Effect of serum panel reactive antibodies on allogeneic hematopoietic stem cell transplantation in pediatric thalassemia patients: A single-center experience.

BACKGROUND: The aim of this study was to assess the impact of serum panel reactive antibodies (PRA) on the outcomes of allogeneic hematopoietic stem cell transplantation (HSCT) in pediatric thalassemia patients. METHODS: A total of 73 pediatric patients with thalassemia were included in this single-center study. Pre-transplant PRA levels were evaluated, and the patients were divided into two groups: PRA-negative (group 1; n = 44) and PRA-positive (group 2; n = 29). Patient characteristics, including age, gender, donor type, stem cell source, and HLA compatibility, were analyzed. Transplant outcomes, including engraftment, transfusion requirements, and transplant-related complications, were compared between the two groups. Further subgroup analysis was performed based on MFI values. RESULTS: At the time of transplantation, patients in group 1 were younger than those in group 2 (p = .008). The number of fully matched donors within the family (MSD and MFD) was significantly higher in group 1 (p = .049). Additionally, Rh blood group incompatibility was higher in group 2 (p = .03). There was no statistically significant difference in the engraftment days of neutrophils, platelets, and erythrocytes between the two groups. The frequency of poor graft function and graft failure was higher in the group 2, but there was no statistically significant difference. Post-transplant transfusion requirements for platelets and red blood cells were significantly higher in the group 2 (p < .001). Transplant-related complications such as VOD, PRES, and aGvHD were more common in the group 2, but no statistical significance was detected. CONCLUSIONS: Serum PRA in pediatric thalassemia patients may impact the outcomes of HSCT. PRA-positive patients had higher rates of blood product transfusion requirements. Although poor graft function, graft failure, and post-transplant complications were more common in the group 2, statistical significance was not observed. Identifying patients with high PRA levels can assist in optimizing transplant strategies and post-transplant care, leading to improved outcomes for the patients.

COVID-19 disease in children and adolescents following allogeneic hematopoietic stem cell transplantation: A report from the Turkish pediatric bone marrow transplantation study group.

BACKGROUND: Data on the risk factors and outcomes for pediatric patients with SARS-CoV-2 infection (COVID-19) following hematopoietic stem cell transplantation (HSCT) are limited. OBJECTIVES: The study aimed to analyze the clinical signs, risk factors, and outcomes for ICU admission and mortality in a large pediatric cohort who underwent allogeneic HSCT prior to COVID-19 infection. METHOD: In this nationwide study, we retrospectively reviewed the data of 184 pediatric HSCT recipients who had COVID-19 between March 2020 and August 2022. RESULTS: The median time from HSCT to COVID-19 infection was 209.0 days (IQR, 111.7-340.8; range, 0-3845 days). The most common clinical manifestation was fever (58.7%). While most patients (78.8%) had asymptomatic/mild disease, the disease severity was moderate in 9.2% and severe and critical in 4.4% and 7.6%, respectively. The overall mortality was 10.9% (n: 20). Deaths were attributable to COVID-19 in nine (4.9%) patients. Multivariate analysis revealed that lower respiratory tract disease (LRTD) (OR, 23.20, p: .001) and lymphopenia at diagnosis (OR, 5.21, p: .006) were risk factors for ICU admission and that HSCT from a mismatched donor (OR, 54.04, p: .028), multisystem inflammatory syndrome in children (MIS-C) (OR, 31.07, p: .003), and LRTD (OR, 10.11, p: .035) were associated with a higher risk for COVID-19-related mortality. CONCLUSION: While COVID-19 is mostly asymptomatic or mild in pediatric transplant recipients, it can cause ICU admission in those with LRTD or lymphopenia at diagnosis and may be more fatal in those who are transplanted from a mismatched donor and those who develop MIS-C or LRTD.

A homozygous duplication of the FGG exon 8-intron 8 junction causes congenital afibrinogenemia. Lessons learned from the study of a large consanguineous Turkish family.

