Prognostic significance of (18)F-fluorodeoxyglucose positron emission tomography in patients with diffuse large B cell lymphoma undergoing autologous stem cell transplantation / 中华血液学杂志

Objective: To evaluate the prognostic value of (18)F-fluorodeoxyglucose positron emission tomography (PET)/computed tomography (CT) in patients with diffuse large B cell lymphoma (DLBCL) undergoing autologous hematopoietic stem cell transplantation (auto-HSCT). Methods: Forty-eight patients with DLBCL treated at Peking University Cancer Hospital between November 2010 and December 2014 were assessed. All patients underwent PET/CT scanning prior to or after auto-HSCT. Correlation analysis was done based upon patients characteristics, PET/CT scan results and survival. Results: ①Among 48 patients, 27 was male, 21 female, median age was 43 (17-59) years old. ② Patients with negative pre-auto-HSCT PET/CT assessment demonstrated significantly better 3-year progression free survival (PFS) (87.1% vs 53.3%, χ(2)=7.02, P=0.019) and overall survival (OS) (90.3% vs 60.0%, χ(2)=6.51,P=0.022) than patients with positive pre-auto-HSCT PET/CT assessment. Three-year PFS (94.1% vs 30.0%, χ(2)=22.75, P=0.001) and OS (97.1% vs 40.0%, χ(2)=21.09, P=0.002) were also significantly different between patients with negative and positive post-auto-HSCT PET/CT assessment. ③ Multivariate analysis indicated a significant association of PFS (HR=13.176, P=0.005) and OS (HR=20.221, P=0.007) with post-auto-HSCT PET/CT assessment. Number of prior treatment regimens was associated with PFS (HR=10.039, P=0.040). ④ Harrell's C index revealed that the value of combined use of number of prior treatment regimens and post-auto-HSCT PET/CT assessment was superior to either one used alone in PFS (Harrell's C values were 0.976, 0.869 and 0.927 in combined use, number of prior treatment regimens and post-auto-HSCT PET/CT assessment, respectively), and the combined use of ECOG performance status and post-auto-HSCT PET/CT assessment significantly increased the Harrell's C index in OS (Harrell's C values were 0.973, 0.711 and 0.919 in combined use, ECOG performance status and post-auto-HSCT PET/CT assessment, respectively). Conclusions: Post-auto-HSCT PET/CT assessment is the main predictor of outcomes in DLBCL patients receiving auto-HSCT. Combined use of post-auto-HSCT PET/CT assessment and number of prior treatment regimens and ECOG performance status is a better prognostic tool in patients with DLBCL undergoing transplantation.

Clinical characteristics and prognosis analysis of patients with LMP-1 positive Hodgkin's lymphoma after EBV infection / 中国实验血液学杂志

This study was purposed to investigate the expression of latent membrane protein 1 (LMP-1) and CD68 in Hodgkin's lymphoma (HL) patients with EB virus infection and to analyze the relation of LMP-1 expression and CD68(+) tumor-associated macrophage count with clinical features and prognosis of HL patients. The expression of LMP1 and count of CD68(+) TAM were detected by immunohistochemical staining in tissue specimens of 72 HL patients; their correlation with clinical features and prognosis of HL patients was analyzed by using statistical method. The results showed that among tissue specimens of 72 HL patients, the positive rate of LMP-1 expression was 18.1% (13/72), the CD68(+) TAM count was more higher in LMP-1 positive expression [250 of CD68(+) TAM/high power field (hpf) is used as demarcation point] (P = 0.003). The statistical analysis showed that the LMP-1 positive expression was more observed in mixed type HL patients (P = 0.000); the positive rate of LMP-1 expression was much high in HL patients with albumin <40 g/L and age ≥ 45 years (P < 0.05). There was no relation of LMP-1 expression and CD68(+) TAM count with the short term therapeutic efficacy of HL patients, but the overall survival time of LMP-1 positive patients among patients followed-up for ≥ 5 years was short (P < 0.05). Moveover, no correlation of CD68(+) TAM count with the overall survival time of HL patients was found. It is concluded that the high count of CD68(+) TAM is more observed in LMP-1 positive expression of HL tissue, the LMP-1 expression states relates both with the pathological types, age and albumin level of patient with HL. The HL patients with LMP-1 positive expression have poor prognosis, suggesting that LMP-1 may be a new prognostic marker for HL patients.

The role of cytokines in lymphoma with anemia / 中国实验血液学杂志

This study was purposed to investigate the role of cytokines in pathogenesis of lymphoma-associated anemia. The levels of IFN-γ, IL-1β, IL-6, TNF-α and EPO in serum from 45 lymphoma patients and 12 normal controls were detected by using ELISA, the EPOR level on bone marrow cells were detected by flow cytometry, the CFU-E of bone marrow cultured in vitro was counted under inverted microscope. The results showed that 25 (55.6%) out of 45 newly diagnosed lymphoma patients had anemia before diagnosis, 13 (28.9%) had anemia during therapy, 7 (15.5%)never had anemia. The IFN-γ and TNF-α levels in serum of patients with moderate and severe anemia were significantly higher than those in patients with mild anemia and without anemia as well as normal controls. The EPO, IL-6 and IFN-γ levels correlated negatively with Hb concentration in patients, the EPOR level in patients without anemia significantly higher than that in patients with anemia and normal controls. The bone marrow CFU-E amount in patients showed positive correlation with Hb and EPOR levels. It is concluded that the increased IFN-γ, TNF-α and IL-6 may contribute to the anemia in lymphoma, and yet the EPO and EPOR levels are elevated to balance negative regulatory effects on hematopoiesis and maintain normal hematopoiesis.

