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Aplastic Anemia (aplastic + anemia)
Kinds of Aplastic Anemia Selected AbstractsAPLASTIC ANEMIA , PATHOPHYSIOLOGY AND TREATMENT.HEMATOLOGICAL ONCOLOGY, Issue 3 20012000. No abstract is available for this article. [source] Excessive production of tumor necrosis factor-alpha by bone marrow T lymphocytes is essential in causing bone marrow failure in patients with aplastic anemiaEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 1 2004Takeshi Hara Abstract:, Aplastic anemia (AA) is regarded as an immunological disorder because of the clinical effect of immunosuppressive therapy. Recent studies have reported that cytokines play an important role in the development of AA. In the present study, we measured levels of T-cell derived intracellular cytokine production in peripheral blood and bone marrow (BM) of patients with AA. We demonstrated that BM lymphocytes, particularly CD4+ and CD8+ T cells, in patients with AA produced significantly higher amounts of tumor necrosis factor-alpha (TNF- ,), compared with lymphocytes in normal controls. We have previously reported that expression of TNF receptor (R)1 and TNFR2 in the CD34+ CD38, and CD34+ CD38+ fractions of patients with AA is significantly higher than those in normal control. These results indicate that BM stem cells in patients with AA may possess high sensitivity to TNF- ,. This in turn suggests that TNF- , affects hematopoiesis at an earlier stage in AA patients than in normal controls. We strongly support the hypothesis that a simultaneous increase in TNF- , production by BM lymphocytes and sensitivity of stem cells to TNF- , leads to BM failure in AA. [source] Post-liver-transplant anemia: Etiology and managementLIVER TRANSPLANTATION, Issue 2 2004Anurag Maheshwari Anemia is common after liver transplantation, with the incidence ranging from 4.3% to 28.2% depending on the criteria used to define anemia. The cause of anemia is unidentified in the majority of patients, and it is likely to be multifactorial. Immunosuppressive-medication-induced bone marrow suppression is perhaps the most common cause of unexplained anemia. Chronic blood loss, iron deficiency, hemolysis, and renal insufficiency are other potential causes of chronic anemia. Rare causes, somewhat unique to transplantation, include aplastic anemia, graft-versus-host disease (GVHD), and lymphoproliferative disease. Anemia due to immunosuppressive medication is challenging, since almost all drugs currently used for this purpose cause anemia, but the renal-sparing property of sirolimus may benefit the subgroup in which renal insufficiency is contributing to anemia. Aplastic anemia is seen in young patients transplanted for non-A, non-B, non-C, fulminant hepatic failure. It is thought to be immunologically mediated, secondary to an unknown viral infection, and is associated with a grave prognosis. GVHD is another infrequent (approximately 1% of transplant recipients) but serious cause of severe anemia that carries a dismal prognosis. Lymphoproliferative disorder, too may rarely rare cause anemia and it may respond to reduction of immunosuppression. Recipients of solid-organ transplants do not mount a significant increase in erythropoietin in response to anemia. In conclusion, though there are no data on the response of anemia to erythropoietin in liver transplant recipients, it appears to benefit other solid-organ-transplant recipients with anemia. (Liver Transpl 2004;10:165,173.) [source] Diagnosing PNH with FLAER and multiparameter flow cytometryCYTOMETRY, Issue 3 2007D. Robert Sutherland Abstract Background: PNH is an acquired hematopoietic stem cell disorder leading to a partial or absolute deficiency of all glycophosphatidyl-inositol (GPI)-linked proteins. The classical approach to diagnosis of PNH by cytometry involves the loss of at least two GPI-linked antigens on RBCs and neutrophils. While flow assays are more sensitive and specific than complement-mediated lysis or the Hams test, they suffer from several drawbacks. Bacterial aerolysin binds to the GPI moiety of cell surface GPI-linked molecules and causes lysis of normal but not GPI-deficient PNH cells. FLAER is an Alexa488-labeled inactive variant of aerolysin that does not cause lysis of cells. Our goals were to develop a FLAER-based assay to diagnose and monitor patients with PNH and to improve detection of minor populations of PNH clones in other hematologic disorders. Methods: In a single tube assay, we combined FLAER with CD45, CD33, and CD14 allowing the simultaneous analysis of FLAER and the GPI-linked CD14 structure on neutrophil and monocyte lineages. Results: Comparison to standard CD55 and CD59 analysis showed excellent agreement. Because of the higher signal to noise ratio, the method shows increased sensitivity in our hands over single (CD55 or CD59) parameter analysis. Using this assay, we were able to detect as few as 1% PNH monocytes and neutrophils in aplastic anemia, that were otherwise