Congenital afibrinogenemia is the most severe congenital fibrinogen disorder, characterized by undetectable fibrinogen in circulation. Causative mutations can be divided into two main classes: null mutations with no protein production at all and missense mutations producing abnormal protein chains that are retained inside the cell. The vast majority of cases are due to single base pair mutations or small insertions or deletions in the coding regions or intron-exon junctions of FGB, FGA and FGG. Only a few large rearrangements have been described, all deletions involving FGA. Here we report the characterization of a 403 bp duplication of the FGG exon 8-intron 8 junction accounting for congenital afibrinogenemia in a large consanguineous family from Turkey. This mutation, which had escaped detection by Sanger sequencing of short polymerase chain reaction (PCR) amplicons of coding sequences and splice sites, was identified by studying multiple alignments of reads obtained from whole exome sequencing of a heterozygous individual followed by PCR amplification and sequencing of a larger portion of FGG. Because the mutation duplicates the donor splice site of intron 8, we predicted that the impact of the mutation would be on FGG transcript splicing. Analysis of mRNA produced by cells transiently transfected with normal or mutant minigene constructs showed that the duplication causes production of several aberrant FGG transcripts generating premature truncating codons.

Hepatitis-Associated Aplastic Anemia: Etiology, Clinical Characteristics and Outcome.

Hepatitis-associated aplastic anemia (HAA) is a form of acquired aplastic anemia (AA) in which bone marrow failure develops after an acute attack of hepatitis. Bone marrow failure leading to AA is generally severe in cases of HAA and fatal if left untreated. This retrospective multicenter study investigated clinical and laboratory characteristics, possible causes, treatment, and outcome of HAA in children. Twenty patients from 8 centers were included in the study. Aspartate aminotransferase and alanine aminotransferase were <3 to 5×upper limit of normal (ULN) in 2 patients, <5 to 10×ULN in 2 patients, and >10×ULN in 16 patients. Acute liver failure developed in 5 (29%) patients. Pancytopenia was simultaneously present in 6 of 20 (30%) patients. Eleven of the 20 patients (55%) were alive, in remission and transfusion free. Those who were alive either had undergone hematopoietic stem cell transplantation and/or immunosuppressive treatment, except 1 patient who had received no treatment. Patients with the diagnosis of acute hepatitis should be evaluated and followed up carefully for presence of cytopenia, so that definitive treatment of AA can be initiated in a timely and appropriate manner when needed.

Posterior Reversible Encephalopathy Syndrome in Childhood Hematological/Oncological Diseases: Multicenter Results.

The aim of the study was to analyze the characteristics of posterior reversible encephalopathy syndrome (PRES) cases treated at 10 different institutions in our country. Fifty-eight patients diagnosed with PRES were included in this study. The data of PRES cases from 10 departments of pediatric hematology/oncology were analyzed. The mean age of the patients at the time of diagnosis of PRES was 8.95±3.66 years. Most patients (80.4%) had a primary diagnosis of acute leukemia. Patients received chemotherapy (71.4%) and/or used steroids within 14 days before the diagnosis of PRES (85.7%). Hypertension was found in 83.9% of the patients. Twenty-six patients had infections and 22 of them had febrile neutropenia. The most common electrolyte disorders were hypocalcemia, hypomagnesemia, and hypopotassemia. Six patients had tumor lysis syndrome and 4 had inappropriate antidiuretic hormone syndrome. Magnetic resonance imaging was used for diagnosis in all patients. The most commonly involved regions by magnetic resonance imaging were occipital (58%), parietal (51%), and frontal lobes (45%), respectively. Twenty-five patients required intensive care and 7 patients were intubated. In conclusion, PRES may develop during the follow-up and treatment of hematological diseases. In addition to steroid and intense combined chemotherapies, immunosuppressive agents and hypertension are also factors that may be responsible for PRES.

