OBJECTIVETo enrich our national database with data of rare diseases by analyzing molecular diagnosis and hematopoietic stem cell transplantation (HSCT) in children with inherited bone marrow failure syndromes (IBMFS).

METHODNext-generation sequencing (NGS)-based genetic diagnosis panel was applied for the clinical diagnosis and management of IBMFS. Retrospective analysis was performed on clinical and genetic data of 17 consecutive children who received HSCT over a long time interval (November. 2005-June 2015).

RESULTThree patients were diagnosed only by clinical manifestation before 2012. After that NGS-based genetic diagnosis panel was used to identify IBMFS-related genes in 12/14.IBMFS patients (except two Diamond-Blackfan anemia (DBA) patients). Two Fanconi anemia (FA) patients were confirmed to be new variations through family-genotype-analysis and 3 families accepted prenatal diagnosis to avoid birth of affected fetuses. Seventeen IBMFS patients (10 FA,5 DBA and 2 dyskeratosis congenital (DKC)) were treated with HSCT from matched sibling donors (n=2), matched unrelated donors (n=8) or mismatched unrelated donors (n=7). The source of stem cells for transplantation included peripheral blood (n=12) and cord blood (n=5). With regard to the conditioning regimens, FA and DKC patients received fludarabine-based reduced intensity conditioning, while DBA patients received classical busulfan-based myeloablative conditioning. Median age at the time of HSCT was 36 months (7-156 months). The number of infused mononuclear cells and CD34⁺ cells was (10.6 ± 6.7) × 10⁸ and (5.9 ± 7.0) × 10⁶ per kilogram of recipient body weight, respectively. The median number of days to neutrophil recovery was 13 days after HSCT (range: 10-19 days). Platelet recovery was faster in the PBSCT group than in the CBT group ((16.3 ± 6.0) days vs. (30.0 ± 17.1) days,t=-2.487,P=0.026). During a median follow-up of 17 months (range: 2-114 months), except one FA patient who was transplanted with HLA-matched unrelated cord blood (CB) died from pneumonia and heart failure because of engraftment failure, other 16 children are alive after the successful HSCT. The failure-free survival rate of the patients three years after HSCT was 94%.

CONCLUSIONNGS-based molecular diagnosis technology and effective HSCT have significantly facilitated the treatment of children with IBMFS in our country, and our national database about this rare disease is to be further exploited.

Anemia, Aplastic ; Anemia, Diamond-Blackfan ; therapy ; Bone Marrow Diseases ; Child ; Dyskeratosis Congenita ; therapy ; Fanconi Anemia ; therapy ; Fetal Blood ; Hematopoietic Stem Cell Transplantation ; Hemoglobinuria, Paroxysmal ; diagnosis ; genetics ; therapy ; Humans ; Retrospective Studies ; Siblings ; Survival Rate ; Transplantation Conditioning ; Unrelated Donors ; Vidarabine ; analogs & derivatives ; therapeutic use

No abstract available.
Anemia, Aplastic*

No abstract available.
Anemia, Aplastic*

No abstract available.
Anemia, Aplastic*

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Anemia, Aplastic*

No abstract available.
Anemia, Aplastic*

PURPOSE: Paroxysmal nocturnal hemoglobinuria (PNH) has been known to be a late clonal complication of aplastic anemia (AA). Flow cytometric analysis using CD55 and CD59 antibodies became the gold standard of diagnosing PNH, replacing a traditional, less sensitive Ham's test, as the pathophysiologic mechanism was identified as the deficiency of glycophosphatidyl-inositol anchored protein. Although the incidence of AA seems to be higher in Korea than that of other Western countries, the study of PNH in Korean pediatric AA has never been accomplished. We studied the frequency of PNH in AA, and tried to compare the characteristics of them with those from other countries. METHODS: Twenty-two pediatric AA patients were enrolled for the study. As a control, 5 patients with inherited bone marrow failure syndromes (Fanconi anemia, 1; Diamond-Blackfan anemia, 3; dyskeratosis congenita, 1) and 11 normal children were pooled. For the flow cytometry, 10muL each of CD55-PE and CD59-FITC was mixed with 50muL of whole blood and incubated for 15 min. Red cells were lysed with Q-prep apparatus (Coulter, Fullerton, USA). Beckman Coulter XL flow cytometer was used for the analyses. RESULTS: The median age for the patients was 14 years (range, 2~21). CD55- and CD59-negative cells from controls were 0.13+/-0.18%. Cut-off value for the diagnosis for PNH was designated as > 0.49%, which was mean +2 S.D. of controls. All the patients showed CD55- and CD59-negative PNH cell proportions within the normal ranges, except for a 19-year-old boy who was still cyclosporine-dependent after initial response to immunosuppressive therapy 4 years before. He had 4.79% of CD55- and CD59-negative PNH population. CONCLUSION: The frequency of PNH clones in Korean children with AA was low (1/22=4.5%). This might reflect the relatively low association of PNH in childhood AA, the limitation caused by small numbers of the study population, or true ethnic differences. A further study incorporating more patients seems to be warranted.
Anemia ; Anemia, Aplastic* ; Anemia, Diamond-Blackfan ; Antibodies ; Bone Marrow ; Child ; Clone Cells ; Diagnosis ; Dyskeratosis Congenita ; Flow Cytometry* ; Hemoglobinuria, Paroxysmal* ; Humans ; Incidence ; Korea ; Male ; Reference Values ; Young Adult