undetectable using CD55 and CD59 on RBC's. We also observed abnormal FLAER staining of blast populations in acute leukemia. In these cases, the neutrophils stained normally with FLAER, while the gated CD33bright cells failed to express normal levels of CD14 and additionally showed aberrant CD45 staining and bound lower levels of FLAER. Conclusion: FLAER combined with multiparameter flow cytometry offers an improved assay for diagnosis and monitoring of PNH clones and may have utility in detection of unsuspected myeloproliferative disorders. © 2007 Clinical Cytometry Society [source] Graft rejection and hyperacute graft-versus-host disease in stem cell transplantation from non-inherited maternal antigen complementary HLA-mismatched siblingsEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 2 2007Hirokazu Okumura Abstract Human leukocyte antigen (HLA)-mismatched stem cell transplantation from non-inherited maternal antigen (NIMA)-complementary donors is known to produce stable engraftment without inducing severe graft-versus-host disease (GVHD). We treated two patients with acute myeloid leukemia (AML) and one patient with severe aplastic anemia (SAA) with HLA-mismatched stem cell transplantation (SCT) from NIMA-complementary donors (NIMA-mismatched SCT). The presence of donor and recipient-derived blood cells in the peripheral blood of recipient (donor microchimerism) and donor was documented respectively by amplifying NIMA-derived DNA in two of the three patients. Graft rejection occurred in the SAA patient who was conditioned with a fludarabine-based regimen. Grade III and grade IV acute GVHD developed in patients with AML on day 8 and day 11 respectively, and became a direct cause of death in one patient. The findings suggest that intensive conditioning and immunosuppression after stem cell transplantation are needed in NIMA-mismatched SCT even if donor and recipient microchimerisms is detectable in the donor and recipient before SCT. [source] Fulminant hepatitis after allogenic bone marrow transplantation caused by reactivation of hepatitis B virus with gene mutations in the core promotor regionEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 3 2006Kiyoshi Kitano Abstract:, Under immunosuppressive conditions after hematopoietic stem cell transplantation (HSCT), even if hepatitis B virus (HBV) antigen is negative but hepatitis B surface antibody (HBsAb) or hepatitis B core antibody (HBcAb) is presented, HBV reactivates and sometimes causes fulminant hepatitis. However, it remains unclear which patients will develop fulminant hepatitis, or whether fulminant hepatitis is caused by host-related factors or by virus-related factors. A 30-yr-old man with a history of aplastic anemia since 3 yr of age underwent allogenic BMT, when HBsAb and HBcAb were positive but HBs antigen (HBsAg) was negative. The donor was negative for HBsAg, HBsAb and HBcAb. After transplantation, the patient was complicated by acute graft-vs.-host disease (GVHD), cytomegalovirus infection, intestinal thrombotic microangiopathy and aspergillus colitis. Chronic GVHD was well controlled by FK506 and prednisolone. Twenty months after transplantation, the patient was admitted with general fatigue and liver dysfunction and was found to be positive for HBsAg and HBeAg. His serum HBV-DNA level was >8.8 log of the genome equivalent (LGE)/mL. Therefore, he was diagnosed as having hepatitis B caused by HBV reactivation and 100 mg/d lamivudine treatment was started. However, jaundice and hepatic failure deteriorated and became fatal. On analysis of the HBV-DNA, two adjacent gene mutations in the core promoter region (T1762/A1764) were detected. Increased replication of the mutated HBV might have caused HBV reactivation which progressed to fulminant hepatitis. [source] Sustained and stable hematopoietic donor-recipient mixed chimerism after unrelated cord blood transplantation for adult patients with severe aplastic anemiaEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 5 2005P. Mao Abstract:, We evaluated the engraftment of donor cells from unrelated cord blood into adult patients with severe aplastic anemia (SAA) and the outcome of allo-CBSCT (cord blood stem cell transplantation). Nine patients were conditioned with decreased dosage of immunosuppressive agents of CTX (60 mg/kg) and ALG (120 mg/kg). The prophylaxis of GVHD consisted of standard CsA and MTX. Patients have a media age of 25.3 yr (range: 15,37), and a median weight of 57.2 kg (range: 52.5,60) at the time of transplantation. Cord blood searches were all conducted at Guangzhou Cord Blood Bank. The engraftment state of the donor cells into recipients was confirmed by microsatellite DNA fingerprinting and fluorescent quantitative PCR analysis. Engrafted evidence has been found in seven patients involved by biomolecular analyses showing donor-recipient mixed chimerism post-transplant which was stable and persistent. After a median follow up of 32.2 months (range: 4,69), seven patients were alive and