Prognostic value of (18)F-FDG PET/CT after first-line treatment in patients with diffuse large B cell lymphoma / 中华血液学杂志

<p><b>OBJECTIVE</b>To evaluate the value of (18)F-FDG PET/CT in detecting residual disease and predicting relapse following first-line treatment in patients with diffuse large B cell lymphoma (DLBCL).</p><p><b>METHODS</b>The clinical data of 39 patients with DLBCL, who underwent PET/CT scan after first-line treatment, were analyzed retrospectively. Kaplan-Meier method was used to analyze the survival of patients.</p><p><b>RESULTS</b>PET/CT findings were interpreted as negative, mild metabolism and positive. Seventeen patients' PET/CT findings were judged as negative, none of them relapsed with a median follow-up of 24.1 months, 13 were judged as mild metabolism, 2 of them relapsed with a median follow-up of 17.1 months. Of the rest 9 findings were judged as positive with a median follow-up of 16.3 months, 4 patients were considered as disease progression according to clinical manifestations and other radiographic results, 2 patients relapsed at the time points of 13.5 and 6.8 months after PET/CT scan respectively, the other 3 patients were diagnosed as negative by biopsy, none of them relapsed at the time points of 5.9, 9.6 and 20.0 months after PET/CT scan respectively. One-year progression-free-survival (PFS) for negative, mild metabolism and positive groups was 100%, 83% and 56%, respectively. Two-year PFS was 100%, 83% and 42%, respectively. Overall survival (OS) at 1 year for negative, mild metabolism and positive groups was 100%, 100% and 89%, respectively. Two-year OS was 100%, 100% and 63%, respectively (P = 0.004).</p><p><b>CONCLUSION</b>DLBCL patients with negative and mild metabolism PET/CT following first-line treatment had good prognosis, who needed no additional therapy. While patients with positive PET/CT had poor prognosis, those patients should receive biopsy before adjusting treatment regimen because of the high false-positive rate.</p>

The clinical features, therapeutic responses, and prognosis of the patients with mantle cell lymphoma / 癌症

Mantle cell lymphoma(MCL), a special type of non-Hodgkin's lymphoma, is incurable through conventional treatment. This study aimed to analyze the clinical features, therapeutic responses, and prognosis of patients with MCL. Clinical data of 30 patients with MCL treated in our hospital between April 2006 and July 2011 were analyzed. Eighteen patients were treated with CHOP plus rituximab (R-CHOP) regimen, 12 underwent conventional chemotherapy. The median age of the 30 patients was 58 years, 23 were men, all patients had Cyclin D1 overexpression, 29 (96.7%) had advanced disease, 11 (36.7%) had bone marrow involvement, 9 (30.0%) had gastrointestinal involvement, and 15 (50.0%) had splenomegaly. The complete response(CR) rate and overall response rate(ORR) were significantly higher in patients undergoing R-CHOP immunochemotherapy than in those undergoing conventional chemotherapy (38.9% vs. 16.7%, P = 0.187; 72.2% vs. 41.4%, P = 0.098). The difference of 2-year overall survival rate between the two groups was not significant (P = 0.807) due to the short follow-up time. The 2-year progression-free survival (PFS) rate was higher in R-CHOP group than in conventional chemotherapy group (53% vs. 25%, P = 0.083), and was higher in patients with a lower mantle cell lymphoma international prognostic index (MIPI) (51% for MIPI 0-3, 33% for MIPI 4-5, and 0% for MIPI 6-11, P = 0.059). Most patients with MCL were elderly; in an advanced stage; showed a male predominance; and usually had bone marrow involvement, gastrointestinal involvement, or splenomegaly. R-CHOP regimen could improve the CR rate and ORR of MCL patients. MIPI can be a new prognostic index for predicting the prognosis of advanced MCL.

Plasma levels of VEGF-C, VEGF-D, VEGFR-2 and VEGFR-3 in patients with newly diagnosed lymphomas / 中国实验血液学杂志

The objective of this study was to detect the expression levels of VEGF-C, VEGF-D, VEGFR-2 and VEGFR-3 in plasma of newly diagnosed lymphoma patients, and analyze their possible relationships with clinicopathological characteristics and prognosis. The expression levels of VEGF-C, VEGF-D, VEGFR-2 and VEGFR-3 in plasma from 86 newly diagnosed lymphoma patients were detected by enzyme-linked immunosorbent assay (ELISA). As a results, the multivariate analysis showed that VEGF-C level in non-Hodgkin's lymphoma patients was low, but high in Hodgkin's lymphoma patients; VEGFR-2 level was higher in patients > 60 years, while VEGF-D level was lower in patients with IPI > 2. The univariate analysis showed that VEGF-D level was lower in patients with IPI > 2, while VEGF-D and VEGF-C levels were higher in patients without B symptoms. Relationship analysis between these factors indicated that the relation of VEGF-D expression level with VEGFR-2 and VEGFR-3 was positive. It is concluded that VEGF-C, VEGF-D, VEGFR-2 and VEGFR-3 play important roles in the pathogenesis of lymphoma, and may be used as indicators of prognosis evaluation or even guide for the antiangiogenesis treatment of lymphoma.

