Efficacy and safety of IA regimen containing different doses of idarubicin in de-novo acute myeloid leukemia for adult patients / 中华血液学杂志

Objective@#To investigate the efficacy and safety of IA regimen which contains idarubicin (IDA) 8 mg/m2, 10 mg/m2 or 12 mg/m2 as induction chemotherapy for adult patients with de-novo acute myeloid leukemia (AML) .@*Methods@#A total of 1 215 newly diagnosed adult AML patients, ranging from May 2011 to March 2015 in the First Affiliated Hospital of Soochow University and other 36 clinical blood centers in China were enrolled in the multicenter, single-blind, non-randomized, clinical controlled study. To compare the response rate of complete remission (CR) , adverse events between different dose idarubicin combined with cytarabine (100 mg/m2) as induction chemotherapy in newly diagnosed patients of adult AML.@*Results@#Of 1 207 evaluable AML patients were assigned to this analysis of CR rate. The CR rates of IDA 8 mg/m2 group, IDA 10 mg/m2 group and IDA 12 mg/m2 group were 73.6% (215/292) , 84.1% (662/787) and 86.7% (111/128) , respectively (P<0.001) . After adjusted for age, blast ratio of bone marrow, FAB classification and risk stratification, the odds ratios (95% CI) of IDA 10 mg/m2 group and IDA 12 mg/m2 group were 0.49 (0.34-0.70) and 0.36 (0.18-0.71) , as compared with the IDA 8 mg/m2 group (P<0.001, P=0.003) . In the intermediate and favorable groups, CR rates was 76.5% (163/213) , 86.9% (506/582) and 86.1% (68/79) in different doses of IDA (P=0.007) . Interestingly, IA regimen with IDA 10 mg/m2 was the only beneficial factor affecting CR in this group after adjusted for age, blast ratio of bone marrow and FAB classification[OR=0.47 (95% CI 0.31-0.71) , P<0.001]. CR rates in adverse group was 50.0% (18/36) , 60.6% (43/71) and 81.8% (18/22) respectively (P=0.089) . However, the odds ratios (95% CI) of IDA 12 mg/m2 when compared with the IDA 8 mg/m2 was 0.22 (0.06-0.80) , after adjusted for age, blast ratio of bone marrow and FAB classification. The median time (days) of neutrophil count less than 0.5×109/L in IDA 8 mg/m2 group, IDA 10 mg/m2 group and IDA 12 mg/m2 group were 14 (11-18) , 15 (11-20) and 18 (14-22) , respectively (P=0.012) and of platelet count lower than 20×109/L were 14 (7-17) , 15 (11-20) and 17 (15-21) , respectively (P=0.001) . The incidences of lung infection in the three groups were 9.8%, 13.5% and 25.2%, respectively (P<0.001) .@*Conclusions@#For young adult patients (aged 18-60 years) with AML in China, intensifying induction therapy with idarubicin 10 mg/m2 is clinically superior to IDA 8 mg/m2 and IDA 12 mg/m2 in favorable intermediate AML subgroup. However, idarubicin 12 mg/m2 is more suitable to adverse AML subgroup.

