Clinical Analysis of B-CLPD with Cytopemia as the Predominant Characteristic / 中国实验血液学杂志

OBJECTIVE@#To investigate the clinical characteristics and therapeutic responte of patients with B-CLPD mainly manifested as cytopenia, so as to deeply understand this disease.@*METHODS@#The clinical data of 13 B-CLPD patients with hematocytopenia as main manifestation, and the absolute count of lymphocytes＜5×10/L, absence of hepatosplenic lymph-nodes and extramedullary invasion tin our department fron 2003 to 2018 were analyzed retrospectively. The clinical characteristics, therapeutic efficacy and adverse reactions of 3 patients were summarized.@*RESULTS@#The median age of patients was 59 (43-76) years old, the median of lymphocyte was 1.86 (0.69-4.8) ×10/L, the levels of LDH and β2-microglubulin were normal in most patients, the monolineage and multilencage hematopoietic failure of different degrees existed in most all patients. The lymphocyte ratio in patients was 18.5%-94.0%, CD20 was positive in all patients, and yet the CD5-positive and CD-negative existed in 7 and 6 cases respectively. There was no significant difference in ratio of lymphocyte invasion among different immunophemtype. The FISH detection showed that there were no high risk genetic types. 92.3% of patients received rituximab treatment, most of them received chemotherapy of rituximab combined with C0P/CHOP like regimen, only 2 patients received fludarabine for comparatively short course. The analysis indicated that 8 out of 13 patients showed a certain theropeutic efficacy, however the drug-related hematopoietic suppression occurred in both 2 patients treated with fludarabin.@*CONCLUSIONS@#The B-CLPD accompanied with hematocytopenia often displays bone marrow hypohematopoiesis of different degree and easily confuses with the congenital and acquired hemotopoietic faiture diseases. The rituximab treatment may be more appropreate for these patients, but for patients received chemotherapy containing fludarabin, the persistant hematopoietic failure must be especially watched out.

Chronic Lymphocytic Leukemia Prognostic Index: A New Integrated Scoring System to Predict the Time to First Treatment in Chinese Patients with Chronic Lymphocytic Leukemia / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The established clinical staging systems (Rai/Binet) of chronic lymphocytic leukemia (CLL) cannot accurately predict the appropriate treatment of patients in the earlier stages. In the past two decades, several prognostic factors have been identified to predict the outcome of patients with CLL, but only a few studies investigated more markers together. To predict the time to first treatment (TTFT) in patients of early stages, we evaluated the prognostic role of conventional markers as well as cytogenetic abnormalities and combined them together in a new prognostic scoring system, the CLL prognostic index (CLL-PI).</p><p><b>METHODS</b>Taking advantage of a population of 406 untreated Chinese patients with CLL at early and advanced stage of disease, we identified the strongest prognostic markers of TTFT and, subsequently, in a cohort of 173 patients who had complete data for all 3 variables, we integrated the data of traditional staging system, cytogenetic aberrations, and mutational status of immunoglobulin heavy chain variable region (IGHV) in CLL-PI. The median follow-up time was 45 months and the end point was TTFT.</p><p><b>RESULTS</b>The median TTFT was 38 months and the 5-year overall survival was 80%. According to univariate analysis, patients of advanced Rai stages (P < 0.001) or with 11q- (P = 0.002), 17p- (P < 0.001), unmutated IGHV (P < 0.001), negative 13q- (P = 0.007) and elevated lactate dehydrogenase levels (P = 0.001) tended to have a significantly shorter TTFT. And subsequently, based on multivariate Cox regression analysis, three independent factors for TTFT were identified: advanced clinical stage (P = 0.002), 17p- (P = 0.050) and unmutated IGHV (P = 0.049). Applying weighted grading of these independent factors, a CLL-PI was constructed based on regression parameters, which could categorize four different risk groups (low risk [score 0], intermediate low [score 1], intermediate high [score 2] and high risk [score 3-6]) with significantly different TTFT (median TTFT of not reached (NR), 65.0 months, 36.0 months and 19.0 months, respectively, P < 0.001).</p><p><b>CONCLUSIONS</b>This study developed a weighted, integrated CLL-PI prognostic system of CLL patients which combines the critical genetic prognostic markers with traditional clinical stage. This novel modified PI system could be used to discriminate among groups and may help predict the TTFT and prognosis of patients with CLL.</p>