An analysis of hepatitis B virus infection rate in 405 cases of non-Hodgkin lymphoma / 中华血液学杂志

<p><b>OBJECTIVE</b>To analyze the status of hepatitis B virus (HBV) infection in non-Hodgkin lymphoma (NHL) patients.</p><p><b>METHODS</b>The serum HBV markers in NHL patients were detected by enzyme-linked immunosorbent assay (ELISA). The infection rate of HBV in NHL patients was compared with that in nationwide general population.</p><p><b>RESULTS</b>The positive rates of HBsAg, anti-HBs and anti-HBc in 405 cases of NHL were 11.6%, 39.8% and 47.9%, respectively, which were statistically different from those in general population (P < 0.01). The positive rates of HBsAg, anti-HBs and anti-HBc in B-cell NHL and T-cell NHL were 13.3% vs 7.1% (P = 0.083), 40.6% vs 37.5% (P = 0.567), 53.2% vs 33.9% (P = 0. 001), respectively. The HBV DNA positive rate was 23.7% in 93 cases of NHL, and was 50.0% in 38 cases of HBsAg-positive NHL while 5.5% in 55 cases of HBsAg-negative but HBcAb-positive NHL.</p><p><b>CONCLUSIONS</b>The infection rate of HBV in NHL patients is higher than that in general population, in which occult hepatitis B virus infection can not be ignored. The positive rate of anti-HBc in B-cell NHL is significantly higher than that in T-cell NHL. For NHL patients infected with HBV, prophylactic anti-HBV therapy to prevent viral reactivation should be given before the anti-cancer treatment. Further study in the relationship between HBV and NHL should be carried out in the future.</p>

The quantity, subsets and expression of costimulatory molecules of circulating dendritic cells in the patients with myelodysplastic syndromes / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the quantity, subset of dendritic cells (DC) and their costimulatory molecule expression in peripheral blood (PB) of the patients with myelodysplastic syndromes (MDS).</p><p><b>METHODS</b>Total DC (Lin1(+) HLA-DR(+)), myeloid DC (mDC) (Lin1(-) HLA-DR(+) CD11c(+)) and plasma DC (pDC) (Lin1(-) HLA-DR(+) CD123(+)) in fresh PB samples of 38 MDS patients and 19 normal controls were assayed by flow cytometry with the monoclonal antibodies. The expressions of costimulatory molecules CD80, CD86 and CD40 on these DCs were also assayed in the same way.</p><p><b>RESULTS</b>The number of total DC in PB of low-risk and high-risk MDS patients was significantly higher than that in normal controls [(33.7 +/- 7.0) x 10(6)/L, (56.3 +/- 29.0) x 10(6)/L vs (12.1 +/- 1.4) x 10(6)/L, respectively] (P < 0.05), that of mDC in PB of low-risk and high-risk MDS patients was higher than that of normal controls too [(16.7 +/- 6.3) x 10(6)/L, (28.7 +/- 17.6) x 10(6)/L vs (5.5 +/- 0.9) x 10(6)/L] (P < 0.05), but pDC in low-risk and high-risk MDS patients was not significantly higher than that in normal controls (P > 0.05). The percentage of total DC in PB mononuclear cells (PBMNC) of low-risk and high-risk MDS patients [(2.37 +/- 0.53)% and (3.58 +/- 1.39)% respectively and that of mDC (0.90 +/- 0.35)%, (1.51 +/- 0.70)% respectively] were higher than that of normal controls [(0.68 +/- 0.08)%, and (0.32 +/- 0.05)% respectively] (P < 0.05), but that of pDC in MDS cases was not higher than that of normal controls (P > 0.05). The expressions of CD80 and CD86 between MDS patients and normal controls had significant difference (P < 0.05).</p><p><b>CONCLUSIONS</b>Total DC and mDC were increased significantly in MDS, but pDC did not. The costimulatory molecules (CD80 and CD86) except CD40 expressed higher on the DC of MDS patients. It suggested that the inflammatory injury related APC increased in MDS, but the antitumour immunity related APC did not . What found here might be one of the mechanisms involved in the pathogenesis of MDS.</p>

Subtypes of B lymphocytes in patients with autoimmune hemocytopenia / 中国医学科学杂志(英文版)