Efficacy and safety of anagrelide in treatment of essential thrombocythemia: multicenter, randomized controlled clinical trial / 中华血液学杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of anagrelide in essential thrombocythemia (ET).</p><p><b>METHODS</b>Patients who diagnosed as ET according to the World Health Organization classification were enrolled. Each patient was assigned to take anagrelide hydrochloride capsule or hydroxyurea tablet by random 1∶1 ratio. Dose of anagrelide started at 2 mg/d, then increased gradually and the maximum dose was 10 mg/d until the platelet counts dropped to (100-400) × 10⁹/L, one month later gradually reduced to maintain dose. The dose of hydroxyurea was 1000 mg/d at beginning, then increased gradually, when platelet counts dropped to (100-400)×10⁹/L and kept for one month, reduced to maintain dose as 10 mg·kg⁻¹·d⁻¹. The observation period was 12 weeks.</p><p><b>RESULTS</b>A total of 222 patients were enrolled in seventeen centers (including 113 patients treated with anagrelide and 109 with hydroxyurea). Therapy efficacy can be evaluated in 198 patients (including 97 patients administered with anagrelide and 101 with hydroxyurea). At 12th weeks of therapy, the hematologic remission rate was 87.63% (85/97) in anagrelide group and 88.12% (89/107) in hydroxyurea group, the differences between the two groups were not significant (P=0.173). Treatment with anagrelide lowered the platelet counts by a median of 393 (362-1 339) × 10⁹/L from a median of 827 (562-1657) × 109/L at the beginning of the observation to 400(127-1130)×10⁹/L after 12 weeks (P<0.001), which were similar to the treatment result of hydroxyurea by a median drop of 398 (597-1846)× 10⁹/L (P=0.982). The median time to achieving response of anagrelide group was 7 (3-14) days, superior to that of hydroxyurea for 21 (14-28) significantly (P=0.003). Frequency of anagrelide related adverse events was 65.49 % (74/113), including cardiopalmus (36.28% ), headache (21.24% ), fatigue (14.16% ) and dizzy (11.50% ).</p><p><b>CONCLUSION</b>Anagrelide was effective in patients with ET which had similar hematologic remission rate to hydroxyurea and could take effect more quickly than hydroxyurea. Incidence of adverse events was undifferentiated between anagrelide and hydroxyurea, but anagrelide treatment had tolerable adverse effects and no hematologic toxicity.</p>

Significance of BCL6, MYC, P53 genes abnormalities for the prognosis of diffuse large B-cell lymphoma / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To explore the influence of BCL6, MYC, P53 genes abnormalities can on the prognosis of diffuse large B-cell lymphoma (DLBCL), and to identify independent prognostic factors for DLBCL in order to facilitate clinical prognosis and selection of stratification treatment for the patients.</p><p><b>METHODS</b>Sixty five newly diagnosed DLBCL pathological specimens were collected from 2009 to 2012. Interphase fluorescence in situ hybridization technique (I-FISH) was used to detect the status of BCL6, MYC and P53 genes. Clinical factors were combined with immunohistochemical results for multiple-factor survival analysis.</p><p><b>RESULTS</b>The rates of BCL6 gene rearrangement, P53 gene deletion and MYC rearrangement were 21.5% (14/65), 35.4% (23/65) and 7.7% (5/65), respectively. BCL6 rearrangement group has obviously poorer overall survival (OS)(P< 0.05). COX proportional hazards model analysis showed that gender, BCL6 protein, BCL6 rearrangement, Ki67 index were prognosis factors independent of international prognostic index (IPI).</p><p><b>CONCLUSION</b>BCL6 can influence the prognosis of patients with DLBCL at gene and protein levels and both are independent prognostic factors for DLBCL.</p>

Clinical significance of bcl-6, p53, c-myc aberrations in diffuse large B-cell lymphoma / 白血病·淋巴瘤

Objective To investigate aberrations of bcl-6,p53,c-myc genes in diffuse large B-cell lymphoma (DLBCL) and its clinical significance.Methods Interphase fluorescence in situ hybridization (I-FISH) was detected in 59 DLBCL patients in vivo tissue bcl-6,p53 protein,c-myc gene status.The patients were treated with CHOP or R-CHOP chemotheralpy,and the survival rates and treatment efficiency were compared.Results The p53 deletion was detected in 18 of the 59 cases (30.5 ％),bcl-6 rearrangement in 11 cases (18.6 ％),5 cases with c-myc rearrangement (8.5 ％).In the aspects of remission rate,p53 deletion positive group contained less advantage than negative ones (33.3 ％ vs 75.6 ％,x2 =9.560,P =0.002).The prognosis of bcl-6 gene rearrangement positive group different from negative group,but the difference was not statistically significant (OS,P =0.107; PFS,P =0.094),p53 deletion positive patients was in significantly worse prognosis than the negative group (OS,P =0.031; PFS,P =0.028),c-myc rearrangement positive group difference in gene rearrangement negative group,but the difference was not statistically significant (OS,P =0.163; PFS,P =0.167).In the CHOP group,prognosis of p53 deletion,c-myc rearrangement positive group were significantly worse than the negative group,the difference was statistically significant (P ＜ 0.05).In R-CHOP group,the prognostic significance of bcl-6 gene rearrangement positive group were worse (OS,P =0.003; PFS,P =0.007).Conclusion DLBCL patients with bcl-6,p53,c-myc genes aberrations are related with poor prognosis,and they can be used as prognostic factors for predicting DLBCL and guiding therapy.