Efficacy of Rituximab for Patients with Chronic Lymphocytic Leukemia / 中国医学科学院学报

Objective To evaluate the efficacy of rituximab in treating chronic lymphocytic leukemia (CLL). Methods The clinical data of CLL patients receiving fludarabine,cyclophosphamide±rituximab (with or without rituximab) regimen or cyclophosphamide,vincristine,and prednisone±doxorubicin±rituximab regimen in our hospital from March 2000 to February 2015 were analyzed retrospectively. Therapeutic efficacies and survivals of patients treated with different regimens were evaluated and compared. Results The complete response (CR) rate and the overall response rate (ORR) in 72 patients (43.6%) treated with rituximab were significantly higher than those treated without rituximab (38.9% vs. 21.5%,P=0.015;83.3% vs. 60.2%,P=0.001). The median PFS and OS for patients treated with rituximab were 53.0 (27.0-79.0) months and 112.0 (81.1-142.9) months,and the median PFS and OS for patients treated without rituximab were 28.0 (18.3-37.7) months and 89.0(72.0-106.0),but the results were not statistically significant (P=0.094,P=0.109). According to the cytogenetic features,patients were further divided into high-risk subgroup (with chromosome 17p deletion or 11q deletion) and non-high-risk subgroup. And in the high-risk subgroup,the ORR of patients treated with rituximab was 86.4%,which was significantly higher than that in patients treated without rituximab (53.3%)(P=0.012);in the non-high-risk subgroup,the PFS was marginally prolonged in patients treated with rituximab,but the difference was not statistically significant(P=0.050). Conclusions Compared with traditional chemotherapy,the chemoimmunotherapies with rituximab result in higher CR rate and ORR in CLL patients. In patients without 17p deletion or 11q deletion,the use of rituximab can marginally prolong PFS.

Divergence Analysis of Hepatitis Virus Infection between Aggressive and Indolent B Cell Non-Hodgkin's Lymphoma / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the prevalence rate of hepatitis B virus(HBV)and hepatitis C virus(HCV)between aggressive and indolent B cell non-Hodgkin's lymphoma (B-NHL), and to compare the different infection rate of Hepatifis Virus between the 2 groups.</p><p><b>METHODS</b>Integrated clinical information of 733 newly diagnosed indolent B-NHL patients and 148 aggressive B-NHL patients from January 1994 to January 2014 was retrospectively analyzed. The difference of hepatitis virus infection was compared between the 2 groups.</p><p><b>RESULTS</b>The positive rate of HCV-Ab was 1.8% in 881 newly diagnosed B-NHL patients. The HCV prevalence was 1.9% and 1.35% in the indolent and aggressive B-NHL group respecitvely. Compared with general population, the HCV positive rate was significantly higher in the whole B-NHL group and the indolent group(1.8% vs 0.4%,1.9% vs 1.4%)(P<0.01), while it was not significantly different in the aggressive group (1.35% vs 0.4%)(P=0.068). The positive rate of HCV-Ab was not significantly different between the indolent and the aggressive group (1.9% vs 1.35%)(P=0.639). The HBs-Ag positive rate in the whole B-NHL group was 9.0%, which was significantly higher than that in the general population (9.0% vs 7.2%)(P<0.05). The positive rate of HBs-Ag in the indolent and aggressive B-NHL group was 7.9% and 14.2%, respectively. It was significantly higher in the aggressive group than that in the indolent one (14.2% vs 7.2%)(P<0.01). Compared with the general population, the aggressive group had significantly higher prevalence rate of HBV. However, it was not significantly different between the indolent group and the general population (7.9% vs 7.2%)(P>0.05).In the aggressive B-NHL group,the co-expression of HBs-Ag,HBe-Ag and anti-HBc-Ab was 4.4%, which was higher than that in the indolent one (4.7% vs 1.2%)(P<0.01). However, compared with the indolent group, the co-expression of HBs-Ag, anti-HBe-Ab and anti-HBc-Ab was not significantly different in the aggressive group (5.5% vs 6.1%)(P>0.05).</p><p><b>CONCLUSION</b>The HCV is more relevant with indolent B-NHL, the HBV has more relevance with the aggressive patients.</p>