<p><b>OBJECTIVE</b>To investigate the quantities of bone marrow CD5+ B lymphocytes in the patients with autoimmune hemocytopenia and the relationship between quantities of CD5+ B lymphocytes and clinical or laboratorial parameters.</p><p><b>METHODS</b>Quantities of CD5+ B lymphocytes in the bone marrow of 14 patients with autoimmune hemolytic anemia (AIHA) or Evans syndrome, 22 immunorelated pancytopenia (IRP) patients, and 10 normal controls were assayed by flow cytometry. The correlation between their clinical or laboratorial parameters and CD5+ B lymphocytes was analyzed.</p><p><b>RESULTS</b>The quantity of CD5+ B lymphocytes of AIHA/Evans syndrome (34.64% +/- 19.81%) or IRP patients (35.81% +/- 16.83%) was significantly higher than that of normal controls (12.00% +/- 1.97%, P < 0.05). However, there was no significant difference between AIHA/Evans syndrome and IRP patients (P > 0.05). In all hemocytopenic patients, the quantity of bone marrow CD5+ B lymphocytes showed significantly negative correlation with serum complement C3 level (r = -0.416, P < 0.05). In the patients with AIHA/Evans syndrome, the quantity of bone marrow CD5+ B lymphocytes showed significantly positive correlation with serum indirect bilirubin level (r = 1.00, P < 0.05). In Evans syndrome patients, the quantity of CD5+ B lymphocytes in bone marrow showed significantly positive correlation with platelet-associated immunoglobulin G (r = 0.761, P < 0.05) and platelet-associated immunoglobulin M ( r = 0.925, P < 0.05). The quantity of CD5+ B lymphocytes in bone marrow of all hemocytopenic patients showed significantly negative correlation with treatment response (tau-b = -0.289, P < 0.05) , but had no correlation with colony forming unit-erythroid (r = -0.205, P > 0.05) or colony forming unit-granulocyte-macrophage colonies (r = -0.214, P > 0.05).</p><p><b>CONCLUSIONS</b>The quantity of bone marrow CD5+ B lymphocytes in the patients with autoimmune hemocytopenia significantly increases and is correlated with disease severity and clinical response, which suggest that CD5+ B lymphocytes might play an important role in the pathogenesis of autoimmune hemocytopenia.</p>

Study on the peripheral blood dendritic cells subtypes and the expression of co-stimulating molecules on dendritic cells and B cells in severe aplastic anemia patients / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the quantities of monocyte-derived dendritic cell precursors (pDC1) and plasmacytoid dendritic cell precursors (pDC2) in peripheral blood mononuclear cells (PBMC) of severe aplastic anemia (SAA) patients before and after immune suppressive therapy (IST), the ratio of the pDC1 to pDC2, and the expression of co-stimulating molecules (CD80, CD86, CD40) on dendritic cells (DC) and B cells in SAA patients.</p><p><b>METHODS</b>By means of three color monoclonal antibody labeling technology, the quantities and ratio of pDC1 and pDC2 in PBMC were detected in 26 SAA patients at active phase, 13 at recovery phase and 15 normal controls respectively. The aforementioned parameters of 10 SAA patients were tested before and 2 months after IST. The expression of CD80, CD86 and CD40 on DC and B lymphocytes were detected in 16 SAA patients and 15 normal controls.</p><p><b>RESULTS</b>The percentages of pDC1 and the ratio of pDC1/pDC2 of controls were (0.41 +/- 0.05)% and 1.58 +/- 0.18 respectively, and those of SAA patients at active phase were (0.67 +/- 0.13)% and 2.70 +/- 0.32 respectively, [pDC1 (P < 0.05); pDC1/ pDC2 ratio (P < 0.01)]. The aforementioned parameters in convalescent SAA patients decreased to (0.43 +/- 0.10)%, and 1.78 +/- 0.36 respectively, being no difference from those of normal controls. The percentages of pDC1 and pDC2 in 10 SAA patients were (0.87 +/- 0.31)%, and (0.35 +/- 0.09)%, before IST, and (0.24 +/- 0.09)%, (0.14 +/- 0.04)%, after IST, being significantly decreased (P < 0.05). The percentages of CD86 expression on DC of controls was (11.97 +/- 4.31)%, and that of SAA patients was (29.84 +/- 3.02) % (P < 0.05). The percentages of CD80, CD40 and CD86 expression on lymphocytes of controls were (2.57 +/- 0.44)%, (7.34 +/- 1.22)% and (1.86 +/- 1.11)%, respectively, and those of SAA patients were (5.17 +/- 0.68)%, (8.85 +/- 2.94)% and (5.98 +/- 0.96)% respectively (P < 0.05, P < 0.01). The percentage of CD86 expression on B lymphocytes in controls was 8.04 +/- 0.66%, and in SAA patients was (20.46 +/- 2.78)%, (P < 0.05).</p><p><b>CONCLUSION</b>The pDC subtypes were abnormal and the percentage of pDC1 is increased in SAA patients, which are associated with stage of this disease. DC and B Lymphocytes in SAA patients upregulated expression of costimulatory molecules (CD86) which cause the T lymphocyte abnormally activated.</p>