Ifosfamide induced encephalopathy in a child with osteosarcoma.

BACKGROUND: Ifosfamide (IFO) is an alkylating agent used to treat broad range of malignancies. One of the life-threatening toxic effects is reversible neurotoxicity. In this report; we presented a case report of ifosfamide induced encephalopathy (IIE) in a child with osteosarcoma in order to emphize that it is important to continue ifosfamide treatment as well as the importance of this potentially fatal complication. CASE REPORT: Following the 20th week of ifosfamide treatment, the patient's follow-up with the diagnosis of osteosarcoma developed neurological findings. Laboratory analyzes before and after ifosfamide infusion were normal. No pathological findings were seen on MR imaging. Hypoglycemia, electrolyte disturbances, encephalitis, meningitis, metastasis and posterior reversible encephalopathy syndrome (PRES) were not considered. Electroencephalography was found compatible with neuronal hyperexcitability originating from the left hemisphere. With the diagnosis of ifosfamide induced encephalopathy, prophylaxis with methylene blue was received before the next infusion of ifosfamide. Neurological findings were not observed in the patient's follow-up. CONCLUSION: Patients who develop IIE can continue their treatment protocol with methylene blue prophylaxis and supportive therapy.

Ophthalmologic findings and complications before and after hematopoietic stem cell transplantation: single-center study.

PURPOSE: Different and various system complications and late effects may occur after hematopoietic stem cell transplantation (HSCT). It was aimed to obtain information about the frequency of ophthalmologic complications and their relationship with treatment. METHODS: This retrospective study includes 104 children who underwent HSCT between February 2019 and June 2020 at the Pediatric Bone Marrow Transplant Unit. Patients' ages, genders, diagnosis, transplant types, chemotherapy regimens, transplantation details, conditioning regimens, supportive cares, graft versus host disease (GvHD) prophylaxis, infection episodes, and ophthalmologic findings were evaluated. RESULTS: Of the 104 patients included in the study, 38 (36.5%) were female and 66 (63.5%) were male. Average age ± SD was 8.7 ± 4.91. Considering the diagnoses, the majority of the patients were acute lymphoblastic leukemia (46 patients-44%). Myeloablative regimen was used in 93 (89%) of the patients, and reduced intensity conditioning (RIC) was used in 11 patients (10%). While total body irradiation was applied in 16 (15%) patients, one patient was received cranial radiotherapy. Cyclosporine was used in 96 (92%) patients. CMV reactivation was detected in 54 (51%) of the patients. CMV retinitis was not seen. Ocular pathology was detected in 20 (19%) patients before HSCT and in 12 (11%) patients after HSCT. The most common pathology was dry eye. CONCLUSION: Routine ophthalmologic examinations are important in terms of early diagnosis. In addition, GvHD and CMV prophylaxis is important because of reducing the risk of ocular complications after HSCT.

Refugee children with beta-thalassemia in Turkey: Overview of demographic, socioeconomic, and medical characteristics.

AIM: Since the beginning of the Syrian civil war, more than 3.5 million Syrians have been under temporary protection status in Turkey. Because beta-thalassemia (BT) is a prevalent disorder in the Mediterranean countries, we decided to estimate the prevalence of and make an overview of the demographic, socioeconomic, medical characteristics, and healthcare problems of refugee children with BT. PATIENTS: Eighteen Turkish Pediatric Hematology Oncology Centers (PHOC) with 318 refugee children from 235 families participated in the study. The mean age of the patients was 8.1 ± 4.8 years (0.5-21 years). The mean time after immigration to Turkey was 2.5 ± 1.5 years (range, 0.1-7 years). Seventy-two (22.6%) of them were born and diagnosed with BT in Turkey. On physical examination, 82 patients (26%) were underweight and 121 patients (38%) were stunted. The appearance of a thalassemic face was reported for 207 patients (65.1%). Hepatomegaly and splenomegaly were reported in 217 (68.2%) and 168 (52.8%) patients, respectively. The median ferritin level was 2508 ng/mL (range, 17-21 000 ng/mL) at the first admission, and 2841 ng/mL (range, 26-12 981 ng/mL) at the last visit after two years of follow-up in a PHOC (P > 0.05). The most frequently encountered mutation was IVSI-110 (G>A) (31%). Before immigration, only 177 patients (55.6%) reported the use of chelators; after immigration it increased to 268 (84.3%). CONCLUSION: Difficulties in communication, finding a competent translator capable in medical terminology, nonregular use of medications, and insensitivity to prenatal diagnosis were preliminary problems. The current extent of migration poses emerging socioeconomic and humanitarian challenges for refugee patients with BT.