Analysis of Clinical Curative Efficacy for 91 Cases of Splenic Marginal Lymphoma / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the clinical characteristics, treatment and prognosis of splenic marginal zone lymploma (SMZL).</p><p><b>METHODS</b>A total of 91 cases of SMZL admitted in our hospital from January 2002 to March 2013 were enrolled in this study. The clinical characteristics and immunophenotypes were summarized, and the clinical therapeute response and prognostic factors were analyzed statistically.</p><p><b>RESULTS</b>The median age of 91 patients was 56 (28-79); all the patients displayed splenomegaly with 73.6% of large spleen, hepatomegaly (14.6%) and lymphadenophathy (28.2%); the bone marrow involvement was observed in 98.9% patients, the B symptom was found in 47.1% patients. The positive expression of CD20 was observed in 100% patients, the positive expression of CD5 was in 8.3% patients, the positive expression of CD23 was found in 47.6% patients, no specific antigen was observed by now for SMZL. The clinical treatment showed that total ORR was 87.7%, CRR was 53.8% in chemotherapy group, chemotherapy combined with rituximab showed a better response than that of chemotherapy alone, which ORR was 100%, CRR was 72.4%, the difference between them was statistically significant. The Hb < 120 g/L, elevated LDH level and treatment without rituximab were the poor prognostic factors for PFS, while the elevated LDH level was related with OS of patients.</p><p><b>CONCLUSION</b>The patients with SMZL often display splenomegaly, involvement in bone marrow and absence of specific immunophenotypes. Chemotherapy combined with rituximab can definitely improve the outcome of SMZL. The Hb level, LDH level and treatment combined with or without rituximab seem to be related to the prognosis of the disease.</p>

Research progression of extralevator abdominoperineal excision / 中华胃肠外科杂志

The application of extralevator abdomino-perineal excision (ELAPE) and total mesorectal excision has improved the prognosis of rectal cancer. However, compared with anterior resection for rectal cancer, the circumferential resection margin (CRM) positive rate and intraoperative perforation (IOP) rate are still high. The ELAPE can reduce the CRM positive rate and IOP rate, therefore reduce postoperative local recurrence rate and increase the survival rate of patients. The disadvantage of its trauma, longer operative time, and higher perineum complication in ELAPE is controversial. This review mainly discusses the key points of operative procedure, advantages and disadvantages, research status and development prospects of ELAPE.

Clinical and laboratory features of T-cell prolymphocytic leukemia in China / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the clinical and laboratory characteristics and survival of Chinese patients with T- cell prolymphocytic leukemia (T-PLL).</p><p><b>METHODS</b>Eleven patients with T-PLL admitted in our hospital from Jan 2006 to Oct 2012 were retrospectively analyzed.</p><p><b>RESULTS</b>Of the 11 patients, nine were males and two females, with the median age of 56.0(19-69) years old. All the patients, except for three, presented with leukocytosis. The incidence of hyperleukocytosis (1/11) was less frequent than that in the British series (75%) (P=0.000). Lymphocyte counts in peripheral blood were increased in 9 of the 11 patients with the median absolute lymphocyte count (ALC) of 17.22(0.58-148.83)×10⁹/L. Superficial lymphadenopathy and splenomegaly were the most common physical signs. It was common that serum lactate dehydrogenase (LDH) and beta 2 microglobulin(β2-MG)were higher than normal level. All cases were positive for CD2/CD3/CD5/TCRαβ, negative for CD1a /HLA-DR and TdT, and most of them were strong positive for CD7 expression. By chromosome analyses, most cases. (9/10) have normal chromosome. This rate is significantly higher than that of the British and American series (3% and 25%, respectively) (P=0.000, P=0.001). The 14q11 abnormality and trisomy 8q, which are common among Western cases, were not observed in any of our cases. With a median follow-up of 23.0 months, three patients died. Two year progress free survival (PFS) and overall survival (OS) were 53.3% and 50%, respectively. There were 3 patients with PFS over a number of years, whether it should be considered as the T-chronic lymphocytic leukemia (T-CLL) is worthy of further studies.</p><p><b>CONCLUSION</b>The common clinical manifestations of T-PLL patients were increased lymphocyte counts and lymphadenopathy as well as splenomegaly. And most cases have high level of blood LDH and β2- MG and normal chromosome karyotype.</p>