The prognostic value of quantitative chromosomal abnormality in myelodysplastic syndromes / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the prognostic value of quantitative chromosomal abnormality in myelodysplastic syndromes (MDS).</p><p><b>METHODS</b>Chromosomal karyotypes in seventy-one MDS patients' were analyzed quantitatively. Based on the number of abnormal metaphase in 20 counted metaphases, the patients were divided into three groups: no abnormal karyotypes, abnormal metaphases less than or equal to five, and that more than five. The leukemia transformation rate, death rate and survival time between these three groups were compared.</p><p><b>RESULTS</b>Forty-four cases (62.0%) had abnormal karyotypes. The incidences of abnormal karyotypes in RA, RCMD and RAEB were 76.9%, 55.8% and 75.0%, respectively, being no significant difference (P > 0.05). Among the abnormal karyotypes, complex abnormality with two or more abnormal karyotypes was most common and accounted for 47.7%. The frequencies of trisomy 8, monosomy 7 and del 20q were 18.2%, 4.5% and 4.5%, respectively. Other kinds of abnormal karyotypes totally accounted for 25%. There were 27 cases of group 1, 28 of group 2 and 16 of group 3. Eighteen cases (25.4%) transformed to acute leukemia. The incidences of leukemia transformation in group 1, 2 and 3 were 18.5%, 25% and 37.5%, and the death rates were 29.6%, 42.9% and 56.3%, respectively. The median survival times were 60, 47 and 24 months respectively.</p><p><b>CONCLUSION</b>The quantitative chromosome abnormality has prognostic value in MDS.</p>

The clinical features of the autoimmune hemolytic anemia with both warm and cold autoantibodies / 中华血液学杂志

<p><b>OBJECTIVE</b>To study the clinical characteristics of autoimmune hemolytic anemia (AIHA) with both warm and cold autoantibodies.</p><p><b>METHODS</b>Clinical and laboratory characteristics of 23 cases of AIHA with both warm and cold autoantibodies admitted to our hospital between January 1994 and April 2004 were analyzed retrospectively.</p><p><b>RESULTS</b>In comparison with the AIHA patients with both warm and cold autoantibodies in the 1980s, the present patients showed the following features: The proportion of this kind AIHA in all AIHA patients increased from 17.6% to 22.1%. There were more females, more primary cases (73.9%), more mixed subtypes of autoantibodies and more of IgM (56.5%). The hemolysis was related with thermal amplitude of autoantibodies and quantity of complement. The response to cortisone and other immunosuppressive drugs was good. The relapse rate was 77.8% in a median follow-up time of 4 months.</p><p><b>CONCLUSIONS</b>AIHA with both warm and cold autoantibodies is related with the type and thermal amplitude of the autoantibody and the activation of complement. It can be treated effectively with combined immunosuppressive therapy, but the relapse rate is high.</p>

Burden of abnormal hematopoietic clone in patients with myelodysplastic syndromes / 中国医学科学杂志(英文版)

<p><b>OBJECTIVE</b>To investigate the role of the burden of abnormal hematopoietic clone in the development of myelodysplastic syndromes (MDS).</p><p><b>METHODS</b>The ratio of the bone marrow cells with abnormal chromosomes to the total counted bone marrow cells was regarded as the index of MDS clone burden. The disease severity related parameters including white blood cell count, hemoglobin, platelet count, lactate dehydrogenase level, bone marrow blast, myeloid differentiation index, micromegakaryocyte, transfusion, interleukin-2, tumor necrosis factor (TNF), CD4+ and CD8+ T cells of MDS patients were assayed, and the correlations between those parameters and MDS clone burden were also analyzed.</p><p><b>RESULTS</b>The clone burden of MDS patients was 67.4% +/- 36.2%. MDS clone burden positively correlated with bone marrow blasts (r = 0.483, P < 0.05), negatively with hemoglobin level (r = -0.445, P < 0.05). The number of blasts, hemoglobin, and erythrocytes in high clone burden (> 50%) and low clone burden ( < or = 50%) groups were 7.78% +/- 5.51% and 3.45% +/- 3.34%, 56.06 +/- 14.28 g/L and 76.40 +/- 24.44 g/L, (1.82 +/- 0.48) x 10(12)/L and (2.32 +/- 0.66) x 10(12)/L, respectively (all P < 0.05). CD4+ T lymphocytes of MDS patients and normal controls were (0.274 +/- 0.719) x 10(9)/L and (0.455 +/- 0.206) x 10(9)/L, respectively (P < 0.05). CD8+ T lymphocytes of MDS patients and normal controls were (0.240 +/- 0.150) x 10(9)/L and (0.305 +/- 0.145) x 10(9)/L, respectively. The serum level of interleukin-2 of MDS patients (6.29 +/- 3.58 ng/mL) was significantly higher than normal control (3.11 +/- 1.40 ng/mL, P < 0.05). The serum level of TNF of MDS patients and normal control group were 2.42 +/- 1.79 ng/mL and 1.68 +/- 0.69 ng/mL, respectively. The ratio of CD4 to CD8 was higher in high clone burden MDS patients (1.90 +/- 0.52) than that in low clone burden patients (0.97 +/- 0.44, P < 0.05).</p><p><b>CONCLUSION</b>The quantitive clonal karyotype abnormalities and deficient T cell immunity are important parameters for evaluating MDS severity and predicting its progression.</p>

Expression of apoptosis-related proteins in bone marrow neutrophils of patients with paroxysmal nocturnal hemoglobinuria / 中国实验血液学杂志