The clinical observation of reduced dose idarubicin combined with cytarabine, semustine regimen in the treatment of patients with acute myeloid leukemia / 中国综合临床

ObjectiveTo evaluate the clinical efficacy and toxicity of reduced dose idarubicin and cytarabine,semustine(IAS) regimen as induction therapy in patients with acute myeloid leukemia.MethodsA total of fifty-eight newly acute myeloid leukemia(AML) patients were randomly divided into 2 groups,including 30 cases with IAS regimen,28 cases with DA regimen The IAS regimen was treated with reduced dose idarubicin (8 ～ 10 mg/m2,days 1 to 3) and cytarabine( 100 ～ 150 mg/m2,days 1 to 7),semustine(200mg,d0).The DA regimen was treated with daunorubicin(40 ～60 mg/m2,days 1 to 3) and cytarabine ( 100 ～ 150 mg/m2,days 1 to 7).The responses ( CR and overall response rate ) were compared between the 2 groups.Results Complete remission(CR) rate in IAS and DA groups were 24 of 30( 80.0％ ) and 16 of 28 (57.1％ ) respectively,while the overall response rate were 26 of 30 ( 86.7％ ) and 18 of 28 ( 64.3％ ) respectively.There was significant difference in CR rate and overall response rate between IAS group and DA group( P ＜ 0.05 ).Myelosuppression and infections due to neutropenia were the most frequent adverse effects,severe nonhematologic toxicity was not observed.The incidence rates of toxicities in the 2 groups were not significantly different ( P ＞ 0.05 ).Conclusion The effect of reduced dose idarubicin and cytarabine,semustine regimen in the treatment for acute myeloid leukemia is superior to that of DA regimen,and the toxicities are tolerable.IAS regimen can be as the optional induction therapy in newly patients with acute myeloid leukemia.

Clinical significance of the changes of coagulation and fibrolysis parameters in malignant lymphomas / 白血病·淋巴瘤

Objective To explore the clinical significance of the coagulation and fibrolysis parameters changes for the knowledge of complicated thrombosis after chemotherapy in malignant lymphomas. Methods Morning fasting anti-coagulation blood samples were taken to detect plasma prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB) and thrombin time (TT) with automatic coagulation analyzer in 71 hospitalized malignant lymphomas and 20 normal controls. The plasma D-dimer levels of the two groups were detected with immunoturbidimetry. Results The levels of plasma APTT, Fib and D-dimer in 71 malignant lynphomas were (30.44±1.43) s, (3.28±0.20) g/L, (297.05±56.59) μg/L respectively, which were significantly higher than those in normal controls at the levels of (23.72±0.76) s, (2.57±0.22) g/L, (94.50±26.07) μg/L respectively (P ＜0.05). The coagulation and fibrolysis parameters were of no statistic differences between the normal controls and lymphomas of stage Ⅰ and Ⅱ (P ＞0.05). The APTT and Fib levels in lymphomas of stage Ⅲ and Ⅳ were higher than those in normal controls and lymphomas of stage Ⅰ and Ⅱ (P ＜0.05). There are 7 malignant lymphomas complicated venous thrombosis . Of the 7 cases, the FIB and D-dimer levels were higher than those of stage Ⅰ and Ⅱ, furthermore the D-dimer levels were higher than those of stage Ⅲ and Ⅳ. Conclusion The abnormalities of coagulation and fibrolysis parameters occurred in malignant lymphomas with requirement of periodic monitoring. After chemotherapy, the lymphoma patients had a high incidence of venous thrombosis, which need early prevention for prolongation of the survival.

