Abnormal epigenetics play important roles in the pathogenesis of myelodysplastic syndromes (MDS). DNA hypermeth-ylation is the most common epigenetic abnormality in MDS. Demethylating DNA hypermethylation may improve the quality of life of MDS patients and prolong their overall survival. Azacitidine and decitabine are the demethylating drugs approved for MDS treatment. These drugs showed clinical effects on all subgroups of MDS patients.

Idiopathic cytopenia of uncertain significance is a new term which describes a cytopenia in one or more myeloid lineages that is constant,does not meet the minimal criteria of an MDS and cannot be explained with any other hematologic or non-hematologic diseases.The proposal,diagnosis and therapy of ICUS are reviewed in this paper.

Objective To investigate the function of myeloid dendritic cells (mDCs) from severe aplastic anemia ( SAA ) patients in stimulating allogeneic T lymphocytes proliferation in vitro and then explore the immunopathogenesis of SAA. Methods Twenty-five SAA patients ( 15 untreated and 10 recovered after immunosuppressive therapy) and 12 normal controls were enrolled in this study. Their mature mDCs were induced from their bone marrow monocytes with recombined human interleukin-4 ( rhIL-4) , recombined human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) and recombined human tumor necrosis factor (rhTNF) in vitro. Then mDCs were co-cultured with allogeneic lymphocytes (mixture lymphocyte reaction, MLR) at a ratio of 1: 100 or 1: 50. The growth rate of lymphocyte was measured with methyl thiazolyl tetrazolium ( MTT) colorimetry.The concentrations of interleukin( IL) -12 and inlerferon -y (IFNγ) in MLR supernatant were measured with EL1SA. The correlation between the growth rate and the concentration of IL-12 or IFNγ was analyzed. Results When mDCs and lymphocytes were co-cultured at the ratio of 1: 100, the growth rates of lymphocytes stimulated with mDCs from untreated, recovered SAA patients and controls were (219. 8 ±94. 0)% , (159. 1 ±66. 0)% and (160. 1 ±91. 9)% respectively. The concentrations of IL-12 in MLR supernatant were (8. 2 ± 3. 6) ng/L, (6. 5 ± 2. 8) ng/L and (6. 1 ± 2. 6) ng/L and the concentrations of IFNγ were (21. 8 ± 8. 7) ng/L, (25. 5 ± 9. 1) ng/L and (22. 6 ± 7. 8) ng/L respectively. All of them had no statistical differences among the three groups ( P > 0. 05 ). When mDCs and lymphocytes were co-cultured at the ratio of 1: 50, the growth rate of lymphocytes stimulated with mDCs from untreated patients was (322. 1 ± 171. 1)% , which was higher than that of recovered patients [ (180. 9 ±79. 1)% and controls (192. 3 ±91. 9)% ]. The concentrations of IL-12 in MLR supernatant in the three groups were (12.6 ±4.4) ng/L, (9.4 ±3.3) ng/L and (8.5 ±3.7) ng/L, and the concentrations of IFNγ were (32. 3 + 9. 2 ) ng/L, ( 27. 4 ± 6. 5) ng/L and (24. 4 ± 7. 4 ) ng/L Both of the values in untreated cases were higher than those of the recovered cases or controls (P < 0. 05 ) , but there were no statistical difference between the recovered and control groups ( P >0. 05 ). The concentration of IL-12 in MLR supernatant correlated positively with the growth rate of lymphocyte (r=0. 529,P <0. 01) and so did the concentration of IFNγ (r = 0. 381, P < 0. 05). Conclusion The function of mDCs to stimulate T lymphocytes proliferation in SAA was enhanced; it might play an important role in the immunopathogenesis of SAA.