disease free. This study shows that durable donor-recipient stable mixed chimerism can be achieved by unrelated CBSCT in patients with SAA. Umbilical cord blood could be employed as a source of hematopoietic stem cell for adult transplantation. [source] Excessive production of tumor necrosis factor-alpha by bone marrow T lymphocytes is essential in causing bone marrow failure in patients with aplastic anemiaEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 1 2004Takeshi Hara Abstract:, Aplastic anemia (AA) is regarded as an immunological disorder because of the clinical effect of immunosuppressive therapy. Recent studies have reported that cytokines play an important role in the development of AA. In the present study, we measured levels of T-cell derived intracellular cytokine production in peripheral blood and bone marrow (BM) of patients with AA. We demonstrated that BM lymphocytes, particularly CD4+ and CD8+ T cells, in patients with AA produced significantly higher amounts of tumor necrosis factor-alpha (TNF- ,), compared with lymphocytes in normal controls. We have previously reported that expression of TNF receptor (R)1 and TNFR2 in the CD34+ CD38, and CD34+ CD38+ fractions of patients with AA is significantly higher than those in normal control. These results indicate that BM stem cells in patients with AA may possess high sensitivity to TNF- ,. This in turn suggests that TNF- , affects hematopoiesis at an earlier stage in AA patients than in normal controls. We strongly support the hypothesis that a simultaneous increase in TNF- , production by BM lymphocytes and sensitivity of stem cells to TNF- , leads to BM failure in AA. [source] Comparative analysis of G-CSFR and GM-CSFR expressions on CD34+ cells in patients with aplastic anemia and myelodysplastic syndromeINTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 6 2009H. XU Summary The aim of this article was to explore the pathogenetic differences, as well as to provide a new way for the differential diagnosis of these two diseases by comparative analysis of CD34+ cells numbers and their surface expression of granulocyte colony-stimulating factor receptor (G-CSFR) and granulocyte-macrophage colony-stimulating factor receptor (GM-CSFR) in patients with aplastic anemia (AA) and myelodysplastic syndrome (MDS). Twenty-seven patients with AA, 45 patients with MDS, and 20 normal controls were enrolled in this study. The ratio of CD34+ cells and their surface expression of G-CSFR and GM-CSFR were detected by flow cytometry (FCM). The ratio of CD34+ cells in BMMNC of AA, MDS patients and controls were 0.2438 ± 0.1129%, 2.1677 ± 1.1345% and 1.0792 ± 0.3221%, respectively. Compared with normal controls as well as MDS patients, the ratio of CD34+ cells in BMMNC of AA was significantly reduced (P < 0.05). The ratio of CD34+ cells in MDS was significantly elevated than controls (P < 0.05). The ratio of CD34+ cells in BMMNC of MDS-RA and MDS-RAEB patients were 1.2821 ± 0.4658% and 3.7729 ± 2.3360%, respectively. Compared with normal controls and MDS-RA patients, the ratio of CD34+ cells in MDS-RAEB was significantly elevated (P < 0.05). The ratio of CD34+ cells in MDS-RA was significantly elevated than AA patients (P < 0.05). The surface expression of G-CSFR on CD34+ cells of AA, MDS patients and controls were 34.402 ± 21.8357%, 26.376 ± 15.2895% and 21.443 ± 7.4465%, respectively. The surface expression of G-CSFR on CD34+ cells of MDS-RA and MDS-RAEB patients were 22.788 ± 14.7628% and 30.682 ± 15.5346%. The surface expression of GM-CSFR on CD34+ cells of AA, MDS patients and controls were 6.5961 ± 4.4322%, 18.2737 ± 10.9841% and 4.2753 ± 2.6249%, respectively. Compared with AA and controls, the expression of GM-CSFR in MDS patients was significantly elevated (P < 0.05). The surface expression of GM-CSFR on CD34+ cells of MDS-RA and MDS-RAEB patients were 16.1625 ± 6.9487% and 22.1003 ± 14.2983%. In AA patients, the ratio of CD34+ cells in BMMNC less than 0.1% accounts for 75% (6/8) SAA patients, compared with 10.55% (2/19) in CAA (P < 0.05). The detection of CD34+ cells and their surface expression of granulocyte (macrophage) colony-stimulating factor receptors G (M)-CSFR in AA and MDS are helpful in the differential diagnosis or prognosis of these two disorders. [source] Adhesion molecule expression by bone marrow CD34-positive cells in aplastic anemia before and after immunosuppressive therapyINTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 6 2003K. Kaito Summary Appropriate adhesion between bone marrow stem cells and the marrow microenvironment is necessary for hematopoiesis, since signals that promote maturation or apoptosis are transmitted from stromal cells to stem cells. In aplastic anemia (AA), interferon- , produced by stromal cells has more influence on the pathogenesis of marrow failure than interferon- , produced by lymphocytes. We evaluated the expression of cell adhesion molecules, such as very late antigen-4 (CD49d), and -5 (CD49e) or c-kit receptor (CD117), by CD34-positive bone marrow cells in patients with AA who achieved hematological complete remission after immunosuppressive therapy. Before treatment, CD34-positive cells showed markedly higher expression of CD49d and CD49e than cells from healthy controls, indicating the strong adhesion of stem cells to the bone marrow stroma. Expression of CD49d and CD49e was significantly decreased, reaching normal levels, after hematological recovery. These findings suggest that changes in adhesion molecule expression by stem cells are important in the pathology of AA. [source] Fanconi anemia protein complex is a novel target of the IKK signalsomeJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 4 2002Tetsuya Otsuki Abstract Fanconi anemia (FA), a genetic disorder predisposing to aplastic anemia and cancer, is characterized by hypersensitivity to DNA-damaging agents and oxidative stress. Five of the cloned FA proteins (FANCA, FANCC, FANCE, FANCF, FANCG) appear to be involved in a common functional pathway that is required for the monoubiquitination of a sixth gene product, FANCD2. Here, we report that FANCA associates with the I,B kinase (IKK) signalsome via interaction with IKK2. Components of the FANCA complex undergo rapid, stimulus-dependent changes in phosphorylation, which are blocked by kinase-inactive IKK2 (IKK2 K,>,M). When exposed to mitomycin C, cells expressing IKK2 K,>,M develop a cell cycle abnormality characteristic of FA. Thus, FANCA may function to recruit IKK2, thus providing the cell a means of rapidly responding to stress. J. Cell. Biochem. 86: 613,623, 2002. © 2002 Wiley-Liss, Inc. [source] CD41+ and CD42+ hematopoietic progenitor cells may predict platelet engraftment after allogeneic peripheral blood stem cell transplantationJOURNAL OF CLINICAL APHERESIS, Issue 2 2001T. Demirer Abstract The objective of this study was to quantify subpopulations of CD34+ cells such as CD41+ and CD42+ cells that might represent megakaryocyte (MK) precursors in peripheral blood stem cell (PBSC) collections of normal, recombinant human granulocyte-colony stimulating factor (rhG-CSF) primed donors and to determine whether there is a statistical association between the dose infused megakaryocytic precursors and the time course of the platelet recovery following an allogeneic PBSC transplantation. Twenty-six patients with various hematologic malignancies transplanted from their HLA identical siblings between July 1997 and December 1999 were used. All patients except one with severe aplastic anemia who had cyclophosphamide (CY) alone received busulfan-CY as preparative regimen and cyclosporine-methotrexate for GVHD prophylaxis. Normal healthy donors were given rhG-CSF 10 ,g/kg/day subcutaneously twice daily and PBSCs were collected on days 5 and 6. The median number of infused CD34+, CD41+ and CD42+ cells were 6.61 × 106/kg (range 1.47,21.41), 54.85 × 104/kg (5.38,204.19), and 49.86 × 104/kg (6.82,430.10), respectively. Median days of ANC 0.5 × 109/L and platelet 20 × 109/L were 11.5 (range 9,15) and 13 (8,33), respectively. In this study, the number of CD41+ and CD42+ cells infused much better correlated than the number of CD34+ cells infused with the time to platelet recovery of 20 × 109/L in 26 patients receiving an allogeneic match sibling PBSC transplantation (r = ,0.727 and P < 0.001 for CD41+ cells, r = ,0.806 and P < 0.001 for CD42+ cells, r = ,0.336 and P > 0.05 for CD34+ cells). There was an inverse correlation between the number of infused CD41+ and CD42+ cells and duration of platelet engraftment. Therefore, as the number of CD41+ and CD42+ cells increased, duration of platelet engraftment (time to reach platelet count of , 20 × 109/L) shortened significantly. Based on this data we may conclude that flow cytometric measurement of CD41+ and CD42+ progenitor cells may provide an accurate indication of platelet reconstitutive capacity of the allogeneic PBSC transplant. J. Clin. Apheresis. 16:67,73, 2001. © 2001 Wiley-Liss, Inc. [source] Hydroquinone and its analogues in dermatology , a potential health riskJOURNAL OF COSMETIC DERMATOLOGY, Issue 2 2005W Westerhof Summary Hydroquinone has been used for decades as a skin lightening agent. Since January 1, 2001, its use in cosmetics has been banned. This ban is as a result of mid-term effects such as leukoderma-en-confetti/occupational vitiligo and exogenous ochronosis. However, a recent literature search on hydroquinone as a skin lightening agent suggests that possible long-term effects such as carcinogenesis may be expected as well. Metabolites of hydroquinone formed in the liver, e.g., p-benzoquinone and glutathione conjugates of hydroquinone, are mainly responsible for this. In the bone marrow, hydroquinone is oxidized into p-benzoquinone because of the high myeloperoxidase activity. Topically applied hydroquinone-containing creams may give rise to accumulation of these compounds, which can cause DNA damage and mutations. They also have the capability to disrupt protective