The prognostic impact of 1p21 deletion on newly diagnosed multiple myeloma patients receiving thalidomide-based first-line treatment / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the deletion rate, clinical correlation and prognostic significance of 1p21 deletion, a novel genetic prognostic index, in patients with multiple myeloma (MM).</p><p><b>METHODS</b>The interphase fluorescence in situ hybridization (I-FISH) was performed on purified CD138⁺ plasma cells from 78 newly diagnosed patients from Sep 2007 to Sep 2012 receiving thalidomide-based chemotherapy by using BAC probe covered 1p21.2 region that contains the human cell division cycle 14A (HCDC14A) gene. Deletion rate, the cell percentage of deletion, clinical relevance and prognostic significance were analyzed in myeloma patients.</p><p><b>RESULTS</b>Among 78 patients, there were 51 males and 27 females, the median age was 59(42-81). The deletion rate of 1p21.2 was 23.1%. Some patients had amplification (amp) of 1p with amp rate of 5.1% in 1p21.2, the amp rate was significantly lower than the deletion rate (P=0.001). 1p21.2 deletion was positively correlated with renal lesion (Cr≥177 μmol/L), high percentage of plasma cells in bone marrow, high LDH (≥220 U/L) and high β2-MG (P=0.014, 0.000, 0.010 and 0.022, respectively). With a median follow-up time of 15.0(1.0-53.5) months, the estimated median progressionfree survival (PFS) and overall survival (OS) time for patients with 1p21 deletion was (12.0±2.7) and (14.0±3.4) months, however those were (30.0±8.0) and (38.5±1.8) months in patients without 1p21 deletion, respectively (P=0.000). On multivariate analysis, which included complex karyotype, LDH≥220 U/L, renal lesion and del(17p13), 1p21 deletion remained as an independent risk factor for PFS (HR: 3.312, 95% CI: 1.095-10.017, P=0.034) and OS (HR: 4.961, 95% CI: 1.487-16.552, P=0.009).</p><p><b>CONCLUSION</b>1p21 deletion is an important genetic prognosis indicator in multiple myeloma patients.</p>

Inhibitory effect of silencing of HMGB1 gene expression on the invasive and metastatic abilities of MGC-803 gastric cancer cells / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the effect of high mobility group box-1 (high mobility group box B 1, HMGB1) on the invasive and metastatic abilities of gastric cancer cell line MGC-803 and analyze the possible mechanisms.</p><p><b>METHODS</b>HMGB1 gene targeting siRNA was designed and synthesized, and HMGB1 siRNA oligonucleotides were transfected into the MGC-803 cells with Lipofectamine 2000. The invasive and migratory abilities were detected by transwell assay and scratch assay. The Matrigel matrix glue adhesive ability of MGC-803 cells was evaluated by MTT assay. NF-κB activity was detected by electrophoretic mobility shift assay. The mRNA and protein levels of HMGB1 and MMP-9 were determined by RT-PCR and Western blot, respectively.</p><p><b>RESULTS</b>The siRNA down-regulated the levels of HMGB1 mRNA and protein. Compared with that of the control group, the number of invasive (142.7 ± 3.4 /view vs. 303.5 ± 4.3/view) and migratory (293.7 ± 4.4/view vs. 445.5 ± 5.6/view) cells was significantly increased (P < 0.05) and the adhesive ability of MGC-803 cells to Matrigel was significantly elevated (33.4 ± 0.03% vs. 57.4 ± 4.2%, P < 0.05). In addition, silencing of HMGB1 gene significantly inhibited the activity of NF-κB and the relative expression folds of mRNA (0.2 ± 0.1 vs. 1.4 ± 0.4, P < 0.05)and protein (0.4 ± 0.1 vs. 2.3 ± 0.7, P < 0.05) of MMP-9.</p><p><b>CONCLUSION</b>Silencing of HMGB1 can effectively inhibit the invasion and migration of gastric cancer cells and this effect of HMGB1 may be partly due to its regulation of NF-κB and MMP-9 expressions.</p>

