitrous oxide-free group). Complete blood counts obtained before and up to 4 days after surgery were assessed for anemia, macrocytosis/microcytosis, anisocytosis, hyperchromatosis/hypochromatosis, thrombocytopenia, and leukopenia. The change (Δ) from preoperative to the highest postoperative value was calculated for mean corpuscular volume (MCV) and red cell distribution width (RDW). No pancytopenia was present in any patient after surgery. All patients had postoperative anemia, and none had macrocytosis. Postoperative MCV (mean [99% confidence interval]) peaked at 86 fL (85-88 fL), 85 fL (81-89 fL), and 88 fL (80-96 fL) and postoperative RDW at 13.2% (12.8-13.5%), 13.3% (12.7-13.8%), and 13.0% (11.4-14.6%) for the maintenance group, the induction/emergence group, and the nitrous oxide-free group. Two patients in the maintenance group (5%) developed anisocytosis (RDW >14.6%), but none in the induction/emergence group or in the nitrous oxide-free group (P = 0.43). Both ΔMCV (P = 0.52) and ΔRDW (P = 0.16) were similar across all groups. Nitrous oxide exposure for up to 8 hours is not associated with megaloblastic anemia in pediatric patients undergoing major spinal surgery.

Prevalence and risk factors of anaemia in paediatric patients in South-East Nigeria

Background. The causes of anaemia have regional variations, and further variation is expected among paediatric hospital patients. How­ever, the prevalence of anaemia and its contributing risk factors among paediatric patients remain understudied in South-East Nigeria. Methods. The study involved 286 anaemic (haemoglobin (Hb) ≤10 g/dL) and 295 non-anaemic preschool children attending a hospital outpatient department. A clinical research form was used to document demographic data, anthropometric measurements, disease details and packed cell volume. Common anaemia risk factors previously documented were studied. The prevalence rates of the independent variables were calculated and level of significance was determined, using χ 2 . Results. The prevalence of anaemia was 49.2%, with the highest prevalence among children <12 months old ( p =0.009). There was a significant association between anaemia and maternal education above primary education ( p =0.01), but there was no association with socioeconomic status ( p =0.7) or nutritional status ( p =0.1). The prevalence of the major risk factors among anaemic children was: malaria parasitaemia 48.3% ( p =0.03), iron deficiency 42.3% ( p =0.001), glucose-6 phosphate dehydrogenase (G6PD) deficiency 24.8% ( p =0.02), HIV seropositivity 13.3% ( p =0.02), sickle cell anaemia 2.4% ( p =0.3) and helminth infection 1.1% ( p =0.32). Conclusions. Malaria and iron deficiency remain common among ill children <5 years old who are anaemic. The treatment of these con­ditions should be considered when managing an anaemic ill child in order to reduce morbidity and mortality.

Evaluation of clinical and laboratory variables associated with anemia in pediatric patients on hemodialysis

ObjectiveTo identify the occurrence of anemia in pediatric patients on hemodialysis and the association between hemoglobin levels and anemia in CKD‐related variables. MethodsThis was a retrospective study. Patients aged up to 18 years with chronic kidney disease undergoing hemodialysis at this service between January of 2009 and December of 2010 were selected. Clinical and laboratory data were obtained from medical records. Statistical analysis was performed with chi‐squared test, Student's t‐test and general estimating equations (GEE) using SPSS 20.0, assuming a significance level of 5%. ResultsA total of 357 medical records depicting the monthly evolution of 29 patients were analyzed. The most common etiology for chronic kidney disease was malformations of the genitourinary tract (28%). Hemoglobin showed a mean (standard deviation) value of 9.20 (1.8) g/dL, with the occurrence of anemia in 65.3% of cases. Anemia was associated with hospitalization; antibiotic use; transfusion; use of intravenous iron hydroxide; low values of creatinine, hematocrit, and albumin; and high values of ferritin, aluminum, and equilibrated Kt/V (p<0.05). The odds ratio for anemia with the use of intravenous iron hydroxide was 0.36 (95% CI: 0.25 to 0.89), i.e., a 2.78‐fold higher chance of developing anemia without the use of this medication. ConclusionsAnemia predominated in children and adolescents with chronic kidney disease; intravenous iron hydroxide use was a protective factor.