mechanisms, whereby they facilitate further development of cancer. In the bone marrow, long-term effects such as aplastic anemia and acute myeloid leukemias may occur. Most of the evidence stems from research on benzene toxicity, which appears to arise via its metabolite hydroquinone. There is no report yet demonstrating carcinogenesis resulting from the application of hydroquinone-containing creams. However doctors should be aware of these potential health risks which were up until now disregarded. [source] Evaluation of platelet kinetics in patients with liver cirrhosis: Similarity to idiopathic thrombocytopenic purpuraJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 1 2007Mikio Kajihara Abstract Background:, Thrombocytopenia is a common manifestation of liver cirrhosis (LC), but its underlying mechanism is not fully understood. The purpose of the present paper was to evaluate the platelet kinetics in LC patients by examining several non-invasive convenient markers. Methods:, Fifty-seven LC patients, 32 patients with idiopathic thrombocytopenic purpura (ITP), 12 with aplastic anemia (AA), and 29 healthy individuals were studied. Plasma thrombopoietin was measured by enzyme-linked immunosorbent assay. Absolute reticulated platelet (RP) count and plasma glycocalicin were used as indices for thrombopoiesis, and the indices for platelet turnover were the RP proportion and the plasma glycocalicin normalized to the individual platelet count (GCI). Results:, There was no difference in thrombopoietin levels between LC patients and healthy controls. The RP proportion and GCI were significantly higher and the absolute RP count and glycocalicin significantly lower in LC patients than in healthy controls. These markers in ITP and LC patients were comparable, but significantly different from those in AA patients. The bone marrow megakaryocyte density in LC and ITP patients was similar, and significantly higher than in AA patients. Conclusions:, Cirrhotic thrombocytopenia is a multifactorial condition involving accelerated platelet turnover and moderately impaired thrombopoiesis. Thrombopoietin deficiency is unlikely to be the primary contributor to cirrhotic thrombocytopenia. [source] Efficacy and safety of recombinant factor VIIa in the treatment of bleeding episodes in patients with aplastic anemiaJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 2 2007A. M. AL HAMMADI [source] Systematic review: hepatitis-associated aplastic anaemia , a syndrome associated with abnormal immunological functionALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2009R. GONZALEZ-CASAS Summary Background, Hepatitis-associated aplastic anaemia is a syndrome in which marrow failure follows the development of hepatitis. Aim, To review systematically the aetiology, immunopathogenesis, clinical presentation, diagnosis and treatment of hepatitis-associated aplastic anaemia. Methods, Literature searches were undertaken on the MEDLINE electronic database up to December 2008. Twenty-four relevant studies were identified. The clinical and laboratory characteristics of the patients were analysed and reviewed. Results, Hepatitis-associated aplastic anemia is a variant of acquired aplastic anemia in which an episode of hepatitis precedes the onset of aplastic anemia. The hepatitis may be acute and severe, even fulminant; it may be self-limiting or chronic. The pathology is often not attributable to a recognized cause of viral hepatitis. The syndrome occurs in 28 percent of young adults after liver transplantation for non-A, non-B, non-C hepatitis. Several features of the syndrome suggest that the marrow aplasia is mediated by immunological mechanisms, possibly mediated by gamma interferon or the cytokine cascade. Survival of patients treated with hematopoietic cell transplantation has been 82%, and the response rate to immunosuppressive therapy 70%. Conclusions, Hepatitis-associated bone marrow aplasia is mediated by immunological mechanisms. Treatment options include hematopoietic cell transplantation and immunosuppressive therapy. [source] Post-liver-transplant anemia: Etiology and managementLIVER TRANSPLANTATION, Issue 2 2004Anurag Maheshwari Anemia is common after liver transplantation, with the incidence ranging from 4.3% to 28.2% depending on the criteria used to define anemia. The cause of anemia is unidentified in the majority of patients, and it is likely to be multifactorial. Immunosuppressive-medication-induced bone marrow suppression is perhaps the most common cause of unexplained anemia. Chronic blood loss, iron deficiency, hemolysis, and renal insufficiency are other potential causes of chronic anemia. Rare causes, somewhat unique to transplantation, include aplastic anemia, graft-versus-host disease (GVHD), and lymphoproliferative disease. Anemia due to immunosuppressive medication is challenging, since almost all drugs currently used for this purpose cause anemia, but the renal-sparing property of sirolimus may benefit the subgroup in which