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Hematology AND Aplastic anemia [keywords]
- Pregnancy and delivery in a PNH patient treated with eculizumab. [JOURNAL ARTICLE]
- Rinsho Ketsueki 2014; 55(11):2288-2293.
We report a 37-year-old pregnant woman with paroxysmal nocturnal hemoglobinuria (PNH) treated with eculizumab. She had been diagnosed with PNH-aplastic anemia at age 19 years, and started to receive eculizumab at age 35 years. Thereafter, she had no hemolytic attacks. She became pregnant 2 years later, and treatment with eculizumab was continued. During her pregnancy, she showed no exacerbation of hemolysis. She delivered a girl by Caesarean section at 37 weeks and 3 days of gestation. Postpartum, anticoagulant therapy was started. Although mild hemolysis and a rise in FDP/Ddimer were seen, she had no symptoms of thrombosis. Ten days after delivery, she and her baby were discharged. Eculizumab was present in the first breast milk and cord blood but was below detectable levels. The cord blood showed blockage of hemolysis.
- TRAF1/C5 rs10818488 polymorphism is not a genetic risk factor for acquired aplastic anemia in a Chinese population. [JOURNAL ARTICLE]
- Hum Immunol 2014 Dec 11.
The tumor necrosis factor receptor-associated factor 1/complement C5 (TRAF1/C5) genes have been suggested as two candidate genes for conferring susceptibility to autoimmunity and inflammation. The aim of the present study was to investigate the association of single nucleotide polymorphisms (SNP) of TRAF1/C5 genes with the risk for aplastic anemia (AA). In this case-control study, the genotyping of TRAF1/C5 rs10818488 polymorphism was detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The frequencies of AA, AG and GG genotypes, and A and G alleles were 21.9%, 52.4%, 25.7%, 48.1% and 51.9%, respectively, in AA patients. There was no significant differences in terms of genotype and allele distributions between AA patients and healthy controls (P=0.687 and 0.955, respectively). Similar results were found between the two groups when stratified by the disease severity including very severe AA (vSAA), SAA and non-SAA (NSAA). Our results indicated that TRAF1/C5 rs10818488 polymorphism might not contribute to susceptibility to AA in a Chinese population.
- THPO-MPL pathway and bone marrow failure. [EDITORIAL]
- Hematol Oncol Stem Cell Ther 2014 Nov 29.
Single or multilineage bone marrow failure can be a serious health problem caused by hereditary and non-hereditary causes such as exposure to drugs or environmental toxins. Normal hematopoiesis requires the integrity of several pathways including the THPO-MPL pathway. Over the last two decades, significant advances in the understanding of normal and abnormal functions of this and related pathways have led to novel diagnostic and therapeutic options.
- Multiparameter FLAER-based flow cytometry for screening of paroxysmal nocturnal hemoglobinuria enhances detection rates in patients with aplastic anemia. [JOURNAL ARTICLE]
- Ann Hematol 2014 Dec 4.
Flow cytometry is the gold standard methodology for screening of paroxysmal nocturnal hemoglobinuria. In the last few years, proaerolysin conjugated with fluorescein (FLAER) has become an important component of antibody panel used for the detection of paroxysmal nocturnal hemoglobinuria (PNH) clone. This study aimed to compare PNH clone detection by flow cytometry in the pre-FLAER era versus the FLAER era. This was a retrospective analysis of 4 years and included 1004 individuals screened for PNH clone, either presenting as hemolytic anemia or as aplastic anemia. In the pre-FLAER time period, the RBCs and neutrophils were screened with antibodies against CD55 and CD59. With the introduction of FLAER, neutrophils were screened with FLAER/CD24/CD15 and monocytes with FLAER/CD14/CD33 combination. A comparative analysis was done for detection of PNH clone in aplastic anemia patients versus non-aplastic anemia patients, as well as between pre-FLAER and FLAER era. Out of a total of 1004 individuals, 59 (5.8 %) were detected to have PNH clone positivity. The frequency of PNH clone detected in aplastic anemia and non-aplastic anemia groups was 12.02 and 3.36 %, respectively. The detection rate of PNH clone increased from 4.5 % (32/711) in the pre-FLAER era to 9.2 % (27/293) with the introduction of FLAER. However, this increase could be attributed to increased detection of PNH clone in the aplastic anemia group, which showed a significant increase from 8.3 to 18.2 % after use of FLAER. In the non-aplastic group, PNH clone was detected with similar frequencies before and after use of FLAER (3.2 versus 3.8 %, respectively). Mean PNH clone size was lower in the aplastic anemia group when compared with the non-aplastic group. RBCs always showed a lower clone size than neutrophils. PNH clone on neutrophils and monocytes was however similar. Inclusion of FLAER increases the sensitivity of the test which is especially useful in picking up small PNH clones in patients of aplastic anemia.