Analysis of the efficacy and prognosis on first-line autologous hematopoietic stem cell transplantation of patients with multiple myeloma / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the efficacy and prognosis of first-line autologous hematopoietic stem cell transplantation (ASCT) for newly diagnosed patients with multiple myeloma(MM).</p><p><b>METHODS</b>From January 2005 to December 31, 2012, 60 patients with MM were enrolled. All patients received thalidomide or/and bortezomib-based induction therapy, then received high-dose melphalan (200 mg/m²) and autologous stem cell support to get a ≥ partial response (PR), and followed by thalidomide-dexamethasone (TD) ±bortezomib as consolidation or maintenance treatment. With the follow up to December 31, 2012, the overall survival (OS), progression free survival (PFS) and the prognostic factors, including ISS stage, response and fluorescent in situ hybridization (FISH) data of cytogenetics were analyzed.</p><p><b>RESULTS</b>With a median follow up of 36.8 (12.0-102.5) months, the median OS and PFS estimate were not reached and 86.5 months, respectively. After transplantation, all (100%) patients received very good partial response (VGPR), and 34 (56.7%) patients achieved complete response (CR) after consolidation or maintenance treatment. The patients that achieved CR resulted in long term PFS (P=0.030), with no difference in OS (P=0.942). The univariate analysis showed that the abnormalities, including 13q14 deletion, 1q21 gain, IgH location and p53 deletion had the prognostic impacts. If the t(4;14) or p53 deletion was excluded, there would be no correlation between 13q14 deletion or 1q21 gain with PFS and OS. The patients with p53 deletion had a worst survival.</p><p><b>CONCLUSION</b>There has been significant improvement in the outcome for young MM patients by using ASCT and novel drugs. Cytogenetic abnormalities and response to therapy are the main factors affecting the survival of patients.</p>

Clinical efficacy and safety of chemoimmunotherapy with rituximab,fludarabine and cyclophosphamide for chronic lymphocytic leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of a chemoimmunotherapy regimen of rituximab, fludarabine and cyclophosphamide (FCR) for patients with chronic lymphocytic leukemia(CLL).</p><p><b>METHODS</b>The clinical data of 26 CLL patients receiving FCR regimen in our hospital from April 2003 to January 2012 were analyzed retrospectively. Patients were grouped according to indicators including Rai risk stratification, β(2)-MG, LDH, ZAP-70, CD38, cytogenetics and immunoglobulin heavy chain variable region gene (IgVH) mutation status. Therapy efficacy and survival were evaluated and the safety of FCR regimen was assessed.</p><p><b>RESULTS</b>Among 26 patients, the overall response rate ( ORR ) was 76.9%, 10 patients (38.5%) achieved complete remission(CR) and 10(38.5%) partial remission(PR). With a median follow-up time of 30 ( 3-98 ) months, the median estimated progression-free survival(PFS) for all patients was 42(16-68) months and median overall survival(OS) was 63(41-85)months. Clinical parameters associated with higher CR rates were ＜2 courses of prior treatment regimens, proportions of bone marrow lymphocytes declining ≥ 50% after 2 courses of FCR, low LDH, low β(2)-MG and ZAP-70 negative (P = 0.014, 0.008, 0.027, 0.035 and 0.013, retrospectively). PFS and OS time in minimal residual disease(MRD)-negative, normal LDH and proportions of bone marrow lymphocytes declining ≥ 50% after 2 courses of FCR patients were significantly better than that of the control group (P＜0.05), PFS in the non-high-risk genetics group was significantly better than that in the high-risk genetics group (P = 0.005), while OS between two groups showed no statistically significant difference. The most common toxicities were gastrointestinal reactions (88.5%), followed by bone marrow suppression (80.8%): including neutropenia, anemia and thrombocytopenia. Infections accounted for 30.8%, mainly lung infection.</p><p><b>CONCLUSION</b>FCR is an effective and well-tolerated therapy for patients with CLL. Patients with MRD-positive, elevated LDH, proportions of bone marrow lymphocytes declining＜50% after 2 courses of FCR and high risk genetics patients are suitable for more effective treatment after achieving treatment response.</p>