Evaluation of clinical and laboratory variables associated with anemia in pediatric patients on hemodialysis

ObjectiveTo identify the occurrence of anemia in pediatric patients on hemodialysis and the association between hemoglobin levels and anemia in CKD-related variables. MethodsThis was a retrospective study. Patients aged up to 18 years with chronic kidney disease undergoing hemodialysis at this service between January of 2009 and December of 2010 were selected. Clinical and laboratory data were obtained from medical records. Statistical analysis was performed with chi-squared test, Student's t-test and general estimating equations (GEE) using SPSS 20.0, assuming a significance level of 5%. ResultsA total of 357 medical records depicting the monthly evolution of 29 patients were analyzed. The most common etiology for chronic kidney disease was malformations of the genitourinary tract (28%). Hemoglobin showed a mean (standard deviation) value of 9.20 (1.8) g/dL, with the occurrence of anemia in 65.3% of cases. Anemia was associated with hospitalization; antibiotic use; transfusion; use of intravenous iron hydroxide; low values of creatinine, hematocrit, and albumin; and high values of ferritin, aluminum, and equilibrated Kt/V (p<0.05). The odds ratio for anemia with the use of intravenous iron hydroxide was 0.36 (95% CI: 0.25 to 0.89), i.e., a 2.78-fold higher chance of developing anemia without the use of this medication. ConclusionsAnemia predominated in children and adolescents with chronic kidney disease; intravenous iron hydroxide use was a protective factor.

Immunosuppressive Therapy in Aplastic Anemia

To assess the response to antithymocyte globulin based immunosuppressive therapy (IST) in pediatric patients with idiopathic aplastic anemia. Thirty patients (19 boys and 11 girls) with aplastic anemia received antithymocyte globulin and cyclosporine. Twenty-two patients had severe and 8 had very severe aplastic anemia. Mean age of the patients was 9.19 ± 2.56y. Three patients died within 1mo of therapy, two due to sepsis and one due to intracranial hemorrhage. Twenty-seven patients were analyzed for response to therapy. Eight patients (29.7%) responded at 3mo: 3 complete response (CR) and 5 partial response (PR). Six mo after the therapy, overall response (OR) was seen in 9/27 (33.3%), with one more patient in no response group achieving partial response. At 1year, patients in CR maintained their status and 1 patient in PR group relapsed. He again achieved partial response with repeat course of ATG. Responders had significantly shorter duration of illness and higher absolute neutrophil count as compared to non responders to IST. None of the patients developed acute leukemia in the follow up. The treatment of aplastic anemia in pediatric patients is a challenging task. One third of the patients achieved overall response which included both complete and partial response.

The First Reported Case of Prenatal Diagnosis for Pyruvate Kinase Deficiency in a Chinese Family