- Bone Marrow Transplantation for Acquired Severe Aplastic Anemia. [REVIEW]
- Hematol Oncol Clin North Am 2014 Dec; 28(6):1145-1155.
This article addresses current transplant options for patients with acquired severe aplastic anemia (SAA). This discussion includes ongoing progress in the use of SAA in the setting of unrelated donor transplants, which now provide outcomes similar, though still not identical, to HLA-identical sibling transplants. Recent data on stem cell source, conditioning regimens, and graft-versus-host disease prophylaxis are outlined. Other donor types such as cord blood and haploidentical mismatched family donors are also discussed.
- Aplastic Anemia & MDS International Foundation (AA&MDSIF): Bone Marrow Failure Disease Scientific Symposium 2014. [JOURNAL ARTICLE]
- Leuk Res 2014 Nov 16.
Bone marrow failure syndromes (BMFS) are characterized by a failure of the hematopoietic stem cells to produce adequate blood cells, resulting in either cytopenia (defect in one or more blood cell lineages) or pancytopenia (defect in all blood cell lineages). BMFS can be inherited or acquired. The pathogenesis of these diseases is very heterogeneous. Research efforts have been made all over the world to improve the basic knowledge of these diseases. The Aplastic Anemia and MDS International Foundation (AA&MDSIF) is an independent nonprofit organization whose mission is to help patients and family members cope with BMFS. Here, we summarize novel scientific discoveries in several BMFS that were presented at the 4th International Bone Marrow Failure Disease Scientific Symposium 2014 that AA&MDSIF sponsored on March 27-28, 2014, in Rockville, MD.
- Evolution of iron burden in acquired aplastic anemia: a cohort study of more than 3-year follow-up. [JOURNAL ARTICLE]
- Int J Hematol 2014 Nov 28.
Acquired aplastic anemia (AA) is the most common condition linked to transfusion dependence. We conducted a cohort study to explore patterns of the dynamic evolution of iron burden, and to identify the risk factors for iron overload (IO) in 550 AA patients. Of the participants, 13 % presented with IO when diagnosed, including 7 % of patients without a history of transfusion and 22 % of those receiving transfusions. Male patients [hazard ratio (HR) = 3.85, 95 % confidence interval (CI) 1.77-8.36], adults (HR = 3.04, 95 % CI 1.21-7.63), and patients with high transfusion burdens (more than eight units; HR = 11.30, 95 % CI 4.45-28.70) experienced a significantly higher risk of IO. Furthermore, we found a sharply increasing risk of IO within the first 2 years, especially in males, patients with large number of lifetime transfusions, and patients not responding to treatment. More interestingly, after transfusion independence, a significant seesaw effect between erythropoiesis and iron burden was not noted until 6 months later, which continued over 3 years. In contrast to female patients, children, and patients with lower transfusion burdens, male subjects, adults, and subjects with high transfusion burdens experienced a pattern of slow decline in iron burden. AA incurred a high risk of progression to IO and showed distinct patterns in the evolution of iron burden. In light of these data, we offer suggestions for decision-making regarding who should undergo iron chelation and when.
- Combined use of Chinese medicine with allogeneic hematopoietic stem cell transplantation for severe aplastic anemia patients. [Journal Article]
- Chin J Integr Med 2014 Dec; 20(12):903-9.