Correlation between translocation of 14q32 and deletions of 13q14 in multiple myeloma / 白血病·淋巴瘤

Objective To investigate the common chromosome abnormalities in the patients with multiple myeloma and the relationships of cytogenetic abnormalities and clinical features. Methods The interphase fluorescence in situ hybridization (I-FISH) analysis method was designed to detect RB1-/13q14-and 14q32 rearrangements in 49 MM patients. The statistic value of its effect on clinical features were determined. Results FISH disclosed 14q32 translocations in 26 of the 40 (53.1%) patients. 25 out of the 49 (51.02 %) cases were found with deletion of chromosome 13q14 included del(RB1) in 9 (18.4 %) and del(13q14.3) in 18 (36.7 %). 13q14 deletion and 14q32 translocation were simultaneously observed in 18 (36.7 %) cases. Spearman correlation analysis were found associated of 14q32 rearrangement with the percentage of plasma cells in bone marrow (r=0.316, P=0.27). Conclusion The frequency of 13q14 deletion and 14q32 gene translocation in multiple myeloma are high. There is a significant correlation between the presence of 14q32 translocations and chromosome 13 abnormalities in MM patients. The percentage of 14q32 translocation in plasma cells was increased significantly. The 14q32 translocation is an independent prognostic factor.

Killing effects of anti-CD158 monoclonal antibody-modified NK cells against the allogeneic dendritic cells / 中华器官移植杂志

Objective To investigate the killing effect of donor NK cells on recipient dentritic cells (DCs) by blocking KIR2DL1 and KIR2DL3 with monoclonal antibodies CD158a and CD158b,and the possible mechanism about donor NK cells reducing the incidence of graft versus host disease (GVHD).Methods SSP-PCR was used to examine the genotypic makeup of KIR in 15 pairs of patients and their HLA-identical sibling hematopoietic stem cell transplantation (HSCT) donors in our department.Peripheral blood mononuclear cells (PBMC) from 15 pairs of patients and their donors were extracted and preserved,and donor NK cells were isolated by DYNABEADS UNTOUCHED HUMAN NK sorting kit.Methyl thiazolyl tetrazolium (MTT) reduction assay was used to detect the killing activity of donor NK cells against recipients DCs.To observe the different NK killing activity before and after KIR receptors blockade,the anti-CD158a and CD158b monoclonal antibodies were used to block KIR inhibitory receptors.Results The killing effect of donor NK cells was significantly enhanced after inhibitory receptor KIRs blockades,the killing effect of NK cells in HVG KIR ligandmismatching pattern group was significantly higher than GVH or KIR receptor-ligand matched pattern group.The killing effect became stronger when the dose of antibody was increased.ConclusionIt is demonstrated in vitro that the killing effect of alloreactive NK cells could be enhanced by KIR functional modification,and the infusion of alloreactive NK cells could be used as a new strategy of immunotherapy for GVHD.

Association of killer cell immunoglobin-like receptor gene with bone marrow failure syndromes / 中华微生物学和免疫学杂志

Objective To investigate the correlation of killer immunoglobulin-like receptors(KIR)gene polymorphism with bone marrow failure syndromes(BMFS). Methods SSP-PCR was used to examine the genotypic makeup of KIR in patients with aplastic anemia( AA), myelodysplatic syndrome (MDS) and healthy controls in our department. Results All the 16 KIR genes which had been prescribed were identified. The frequencies of KIR-2DS1, 2DS2, 2DS3, 2DS5 and 3DS1 genes were showed increased in patients with AA, MDS than in healthy controls. The patients with AA had lower frequency of KIR-2DS5 than the patients with MDS. Conclusion The increased frequencies of these activated KiRs in patients with MDS and AA suggest that the abnormal immunogenetic might be related to the pathogenesis of BMFS.

Proliferative and apoptotic effects of simvastatin in combination with cytosine arabinoside on K562 cells / 白血病·淋巴瘤