Outcomes of younger than 60 years old adults with Ph/BCR-ABL positive acute lymphoblastic leukemia: a single center clinical trial of BDH ALL 2000/02 / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the treatment options for younger than 60 years old adults with Ph /BCR-ABL positive acute lymphoblastic leukemia (Ph⁺ ALL).</p><p><b>METHODS</b>From January 2001 to June 2012, 42 adult patients were enrolled in the study. All patients received standard VDCP±L ±imatinb (IM) as induction therapy followed by intensive consolidation of modified Hyper-CVAD/MA±IM. At complete remission 1 (CR1), patients with appropriate donor received allogeneic hematopoietic stem cell transplantation (allo-HSCT), the others sequentially received intensive consolidation ±IM and autologous HSCT (ASCT) at molecular CR (MCR), then MM±VP±IM as maintenance therapy. Overall survival (OS), disease free survival (DFS) and relapse rate (RR) were analyzed.</p><p><b>RESULTS</b>CR rate after 1 cycle of induction chemotherapy was 83.3%. 39(92.9%) patients achieved CR. The median DFS and OS were (22.0±3.5) and (37.0±5.3) months respectively, with cumulative RR of (43.7±9.7)% during a median follow-up of 26.5(8-75) months. All 7 patients in CT group relapsed. Two patients received IM pre- and post-ASCT maintained MCR for 35 and 12 months after ASCT. But the other 3 ASCT recipients without IM died of relapse within 1 year. The transplant-related mortality rate in allo-HSCT group was 12.5%. The estimated 3-year OS in allo-HSCT (n=16), ASCT (n=5) and CT (n=7) groups were (66.7±12.2)%, (25.0±21.7)% and (16.7±15.2)%, respectively (P=0.014); meanwhile, the estimated 3-year DFS in those groups were of (56.3±12.4)%, (26.7±22.6)% and 0, respectively (P=0.002).</p><p><b>CONCLUSION</b>IM combined with intensive chemotherapy significantly increased the CR rate with the improved quality of CR, which highlighted the feasibility of SCT. Allo-HSCT could decrease relapse to produce favorable OS and DFS in CR1 of young adults with Ph⁺ ALL. ASCT combined IM might be the treatment of choice for those achieved MCR but without donors.</p>

Expression of SOX11 mRNA in mantle cell lymphoma and its clinical significance / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the expression level of SOX11 mRNA in mantle cell lymphoma (MCL) and other B-cell non-Hodgkin lymphoma (B-NHL) and its prognostic value in MCL.</p><p><b>METHODS</b>The expression level of SOX11 mRNA in 80 B-NHL patients were determined by real-time quantitative RT-PCR, GAPDH was used as internal control. The dispersion of SOX11 expression ratio of groups with different prognostic factors was described by Mann-Whitney U test.</p><p><b>RESULTS</b>The SOX11 mRNA expression level was 2.90 (0.75 - 4.63) in 80 B-NHL patients, and the expression level was significantly higher in MCL than that in other B-NHL (P = 0.014). The SOX11 expression level was statistically lower in the group of MCL with hyperleukocytosis, 12 trisomy, MYC amplification and therapeutic effect < PR (P = 0.042, 0.013, 0.028, 0.009) than that of MCL in other group. But SOX11 expression was not associated with MCL international prognostic index (MIPI) (P = 0.333), lactate dehydrogenase (LDH) (P = 0.790), ATM mutation (P = 0.865) and P53 deletion (P = 0.116). The progression free survival (PFS) and overall survival (OS) were significantly longer in the MCL patients with high level of SOX11 than that of other MCL patients.</p><p><b>CONCLUSION</b>There was statistically significant differences in SOX11 mRNA expression between MCL with other B-NHL. SOX11 maybe a good prognostic factor in MCL.</p>

Expression of B7-H1 gene in leukemia cells and its clinical significance / 中国实验血液学杂志

This study was purposed to investigate the expression of B7-H1 gene in leukemia cells and its clinical significance. The expression of B7-H1 mRNA was detected by SYBR Green I real-time quantitative PCR in a panel of 9 leukemia cell lines, 4 leukemia cell lines induced with IFN-γ, the bone marrow mononuclear cells (BMMNC) from 59 initial leukemia patients and 10 dendritic cells (DC) derived from BMMNC of initial leukemia patients, 2 solid tumour cell lines and BMMNC from 10 normal persons. The correlation between the clinical features of 59 acute leukemia patients and the expression level of B7-H1 mRNA in leukemia cells was analyzed. The results showed that the lower level of B7-H1 mRNA expression was found in leukemia cell lines and primary acute leukemia cells, but the expression level of B7-H1 mRNA was up-regulated significantly in the leukemia cell lines induced by IFN-γ and DC derived from BMMNC of leukemia patients. The expression level of B7-H1 mRNA in non complete remission (CR) patients after therapy was significantly higher than that in CR patients. It is concluded that the expression level of B7-H1 mRNA in leukemia cells is lower, but is up-regulated when affected by some factors. A correlation exists between the expression level of B7-H1 gene in leukemia cells and response of patients to therapy.

