A clinical comparative study on treatment of severe newly diagnosed immune thrombocytopenia by recombinant human thrombopoietin combined with glucocorticoid / 中华血液学杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of recombinant human thrombopoietin (rhTPO) combined with glucocorticoid in treatment of severe newly diagnosed primary immune thrombocytopenia (ITP).</p><p><b>METHODS</b>From June 2009 to December 2012, 24 male patients and 38 female patients with the diagnosis of severe primary ITP in our hospital were randomized into trial group (31 cases) or control group (31 cases), the median age was 50 years (range: 21-84 years). Trial group was treated with rhTPO combined with glucocorticoid, and control group was treated with glucocorticoid only.</p><p><b>RESULTS</b>At the day 3, 7 and 14 from the beginning of treatment, the average platelet count (APC) in trial group[(35.5±24.9)×10⁹/L, (135.2±94.9)×10⁹/L and (192.0±109.1)×10⁹/L]were significantly higher than that in control group[(24.5±15.6)×10⁹/L, (78.2±121.9)×10⁹/L and (95.8±60.5)×10⁹/L, P=0.022, 0.009 and 0.001, respectively]. There was no significant difference in APC between the two groups at day 28 and 90 after treatment[(147.8±59.1)×10⁹/L vs (105.1±56.9)×10⁹/L, P=0.243; (137.4±52.3)×10⁹/L vs (104.3±59.8)×10⁹/L, P=0.568, respectively]. At the day 7, 14 and 28, the complete response rates in trial group were 61.3%, 87.1% and 80.6%, which were also significantly higher than that in control group (16.1%, 29.0% and 48.3%, P=0.000, 0.000 and 0.004, respectively). The median time to response in trial group was 3 days while in the control group was 5 days; the median duration of complete response in trial group was 76 days while in the control group was 54 days. In trial group, there were 4 cases treated with platelet transfusion, while in control group there were 11 cases, respectively.</p><p><b>CONCLUSION</b>For patients with severe primary ITP, rhTPO combined with glucocorticoid could rapidly increase the platelet count, significantly improve the complete response rate and prolonged the effect with a low incidence of tolerable adverse events compared to single use of glucocorticoid. rhTPO combined with glucocorticoid could be a new therapeutic choice to those patients.</p>

Evaluation of the impact of R-CHOP chemotherapy on efficacy, safety and prognosis in newly diagnosed diffuse large B-cell lymphoma patients and its prognostic impact: a multicenter retrospective study with long term follow-up / 中华血液学杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy, safety and prognostic impact of rituximab plus CHOP (R-CHOP) regimen on patients with diffuse large B-cell lymphoma (DLBCL), to access the impact of R-CHOP on patients' prognosis and to compare that with CHOP regimen.</p><p><b>METHODS</b>Five hundred and seven newly diagnosed DLBCL patients were enrolled from Jan. 1, 2000 to May 1, 2010. Patients were administered with 6 cycles of CHOP or at least 4 cycles of R-CHOP treatments. Rituximab was administered intravenously on day 1 at a dose of 375 mg/m(2). The typical CHOP regimen include cyclophosphamide (750 mg/m(2), IV), doxorubicin (50 mg/m(2), IV) and vincristine (1.4 mg/m(2), IV, maximum 2 mg) and prednisone (60 - 100 mg, oral, day 3 - 7). The complete response (CR) rates, overall response (OR) rates, and side events of these 2 groups were compared.</p><p><b>RESULTS</b>Of the 411 analyzable patients, 224 received CHOP regimen and 187 received R-CHOP regimen. CR rate for R-CHOP group and CHOP group was 77.01% and 71.43%, respectively. OR rate in R-CHOP group was higher than that in the CHOP group (95.19% vs 87.95%, P = 0.007). The median follow-up time of R-CHOP group was 28.1 months vs that of 35.2 months in CHOP group. There was significant difference in progression free survival (PFS) and overall survival (OS) between 2 groups (P = 0.018 and 0.034, respectively). At the end of follow-up, the estimated median PFS in R-CHOP group had not been reached, while that was 84.8 months in CHOP group. The median OS in both groups had not yet been reached. The adverse events in R-CHOP group were similar with that in CHOP group.</p><p><b>CONCLUSIONS</b>R-CHOP is a safe and effective regimen for management of newly diagnosed DLBCL, with a better remission rate, PFS and OS.</p>

