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Hematology AND Aplastic anemia [keywords]
- [Recommendations for diagnosis and treatment of acquired aplastic anemia in children]. [Journal Article]
- Zhonghua Er Ke Za Zhi 2014 Feb; 52(2):103-6.
- [Immunosuppressive therapy using antithymocyte globulin and cyclosporin A with or without human granulocyte colony-stimulating factor in children with acquired severe aplastic anemia]. [English Abstract, Journal Article]
- Zhonghua Er Ke Za Zhi 2014 Feb; 52(2):84-9.
To compare the efficacy and safety of four different regimens for pediatric severe aplastic anemia (SAA) with immuno-suppressive therapy (IST) with or without combined human granulocyte colony-stimulating factor (G-CSF).The authors retrospectively analyzed 105 children with SAA treated with IST with or without G-CSF in the hospital from February 2000 to September 2010. Regimen A, without G-CSF in the whole treatment, was used to treat Group A patients, n = 27; Regimen B, G-CSF, was initiated in Group B, n = 24, before the IST until hematologic recovery; Regimen C, G-CSF, was used together with the IST for Group C patients, n = 24, until hematologic recovery; Regimen D,G-CSF was used for Group D, n = 30, after the end of IST until hematologic recovery. The response rate, relapse rate, mortality, infection rate, infection-related death rate, risk of evolving into MDS/AML, survival rate, factors affecting the time of event-free survival and so on.(1) The response (CR+PR) rates 4, 6, 12 and 24 months after IST of the whole series of 105 SAA children were 50.5% (7.6%+42.9%) , 60.0% (21.9%+38.1%) , 67.6% (38.1%+29.5%) and 69.5% (40.0%+29.5%) respectively. The 2-year survival rate was 90.5%; the follow-up of the patients for 13 years showed that the whole survival rate was 87.6%. (2) The differences of the response rates 4, 6, 12 and 24 months after IST of the 4 groups were not significant (P > 0.05). (3) No significant differences were found in the mortalities 4, 6, 12 and 24 months among the 4 groups (P > 0.05). (4) Of the 105 patients, 4 children had relapsed disease in the period of time from 6 to 24 months after IST. All the four patients belonged to the groups with G-CSF. (5) The use of G-CSF could not decrease the infection period before IST (day) (P = 0.273), and it had no impact on the infection rate after IST (P = 0.066). It did not reduce the rates of septicemia and infectious shock. And to the infection-related death rate no significant conclusion can be made. (6) Follow up of the patients for 13 years, showed that 2 had the evolution to MDS/AML in the 105 patients and the two children belonged to the groups with G-CSF. (7) Kaplan-meier curve analysis did not show any differences in the survival rates of the four groups. (8) Cox regression analysis showed that the use of G-CSF had no benefit to the patients' long term survival. While the age of diagnosis and the infection history before IST were significantly related to the patients' long term survival.The use of G-CSF did not contribute to the early response and could not reduce the infection rate, infection-related death rate and the patients' long term survival. There were no significant differences in the survival rates of the four groups. Attention should be paid to the risk of the evolution to MDS/AML.
- Blood stream infection after stem cell transplantation in children with idiopathic aplastic anemia. [JOURNAL ARTICLE]
- Biol Blood Marrow Transplant 2014 Apr 10.
Blood stream infection (BSI) is the most common infectious complication of hematopoietic stem cell transplantation (HSCT) and can cause substantial morbidity and mortality. Identification of risk factors for BSI might be helpful in efforts to reduce transplant-related death. This study analyzed the incidence of BSI and risk factors for BSI after transplantation in pediatric patients with aplastic anemia (AA). BSI occurred in 39 of 351 patients with AA (11.1%). Median onset of BSI was 8 days after transplantation (0 to 92 days). The 5-year overall survival rate was lower in patients with BSI (63.32±7.90%) than in patients without BSI (93.35±1.44%, p<0.0001). Univariate analysis showed that variables associated with BSI included history of immunosuppressive therapy with anti-thymocyte globulin, transplantation from unrelated donors, frequent blood transfusion before transplantation, major or major+minor mismatch of ABO blood type, graft versus host disease prophylaxis without cyclosporine and with tacrolimus, and long interval from diagnosis to transplantation. In these factors, long interval from diagnosis to transplantation was the only statistical significant factor for BSI using multivariate analysis. In patients who underwent HSCT from related donors, age ≥ 14 years at transplantation was risk factor of BSI. By contrast, history of immunosuppressive therapy with ATG, frequent blood transfusion before transplantation, graft failure and major or major+minor mismatch of ABO blood type were risk factors of BSI in patients who underwent HSCT from unrelated donors. Since the overall 5-year survival rate without BSI was over 90%, even in patients who were transplanted from an unrelated donor, control of BSI is very important for success of HSCT in patients with pediatric AA.