Overrepresentation of specific gene segments of expressed immunoglobulin heavy chain variable region among unmutated and mutated patients with chronic lymphocytic leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the overrepresentation of specific gene segments of immunoglobulin heavy chain variable region (IgVH) among unmutated and mutated chronic lymphocytic leukemia (CLL) patients and its prognostic implication.</p><p><b>METHODS</b>Multiplex PCR was used to identify the expression of IgVH segment and its mutation status in CLL.</p><p><b>RESULTS</b>Analyses were successfully performed in 80 of 85 samples. Marked skewed IgVH families were disclosed. The most commonly used VH was VH3 (40.0%), followed by VH4 (30.0%), VHI (13.8%), VH2 (10.0%) and VH5, VH7 (2.5%). Fifty-six patients (70.0%) had mutated VH, 24 (30.0%) unmutated VH. Nine cases (11.3%) were with 100% germline sequence. Fifteen cases (15/24, 62.5%) in VH4, 29 (29/32, 90.7%) in VH3, and 4 (4/11, 36.3%) in VH1 had mutated VH. The most frequently used IgVH gene was VH4-39 (13.8%), and VH4-34 (8.8%). J4 (36/66, 54.5%) and D3 (25/66, 37.8%) were the most frequently used in J and D genes. The progression-free survival (PFS) was 82 and 17 months (P = 0.000), and the overall survival (OS) was 90 and 41 months (P = 0.009), respectively, for mutated and unmutated cases. Recurrent CDR3 sequences were found in our patients and 2 patients with VH1-69 had CDR3 sequences highly similar to those reported in literature.</p><p><b>CONCLUSION</b>There is difference in IgVH gene segment usage and mutational status in different area CLL patients. Recurrent CDR3 sequences were found in specific IgVH gene segments, which highlights the importance of immunoglobulin mediated stimulation in the development of CLL.</p>

The expression of microRNA-155 and microRNA-146a and its' clinical value in chronic lymphoproliferative disorders / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the expression of microRNA-155 and microRNA-146a in the CD19(+) B cells of chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), splenic marginal zone lymphoma (SMZL), and to analyze its clinical significance.</p><p><b>METHODS</b>Peripheral blood (PB) (78 cases) and bone marrow (BM) samples (9 cases) from 53 CLL patients, 13 MCL patients, 19 SMZL patients, and 12 healthy donors were collected. Mononuclear cells were isolated and B cells were purified with a CD19(+) magnetic-bead system. Total RNA was extracted from purified CD19(+) cells and microRNAs expression were measured using the TaqMan microRNA quantitative PCR. The results combined with the clinic data of patients were analysed.</p><p><b>RESULTS</b>(1) The expression of microRNA-155 in CLL (4.49 ± 0.83) was significantly higher than in MCL (3.83 ± 0.45) and SMZL (3.80 ± 0.61) (P < 0.05); (2) The level of microRNA-146a in SMZL (3.81 ± 0.59) was significantly higher than in CLL (2.58 ± 0.90) and MCL (2.27 ± 0.88) (P < 0.01); (3) The level of microRNA-155 was significantly higher in IgVH unmutated patients than in mutated patients in CLL (P = 0.012); (4) The microRNAs expression had no statistical difference between two prognostic groups in CLL.</p><p><b>CONCLUSION</b>(1) The expression of microRNA-155 and microRNA-146a is different in malignant lymphoproliferative disorders (LPD); (2) Deregulation of the microRNAs expression might play a critical role in the pathogenesis and prognosis in the LPD.</p>