This study was aimed to evaluate expression levels of CD166, Fas and apoptosis-related proteins in bone marrow neutrophils of PNH patients and normal controls, and to analyze their correlation in order to explore whether exist apoptosis abnormality in BM neutrophils of PNH patients. The expression levels of CD16b, Fas and Bax, Bcl-2 in BM neutrophils of PNH patients and normal controls were assayed by flow cytometry; the difference of expression levels between patients and controls, and expression correlation between CD16b and apoptosis-related proteins were compared. The results showed that (1) the expression levels of CD16b on BM neutrophils of patients and controls were (20.36 +/- 9.05)% and (71.34 +/- 26.8)% respectively (P = 0.01); (2) the expression levels of CD95 on BM neutrophils of patients and controls were (62.83 +/- 32.11)% and (48.00 +/- 38.52)% respectively, there were no significant difference between CD95 expressions in BM neutrophils of PNH patients and controls and no significant correlation between expression of CD95 and CD16b on BM neutrophils of PNH patients (P > 0.05); (3) the expression levels of Bcl-2 in BM neutrophil cytoplasma of patients and controls were (8.64 +/- 5.40)% and (16.82 +/- 15.39)% respectively, there were no significant difference between Bcl-2 expression of patients and controls, and no significant correlation between the expression of Bcl-2 and CD16b in BM neutrophil cytoplasma of PNH patients (P > 0.05); (4) the expression levels of Bax in BM neutrophil cytoplasma of patients and control were (30.47 +/- 22.15)% and (48.47 +/- 15.99)% respectively, there were no significant difference between the Bax expressions of patients and controls, and no significant correlation between the Bax and CD16b expressions in BM neutrophil cytoplasma of PNH patients. In conclusion, BM neutrophils of PNH patients expressed apoptosis-related CD95, Bcl-2 and Bax without significant difference from the normal controls, and without significant correlation with the CD16b expression. It is suggested that the cell growth and decrease of PNH patients possibly are independent of abnormal apoptosis.

The response of bone marrow hematopoietic cells to G-CSF in paroxysmal nocturnal hemoglobinuria patients / 中华血液学杂志

<p><b>OBJECTIVE</b>To study the response of hematopoietic cells (HSC) to granulocyte colony stimulating factor (G-CSF) in paroxysmal nocturnal hemoglobinuria (PNH) patients.</p><p><b>METHODS</b>(1) Bone marrow mononuclear cells (BMMNC) from 17 PNH patients and 12 normal subjects were inoculated into semisolid culture media containing or not G-CSF (50 ng/ml). The cluster/colony forming unit-granulocyte/monocyte (CFU/cFU-GM) were counted and compared. (2) BMMNC of 20 PNH patients and 12 normal controls were triply stained for CD34, CD59 and G-CSF receptor CD114/stem cell factor receptor (C-KIT) CD117 and assessed by FCM. The CD34(+) cells were identified as CD34(+)/CD59(+) and CD34(+)/CD59(-). Percentage of CD114 and CD117 expression in each cell population was calculated.</p><p><b>RESULTS</b>(1) PNH cFU-GM without G-CSF were (112.41 +/- 22.74)/10(5) BMMNC, while with G-CSF: (133.82 +/- 25.85)/10(5) BMMNC and normal cFU-GM were (190.33 +/- 36.05)/10(5) BMMNC, (309.42 +/- 92.94)/10(5) BMMNC, respectively. Whether with or without G-CSF, PNH BMMNC formed less cFU-GM than control did, both of the two kinds of BMMNC responded to G-CSF well (P < 0.05), but the increment of PNH cFU-GM yields was less than that of the normal control (P < 0.05). CFU-GM yields of PNH BMMNC without G-CSF were (24.29 +/- 9.05)/10(5) BMMNC, with G-CSF were (27.53 +/- 10.65)/10(5) BMMNC, while normal control were (77.42 +/- 36.01)/10(5) BMMNC and (98.00 +/- 43.14)/10(5) BMMNC, respectively. Whether with or without G-CSF, PNH BMMNC showed less CFU-GM yields than that of control (P < 0.05). (2) The percentage of CD114 positive cells in PNH CD34(+)CD59(+) BMMNC was (73.34 +/- 29.40)% and that in PNH CD34(+)CD59(-) BMMNC and in control CD34(+)CD59(+) BMMNC were (32.70 +/- 6.89)% and (58.52 +/- 29.99)%, respectively. The percentage of CD114 expression in PNH CD34(+) CD59(-) BMMNC was less than that in the other two groups (P < 0.05). The percentages of CD117 positivities on the PNH CD34(+)CD59(+) BMMNC were (76.90 +/- 22.08)%, PNH CD34(+) CD59(-) (36.03 +/- 7.69)% and control CD34(+) CD59(+) (80.28 +/- 13.36)%, respectively (P < 0.01).</p><p><b>CONCLUSION</b>In vitro, BMMNC of normal control grow better, and respond better to G-CSF than PNH BMMNC do. PNH CD34(+)CD59(-) BMMNC express less G-CSF receptor and C-KIT than PNH CD34(+)CD59(+) and normal CD34(+)CD59(+) BMMNC do, which may be the reason that abnormal PNH clone grow worse than the normal clones do.</p>