Abstract 5276Pyruvate kinase (PK) deficiency of red cells (EC: 2.7.1.40) is the commonest inherited enzyme deficiency in the glycolytic pathway, leading to chronic non-spherocytic hemolytic anemia (CNSHA). There are over 220 characterized mutations deposited in a public database (PKLR Mutation Database http://www.pklrmutationdatabase.com). Heterozygous carriers are asymptomatic but homozygotes or compound heterozygotes can have significant anemia leading to transfusion dependency, neonatal death and hydrops fetalis. All ethnic groups are affected but data on Chinese are very scanty. We describe the first case of prenatal diagnosis for PK deficiency in Chinese and emphasize that this disease is an important differential diagnosis in pediatric patients with hemolytic anemia.A Han Chinese presented with hepatosplenomegaly, severe anemia and unconjugated hyperbilirubinemia at birth, necessitating exchange transfusion on day 1 and prolonged phototherapy till day 10 of life. Glucose-6-phosphate dehydrogenase level was normal. His parents were unrelated and asymptomatic. Family history was unremarkable. He developed severe CNSHA on follow up, requiring monthly red cell transfusion to relieve symptoms and to maintain satisfactory growth. Iron chelation therapy was started at 2 years of age and splenectomy was performed at 4 years to reduce transfusion requirement. The baseline PK enzyme level was not known but both parents had a mildly reduced PK level.Genetic analysis of PKLR gene was performed. All 11 exons and promoter were screened using polymerase chain reaction (PCR)-denaturing high performance liquid chromatography followed by PCR-sequencing. The father was found to carry a mutation in exon 8: PKLR: c.1073 G>A (p.Gly358Glu) while the sequencing result was normal in the mother. Quantitative multiplex PCR of short fluorescent fragments detected a rare large deletion removing exon 4 to exon 10 of the PKLR gene in the mother. Gap-PCR mapping confirmed that it to be a deletion previously found in a Vietnamese family (Costa C et al Haematologica 2005) and an Australian family (Fermo E et al Br J Haematol 2005). Both mutations have not been previously reported in Chinese. The proband was found to carry the paternal point mutation and the maternal deletion.Because of the severe clinical course of their first child, the couple requested prenatal biopsy was performed at 12 week of gestation. The fetus was found to be simple heterozygous for the paternal mutation. Pregnancy was allowed to continue and a healthy baby was born. A PK assay performed at the age of 9 months was normal. Mutation studies in a peripheral blood sample at 10 months of age confirmed the PKLR genotype. There was no evidence of hemolytic anemia after 3 years of follow up.Because of its perceived rarity and benignity in many ethnic groups, PK deficiency does not enter early into the differential diagnosis of anemia in pediatric patients. Its potential to cause severe disease is often overlooked and delay in diagnosis is common (Pissard S et al J Pediatr 2007). Genetic characterization and genotype-phenotype correlation studies on PKLR in different populations are indicated to better characterize the disease spectrum and to define the role of prenatal diagnosis in PK deficiency. Disclosures:No relevant conflicts of interest to declare.

Ceftriaxone-Induced Hemolysis in Pediatric Patients with Sickle Cell Disease

OBJECTIVE: To provide a review on the case reports of ceftriaxone-induced hemolytic anemia in pediatric patients with sickle cell disease, present a proposed mechanism of the reaction, and provide an alternative antimicrobial regimen for these patients. DATA SOURCES: Literature retrieval was accessed through PUBMED (1985-present) using the terms pediatric, sickle cell disease, ceftriaxone, hemolytic anemia, and hemolysis. In addition, reference citations identified from these publications were reviewed. STUDY SELECTION AND DATA EXTRACTION: All articles in English identified from the data sources were evaluated. All case reports and studies were included in the review. DATA SYNTHESIS: Ceftriaxone, a third-generation cephalosporin that is frequently used for the empiric treatment of suspected infections in pediatric patients with sickle cell disease, has been linked to cases of hemolytic anemia. Ceftriaxone has many favorable attributes to promote its use: broad-spectrum anti-microbial activity, long half-life, and no requirement for dose adjustment in patients with renal dysfunction. Hemolytic anemia is a very serious condition and can be fatal. Children with sickle cell disease have a reduced number of red blood cells, and therefore, hemolytic anemia can potentially be detrimental in these children. Five case reports of ceftriaxone-induced hemolytic anemia are presented, in which the typical onset was three to seven days into therapy and all patients had received ceftriaxone courses during prior hospitalizations. There have been several proposed mechanisms of drug-induced hemolytic anemia and ceftriaxone appears to be inducing hemolysis through an immune reaction involving immunoglobulin M and complement found on the surfaces of red blood cells. The hemolysis can be managed by immediately stopping the offending agent, giving packed red blood cell transfusions, and there is possibly a role for intravenous corticosteroids, plasmapheresis, and intravenous immunoglobulin. Cefotaxime is a safe and effective alternative antibiotic in this patient population. CONCLUSIONS: Although rare, ceftriaxone appears to induce hemolytic anemia in pediatric patients with sickle cell disease. Cefotaxime provides a safe and effective alternative in this population.