Prognostic power of abnormal cytogenetics for multiple myeloma: a multicenter study in China / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Chromosomal abnormalities have been shown to play an important prognostic role in multiple myeloma (MM). Interphase fluorescence in situ hybridization (i-FISH) has been much more effective to identify cytogenetic aberrations in MM than conventional cytogenetic technique (CC). To clearly determine the cytogenetic features of Chinese MM patients and identify their prognostic implications, we designed a multicenter study based on i-FISH including 672 patients from 52 hospitals in China.</p><p><b>METHODS</b>All 672 patients were systematically screened for the following genomic aberrations: del(13q), IgH rearrangement, del(p53) and 1q21 amplifications.</p><p><b>RESULTS</b>The analysis showed that the chromosomal changes were detected in 22.1% patients by CC and in 82.3% patients by i-FISH. The most common abnormalities by CC were chromosome 1 aberrations (48.4%), -13/13q- (37.6%), hyperdiploidy (36.6%), hypodiploidy (30.1%) and IgH rearrangements (23.7%). The most frequent abnormalities by FISH was del(13q), which was found in 60.4% patients, whereas IgH rearrangement, 1q21 amplification and p53 deletions were detected in 57.6%, 49.0% and 34.7% cases, respectively. By statistical analysis, -13/13q- by CC was associated with low level of platelet (P = 0.015), hyperdiploidy was associated with low level of serum albumin (P = 0.028), and IgH rearrangement by FISH was associated with high level of β2 microglobulin (P = 0.019). Moreover, 1q21 amplification and del(p53) by FISH conferred a high incidence of progressive disease (PD) after initial therapy. Metaphase detection of IgH rearrangements and chromosome 1 aberrations concurrently was associated with a short progression free survival (PFS) (P = 0.036). No significant prognostic implications of other cytogenetic abnormalities were found associated with overall survival and PFS.</p><p><b>CONCLUSIONS</b>Chinese MM patients had similar cytogenetic abnormalities compared with the previous reported studies. However, the prognostic significance of FISH aberrations were not clearly determined and further study is required.</p>

Impaired interleukin-10 secretion by CD5(+) B cells in patients with primary immune thrombocytopenia / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the number of peripheral blood CD5(+) B cells and their ability of secreting IL-10 in patients with immune thrombocytopenia (ITP).</p><p><b>METHODS</b>Peripheral blood lymphocytes were isolated from 57 pre-treated, 40 post-treated ITP patients and 25 controls using Ficoll-Hypaque density centrifugation and then stained with PE-CD5/FITC-CD19 for flow cytometric analysis. After 24-hour culture, lymphocytes were stained with APC-IL-10 for intracellular cytokine detection. ELISA assay was employed to determine IL-10 concentration in supernatants.</p><p><b>RESULTS</b>The percentage and absolute number of CD5(+) B cells in peripheral blood from pre-treated ITP patients were significantly higher than that from normal controls (3.75 ± 2.37)% vs (2.10 ± 1.08)%, P < 0.01; (6.29 ± 5.77)× 10(7)/L vs (3.06 ± 1.90)× 10(7)/L, P < 0.01. CD5(+) B cells expressed more intracellular IL-10 than other lymphocyte subsets both in ITP patients and normal controls. The percentages of IL-10(+) cells within CD5(+) B cells in pre-treated ITP patients and normal controls were (29.51 ± 20.73)% and(15.90 ± 9.58)%, respectively(P < 0.01). Intracellular mean fluorescence intensity (MFI) of IL-10 in CD5(+) B cells was 27.95 ± 13.99 in pre-treated patients, which was significantly higher than that in controls (P < 0.01). In contrast, IL-10 concentration in supernatants was (173.05 ± 102.50) ng/L in pre-treated ITP group, which was lower than that (230.61 ± 76.96) ng/L in controls. In patients who achieved remission, the number of CD5(+) B cells decreased to level comparable to normal controls. While intracellular IL-10 MFI of CD5(+) B cells in post-treated ITP patients remained as high as in pre-treated ones, the IL-10 concentration in supernatants increased to level similar to controls.</p><p><b>CONCLUSION</b>The significantly increased number of CD5(+) B cells and accumulated IL-10 in CD5(+) B cells suggested impaired IL-10 secretion in ITP patients. The number and the ability of secreting IL-10 of CD5(+) B cells could be restored after effective treatments in patients with ITP.</p>