Objective To investigate the effect of simvastatin (SV) in combination with cytosine arabinoside (ARA-C) on the proliferation and apoptosis of K562 cells. Methods Human K562 cells were incubated with SV and cytosine arabinoside alone or in combination and K562 cells without any treatment were taken as normal control. Cells in different groups were collected at 24, 48 and 72 h after incubation for further detections. Morphological changes by Wright stain were performed. MTT method was used to assay the growth inhibition rate and cytoflowmetry was used to detect the early stage apoptosis ratio and cell necrosis ratio. Results Compared with Ara-C group and SV group, cells in the group treated with SV combined with Ara-C showed obvious karyopyknosis,apoptosis bodies formation and significant cell growth inhibition, which were positively correlated with culture time. Combination of 15 μmol/L SV and Ara-C showed the most significant cell growth inhibition with a inhibition rate of (72±1) % at 72 h of culture, as was significantly higher than that of 15 μmol/L SV group (45±2) % and 20 μmol/L Ara-C group (44±0) % (P ＜0.01),furthermore, combination of 15 μmol/L simvastatin and Ara-C showed synergistic inhibition with Q value of 1.24 and 1.19 at 24 h and 48 h in each. The apoptosis rates at early stage (AnnexinV) detected by flow cytometry in 20 μmol/L, 15 μmol/L and 10 μmol/L SV treated K562 cells were significantly higher than that in normal K562 cells (P ＜0.01), as were positively correlated with culture time and SV dose (P ＜0.05). There were no significant difference of early apoptosis rate between the 20 μmol/L SV and 15 μmol/L SV groups (P ＞0.05), yet the very two were both higher than that of 10 μmol/L SV group (P ＜0.05). There were no statistic differences of late apoptosis rate (PI) amongdifferent treated groups (P ＞0.05). Conclusion SV inhibited K562 cell proliferation and induced cell apoptosis in vitro, and combination of SV and Ara-C exhibited obvious synergistic inhibition and apoptosis, which may increase the sensitivity of K562 cell to chemotherapy. SV at 15 μmol/L may be the best concentration for K562 cells in vitro.

Clinical significance of serum cholesterol levels in multiple myeloma / 白血病·淋巴瘤

Objective To investigate the relationship between serum cholesterol levels and immunoglobin types and clinical stages in the patients with multiple myeloma (MM). Methods We retrospectively analyzed the blood lipid levels in 65 patients with MM at diagnosis, including total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), apolipoprotein Al (apo-Al) and apolipoprotein B (apo-B), and explored relationship between lipid parameters and immunoglobulin types or clinical stages in patients with MM. Thirty healthy persons were served as controls. Results Of the 65 MM patients, 53.85% were IgG type, 63.1 % were at stage Ⅲ. The levels of TC, HDL-C, LDL-C, apo Al and apo B in the patients with MM were significantly lower than that in the controls (P 0.05). Except one case of IgD type, the levels of TC, HDL-C, LDL-C, apo Al and apo B in Ig G and Ig A types of patients were significantly lower than that in the light chain type among other 64 cases (P <0.05), and TG levels in different immunoglobulin types was found no statistical differences. The levels of TC, HDL-C, LDL-C and apo A1 in the patients with stage Ⅲ were lower than that of stage I and controls (P <0.05), furthermore, the level of LDL in stage Ⅱwas lower than that in stage Ⅰ. Conclusion Hypocholesterolemia are seen in the patients with MM and serum cholesterol levels are related to MM staging.

Molecular cytogenetic abnormalities in chronic lymphocytic leukemia detected by interphase fluorescence in situ hybridization / 白血病·淋巴瘤

Objective To investigate molecular cytogenetic abnormalities in chronic lymphocytic leukemia and clinic prognostic significance. Methods Conventional cytogenetics (CC) examination was performed in 17 cases with CLL by I-FISH with five probes [DI3S25(13q14.3), ATM(11q22.3), RB1(13q14), p53(17p13.1) and CSP12(12p11.1-12q11.1)]to detect molecular cytogenetic abnormalities in CLL. Results Among 17 cases of CLL, by CC examination, only 18.75 % patient were found to have chromosomal abnormalities;whereas on I-FISH, 70.6 % patient were found to have molecular cytogenetic abnormalities including 13q-(47.1%) del(RB1) (23.5 %), del(13q13.4)(29.4 %), trisomy 12 (29.4%), del(17p13.1)(11.8 %), del (ATM)(5.6 %), the frequency of complex abnormalities were 11.8 %. No correlation of molecular cytogenetic abnormalities with sex, age, Binet stage, LDH and β_2-MG were found. Conclusion I-FISH is a more rapid, accurate and sensitive technique for detection of molecular cytogenetic abnormalities in CLL than CC, There was no statistically significant difference between molecular cytogenetic abnormalities and clinic characteristics, but its prognostic significance in CLL needs to be further investigated.