Post-transplant anemia in pediatric patients and its impact on patient and graft survival: single center experience

Introduction: Post-transplantation anemia (PTA)occurs frequently, with prevalence rates between 20and 60% depending on the criteria used for defininganemia. Aim of the work: We aimed to assess the prevalenceof anemia after 6 months of transplantation inpediatric renal transplant patients under differentprotocols of immunosuppression, and to determinethe impact of anemia upon long-term patient andgraft survival. Patients and methods: Based on the data of 108renal transplants performed in our center, patientswere categorized after 6 months according to theirhemoglobin (Hb) levels into two groups. The firstgroup with Hb more than 11gm/dl (group I, 29cases) and the second group with Hb lessthan11gm/dl (group II, 79cases). We compared thetwo groups regarding post transplant complications(rejection episodes, hypertension, diabetes mellitus,infections, hepatic dysfunction, and patient andgraft survival. Results: we found no significant difference betweenthe two groups regarding rejection episodes.However, the percentage of cases with chronicallograft nephropathy was significantly higher in the anemic group. The survivors with functioning graftswere significantly higher in cases with normal Hb.Moreover, living cases with graft failure weresignificantly higher in anemic group. Graft survivalrate was better in the non anemic group. However,no difference in patient survival was detected. Also,we found no difference between the two groupsregarding post-transplant complications. Conclusions: From this study, we can conclude thatthe prevalence of post-transplant anemia is highpediatric renal transplant patients especially thosereceiving CNI and MMF, and it was associated withpoorer graft outcome but no effect on patientsurvival.

23 Years of Management: A Retrospective Review of Treatment for Aplastic Anemia.

Abstract 1091Poster Board I-113 IntroductionAplastic anemia (AA) is a syndrome of bone marrow failure characterized by peripheral pancytopenia and marrow hypoplasia. In the past, AA was considered to be a fatal disease; however, current therapies, including bone marrow transplantation or immunosuppressive therapy (IST) with antithymocyte globulin (ATG) and cyclosporine (CSA), are curative in the majority of patients. IST is effective at restoring hematopoietic stem cell production, but relapse and evolution to myelodysplastic syndromes remain clinical challenges. Additionally, there is no real consensus regarding optimal CSA levels, duration of CSA treatment, or the optimal use of growth factors and their relationship to the development of clonal disease. ObjectivesThe primary objective was to review treatment management for severe AA in pediatric patients in order to elucidate treatment differences and review morbidity and mortality as they relate to treatment variation. Study Design/MethodsA retrospective review of pediatric patients treated at the Children's Hospital of Philadelphia for AA (both severe and moderate) over a 23 year period was performed. ResultsA total of 70 patients with AA were treated at our institution from 1985 to July 2008. Exclusions included: 6 patients who received some type of initial treatment at outside institutions, 4 patients who had missing records, and 2 patients who had a diagnosis of moderate AA. Thus, a total of 58 patient records were included in the analysis. Of the total patients reviewed, 60% were male and 40% were female. 34.5% of patients were African-American, and 57% were diagnosed in 2000 or later. The mean age at diagnosis was 9.5±5.8 years. 52% fell into the category of very severe AA based on published diagnostic criteria, 45% had severe AA, and 2 patients (3%) had moderate AA. 15.5% of patients developed AA in the setting of acute hepatitis. More than half of the patients treated with IST had a complete response (CR). The average time to CR was 15±15 months. Average duration of CSA treatment was 15±13 months and 8.6±10.7 months for growth factor. Two patients (3.5%) died, one from complications unrelated to AA and one from infectious complications post-BMT after initial IST failure. Average time to transfusion independence for all patients was 8±11 months (with a range of 0-54 months). Not surprisingly, the time to transfusion independence was significantly associated with IST failure (p=0.010). Patients who failed treatment had an average time to transfusion independence of 17±16 months as compared to those who were complete responders who had an average time to transfusion independence of 3±3 months. Additionally, there was a significant association between IST failure and CSA levels (p=0.014). Patients who had nontherapeutic CSA levels overall had an increased rate of treatment failure. Of those patients who were nontherapeutic, 56% were noncompliant with CSA administration. There was no significant association between IST failure and bone marrow cellularity (p=0.251). PNH was diagnosed in 5% of patients; there were no patients with evidence of myelodysplastic syndrome (MDS). Two of the 3 patients with PNH failed initial IST. Another 2 patients had evidence of a cytogenetic abnormality (16q deletion), but never progressed to MDS. (Note: averages presented as mean±SD) Conclusions/MethodsWith current IST regimens, AA is curative in the majority of pediatric patients. IST failure was associated with nonadherence to CSA treatment. For patients with confirmed clonal disease, it is possible that IST failure and the ultimate development of clonal disease are related. DisclosuresNo relevant conflicts of interest to declare.