- Dynamics of Graft Function Measured by DNA-Technology in a Patient with Severe Aplastic Anemia and Repeated Stem Cell Transplantation. [Journal Article]
- Case Rep Med 2014.:576373.
Although bone marrow transplantation (BMT) from an HLA identical sibling is considered as treatment of choice in pediatric patients with severe aplastic anemia (SAA), a significant number of them experience graft failure (GF) after BMT. We report a case of an 8-year-old male patient with SAA who presented with a complicated posttransplant course due to parvovirus B19 infection and GF. A subsequent attempt to support the graft by antithymocyte globulin (ATG) and a peripheral stem cell boost resulted in transitory autologous recovery of hematopoiesis followed by mixed chimerism, supported by donor lymphocyte infusions (DLIs) and finally graft rejection with relapse of SAA. Permanent complete chimerism was achieved by a second BMT. Dynamics of graft function, measured by a single nucleotide polymorphism (SNPs) analysis, are discussed.
- STAT3 Inhibitors: Finding a Home in Lymphoma and Leukemia. [JOURNAL ARTICLE]
- Oncologist 2014 Apr 4.
The Janus kinase (JAK) and signal transducer and activator of transcription (STAT) pathway is an active mediator of cytokine signaling in the pathogenesis of solid and hematologic malignancies. The seven-member STAT family is composed of latent cytoplasmic transcription factors that are activated by phosphorylation intertwined in a network with activation that ultimately leads to cell proliferation. An activated kinase enzyme phosphorylates one STAT factor or more, which shuttle to the nucleus to regulate gene expression, promoting cell survival. Somatic STAT3 mutations have been recently reported in large granular lymphocytic leukemia, aplastic anemia, and myelodysplastic syndrome. Furthermore, the relationship between BCL6 and STAT3 in diffuse large B-cell lymphomas, particularly on the activated B-cell subtype, needs to be further explored. The search for therapeutic STAT3 inhibitors that abrogate the JAK/STAT pathway is currently under way. Targeting the STAT pathway, which seems to be critical in tumorigenesis, is promising for multiple malignancies including lymphoma and leukemia. In this paper, we review mechanisms of action, failures, and successes of STAT3 inhibitors.
- Fatal Fusarium Solani Infection After Stem Cell Transplant for Aplastic Anemia. [JOURNAL ARTICLE]
- Exp Clin Transplant 2014 Mar 28.
Fusarium is a saprophytic and opportunistic pathogen that can cause local tissue infection and life-threatening systemic infection. Systemic infection is rare and is observed primarily in immunocompromised patients. The early diagnosis is difficult, and the optimal treatment is unclear. However, the mortality is high. A 21-year-old man with aplastic anemia was treated with an allogeneic stem cell transplant. He developed fatal Fusarium solani infection. Fusarium species may be overlooked pathogenic fungi in immunocompromised patients, especially bone marrow transplant recipients.
- Abnormalities of quantities and functions of Linker for Activations of T cells (LAT) in severe aplastic anemia. [JOURNAL ARTICLE]
- Eur J Haematol 2014 Mar 27.
Severe aplastic anemia (SAA) is a rare immune-regulated disease characterized by severe pancytopenia and bone marrow failure, caused by .destruction of hematopoietic cells by the activated T lymphocytes. Linker for activation of T cells (LAT), a transmembrane adaptor protein, plays a key role in T cell and mast cell function. However it remains unclear how LAT may change in patients with SAA. The present study aims at understanding the role of lymphocyte LAT in SAA.The expression of LAT, related signaling molecules and T cell effector molecules was determined by flow cytometry. LAT mRNA was evaluated by Quantitative real-time PCR. Cytokine production by cultured T cells was determined by ELISA.Patients with SAA had an increased levels of LAT and both total phosphorylated LAT and of the related molecule (ZAP-70) in circulating T cells compared with normal controls. In SAA patients, the expression of LAT was positively associated with the expression of perforin and granzyme B in CD8(+) T cells. Inhibition of LAT expression in T cells from SAA patients decreased the activation of the CD4(+) and CD8(+) T cell subset. Over expression of LAT in T cells from normal controls increased the activation of CD4(+) and CD8(+) T cell subsets with increased apoptosis of K562 cells in coculture.Our findings demonstrate that dysregulation of LAT expression and activation may contribute to over-function of T cells, imbalance of Th1/Th2 subsets and thus lead to hematopoiesis failure in SAA. Immunosuppressive therapy dramatically reduced the expression of LAT making it an attractive therapeutic target in SAA. This article is protected by copyright. All rights reserved.