The clinical features of hepatitis associated aplastic anemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To analyse the proportion of hepatitis associated aplastic anemia (HAAA) in severe aplastic anemia (SAA) and its clinical features of HAAA.</p><p><b>METHODS</b>All newly diagnosed SAA cases in our department in the recent 5 years were analyzed. A case-control study was undertaken to investigate the differences of clinical and laboratory features between HAAA and non-hepatitis associated SAA (non-HASAA) patients.</p><p><b>RESULTS</b>The proportion of HAAA in SAA was 3.3%. There was no significant difference in PB cell counts, bone marrow hematopoiesis status and the amount of blood transfusion between HAAA and non-HASAA patients. Sera from 13 patients with HAAA were tested for antibodies to hepatitis viruses A, B, and C and hepatitis B surface antigen. Twelve (92.3%) of them had negative serologic results for the tests and only one (7.7%) had a positive result for HBsAg and HBeAg. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were decreased prior to the diagnosis in twelve (92.3%) of the 13 HAAA patients. The percentage of CD4(+) cells in HAAA patients was significantly lower than that in non-HASAA patients (P < 0.05). HAAA patients had higher percentages of CD8(+) cells (P < 0.05) and lower ratios of CD4(+)/CD8(+) (P < 0.05). The early infection rate of the HAAA patients was significantly higher than that of non-HASAA patients (84.6% vs 42.3%, P < 0.05), with different mortalities (61.5% vs 15.4%, P < 0.05). The 2-year survival rate of HAAA patients was significantly lower than that of non-HASAA patients (16.6% vs 83.2%, P < 0.01).</p><p><b>CONCLUSION</b>The proportion of HAAA in SAA was 3.3%. Most of HAAA were associated with non-A, non-B and non-C hepatitis virus. Compared with that of non-HASAA, the abnormality of T cell immunity of HAAA was more severe, with a higher frequency of early infection and a higher mortality rate.</p>

Study on the burden of abnormal hematopoietic clone of the patients with myelodysplastic syndromes and its implications / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the abnormal hematopoietic clone burden of the patients with myelodysplastic syndromes (MDS) and its clinical implication.</p><p><b>METHODS</b>The ratio of the metaphase with abnormal karyotypes to the total was regarded as the index of MDS clonal burden. Thirteen parameters were assayed and the correlations between these parameters and MDS clone burden were analysed.</p><p><b>RESULTS</b>The clonal burden of MDS patients was (67.4 +/- 36.2)%. It correlated positively with bone marrow blasts (r = 0.483, P < 0.05), negatively with hemoglobin level (r = -0.445, P < 0.05). The number of blasts, hemoglobin and erythrocytes in high clonal burden (>50%) and low clonal burden (< or = 50%) groups were significantly different (P < 0.05). CD4+ T lymphocytes of MDS patients and normal controls were (274.18 +/-71.85) x 10(6)/L and (454.82 +/- 205.88) x 10(6)/L (P < 0.05) respectively. CD8+ T lymphocytes between MDS patients and normal controls had no difference. The serum level of IL-2 of MDS patients and normal control groups were (6.29 +/- 3.58) g/L and (3.11 +/- 1.40) microg/L (P < 0.05) respectively; but no difference in the serum level of TNF between MDS and control groups. The ratio of CD4+ to CD8+ in high clonal burden patients was 1.90 + 0.52, and in low clonal burden patients was 0.97 +/- 0.44 (P < 0.05).</p><p><b>CONCLUSION</b>The clonal burden and deficient T cell immunity are the indicators for predicting MDS patients clinical progression.</p>

Study of Th cell subsets in bone marrow of myelodysplastic syndromes patients / 中华血液学杂志

<p><b>OBJECTIVE</b>To study the quantity and ratio of Th1, Th2 cells in the bone marrow of myelodysplastic syndromes (MDS) patients, and to evaluate the correlation between the ratio of the blast cells and the number of the Th1 cells in the bone marrow of MDS patients.</p><p><b>METHODS</b>By FACS, the quantity and ratio of IFN-gamma producing CD4(+) T cell (Th1) and IL-4 producing CD4(+) T cell (Th2) cells in the bone marrow were detected in 21 MDS patients, 18 normal controls and 13 severe aplastic anemia (SAA) patients respectively. The karyotypes of 18 MDS patients and 15 normal controls were assayed. The correlation between the ratio of the blast cells in the bone marrow and the number of the Th1 cells in the MDS patients were analyzed.</p><p><b>RESULTS</b>The percentages of Th1 cells, Th2 cells and ratio of Th1/Th2 in the bone marrow of normal controls were (0.48 +/- 0.10)%, (0.24 +/- 0.19)% and 2.31 +/- 0.76 respectively, while those of the MDS patients were (0.36 +/- 0.11)%, (0.76 +/- 0.35)% and 0.51 +/- 0.13. The percentage of Th1 cells of patients with MDS was reduced and the Th1/Th2 ratio was significantly lower than that of normal controls (P < 0.01). Those of the patients with SAA were (4.75 +/- 0.49)%, (0.40 +/- 0.28)% and 26.5 +/- 8.79 respectively, their Th1 cells and Th1/Th2 ratio were markedly higher than those of normal controls (P < 0.01). In all of the 15 normal controls the karyotypes were normal, but that of MDS patients was (50.00 +/- 0.10)%. The lower ratio of the Th1 cells in the bone marrow of the patients with MDS and the AML which progressed from MDS was negatively correlated with the higher percentage of the blast cells (r = -0.563, P < 0.01).</p><p><b>CONCLUSIONS</b>(1) The immune function of T lymphocytes in MDS is abnormal: the balance between Th1 and Th2 cells is broken. (2) With descending of the number of Th1 cells in the bone marrow of the MDS patients, the disease is progressing to leukemia.</p>