Leech endoparasitism: report of a case and review of the literature

We report the case of an 11-year-old boy who presented with fresh blood in his mouth and a history of sore throat during the past 2 weeks that was unresponsive to antibiotic therapy. Inspection of the oral cavity revealed a black circular mass attached to the posterior wall of the oropharynx. This mass was determined to be a live engorged leech. Leech endoparasitism is caused by aquatic leeches that attach themselves to mucus membranes of body cavities after the host has swum in bodies of fresh water or drunk from unsafe water sources. Pharyngeal hirudiniasis may present in different forms depending on the exact location of the parasite in the body and must be included in the list of differential diagnosis for common conditions such as pharyngitis, hemoptysis or anemia in pediatric patients living in endemic areas.

Treatment of acquired severe aplastic anemia in pediatric patients with immunosuppression and allogeneic stem cell hematopoietic transplant

Severe acquired aplastic anemia (SAA) is an uncommon disease of childhood. Patients with SAA receive supportive care with transfusions and timely treatment of opportunistic infections, along with specific therapies, which may be allogenic stem cell transplantation (SCT) from a matched sibling or immunosuppressive therapy (IT). To report the experience in the management of SAA. Twenty five children with acquired SAA were treated from July 1992 to September 2005. Patients with full matched sibling donors received allogenic SCT after conditioning with a cyclophosphamide containing regimen. The other patients received immune suppression with cyclosporine plus methylprednisolone (n= 18) plus ATG (n=17). All received supportive care until recovery of hematopoietic function. Those who had severe opportunistic infections at diagnosis or did not respond to two cycles of ATG were evaluated for unrelated donor SCT. Seven patients received sibling donor SCT and 18 IT, which was repeated in six. Three patients received mismatched related (1) or unrelated (2) SCT. Nineteen patients survived with a median follow up time of 4 years, 14 with full hematologic recovery. Six patients died: four due to infections after IT or SCT, one due to intracranial hemorrhage and one with secondary myelodysplasia 12 years after IT. Most children with SAA can be treated successfully with sibling donor SCT or IT. Patients without a histocompatible sibling who fail to respond to IS have a worse prognosis.

Darbepoetin, effective treatment of anaemia in paediatric patients with chronic renal failure

Darbepoetin alfa (DA) is a unique long-acting treatment for anaemia in patients with chronic renal failure (CRF). This study assessed the mean dose of DA to achieve and maintain haemoglobin (Hb) levels between 11 g/dl and 13 g/dl in CRF children aged 11 years to 18 years. This observational, prospective study was conducted in 39 patients treated with DA. Twenty-nine patients were switched from recombinant human erythropoietin (r-HuEPO), and ten patients were naive to r-HuEPO. Naive patients received initial doses of 0.45 μg/kg of DA. Switched patients received a dose adjusted to the prior dose of r-HuEPO (200 IU r-HuEPO:1 μg DA). Among the switched patients, 79.3% received dialysis. No naive patients underwent dialysis. Overall, 74% of patients showed increased Hb level, with a mean value of 11.6 ± 1.6 g/dl, using a mean DA dose of 0.63 ± 0.48 μg/kg per week, and 66.7% patients reached the target Hb level. Hb increased in naive patients from 9.5 (95% CI: 7.7, 11.4) to 11.7 (95% CI: 10.9, 12.6) g/dl and in switched patients from 11.1 (95% CI: 10.6, 11.5) to 11.5 (95% CI: 10.8, 12.2) g/dl). Higher doses of DA were needed in the “switched” than in the “naive” patients to maintain Hb levels over 11 g/dl, respectively 0.73 (95% CI: 0.54, 0.92) and 0.34 (95% CI: 0.16, 0.52) μg/kg per week. Our results indicate the doses of DA necessary to treat CRF patients aged 11 years to 18 years. DA was an effective treatment to stabilise CRF patients at extended dosing intervals.