A Case of Allergic Broncopulmonary Aspergillosis Associated With Hematopoietic Stem Cell Transplantation Due to Chronic Granulomatous Disease.

Allergic bronchopulmonary aspergillosis is an immunologic pulmonary disorder caused by hypersensitivity to Aspergillus fumigatus. This disorder is most commonly seen in patients with poorly controlled asthma and cystic fibrosis. It is rarely reported in chronic granulomatous disease patients; however, there are no cases reported with hematopoietic stem cell transplantation in the English literature. Herein, we report a patient with chronic granulomatous disease who had hematopoietic stem cell transplantation and subsequently developed allergic bronchopulmonary aspergillosis.

Phenotype and genotype of 87 patients with Mowat-Wilson syndrome and recommendations for care.

PURPOSE: Mowat-Wilson syndrome (MWS) is a rare intellectual disability/multiple congenital anomalies syndrome caused by heterozygous mutation of the ZEB2 gene. It is generally underestimated because its rarity and phenotypic variability sometimes make it difficult to recognize. Here, we aimed to better delineate the phenotype, natural history, and genotype-phenotype correlations of MWS. METHODS: In a collaborative study, we analyzed clinical data for 87 patients with molecularly confirmed diagnosis. We described the prevalence of all clinical aspects, including attainment of neurodevelopmental milestones, and compared the data with the various types of underlying ZEB2 pathogenic variations. RESULTS: All anthropometric, somatic, and behavioral features reported here outline a variable but highly consistent phenotype. By presenting the most comprehensive evaluation of MWS to date, we define its clinical evolution occurring with age and derive suggestions for patient management. Furthermore, we observe that its severity correlates with the kind of ZEB2 variation involved, ranging from ZEB2 locus deletions, associated with severe phenotypes, to rare nonmissense intragenic mutations predicted to preserve some ZEB2 protein functionality, accompanying milder clinical presentations. CONCLUSION: Knowledge of the phenotypic spectrum of MWS and its correlation with the genotype will improve its detection rate and the prediction of its features, thus improving patient care.

Neuroimaging findings in Mowat-Wilson syndrome: a study of 54 patients.

PURPOSE: Mowat-Wilson syndrome (MWS) is a genetic disease characterized by distinctive facial features, moderate to severe intellectual disability, and congenital malformations, including Hirschsprung disease, genital and eye anomalies, and congenital heart defects, caused by haploinsufficiency of the ZEB2 gene. To date, no characteristic pattern of brain dysmorphology in MWS has been defined. METHODS: Through brain magnetic resonance imaging (MRI) analysis, we delineated a neuroimaging phenotype in 54 MWS patients with a proven ZEB2 defect, compared it with the features identified in a thorough review of published cases, and evaluated genotype-phenotype correlations. RESULTS: Ninety-six percent of patients had abnormal MRI results. The most common features were anomalies of corpus callosum (79.6% of cases), hippocampal abnormalities (77.8%), enlargement of cerebral ventricles (68.5%), and white matter abnormalities (reduction of thickness 40.7%, localized signal alterations 22.2%). Other consistent findings were large basal ganglia, cortical, and cerebellar malformations. Most features were underrepresented in the literature. We also found ZEB2 variations leading to synthesis of a defective protein to be favorable for psychomotor development and some epilepsy features but also associated with corpus callosum agenesis. CONCLUSION: This study delineated the spectrum of brain anomalies in MWS and provided new insights into the role of ZEB2 in neurodevelopment.Genet Med advance online publication 10 November 2016.