Objective To explore the expression of antigen activated of macrophages ( MΦ) of bone marrow and its clinical significance in pancytopenia patients with positive bone marrow mononuclear cells (BMMNC)-Coombs test ( immunorelated pancytopenia, IRP) . Methods Sixty-one IRP patients, 10 severe aplastic anemia (SAA) patients and 13 healthy controls were enrolled in this study. The categories of auto-antibodies(IgG, IgM) on BMMNC(CD_(34)~+/CD_(15)~+/GlycoA~+ hematocytes), the quantity (CD_(68)~+/CD_(45)~+)% and expression of antigen activated ( CD_(69) ) of MΦ ( CD_(68)~+ CD_(69)~+/CD_(68)~+ ) % in bone marrow of all cases and controls were measured by fluorescence activated cell sorting( FACS). Results The quantity and expression ratio of activated antigen of bone marrow ( BM ) MΦ in IRP patients [ ( 0. 57 ± 0. 30 ) % and ( 40. 30 ± 18.49)%] were respectively significantly higher than those in SAA [ (0.46 ± 0. 08)% and ( 32. 44 ± 19.37)%] and healthy controls [ (0. 44 ± 0. 69)% and (29.71 ± 11. 67 )% ] ( both P < 0. 05 ). The quantity presented high-positive correlation with the expression ratio of activated antigen of BM MΦ ( r = 0.89, P<0. 01). Patients with IRP were classified into two subgroups according to the quantity of MΦ: Group A (MΦ≥0. 5% , 34 cases) and Group B ( MΦ <0. 5% , 27 cases). Thirty-two cases (94. 12%) were with auto antibody ( IgG) in Group A, while only 2 (7. 41% ) with auto antibody ( IgG) in Group B. There was significant difference in expression ratio of activated antigen of BM MΦ between Group A (49. 19 ± 16. 63) % and Group B (29. 11 ± 14. 30) % ( P < 0. 05 ) , but no difference was found between Group B and the control group (P >0. 05). Total curative rates at 3 and 6 month (47. 06% and 79. 41% ) of Group A were better than those of Group B (22.22% and 51.85%). Thirty-four IRP patients with autoantibody ( IgG) ( + ) were divided into two subgroups according to the quantity of MΦ: high level group ( >0. 75% , 9 cases) and low level group( <0. 75% , 25 cases) , 24 cases (96% ) in MΦ low level group were found auto-antibody (IgG) on one hemotopoietic cell lineage, 1 on two lineages, while 8 (88. 89% ) in MΦ high level group were detected auto-antibody (IgG) on two cell lineages, and 1 on three cell lineages. Expression ratio of activated antigen (56. 12 ± 15. 11) % was much higher in MΦ high level group than that in MΦ low level group (44. 58 ± 18. 16)% (P < 0. 05 ). The count of red blood cell concentration of hemoglobin and platelet in peripheral blood in MΦ high level group were respectively lower than those in MΦ low level group, while the percentage of Ret, the level of total bilirubin and indirect bilirubin, the ratio of erythroid of sternal bone marrow in MΦ high level group were higher than those in MΦ low level group. Conclusion The expression of activated antigen of BM MΦ was enhanced in IRP especially with autoantibody (IgG) , which might be involved in damage process of hemotopoietic cell.

Objectives To detect the abnormalities of CD34+ cells differentiation and bone marrow cell cycle in myelodysplastic syndrome (MDS). Methods Fifty newly diagnosed MDS ( 17 in low risk and 33 in high risk), 8 acute myeloid leukemia preceded by MDS (MDS-AML) and 25 normal controls were enrolled into this study. Their CD34+ CD38+, CD34+CD38- bone marrow cells and bone marrow cell cycle were measured with flow cytometry. Results The mean percentages of CD34+ cells in bone marrow karyocyte of high risk [ (2.29 ±2.17)% ] and MDS-AML groups [ ( 18.69 ± 17.47)% ] were significantly higher than that of control group [ ( 0.36 ± 0.49 )%, P ＜ 0.05 ]. The mean percentages of CD34+CD38+ cells were significantly lower in low risk, high risk and MDS-AML groups [ ( 86.09 ± 7.79 )%, ( 81.68 ± 11.82)% and (82.88 ±2.60)%, respectively] than that in control group [ (92.21 ±3.85)%, P＜0.05], thus the percentages of CD34+CD38- cells were significantly higher in either MDS (low risk and high risk) or MDS-AML groups [ (13.91 ±7.79)%, (18.32 ±11.82)% or (17.13 ±2.60)%, respectively] than that in control group [ (7.79 ± 3.85 )%, P ＜ 0.05 ]. The percentages of CD+34 CD-38 cells of MDS cases correlated directly with their International Prognostic Scoring System (IPSS) (r =0.493, P =0.001 ) and WHO Adapted Prognostic Scoring System (WPSS) ( r = 0.586, P = 0.000 ) scores. The percentages of bone marrow mononuclea cells (BMMNCs) in G0/G1 phase of in low risk, high risk and MDS-AML groups [ (94.52 ±4.32)%, (96.07 ± 3.88 )% and (94.65 ± 4.55 )%, respectively ] were significantly higher than that in control group[ (88.94 ±7.30)%, P ＜0.01 ], thus the percentages of BMMNCs in S and G2/M phase were significantly lower in either MDS (low risk and high risk) or MDS-AML groups than that in control group (P＜0.05). MDS patients with low percentages of CD34+CD38- cells presented higher therapeutic efficacy than those with high percentages of CD34+CD38- cells, while without significant differences ( P ＞ 0.05 ) .Conclusions There are abnormalities of differentiation of CD34+ bone marrow cells and high proportion of G0/G1 cells which indicates a G1 phase arrest in MDS that might be involved in the pathogenesis of MDS. So the examination of CD34+ bone marrow cells and cell cycle might be helpful for MDS diagnosis and assessment of prognosis and therapeutic effects.