P53 abnormality and clinical prognosis of leukemia patients with complex chromosomal abnormalities / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the p53 deletion in leukemia patients with complex chromosomal abnormalities (CCA) and the clinical significance.</p><p><b>METHODS</b>The p53 deletion status of 38 leukemia cases with CCA and 24 cases without CCA were analyzed by interphase fluorescence in situ hybridization (I-FISH).</p><p><b>RESULTS</b>The frequency of p53 deletion in the 38 patients with CCA (44.74%) was significantly higher than that in the 24 cases without CCA (4.16%) (P<0.01). The rate of complete remission in 13 cases of acute leukemia with CCA was 15.4%, with median survival time (MST) of 105 days.</p><p><b>CONCLUSION</b>I-FISH is a rapid, accurate and sensitive technique for detection of p53 deletion, patients with CCA have a higher p53 deletion and a lower complete remission rate and MST.</p>

Variation of serum ferrin, folic acid and vitamin B_(12) levels in patients with acute promyelocytic leukemia / 肿瘤

Objective:To observe the dynamic variation of serum ferritin (SF), folic acid, and vitamin B_(12) levels in patients with acute promyelocytic leukemia (APL) at different disease stages. Methods:Serum SF, folic acid and vitamin B_(12) levels were successively tested in thirty-six patients with primary APL every 1 to 3 months by using chemiluminescence analysis. Five different disease stages were selected as dynamic observation time points: first diagnosed, first complete remission (CR1), six months after CR1, relapsed stage,and CR1 for three years. Results:There were 75.0%(27/36)of patients with abnormal high levels of SF, 77.8% (28/36)of patients with abnormal low levels of folic acid, and 100%(36/36)of patients with increased vitamin B_(12) levels in first diagnosed stage. The number of patients with abnormal variations of SF, folic acid and vitamin B_(12) level was decreased in CR1 stage compared with those in first diagnosed stage (SF: P0.05). The serum SF, folic acid and vitamin B_(12) levels were in normal ranges in the patients who had 3-year CR. Conclusion:The serum SF, folic acid and vitamin B_(12) levels had dynamic variation in APL course. Increase in serum SF and vitamin B_(12) as well as decrease in folic acid are related with the active degree of APL and its tumor load.

Immunophenotype diversity of leukomonocytes cultured with fludarabine in vitro / 中国组织工程研究

BACKGROUND:Recently,some overseas in vitro researches and animal models confirmed that donor leukomonocyte cultured by fludarabine can significantly reduce acute graft-versus-host disease,but the mechanism of action is not clear.OBJECTIVE:To explore immunophenotype changes of donor leukomonocyte cultured with fludarabine in vitro.DESIGN,TIME AND SETTING:The observational cytology experiment was performed at the Department of Hematology,First People's Hospital from July 2007 to January 2008.MATERIALS:Leukomonocytes were collected from four hour healthy persons as donors of allogenic peripheral blood hematopoietic stem cell transplantation.Fludarabine was offered by Schering AG,Germany.METHODS:Peripheral blood hematopoietic stem cells collected by COBO SPECTRA were washed with RPMI1640 twice.These cells were cultured in RPMI1640 containing 0.10 volume fraction of fetal bovine serum till cell density of 2?109 L-1.1 mL of hematopoietic stem cells were washed with phosphate-buffered saline,and added CD3,CD4,CD8,CD44mAb 10 ?L,and added Mouse Ig-G1-FITC/PE as control group.These cells were attenuated with phosphate-buffered saline after incubated for 30 minutes at a low temperature,then detected by flow cytometry.Other cells were put in 24-well cultivate plate,added 8 mmol /L fludarabine as a final concentration for 24 hours(5% CO2,37 ℃).MAIN OUTCOME MEASURES:Studying immunophenotypic changes of donor leukomonocytes by flow cytometry.RESULTS:There was no significant change in the ratio of CD4+CD44+T cells before or after donor leukomonocytes cultured with fludarabine for 24 hours,and proportion of CD8+CD44+T cells declined significantly(P