Trend in the incidence and geographic variations of acute lymphoblastic leukemia in Shanghai, China from 2002 to 2006 / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Great advances have been made in the diagnosis, molecular pathogenesis and treatment of acute lymphoblastic leukemia (ALL) in the past decade. Due to the lack of large population-based studies, the recent trends in the incidence and geographic variations of ALL in Shanghai, China have not been well documented. To better understand the incidence and epidemiological features of ALL in Shanghai, we conducted a retrospective survey based on the database from the Shanghai Center for Disease Control and Prevention (CDC) and the medical records in all large-scale hospitals in Shanghai, especially those 30 major hospitals with hematology department.</p><p><b>METHODS</b>According to the data from Shanghai CDC, 544 patients, with a median age of 32 years (ranging 1.2 - 89 years), were diagnosed as de novo ALL from January 1, 2002 to December 31, 2006, and they were followed up until December 31, 2007.</p><p><b>RESULTS</b>The average annual incidence of ALL in Shanghai was 0.81/100 000. The incidence in men (0.86/100 000) was slightly higher than that in women (0.75/100 000). The age-stratified incidence showed that the incidence was 2.31/100 000 in patients ≥ 17 years old, 0.54/100 000 in those 18 - 34 years old, 0.46/100 000 in those 35 - 59 years old, and 0.94/100 000 in those ≥ 60 years old. Moreover, there were substantial geographic variations in the incidence of ALL, with the incidence in Chongming county, an island in the east of Shanghai city being 0.60/100 000, much lower than those of other districts. Both French-American-British (FAB) and World Health Organization (WHO) classification systems were applied in the present study. Eighty-eight patients were diagnosed as L1 (26.2%), 193 L2 (57.4%), and 55 L3 (16.4%). For 302 patients with immunophenotypic results, 242 were identified as B cell origin (80.1%), 59 as T cell origin (19.5%), and 1 as biphenotype (0.4%). The leukemia cells in 61 patients co-expressed one or two myeloid antigen (20.2%). For 269 patients with cytogenetic results, the incidences of t(9;22) in patients aged < 10, 11 - 17, 18 - 44, 45 - 59 and ≥ 60 years old were 4.2%, 11.4%, 19.2%, 23.1% and 5.3%, respectively.</p><p><b>CONCLUSION</b>Compared with the previous data, the incidence of ALL is increased in Shanghai, and has a geographic distribution characteristic.</p>

Conventional dose of prednisone regulates Th-associated gene expression in de novo ITP patients / 中国实验血液学杂志

This study was aimed to investigate the T cell (helper T cells) immune status in ITP patients and its relation with therapeutic response. 20 de novo ITP patients were enrolled (8 males, 12 females) with a median age of 41 (20 to 81). Real-time RT-PCR method was used to measure the gene expression of Th cells including T-bet, IFN-γ, GATA-3, TGF-β, Foxp3, IL-2, IL-4 in PBMNC of ITP patients before and after conventional dose of prednisone therapy [1 mg/(kg·d)] and in PBMNC of 20 normal controls. The results showed that T-bet, IFN-γ and IL-2 were significantly over-expressed in PBMNC of ITP patients before treatment compared with that in normal controls (p < 0.01), and compared with that before treatment, T-bet, IFN-γ, and IL-2 were markedly down-regulated in ITP patients after treatment. Before treatment, the expressions of Foxp3, TGF-β, GATA3 and IL-4 in ITP patients did not show difference from normal controls, while after treatment Foxp3 were more up-regulated than that before treatment (p < 0.05). After treatment, TGF-β expression showed a different pattern between old and young patients. TGF-β expression was down-regulated (p < 0.05) among ITP patients younger than 60, while up-regulated in older patients. It is concluded that there is an imbalance of Th1/Th2/Treg cytokines in ITP patients, which can be reversed by glucocorticoid treatment. The conventional dose of glucocorticoid may be regarded as effective therapy for de novo ITP patients, it may correlate with improvement of imbalance between Th1/The2/Treg cytokines.

An epidemiological survey of acute lymphocytic leukemia from 2002 to 2006 in Shanghai / 中华血液学杂志

<p><b>OBJECTIVE</b>To analyse the epidemiological data of acute lymphoblastic leukemia (ALL) in Shanghai.</p><p><b>METHODS</b>ALL cases in Shanghai from 2002 to 2006 were retrospectively investigated.</p><p><b>RESULTS</b>All together there were 544 newly diagnozed ALL cases. The yearly incidence of ALL was 0.81/10(5), which was slightly higher in men (0.86/10(5)) than in women (0.75/10(5)). The age-stratified incidence showed 2.31/10(5) in patients (pts) </= 17y, 0.54/10(5) in 18 - 34 y, 0.46/10(5) in 35 - 59 y, and 0.94/10(5) in pts > 60 y. The incidences in Chongming County was 0.60/10(5), being the lowest in all districts. The morphological types of ALL was L(1) (26.2%), L(2) (57.4%) and L(3) (16.4%); the immunophenotype was B (80.1%) and T (19.5%). The incidence of ALL with myeloid antigen expression was 20.2%. Genetic examination revealed that chromosome aberration of t(9;22) was the most common one.</p><p><b>CONCLUSIONS</b>The incidence of ALL in Shanghai is 0.81/10(5). Compared with the national standard (1986 - 1998), the incidence in adolescents is obviously increased. Chongming County has the lowest incidence, indicating a role of environment factor in ALL incidence.</p>