PURPOSE: The primary purpose of this study was to evaluate the growth and neuropsychologic function following treatments for pediatric hematologic and oncologic diseases. Healthy monozygotic twins served as ideal controls for comparison to exclude possible confounding factors. METHODS: Seven children treated with various hematologic and oncologic diseases were included in the study: acute lymphoblastic leukemia (ALL; n=2), Diamond-Blackfan anemia twins (n=2), and aplastic anemia (n=3). The median age at the diagnosis was 5.2 (0.3-15) years. The median duration of follow-up was 7.2 (4.9-10) years. Controls were healthy monozygotic twins. Growth was measured and the percentile channels were evaluated sequentially for patients. The K-WISC III was applied and compared in 5 pairs of patients and controls. RESULTS: Similar growth profiles were noted for the twins. The percentiles at diagnosis was 3-10 in 3, 25-50 in 2, and 50-75 in 2 cases. All patients stayed in their growth percentiles through follow-up, except for 1 patient who became obese. For IQ tests, the mean behavioral, verbal and full scale IQ scores of patients were 88.0, 93.8, and 89.8, respectively, and those from their corresponding controls were 92.2, 97.0, and 91.7 (P>0.05). However, 2 children who were treated for ALL had lower IQ scores. CONCLUSION: Similar growth profiles were observed in the monozygotic twins in terms of height and weight. The IQ scores of patients were similar to those of monozygotic twins. However, prophylactic CNS-directed therapy for leukemia might adversely affect the IQ scores. A further prospective study on larger number of twins is warranted.
Anemia, Aplastic ; Anemia, Diamond-Blackfan ; Child ; Diagnosis ; Follow-Up Studies ; Humans ; Leukemia ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Stem Cell Transplantation ; Twins, Monozygotic*

BACKGROUND: Fanconi's anemia (FA) is an autosomal recessive disease characterized by aplastic anemia, pre-malignancy, congenital malformations and chromosome breakage syndromes. As up to 30% of patients have no detectable congenital anomalies, the modern diagnosis of FA rests on chromosomal breakage of patient's cells induced by chemical clastogens such as diepoxybutane (DEB) or mitomycin-C (MMC). METHODS: We have done chromosome breakage test to differentiate FA from 11 aplastic anemia, three Diamond-Blackfan syndrome, three myelodysplastic syndrome, one acute leukemia with congenital anomaly and three siblings of FA. The peripheral blood lymphocytes from each individual were co-cultured in phytohemagglutinin-containing medium by the three methods, i.e., DEB treated, MMC treated and un-treated. RESULTS: Five cases were found to have increased chromosomal breakages to DEB and MMC, confirming diagnosis of FA. Other 21 cases showed no increased chromosomal breakages. No overlap was found between FA group and others (P<0.01). In one FA, there was no increased spontaneous breakage, but increased breakage to DEB and MMC. Of five FA, one case showed no congenital anomalies. CONCLUSIONS: Chromosme breakage test was shown to be simple, reliable and useful in ascertaining the diagnosis of FA.
Anemia, Aplastic ; Chromosome Breakage* ; Diagnosis* ; Fanconi Anemia* ; Humans ; Leukemia ; Lymphocytes ; Mitomycin ; Mutagens ; Myelodysplastic Syndromes ; Siblings

No abstract available.
Anemia, Aplastic* ; Preleukemia*