renal insufficiency is contributing to anemia. Aplastic anemia is seen in young patients transplanted for non-A, non-B, non-C, fulminant hepatic failure. It is thought to be immunologically mediated, secondary to an unknown viral infection, and is associated with a grave prognosis. GVHD is another infrequent (approximately 1% of transplant recipients) but serious cause of severe anemia that carries a dismal prognosis. Lymphoproliferative disorder, too may rarely rare cause anemia and it may respond to reduction of immunosuppression. Recipients of solid-organ transplants do not mount a significant increase in erythropoietin in response to anemia. In conclusion, though there are no data on the response of anemia to erythropoietin in liver transplant recipients, it appears to benefit other solid-organ-transplant recipients with anemia. (Liver Transpl 2004;10:165,173.) [source] Long term follow-up of allogeneic stem cell transplantation in patients with myelodysplastic syndromes using busulfan, cytosine arabinoside, and cyclophosphamide,AMERICAN JOURNAL OF HEMATOLOGY, Issue 8 2010Ehab Atallah We report here the 10-year follow-up of 86 patients who underwent allogeneic stem cell transplantation (ASCT) for myelodysplastic syndrome (MDS). All patients received the busulfan, cytosine arabinoside, and cyclophosphamide (BAC) preparative regimen which consisted of busulfan 16 mg/kg, cytosine arabinoside 8 g/m2 IV, and cyclophosphamide 120 mg/kg IV. Fifty-nine patients (69%) had de novo MDS; 26 (30%) had secondary MDS (treatment related), and one had a preceding aplastic anemia which progressed to MDS before transplant. Cytogenetics (80 patients) was classified as good (34%), intermediate (17%), or poor (42%). With a median follow-up for survivors of 124 months, the 10-year Kaplan-Meier estimates for overall survival (OS) was 43% (95% confidence interval [CI]: 31,53%). Cumulative nonrelapse mortality (NRM) and relapse was 43% (95% CI: 32,54%) and 19% (95% CI: 11,27%), respectively. No patient relapsed after 2 years. In patients with RAEB-T/AML, 10-year relapse-free survival (RFS), relapse, and NRM was 36%, 36%, and 27%, respectively. Younger age (P = 0.05), human leukocyte antigen (HLA) match (P = 0.002), good risk cytogenetics (P = 0.008), and having a related donor (P = 0.03) significantly improved overall and RFS in the multivariable analysis. The long-term follow-up of patients receiving the BAC regimen with ASCT in this study indicated durable relapse-free and OS with acceptable toxicity in this group of patients with high-risk features. Am. J. Hematol., 2010. © 2010 Wiley-Liss, Inc. [source] Successful unmanipulated stem cell transplantation from HLA-haploidentical 3-loci-mismatched parents in two children with severe aplastic anemia not responding to immunosuppressive therapyAMERICAN JOURNAL OF HEMATOLOGY, Issue 5 2010Zhidong Wang No abstract is available for this article. [source] Wilms' tumor 1 message and protein expression in bone marrow failure syndrome and acute leukemiaPATHOLOGY INTERNATIONAL, Issue 10 2007Takashi Iwasaki Wilms' tumor 1 (WT1) is a useful marker for the diagnosis of acute leukemia and myelodysplastic syndromes (MDS). In the current study quantitative reverse transcription,polymerase chain reaction and immunostaining were used simultaneously to examine the relationship between WT1 RNA and protein level and also to evaluate WT1 as a tool to differentiate aplastic anemia (AA) and MDS refractory anemia (RA). Three types of WT1 messages (total, exon 5(+) and KTS(+)) and WT1 immunostaining of these diseases were analyzed. An increase of all three WT1 messages in high-grade MDS and acute leukemia was observed as compared with the normal control, whereas there was no significant difference in WT1 message between AA and RA, suggesting that WT1 message is not a good tool to discriminate AA and RA. No significant difference was observed between normal and RA, except for exon 5 message. Three WT1 message levels had a significant correlation, suggesting that the total WT1 message is sufficient for clinical practice. Positive immunostaining of WT1 was observed only in the portion of acute leukemia and overt leukemia (OL) transformed from MDS with a high WT1 message level, suggesting the relatively high detection threshold of WT1 protein with the immunostaining method. [source] MRI findings in aplastic anemia,AMERICAN JOURNAL OF HEMATOLOGY, Issue 11 2009Rebecca Loret De Mola No abstract is available for this article. [source] Granulocyte-macrophage colony stimulating factor and immunosuppression in the treatment of pediatric acquired severe aplastic anemiaPEDIATRIC BLOOD & CANCER, Issue 2 2005Michael R. Jeng MD Abstract Background Immunosuppressive therapy (IS) is effective in the treatment of patients with acquired severe aplastic anemia (SAA). An enhanced myeloid response and decreased infection risk may be possible with the addition of a hematopoietic cytokine. Published data on the combination of cytokines and IS in