Imatinib combined with modified hyper-CVAD/MA followed by allogeneic hematopoietic stem cell transplantation in CR1 as the front-line therapy for adult Ph(+) acute lymphoblastic leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the efficacy of imatinib (IM)-based chemotherapy followed by allogeneic hematopoietic stem cell transplantation (allo-SCT) in first complete remission (CR1) for adult Ph(+) acute lymphoblastic leukemia \[Ph(+)-ALL\].</p><p><b>METHODS</b>From March 2006 to December 2010, 16 adult Ph(+)-ALL were enrolled in the study. All patients received IM combined with standard VDCP ± L as induction therapy then intensive consolidation with modified Hyper-CVAD/MA regimen plus IM, and followed by allo-SCT in CR1. Some of them received IM maintenance therapy after allo-SCT. With the follow up to March 31, 2011, the clinical parameters. overall survival (OS), disease free survival (DFS), relapse incidence (RI), non-relapse mortality (NRM) and prognostic factors were analyzed.</p><p><b>RESULTS</b>All 16 patients achieved morphological complete remission (CR), and 10 of them achieved molecular CR. After transplantation, all patients obtained successful engraftments. With a median follow-up of 27.1 (7.4 - 65.8) months, 14 patients were alive, 2 died from NRM, and 2 relapsed. The estimated OS and DFS at 3 year were (85.9 ± 9.3)% and (83.9 ± 10.5)%, and cumulative RI and NRM at 3 year were (16.1 ± 10.5)% and (14.1 ± 9.3)%, respectively. None prognostic factor was found on analysis.</p><p><b>CONCLUSION</b>IM combined with intensive chemotherapy significantly increased the CR rate and improved the quality of CR, which prepared the feasibility of allo-SCT in CR1. IM therapy pre- and post-allo-SCT would be a promising strategy for adult Ph(+)-ALL to decrease relapse and facilitates favorable OS and DFS.</p>

Influence of immunomagnetic sorting on detecting genetic aberration of multiple myeloma cells by interphase fluorescence in situ hybridization / 中国实验血液学杂志

This study was to aimed investigate the influence of immunomagnetic sorting on detecting the genetic aberrations of multiple myeloma (MM) by interphase fluorescence in situ hybridization (FISH) and to explore the detection method suitable to use in our country. The genetic aberrations of immunomagnetically sorted and unsorted bone marrow cells from the same MM patients were detected by interphase FISH and the detectable rate of genetic aberration was compared. The types of probes included 13 q14 (RB-1) and 14q32 (IGH). The 42 and 22 sorted and unsorted marrow samples from MM patients were detected by using 13q14 probe and 14q32 probes respectively, the results indicated that the 13q14 deletion was found in 9 of 42 (21.4%) unsorted marrow samples and in 25 of 42 (56.8%) CD138(+)-sorted marrow samples. The 13q32 rearrangement was found in 7 of 22 (31.8%) unsorted marrow samples and in 14 of 22(63.6%) CD138(+)-sorted marrow samples. Both of the difference was statistically significant (p = 0.001 and p = 0.035 respectively). Percentages of cytogenetic alterations detected in unsorted bone marrow cells correlated positively with percentage of plasma cells tested by bone marrow smears or flow cytometry. When percentage of plasma cells tested by bone marrow smears exceed 50%, or by flow cytometry exceed 10%, there was no difference between 2 methods. It is concluded that immunomagnetic sorting of CD138(+) cells increases the probability of detection of the 13q14 deletion and 14q32 rearrangement in bone marrow samples. The low detectable rate of genetic aberration in unsorted bone marrow cells is associated to the low percentage of plasma cells in bone marrow samples, higher percentage of plasma cells can partly overcome the shortage of unsorted detection method. When percentage of plasma cells tested by bone marrow smears exceed 50%, or by flow cytometry exceed 10%, there was no difference between 2 methods.

MicroRNA profiling in patients with hepatocellular carcinoma / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the differential expression of microRNAs between human hepatocellular carcinoma (HCC) and liver cirrhosis (LC).</p><p><b>METHODS</b>The total RNA was extracted from 25 pairs of HCC and LC tissues. microRNA microarray was used to analyze the microRNA expression profiles, and validation of the microarray results was carried out by real-time quantitative RT-PCR (qRT-PCR).</p><p><b>RESULTS</b>Three microRNAs exhibited higher expression in the HCC samples than in the LC samples. In comparison with the LC samples, the HCC samples showed down-regulated expressions of 9 microRNAs. qRT-PCR verified that has-miR-122a, has-miR-199a, and has-miR-199b were downregulated in HCC, which was in agreement with the microarray results.</p><p><b>CONCLUSION</b>HCC and LC samples have significantly different microRNA expression profiles. These differentially expressed microRNAs may be involved in the pathogensis of HCC.</p>