Primary mediastinal large B-cell lymphoma (PMBCL) is an aggressive large B-cell lymphoma originating in the mediastinum. Because of its distinct clinical and histological features, PMBCL has been reclassified as a separate entity by the World Health Organization classification of lymphoid neoplasms. The diagnosis of PMBCL mainly depends on the pathological features, imaging examination and clinical features. Currently, there are many therapeutic schemes for PMBCL, the most commonly used schemes are R-CHOP and R-EPOCH regimens. Radiotherapy is beneficial in some patients, but it can also lead to long-term toxicity. Research and development of new drugs are ongoing, including chimeric antigen receptor T-cell therapy, anti-programmed death receptor 1 drugs, etc. PET-CT is mainly used to assess the curative effect after treatment and to guide the next treatment strategy.

Objective To assess the efficacy and safety of monoclonal antibody rituximab combined with cyclophosphamide (CTX) in the treatment of refractory and recurrent autoimmune hemolytic anemia.Methods Seven cases with refractory and recurrent autoimmune hemolytic anemia ( including 1 case of Evans syndrome) were recruited during January,2007 to December,2010.Treatment regimens were as follows:rituximab:375 mg/m2,1 time/week,2-6 courses; CTX:1 g,1/10 d,2-7 courses; combined with intravenous immunoglobulin (IVIG) 5 g,1 time/week,given 1 day after rituximab administration.The efficacy and safety of this regimen were assessed during follow-up.Results All the patients showed good responses (7/7).Six patients achieved complete remission (6/7) and one achieved partial remission ( 1/7 ).Average follow-up time for the patients was 27 months.All patients remained in remission during the 12-month follow-up visits.Two patients showed elevated indirect bilirubin and increased reticulocyte counts within 24 months.One patient achieved complete remission after additional rituximab therapy,and another patient remained partial remission after cyclosporine therapy.At the time of 36-month follow-up visit,the patient relapsed and was retreated with 3 courses of rituximab combined with CTX and eventually achieved partial remission.All patients tolerated the treatment well with few mild side effects.Conclusions Rituximab combined with CTX is effective and relatively safe in patients with refractory and recurrent autoimmune hemolytic anemia.Additional treatment to relapse patients about 12-24 months after drug withdrawal continues to be effective.

Objective To study the effect of iron overload on the bone marrow hematopoietic function on immuo-related pancytopenia(IRP)patients by hematopoietic progenitor cell(HPC)culture of bone marrow(BM).Methods BM liquid 4～5 mL was taken from 46 IRP patients of General Hospital Tianjin Medical University from July 2009 to February 2010 to detect colony-forming-unit of erythrocyte,blast-forming-unit of erythrocyte and colony-forming-unit of granulocyte-monocyteby HPC culture of BM.And according to the serum ferritin(SF)level,these patients were classified into 2 groups to compare HPC proliferation,blood cell counts,BM proliferation,blood transfusion and treatment effects.Results The mean values of 3 different colonies of IRP patients with high SF level [(43.33?17.74),(1.50?2.2),(11.06?5.83)/105BMMNC] were significantly lower than those of the patients with normal SF level [(77.43?40.64),(9.57?7.99),(21.25?11.41)/105BMMNC](P

Objective To investigate the effects and related factors of itraconazole in the treatment of invasive fungal infection (IFI) in the patients with blood diseases ( BD). Methods A total of 156 BD patients with IFI treated with itraconazole in General Hospital, Tianjin Medical University from 2005 to 2008, were retrospectively analyzed. Results Of these patients, 92 were with underlying malignant BD, and 64 with non-malignant BD; 77 possible IFI, and others proven IFI. A total of 94 (63. 5% ) patients were responded to itraconazole successfully, while 54 (36. 5% ) failed. The underlying malignant BD, post-chemotherapy, neutrophil count less than 0. 5 x 109/L, positive fungus culture, and bacteria infection were related with the response to itraconazole significantly, while patient's age, application of other antibiotics,positive C test, IFI localization, haemoglobin level and platelet counts were not Five patients was changed other anti-IFI therapy because of side effects, including gastrointestinal ill (3 cases with nausea or vomiting) and tachycardia (2 cases). Conclusions Itraconazole was effective and safe in the treatment of IFI in the patients with BD. Underlying malignant BD, agranulocytosis, bacteria infection, and delayed anti-IFI therapy might reduce itraconazole therapeutic effects.