Darbepoetin alfa for the treatment of anemia in pediatric patients with chronic kidney disease

Darbepoetin alfa, an erythropoiesis-stimulating glycoprotein, has proved efficacious in the treatment of anemia of chronic kidney disease (CKD) in adult subjects. However, little information is available from pediatric populations. We conducted an open-label, non-inferiority, 28-week study comparing the efficacy of darbepoetin alfa with that of recombinant human erythropoietin (rHuEpo) in pediatric subjects with CKD. Subjects, aged 1-18, who were receiving stable rHuEpo treatment (n=124) were randomized (1:2) to either continue receiving rHuEpo or convert to darbepoetin alfa, with doses titrated to achieve and maintain hemoglobin (Hb) levels between 10.0 and 12.5 g/dl. Darbepoetin alfa was considered to be non-inferior to rHuEpo if the lower limit of the two-sided 95% confidence interval (CI) for the difference in the mean change in Hb between the two treatment groups was above -1.0 g/dl. The adjusted mean change in Hb between the baseline and the evaluation period for the rHuEpo and darbepoetin alfa groups was -0.16 g/dl and 0.15 g/dl, respectively, with a difference of 0.31 g/dl (95% CI: -0.45, 1.07) between the means. These results, and the comparable safety profiles, demonstrate that darbepoetin alfa is non-inferior to rHuEpo in the treatment of anemia in pediatric patients with CKD.

Hepatic and hematological markers as predictors for the development of aplastic anemia in pediatric patients with indeterminate fulminant hepatic failure

AIMS: Apfastic anemia occm's intrequently in patients who undergo liver transplantation of indeterminate fulminant hepatic tadure (IFHF). This study evaluates the incidence of aplastic ane:ma and :be value of hepatic and hematological laboratory results that were obtained at the time o[ admission to a major pediatric liver transplant center [or fulminant hepatic failm~ (FHF), METHODS: All cases of pediatric FHF observed at UCLA since 1985 (n = 270) were retrospectively re~aewed. A group of liver transplant patients with indeterminate FHF and aplastie anemia (AA-FHF) (n = 8) was compared to group of patients with IFHF who received liver transplant and survived longer then 3 months (n = 37). Liver function and hematological markers such as albumin, ALT, ammonia, AST, bifirubin, fibrinogen, PT, WBC, hematocrit, hemoglobin and platelets were compared between the two groups. RESULTS: The lFHF group (n = 108) represented 40% of all patients who presented to UCLA with FHF. 65 out of 108 underwent liver transplantation and 83% survived. 20 of the 108 patients (18.5%) who sur~4ved were not transplanted. The AA-FHF groups represents 7.4% of the IFHF. The mean age in the /LR-FHF and control groups was 6.8 years and 6.1 years, respectively. Interestingly', all patients in the AA-FHF group were males, while the control group consisted of 52% males The admitting liver panels were compared between the two groups and there were no statistically s:gnificant differences seen. However, the AA-FHF subgroup had a significantly lower white blood cell count (WBC) (6.5 vs. 102, p = 0.024) and platelet count (123 vs. 195, p =0.042) on admission as compared to the control group. The AA~FHF group also had significantly fewer lymphocytes when compared to the control group, Moreover, the two groups appear to have a distinct pattern of the WBC and platelet counts when e~,afuated over the immediate post-transplant period, and were distinguishable within the first several post-operative days. CONCLUSIONS: Aplastic anemia is a significant complication that develops in a subset of pediatric patients who present with evidence of indeterminate FHF We have determined that patients with AA-FHF are more often to be males arm have early evidence of bone marrow dysfunction montks prior to developing clear clinical evidence of aplastie anemia. However, hepatic markers on admission were not tbnnd to correlate with the nsk of bone marrow dysfunction in this population,