Lupus Anticoagulant Positivity in Pediatric Patients With Prolonged Activated Partial Thromboplastin Time: A Single-Center Experience and Review of Literature.

The presence of lupus anticoagulants (LAs) is an important cause of activated partial thromboplastin time (aPTT) prolongation found in children after an infection or during screening tests before surgical intervention. The authors retrospectively reviewed the charts of 68 patients who have been consulted from surgery departments with prolonged aPTT. These patients were reevaluated with aPTT analysis after 1 week. Thirteen patients had normal aPTTs. Therefore, 55 patients remained with prolonged aPTTs. LA positivity was detected in 39 patients. Sixteen of these had prolonged aPTT prior to surgery (41%). Others with LA positivity had systemic lupus erythematosus (SLE; n = 6), infection (n = 5), leukemia (n = 3), hemolytic uremic syndrome (n = 2), epistaxis (n = 2), antiphospholipid syndrome (APS; n = 1), chronic immune thrombocytopenic purpura (n = 1), acute poststreptococcal glomerulonephritis (n = 1), central nervous system (CNS) thrombosis (n = 1), and congenital heart disease (n = 1). None of the patients had bleeding history. LA positivity rarely leads to bleeding and/or thrombosis. Specific therapy is usually not needed. Further prospective multicenter studies are required to understand clinical outcomes and laboratory correlation in children with positive LA.

CHARGE-like presentation, craniosynostosis and mild Mowat-Wilson Syndrome diagnosed by recognition of the distinctive facial gestalt in a cohort of 28 new cases.

Mowat-Wilson syndrome (MWS) is characterized by moderate to severe intellectual disability and distinctive facial features in association with variable structural congenital anomalies/clinical features including congenital heart disease, Hirschsprung disease, hypospadias, agenesis of the corpus callosum, short stature, epilepsy, and microcephaly. Less common clinical features include ocular anomalies, craniosynostosis, mild intellectual disability, and choanal atresia. These cases may be more difficult to diagnose. In this report, we add 28 MWS patients with molecular confirmation of ZEB2 mutation, including seven with an uncommon presenting feature. Among the "unusual" patients, two patients had clinical features of charge syndrome including choanal atresia, coloboma, cardiac defects, genitourinary anomaly (1/2), and severe intellectual disability; two patients had craniosynostosis; and three patients had mild intellectual disability. Sixteen patients have previously-unreported mutations in ZEB2. Genotype-phenotype correlations were suggested in those with mild intellectual disability (two had a novel missense mutation in ZEB2, one with novel splice site mutation). This report increases the number of reported patients with MWS with unusual features, and is the first report of MWS in children previously thought to have CHARGE syndrome. These patients highlight the importance of facial gestalt in the accurate identification of MWS when less common features are present.

Aplastic anemia and Hoyeraal-Hreidarsson syndrome.

A 2-year-old girl patient was admitted with intractable diarrhea, respiratory infections, and seizures. She was the first child of the first-degree parents. She was born at term with a birth weight of 2300 g. Physical examination revealed weight 6800 g, height 76 cm, and head circumference 41 cm, below the third percentile. Findings included sparse and dull hair, nail dystrophy, and proximally located thumbs (Figure). Aphthous lesions were observed on the oral mucosa. Neurologic examination disclosed poor head control. She could not sit without support and had hyper-reactive deep tendon reflexes.

Epilepsy in Mowat-Wilson syndrome: delineation of the electroclinical phenotype.

