Anemia, Aplastic ; diagnosis ; therapy ; Child ; Diagnosis, Differential ; Humans ; Pediatrics

Severe aplastic anemia (SAA) patients without an HLA-matched sibling donor need alternative treatment options. Umbilical cord blood transplantation (UCBT) has become an alternative means for treating various diseases, but it has not been proved to be a satisfactory method to treat SAA. Here, we report the case of a girl who underwent successful two-unit UCBT after engraftment failure with a single unit. Twounit UCBT is proposed to have better engraftment potential and to offer a better chance of survival, according to some reports. Increased cell dose and graft-versus-graft reaction could contribute to these advantages. With this promising result, two-unit UCBT could be an alternative treatment option for patients with SAA without an HLA-matched donor.
Anemia, Aplastic/diagnosis/*therapy ; Child, Preschool ; *Cord Blood Stem Cell Transplantation ; Female ; Graft vs Host Disease/immunology ; HLA Antigens/immunology ; Histocompatibility ; Humans ; In Situ Hybridization, Fluorescence

Adult ; Aged ; Anemia, Aplastic ; complications ; diagnosis ; therapy ; virology ; Female ; Hepatitis B ; complications ; Hepatitis B virus ; Humans ; Male ; Middle Aged ; Prognosis ; Retrospective Studies ; Young Adult

The pathogenic mechanism of focal segmental glomerulosclerosis (FSGS) and aplastic anemia are associated with immunologic events which lead to glomerular cell injury or hematopoietic cell destruction. We present an extremely rare case of FSGS with aplastic anemia in a 30-yr-old woman. The laboratory examination show-ed hemoglobin 7.2 g/dL, white blood count of 4,200/microliter, platelet count 70,900/microliter. Proteinuria (2+, 3.6 g/day) and microscopic hematuria were detected in urinalysis. The diagnosis of FSGS and aplastic anemia were confirmed by renal and bone marrow biopsy. She was treated with immunosuppressive therapy of prednisone 60 mg/day orally for 8 weeks and cyclosporine A 15 mg/kg/day orally. She responded with gradually improving her clinical manifestation and increasing peripheral blood cell counts. Prednisone was maintained at the adequate doses with tapering after 8 weeks and cyclosporine was given to achieve trough serum levels of 100-200 ng/mL. At review ten month after diagnosis and initial therapy, the patient was feeling well and her blood cell counts increased to near normal (Hb 9.5 g/dL, Hct 32%, WBC 8,300/microliter, platelet 123,000/microliter) and renal function maintains stable with normal range proteinuria (0.25 g/day).
Adult ; Anemia, Aplastic/*complications/*diagnosis/drug therapy ; Cyclosporine/administration & dosage ; Female ; Glomerulosclerosis, Focal/*complications/*diagnosis/drug therapy ; Humans ; Immunosuppressive Agents/administration & dosage ; Prednisone/administration & dosage ; Rare Diseases/complications/diagnosis/therapy ; Research Support, Non-U.S. Gov't ; Treatment Outcome

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

Anemia, Aplastic ; diagnosis ; therapy ; Blood Transfusion ; Bone Marrow Examination ; Child ; Diagnosis, Differential ; Graft vs Host Disease ; prevention & control ; Hematopoietic Stem Cell Transplantation ; Humans ; Immunosuppressive Agents ; therapeutic use ; Transplantation, Homologous

OBJECTIVE: Hepatic dysfunction frequently occurs in patients with hematologic malignancies and aplastic anemia who receive intensive chemotherapy or bone marrow transplantation (BMT). The role of laparoscopic liver biopsy in patients with hematologic disorders is very important to determine the etiological factors and to make treatment decisions. The aim of the present study was to evaluate the possible causes of liver disease in patients with abnormal liver function tests. METHODS: Laparoscopy guided liver biopsy was performed in 38 subjects who were receiving intensive cytotoxic therapy with BMT or without BMT. Two to three pieces of liver tissues were obtained in each patients using Vim-Silverman needle with electrocoagulation on biopsy site. Platelet transfusions were given if platelet count was less than 50,000/mm3. 39 biopsies were obtained in 38 patients. RESULTS: At the time of liver biopsy, platelet count was 170,000+/-138000/mm3 (range: 42,000 - 798,000/mm3). No procedure-related complications were observed. Biopsy findings after BMT (n=16) revealed graft versus host disease (GVHD) (n=9), drug induced hepatitis (n=6), veno-occlusive disease (n=2), viral hepatitis (n=1), and nonspecific reactive hepatitis (n=1). 3 patients of GVHD associated with other liver diseases such as drug-induced hepatitis, veno-occlusive disease and chronic active hepatitis B. The authors compared histologic diagnosis with laparoscopic findings. Laparoscopic findings of the liver surface were classified by Shimada's code number system. 5 patients who were biopsed before BMT showed cholestasis and fatty changes and it was possible to be treated with allogenic BMT. Histologic diagnosis in patients without BMT (n=18) showed viral hepatitis (n=6), drug induced hepatitis (n=5), non-specific reactive hepatitis (n=1), and others (n=6). In 12 cases (31%) laparoscopic liver biopsy led to a change in medical management. CONCLUSION: Laparascopic liver biopsy has been proven to be an effective means of assessing the cause of liver dysfunction in patients with hematologic disorders. The diagnosis obtained at laparoscopic liver biopsy could be changed the therapeutic plan in 12 of 39 (31%) patients.
Anemia, Aplastic ; Biopsy* ; Bone Marrow Transplantation ; Cholestasis ; Diagnosis ; Drug Therapy ; Drug-Induced Liver Injury ; Electrocoagulation ; Graft vs Host Disease ; Hematologic Neoplasms ; Hepatitis ; Hepatitis, Chronic ; Humans ; Laparoscopy ; Liver Diseases ; Liver Function Tests ; Liver* ; Needles ; Platelet Count ; Platelet Transfusion