To determine the effect of combined treatment with Chinese medicine (CM) and allogeneic hematopoietic stem cell transplantation (allo-HSCT) on patients with severe aplastic anemia (SAA).Eleven patients were treated with CM plus allo-HSCT. Nine patients received a conditioning regimen consisting of fludarabine (Flu), anti-thymocyte globulin (pig ALG), or anti-lymphocyte globulin (Rabbit ATG) and cyclophosphamide (CY), and two patients received pig ALG and CY. All patients were treated with Kidney (Shen)-reinforcing, blood-activating, and stasis-removing (KBS) herbal preparation beginning at 1 week before transplantation and ending at 8 weeks after transplantation. Chimerism status was assessed by analyzing short tandem repeat (STR) polymorphisms.All patients recovered hematopoietic function and none had graft failure. The median number of days required for the absolute neutrophil count (ANC) increased to >0.5×10(9)/L was 15 days (12-22 days) and for spontaneous platelet recovery to >20×10(9)/L without post-transplantation transfusion was 17 days (15-27 days). Nine patients were long-term survivors and achieved full donor chimerism. The overall cumulative incidence of acute graft versus host disease (GVHD) grades I-II and III-IV was 18.2% (2/11) and 9.1% (1/11), respectively. The overall accumulated incidence of chronic GVHD was 27.3% and all patients had limited chronic GVHD. At a median follow-up time of 32 months (range: 12-97 months), 9 patients were still alive. The estimated 5-year overall survival (OS) rate was 81.8%. The incidence of treatment-related mortality, 2-year post-transplantation, was 18.2%. Two patients died from GVHD after transplantation.Treatment with the KBS formulation may reduce the rate of graft failure and treatment-related mortality and improve the rate of OS in SAA patients with allo-HSCT.
- Bone marrow immunophenotyping by flow cytometry in refractory cytopenia of childhood. [JOURNAL ARTICLE]
- Haematologica 2014 Nov 25.
Refractory cytopenia of childhood is the most common type of childhood myelodysplastic syndrome. Because the majority of children with refractory cytopenia have a normal karyotype and a hypocellular bone marrow, differentiating refractory cytopenia from the immune-mediated bone marrow failure syndrome (very) severe aplastic anemia can be challenging. Flow cytometric immunophenotyping of bone marrow has been shown to be a valuable diagnostic tool in differentiating myelodysplastic syndrome from non-clonal cytopenias in adults. Here, we performed the first comprehensive flow cytometric analysis of immature myeloid, lymphoid cells and erythroid cells, and granulocytes, monocytes, and lymphoid cells in bone marrow obtained from a large prospective cohort of 81 children with refractory cytopenia. Children with refractory cyotopenia had a strongly reduced myeloid compartment, but not as severe as children with aplastic anemia. Furthermore, the number of flow cytometric abnormalities was significantly higher in children with refractory cytopenia than in healthy controls and in children with aplastic anemia, but lower than in advanced myelodysplastic syndrome. We conclude that flow cytometric immunophenotyping could be a relevant addition to histopathology in the diagnosis of refractory cytopenia of childhood. The multi-center studies EWOG-MDS RC06 and EWOG-MDS 2006 are registered with ClinicalTrial.gov identifiers NCT00499070 and NCT00662090.
- [Increasing peripheral blood neutrophils after G-CSF treatment is a predictor of early response to immunosuppressive therapy in severe aplastic anemia]. [English Abstract, Journal Article]
- Zhonghua Xue Ye Xue Za Zhi 2014 Nov; 35(11):974-9.
To testify whether absolute neutrophil count (ANC) response to preimmunosuppressive-therapy (pre-IST) granulocyte-stimulating factor (G-CSF) treatment could predict early response to IST in severe aplastic anemia (SAA).Clinical data and hematologic response of 125 SAA patients treated with antithymocyte globulin (r-ATG) combined with cyclosporine were retrospectively analyzed. Correlation of ANC response to pre-IST G-CSF treatment and early response to IST were statistically analyzed, and receiver operating characteristic (ROC) curve was used to estimate the value of increased ANC (∆ANC) in predicting early IST response.The hematologic response (HR) rate to IST in ANC reponded patients was significantly higher than non-responded group (3-month HR 49.0% vs 28.9%, P=0.023; 6-month HR 61.2% vs 40.8%, P=0.026). With ∆ANC≥0.5×10⁹/L as cutoff level, the best point to predict early IST response was 10 days after G-CSF (d 10). Response of ANC to pre-IST G-CSF treatment at d 10 was among the independent factors of predicting 3-month (P=0.004), but not for 6-month response to IST. The overall 5-year survival rate was 92.8% and 69.5% in ANC responded and non-responed groups, respectively (P=0.025).Responding to pre-IST G-CSF treatment reflected the residual bone marrow hematopoiesis, and could act as a convenient and practical predictor to early IST response as well as long-term survival in SAA.