Mowat-Wilson syndrome (MWS) is a genetic disease caused by heterozygous mutations or deletions of the ZEB2 gene and is characterized by distinctive facial features, epilepsy, moderate to severe intellectual disability, corpus callosum abnormalities and other congenital malformations. Epilepsy is considered a main manifestation of the syndrome, with a prevalence of about 70-75%. In order to delineate the electroclinical phenotype of epilepsy in MWS, we investigated epilepsy onset and evolution, including seizure types, EEG features, and response to anti-epileptic therapies in 22 patients with genetically confirmed MWS. Onset of seizures occurred at a median age of 14.5 months (range: 1-108 months). The main seizure types were focal and atypical absence seizures. In all patients the first seizure was a focal seizure, often precipitated by fever. The semiology was variable, including hypomotor, versive, or focal clonic manifestations; frequency ranged from daily to sporadic. Focal seizures were more frequent during drowsiness and sleep. In 13 patients, atypical absence seizures appeared later in the course of the disease, usually after the age of 4 years. Epilepsy was usually quite difficult to treat: seizure freedom was achieved in nine out of the 20 treated patients. At epilepsy onset, the EEGs were normal or showed only mild slowing of background activity. During follow-up, irregular, diffuse frontally dominant and occasionally asymmetric spike and waves discharges were seen in most patients. Sleep markedly activated these abnormalities, resulting in continuous or near-to-continuous spike and wave activity during slow wave sleep. Slowing of background activity and poverty of physiological sleep features were seen in most patients. Our data suggest that a distinct electroclinical phenotype, characterized by focal and atypical absence seizures, often preceded by febrile seizures, and age-dependent EEG changes, can be recognized in most patients with MWS.

Low serum lipocalin levels in patients with iron deficiency anemia.

In the recent literature, there are studies on the relationship between anemia and lipocalin, but there is no study regarding the relationship between lipocalin and iron deficiency anemia (IDA) up to date. In this study, we aimed to observe lipocalin levels at admission, and after iron therapy in children with IDA. We also compared our findings to those in healthy children. Sixty-one children admitted in our outpatient clinic were included in the study. Thirty of these children had IDA (study group) and the rest were healthy (control group). Thirty patients, meeting the IDA criteria, received oral ferrous sulfate of 4 mg/kg/d. As soon as the hemoglobin value reached >11 g/dL, half dose of oral ferrous sulfate therapy was continued for another month. Serum lipocalin levels before and after iron therapies were compared. Hematologic parameters and serum lipocalin levels were also compared between the 2 groups. Mean values of serum lipocalin were 31.01±14.46 and 74.77 ng/dL in patients with IDA at admission and at third month of therapy, respectively (P<0.0001). The same figure was 57.35±39.51 ng/dL in the control group. Before treatment, mean values of lipocalin levels in patients with IDA was significantly lower than the control group (P=0.001); however, such a difference was not detected after 3 months of therapy (P=0.102). We suggest that decreased serum lipocalin levels in our patients during iron insufficiency were caused by iron deficiency rather than anemia.

Effects of Zinc Sulfate Supplementation in Treatment of Iron Defi ciency Anemia.