- [Fludarabine-based increased-intensity conditioning regimen for allogeneic hematopoietic stem cell transplantation in acquired severe aplastic anemia]. [English Abstract, Journal Article]
- Zhonghua Xue Ye Xue Za Zhi 2014 Mar; 35(3):221-4.
To observe the effects of increased-intensity conditioning regimen with FBCA (Fludarabine, Busulfan, Cyclophosphamide, and Antithymocyte globublin) for allogeneic hematopoietic stem cell transplantation (allo-HSCT) in acquired severe aplastic anemia (SAA).From January 2000 to June 2011, twenty-two patients (male 12, female 10) with SAA underwent allo-HSCT with FBCA conditioning regimen which consisted of fludarabine (30 mg·m⁻²·d⁻¹×5 d), busulfan (3 mg/kg×2 d), cyclophosphamide (60 mg·kg⁻¹·d⁻¹×2 d) and ATG (2.5 mg·kg⁻¹·d⁻¹×5 d). GVHD prophylaxis was performed by cyclosporine and short-term course methotrexate. Nine patients received mobilized peripheral blood stem cells transplantation and 13 patients underwent mobilized peripheral blood combined with bone marrow stem cells. Fourteen cases were human leukocyte antigen (HLA)-matched related donors, while the other 8 cases were HLA-haploidentical transplantation. Engraftment was documented by short tandem repeats with polymerase chain reaction (STR-PCR) on approximately day + 30, + 90, + 180, + 1 year and + 2 year, respectively. Long-term survival and transplantation-related complications were analyzed.All patients obtained prompt and sustained hematopoietic reconstitution. Median time for neutrophil and PLT engraftment was 15 (range: 11-22) days and 16 (range: 12-27) days, respectively. All patients were full donor chimerism identified by STR-PCR. 2 of the total 22 cases (9.1%) had grade I-III acute GVHD and 3 (15.8%) was chronic GVHD. Three patients (13.6%) died of transplantation related mortality and the other 19 cases were disease-free survival with a median time of 24 (range: 0.5-140.5) months. The causes of death were cytomegalovirus pneumonia (n=1), acute GVHD (n=1) and severe pulmonary infection (n=1).Increasedintensity of FBCA conditioning regimen could favor donor stem cell sustained engraftment for allo-HSCT in SAA.
- An inter-laboratory comparison of PNH clone detection by high-sensitivity flow cytometry in a Russian cohort. [JOURNAL ARTICLE]
- Hematology 2014 Mar 26.
Objectives Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal stem cell disorder characterized by partial or absolute deficiency of glycophosphatidyl-inositol (GPI) anchor-linked surface proteins on blood cells. A lack of precise diagnostic standards for flow cytometry has hampered useful comparisons of data between laboratories. We report data from the first study evaluating the reproducibility of high-sensitivity flow cytometry for PNH in Russia. Methods PNH clone sizes were determined at diagnosis in PNH patients at a central laboratory and compared with follow-up measurements in six laboratories across the country. Analyses in each laboratory were performed according to recommendations from the International Clinical Cytometry Society (ICCS) and the more recent 'practical guidelines'. Follow-up measurements were compared with each other and with the values determined at diagnosis. Results PNH clone size measurements were determined in seven diagnosed PNH patients (five females, two males: mean age 37 years); five had a history of aplastic anemia and three (one with and two without aplastic anemia) had severe hemolytic PNH and elevated plasma lactate dehydrogenase. PNH clone sizes at diagnosis were low in patients with less severe clinical symptoms (0.41-9.7% of granulocytes) and high in patients with severe symptoms (58-99%). There were only minimal differences in the follow-up clone size measurement for each patient between the six laboratories, particularly in those with high values at diagnosis. Conclusions The ICCS-recommended high-sensitivity flow cytometry protocol was effective for detecting major and minor PNH clones in Russian PNH patients, and showed high reproducibility between laboratories.
- Treatment of human papillomavirus infection with interferon alpha and ribavirin in a patient with acquired aplastic anemia. [JOURNAL ARTICLE]
- Int J Infect Dis 2014 Mar 22.
Genital warts caused by human papillomavirus (HPV) are the most frequent sexually transmitted infection. We describe a case of severe perianal and genital HPV infection in a patient with acquired aplastic anemia, unresponsive to traditional therapies and treated effectively with a combination of interferon and ribavirin.