Expression of cell cycle control genes in myelodysplastic syndromes / 中华血液学杂志

<p><b>OBJECTIVE</b>To study aberrant expression of cell cycle control genes in patients with myelodysplastic syndromes (MDS).</p><p><b>METHODS</b>Reverse transcription polymerase chain reaction (RT-PCR) was used to investigate the expression of cell cycle control genes (cyclin D2, cyclin D3, cyclin A1, cyclin E, CDK2, CDK4, CDK6, p21, p27, p57, Rb and E2F1) in bone marrow mononuclear cells (BMMNCs) from 29 normal control, 27 MDS and 19 de novo acute myeloid leukemia (AML).</p><p><b>RESULTS</b>The expression levels of cyclin D3 (0.65 +/- 0.17, P < 0.05) and cyclin A1 (0.48 +/- 0.04, P < 0.05) in MDS were higher than those in normal control and significantly lower than those in AML. The expression rates and levels of cyclin D2 (40.7% and 0.78 +/- 0.21) and cyclin E (51.9% and 0.52 +/- 0.10) in MDS were statistically higher than those in normal control and AML. The expression level of CDK2 in MDS (0.66 +/- 0.19, P < 0.01) was higher than that in normal control (0.42 +/- 0.04) and the expression rate of CDK6 in MDS (25.9%) higher than in normal control (3.4%, P < 0.05). There was no significant difference of the expression rates and levels of CDK4 in MDS, AML and normal control. The expression rates and levels of p21 (77.8% and 1.18 +/- 0.21) and p27 (48.1% and 1.14 +/- 0.40) in MDS were statistically higher than those in normal control and AML. The expression level of p57 in MDS (0.69 +/- 0.06) was higher than that (0.53 +/- 0.05, P < 0.01) in normal control but lower than in AML (0.96 +/- 0.16, P < 0.01). The expression rate (55.6%) and level (0.85 +/- 0.17) of Rb in MDS were significantly higher than those in normal control and AML. The expression rate (7.4%) and level (0.39 +/- 0.04) of E2F1 in MDS were comparable to those in normal control but lower than those in AML.</p><p><b>CONCLUSION</b>MDS clones have aberrant mechanism of cell cycle control: high expressions of cyclin family members, CDK2 and CDK6 may lead to high proliferation; high expression of p21 and p27 may cause the G1 phase arrest.</p>

Transformation of myelodysplastic syndromes into acute myeloid leukemias / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Myelodysplastic syndromes (MDSs), also called preleukemias, are a group of myeloid hematopoietic malignant disorders. We studied the transformation of MDS into acute myeloid leukemia (AML).</p><p><b>METHODS</b>Leukemic transformation in 151 patients with MDS was dynamically followed up. The clinical manifestation, peripheral blood and bone marrow condition, karyotypes, immunophenotypes, response to treatment, and prognosis of AML evolution from MDS (MDS-AML) were also observed.</p><p><b>RESULTS</b>During the course of this study, over the past eight years and seven months, 21 (13.91%) of 151 MDS patients progressed to overt leukemia, with a median interval of 5 (1 - 23) months. There were no significant differences between rates of leukemic transformation in comparison with the refractory anemia (RA), RA with excess of blasts (RAEB), and RAEB in transformation (RAEB-t) patient groups. Transformation occurred either gradually or rapidly. There were five parameters positively correlated to leukemic transformation: under 40 years of age, pancytopenia of 3 lineages, more than 15% blasts in the bone marrow, at least two abnormal karyotypes, and treatment with combined chemotherapy. All of the 21 patients with leukemia suffered from MDS-AML, and most of them were M2, M4, or M5. Two (9.52%) MDS-AML patients developed extramedullary infiltration. Leukopenia was found in 47.62% of these patients. Two thirds of these patients, whose bone marrows were generally hypercellular, suffered from neutropenia. After developing AML, 8 (47.06%) patients developed abnormal karyotypes. High expression of immature myeloid antigens, including CD33 [(49.83 +/- 24.50)%], CD13 [(36.38 +/- 33.84)%], monocytic antigen CD14 [(38.50 +/- 24.60)%], and stem cell marker CD34 [(34.67 +/- 30.59)%], were found on bone marrow mononuclear cells from MDS-AML patients after leukemic transformation. In some cases, lymphoid antigens, such as CD5, CD7, CD9, and CD19, coexisted with myeloid antigens. A low complete remission rate (31.25%) and a short survival time, with median survival of 6 (1 - 28) months, were found in patients with MDS-AML treated by induction chemotherapy.</p><p><b>CONCLUSIONS</b>MDS has a high risk of developing into AML, either gradually or rapidly. Patients with MDS-AML have specific biological characteristics and a worse prognosis.</p>