OBJECTIVE: In this study, we aimed to compare the effect(s) of zinc sulphate on growth and serum iron variables when it is given with ferrous sulphate in iron deficiency anemia (IDA). MATERIALS AND METHODS: Patients (n=79) were randomly divided into two groups. In one group (n=40) 4 mg/kg/d ferrous sulfate was given orally. In the other group (n=39), in addition to ferrous sulfate, 5 mg/d oral zinc sulfate was given. RESULTS: Compared to the initial values statistically significant increase in mean height, weight, and head circumference has been observed in both groups after 3 months. However, there was no statistical difference between two groups concerning mean height, weight, and head circumference at the beginning (83.43±11.3 cm vs 84.62±12.77 cm; 12.36±3.08 kg vs 12.72±3.87 kg; 47.33±2.15 cm vs 47.26±2.73 cm, respectively), at the first month, (84.82±10.97 vs 85.97±12.28; 12.78±3.09 vs 13.09±3.87; 47.76±2.10 vs 47.61±2.67, respectively), and at the third month, (86.4±11.12 vs 87.69±12.13; 12.9±3.06 vs 13.35±3.81; 48.22±1.89 vs 48.07±2.45, respectively). There were no statistical differences between mean hematological parameters of the groups at the beginning, at the first month, and at the third month, either (mean hb of Group 1: 8.78±1.12 g/dL; 11.27±1.09 g/ dL; 12.05±1.00 g/dL respectively and of Group 2: 9.10±1.07 g/dL; 11.12±0.85 g/dL; 11.80±0.79 g/dL, respectively). Mean ferritin and zinc values of the groups were statistically insignificant at the beginning (Mean ferritin: 4.96±4.03 µg/dL vs 4.52±2.94 µg/dL, zinc: 88.64±15.35 ng/mL vs 86.84±17.34 ng/mL). Their increase was statistically significant at the third month (mean ferritin: 15.91±9.57 µg/dL vs 15.25±10.47 µg/dL; zinc: 88.02±15.10 ng/mL vs 95.25±16.55 ng/mL). CONCLUSION: In our study neither positive nor negative effect of zinc administration on IDA treatment was demonstrated. Therefore, in the treatment of IDA zinc together with iron should be used at different times if there is coexistent zinc deficiency. CONFLICT OF INTEREST: None declared.

cDNA sequencing increases the molecular diagnostic yield in Chediak-Higashi syndrome.

Introduction: Chediak-Higashi syndrome (CHS) is rare autosomal recessive disorder caused by bi-allelic variants in the Lysosomal Trafficking Regulator (LYST) gene. Diagnosis is established by the detection of pathogenic variants in LYST in combination with clinical evidence of disease. Conventional molecular genetic testing of LYST by genomic DNA (gDNA) Sanger sequencing detects the majority of pathogenic variants, but some remain undetected for several individuals clinically diagnosed with CHS. In this study, cDNA Sanger sequencing was pursued as a complementary method to identify variant alleles that are undetected by gDNA Sanger sequencing and to increase molecular diagnostic yield. Methods: Six unrelated individuals with CHS were clinically evaluated and included in this study. gDNA Sanger sequencing and cDNA Sanger sequencing were performed to identify pathogenic LYST variants. Results: Ten novel LYST alleles were identified, including eight nonsense or frameshift variants and two in-frame deletions. Six of these were identified by conventional gDNA Sanger sequencing; cDNA Sanger sequencing was required to identify the remaining variant alleles. Conclusion: By utilizing cDNA sequencing as a complementary technique to identify LYST variants, a complete molecular diagnosis was obtained for all six CHS patients. In this small CHS cohort, the molecular diagnostic yield was increased, and canonical splice site variants identified from gDNA Sanger sequencing were validated by cDNA sequencing. The identification of novel LYST alleles will aid in diagnosing patients and these molecular diagnoses will also lead to genetic counseling, access to services and treatments and clinical trials in the future.

Successful treatment of ICE-rituximab chemotherapy and subsequent bone marrow transplantation in a patient with early-relapse Burkitt leukemia and inverted duplication of 1q.

Although childhood acute lymphoblastic leukemias are of good prognosis than leukemias of adulthood, some chromosomal abnormalities may have negative effects on their prognosis. Inverted duplication (1q) is a chromosomal abnormality with negative effect on outcome of Burkitt leukemia and lymphomas. We report a case of CD20 Burkitt leukemia with inverted duplication (1q) mutation, who had an early relapse during NHL-BFM 95 treatment. Two courses of ICE-rituximab treatment were administered after relapse and a successful HLA-full match bone marrow transplantation was carried out. He is in follow-up for 18 months without any problem after the bone marrow transplantation. We suggest the usage of ICE protocol combined with rituximab in childhood CD20 Burkitt leukemia with poor prognostic criteria such as inverted duplication (1q) mutation.