patients with SAA are limited. The addition of G-CSF to IS shortens the time to neutrophil count recovery, but may not improve overall survival. Because GM-CSF acts differently than G-CSF, its use in combination with IS may be different. Procedure A retrospective chart review was performed on patients diagnosed with SAA and treated with IS and GM-CSF at St. Jude Children's Research Hospital. Hematologic recovery, prognostic factors, and infection data were collected. Results Eighteen patients were included in this study. The median age at diagnosis was 7.2 years (range 1.8,17.0). Ten patients (56%) had a complete response, four (22%) a partial response, and four (22%) no response. Median time to erythrocyte and platelet transfusion independence were 90 (18,243) and 64 days (18,243), and to discontinuation of treatment 287 days (90,730). Median time to partial (ANC,>,500) and full (ANC,>,1,500) neutrophil recovery were 41 and 51 days, respectively. Seventeen documented discrete infections occurred in six patients over 36 patient years. Conclusions GM-CSF, in addition to IS, may shorten time to neutrophil count recovery, may be beneficial in decreasing infection rates, and may improve platelet response in patients with SAA. However, consistent with studies utilizing G-CSF, GM-CSF probably does not affect overall response rate. To fully answer whether or not cytokine therapy is of added value to IS in pediatric patients, a multi-institutional randomized trial is needed. © 2004 Wiley-Liss, Inc. [source] Liver transplantation for fulminant hepatic failure in infancy: A single center experiencePEDIATRIC TRANSPLANTATION, Issue 7 2009Annette Strauss Abstract:, FHF is characterized by a high percentage of unknown causes leading to acute liver failure and furthermore by an increased morbidity and mortality prior to and post-Ltx. In different transplant centers, the reasons leading to FHF differ significantly as well as outcome. We report our single center experience with 30 pediatric patients receiving a liver transplant for FHF, out of a total of 83 children presenting with FHF. The time to transfer patients to the transplant center after the diagnosis of FHF was long, with a median of 14 days (Ltx group) and 12 days (controls), respectively. In nearly half of the patients (n = 14) in the Ltx group, we were not able to establish an exact diagnosis prior to Ltx: 50% suffered from encephalopathy, and 13 patients were treated in the intensive care unit prior to transplant. Because of the availability of different surgical techniques, all children received a timely transplant [split (n = 18), living donor (n = 9), whole organ (n = 2), and reduced liver (n = 1)]. Patient survival was 93.4%, and graft survival was 83.4% for at least one yr follow-up. Severe complications following Ltx included three cases with aplastic anemia and one child suffering from systemic mitochondrial depletion syndrome. The survival of patients treated medically was 83%. We conclude that a strong focus should be made on early referral to a specialized center and on improvement of diagnostic tools to timely detect the underlying reason for FHF. Results following Ltx for FHF are good. [source] Transmission of type 1 diabetes by bone marrow transplantation: A case reportPEDIATRIC TRANSPLANTATION, Issue 1 2009Fethi Mellouli Abstract:, T1D after BMT constitutes a human model of autoimmune disease transmission. This case report refers to T1D onset after allogeneic HLA-matched BMT in a six-yr-old recipient affected by aplastic anemia. The donor was his sister who had T1D. The recipient had a complication free course apart from grade 1 acute GVHD, which was resolved spontaneously. With the predictive value and significance of T1D-associated autoantibodies, we tried to consolidate the T1D transfer possibility based on our patient characteristics and a literature review. [source] Fludarabine, cyclophosphamide, anti-thymocyteglobulin, and low-dose total body irradiation conditioning enables 1-HLA-locus-mismatched hematopoietic stem cell transplantation for very severe aplastic anemia without affecting ovarian functionAMERICAN JOURNAL OF HEMATOLOGY, Issue 3 2009Shinya Okuda Allogeneic hematopoietic stem cell transplantation for severe aplastic anemia from an alternative donor is associated with higher risks of graft rejection and severe graft-versus-host disease. We developed a conditioning regimen consisting of rabbit anti-thymocyte globulin, fludarabine, cyclophosphamide, and low-dose total body irradiation. Two adult female patients with transfusion-dependent very severe aplastic anemia underwent 1-locus mismatched transplantation using this regimen. Both patients achieved stable engraftment and the clinical course thereafter was uneventful with persistently normal ovarian function. This novel conditioning regimen may be suitable for alternative donor transplantation for severe aplastic anemia, especially in young female patients. Am. J. Hematol. 