Recent advances in the treatment of aplastic anemia (AA) made most of patients to expect to achieve a long-term survival. Allogeneic stem cell transplantation (SCT) from HLA-matched sibling donor (MSD-SCT) is a preferred first-line treatment option for younger patients with severe or very severe AA, whereas immunosuppressive treatment (IST) is an alternative option for others. Horse anti-thymocyte globuline (ATG) with cyclosporin A (CsA) had been a standard IST regimen with acceptable response rate. Recently, horse ATG had been not available and replaced with rabbit ATG in most countries. Subsequently, recent comparative studies showed that the outcomes of patients who received rabbit ATG/CsA were similar or inferior compared to those who received horse ATG/CsA. Therefore, further studies to improve the outcomes of IST, including additional eltrombopag, are necessary. On the other hand, the upper age limit of patients who are able to receive MSD-SCT as first-line treatment is a current issue because of favorable outcomes of MSD-SCT of older patients using fludarabine-based conditioning. In addition, further studies to improve the outcomes of patients who receive allogeneic SCT from alternative donors are needed. In this review, current issues and the newly emerging trends that may improve their outcomes in near futures will be discussed focusing the management of patients with AA.
Anemia, Aplastic/blood/diagnosis/mortality/*therapy ; Humans ; Immunosuppressive Agents/adverse effects/*therapeutic use ; Iron Chelating Agents/adverse effects/*therapeutic use ; Risk Factors ; *Stem Cell Transplantation/adverse effects/mortality ; Survival Analysis ; Time Factors ; Treatment Outcome

BACKGROUND: We analyzed T cell receptor beta chain (TCRB) gene to investigate the presence of putative T cell clones and its clinicopathologic implications in Korean patients with aplastic anemia (AA). METHODS: Twenty-nine bone marrow specimens were collected from 20 AA patients, 19 specimens from initial diagnosis and 10 from follow-up. T cell clonality assay was performed using IdentiClone(TM) TCRB Gene Clonality Assay kit (InVivoScirbe Technology, USA) and automatic genetic analyzer. Patients' clinical information and laboratory parameters were also analyzed. RESULTS: Five patients had definitive underlying factors related with aplastic anemia, such as hepatitis B virus (4 cases) and benzene exposure (1 case). Putative T cell clones were detected in bone marrow specimens of 11 (58%) out of 19 patients at diagnosis. The location of putative T cell clones of TCRB gene (diversity region, Dbeta; joining region, Jbeta; variable region, Vbeta) was distributed in Dbeta2+Jbeta2 (6 cases), Dbeta1+Jbeta1 (3 cases), Vbeta+Jbeta1 (2 cases), and Dbeta1+Jbeta2 (2 cases). Interestingly, among seven patients who underwent stem cell transplantation, five patients with no T cell clones detected at diagnosis developed new T cell clones during the follow-up. CONCLUSIONS: Putative pathogenetic T cell clones were detected in most of AA patients in the current study. T cell clonality assay would be useful for investigating the pathophysiology of acquired AA.
Adolescent ; Adult ; Aged ; Anemia, Aplastic/*diagnosis/genetics/therapy ; Bone Marrow Transplantation ; Female ; Humans ; Male ; Middle Aged ; Reagent Kits, Diagnostic ; Receptors, Antigen, T-Cell, alpha-beta/*genetics ; Republic of Korea ; T-Lymphocytes/*cytology/immunology

OBJECTIVETo investigate prognostic factors of immunosuppressive therapy (IST) in children acquired severe aplastic anemia(SAA).

METHODSData of 56 consecutive children cases with SAA who had received rabbit anti-thymocyte globulin (R-ATG) [3-5 mg/( kg x d) x 5 d] and cyclosporine A (CSA) from January 2000 to June 2006 were retrospectively analyzed. No repeated courses of R-ATG were given for nonresponders. All the patients also received stanozolol or testosterone propionate. The dose of CSA was adjusted to maintain trough drug levels above 100 microg/L and peak drug levels above 300 microg/L.

RESULTSThe overall response rate to the immunosuppressive therapy (IST) was 62.5% and the complete remission rate was 37.5%. The 5-year overall survival for IST regimens was 66.27% +/- 6.84%, patients who had infections when using ATG had significantly lower response and higher mortality. Patients whose nucleated erythrocyte population in bone marrow was > or =10% had good prognosis. Patients whose granulocytes population in bone marrow was > or =10% had lower mortality.

CONCLUSIONPatients who had infections when using ATG had significantly lower response and higher mortality. Patients whose nucleated erythrocyte population in bone marrow was > or =10% had good prognosis.

Adolescent ; Anemia, Aplastic ; diagnosis ; etiology ; therapy ; Animals ; Antilymphocyte Serum ; therapeutic use ; Child ; Child, Preschool ; Cyclosporine ; therapeutic use ; Female ; Humans ; Immunosuppression ; Immunosuppressive Agents ; therapeutic use ; Infant ; Male ; Prognosis ; Rabbits ; Retrospective Studies ; Treatment Outcome