2009. © 2008 Wiley-Liss, Inc. [source] Successful recovery of aplastic anemia following orthotopic liver transplantation for non-A-E acute liver failurePEDIATRIC TRANSPLANTATION, Issue 4 2005S. R. Rajwal Abstract:, This report describes a teenager who developed aplastic anemia (AA) because of non-A-E acute liver failure (ALF) requiring orthotopic liver transplantation (OLT). His AA did not recover spontaneously and he required treatment with ATG 9 months post-OLT. Bone marrow recovery occurred 4 months after immunotherapy and coincided with further intensification of immunusuppression required to treat early chronic rejection of the liver graft. Three years post-OLT he remains well with good bone marrow and liver function. Intensification of immunosuppression can lead to successful resolution of AA associated with non-A-E ALF. [source] Danazol therapy for aplastic anemia refractory to immunosuppressive therapyAMERICAN JOURNAL OF HEMATOLOGY, Issue 5 2008Tatsuya Chuhjo Although there are anecdotal reports of the efficacy of danazol in the treatment of aplastic anemia (AA), there has been no systematic study to clarify its efficacy and toxicity. Therefore, we assessed the efficacy of danazol for treatment of patients with AA refractory to immunosuppressive therapy (IST) and those who relapsed after IST, in a prospective clinical trial. Sixteen patients (12 males and four females; six severe cases and 10 moderate cases) were treated with 300 mg of danazol daily for 12 weeks. All patients completed the treatment period without occurrence of severe toxicity. Three female patients achieved partial remission, whereas only two of the 12 male patients did so. None of the responders had shown a response to previous IST or an increase in the percentage of paroxysmal nocturnal hemoglobinuria (PNH)-type cells which are known to be a marker for a good response to IST. These findings indicate that danazol is effective for a subset of AA patients, and particularly for female patients with AA refractory to IST. Am. J. Hematol., 2008. © 2007 Wiley-Liss, Inc. [source] Severe aplastic anemia with hot pockets following daily Ecstasy ingestionAMERICAN JOURNAL OF HEMATOLOGY, Issue 4 2008Jesse Richman No abstract is available for this article. [source] G-CSF-mobilized haploidentical peripheral blood stem cell transplantation in children with poor prognostic nonmalignant disordersAMERICAN JOURNAL OF HEMATOLOGY, Issue 2 2008Fikret Arpac Haploidentical hematopoietic stem cell transplantation (HSCT) is currently one of the alternative curative treatment options for some nonmalignant but also for malignant diseases. However, concerns regarding its safety cause delays in time and a successful outcome. Between 2000 and 2005, twenty-one children with poor prognostic nonmalignant disorders, 13 boys and 8 girls, with a median age of 12 months, underwent 28 haploidentical peripheral HSCT. Immunomagnetic bead depletion device (CliniMACS) was used for indirect T-cell depletion. Indications for transplant were severe combined immunodeficiency (n = 16), osteopetrosis (n = 2), MDS (n = 1), amegakaryocytic thrombocytopenia (n = 1), and aplastic anemia (n = 1). Five patients (24%) had lung infection at the time of transplantation. The patients received a median of 25.67 × 106 G-CSF-mobilized peripheral CD34+ progenitor cells and a median of 4.19 × 104 T-lymphocytes per kilogram of body weight with a T-cell depletion rate of median 4.59 logs. The rate of total engraftment was 66.6%. Median times for leukocyte and platelet engraftment were 14 and 16 days, respectively. The 6-year projected survival was 32% for all patients and 29.76% for patients with severe combined immunodeficiency (SCID). The rates of transplant-related mortality, graft failure, and severe GvHD were 14.2, 33.4%, and 8.3%, respectively. Infection was the main cause of death. The poor outcome may be explained with the poor prognostic factors of our patients such as the type of SCID in most cases (T-B, SCID), the median age over 6 months and the presence of lung infection in some children at the time of transplantation. Am. J. Hematol., 2008. © 2007 Wiley-Liss, Inc. [source] Epstein-Barr virus reactivation in a patient treated with anti-thymocyte globulin for severe aplastic anemiaAMERICAN JOURNAL OF HEMATOLOGY, Issue 5 2006Elisabetta Calistri Abstract Epstein-Barr virus (EBV) infection and reactivation is an increasing complication in immune deficient patients, particularly after allogeneic hematopoietic stem cell transplantation (HSCT). Therapy with anti-thymocyte globulin (ATG) is associated with higher incidence of EBV-related disease in HSCT patients, but this risk is not documented in patients receiving ATG for severe aplastic anemia (SAA). We describe the case of a patient who developed an EBV infection, with the clinical features of an infectious mononucleosis, after immune suppression with cyclosporine and two courses of ATG for SAA. Am. J. Hematol. 81:355,357, 2006. © 2006 Wiley-Liss, Inc. [source] | |||||||||||||||||||||||||||||||