Bendamustine treatment of Chinese patients with relapsed indolent non-Hodgkin lymphoma: a multicenter, open-label, single-arm, phase 3 study / 中华医学杂志(英文版)

BACKGROUND@#Bendamustine was approved in China on May 26th, 2019 by the National Medical Product Administration for the treatment of indolent B-cell non-Hodgkin lymphoma (NHL). The current study was the registration trial and the first reported evaluation of the efficacy, safety, and pharmacokinetics of bendamustine in Chinese adult patients with indolent B-cell NHL following relapse after chemotherapy and rituximab treatment.@*METHODS@#This was a prospective, multicenter, open-label, single-arm, phase 3 study (NCT01596621; C18083/3076) with a 2-year follow-up period. Eligible patients received bendamustine hydrochloride 120 mg/m2 infused intravenously on days 1 and 2 of each 21-day treatment cycle for at least six planned cycles (and up to eight cycles). The primary endpoint was the overall response rate (ORR); and secondary endpoints were duration of response (DoR), progression-free survival (PFS), safety, and pharmacokinetics. Patients were classified according to their best overall response after initiation of therapy. Proportions of patients in each response category (complete response [CR], partial response [PR], stable disease, or progressive disease) were summarized along with a two-sided binomial exact 95% confidence intervals (CIs) for the ORR.@*RESULTS@#A total of 102 patients were enrolled from 20 centers between August 6th, 2012, and June 18th, 2015. At the time of the primary analysis, the ORR was 73% (95% CI: 63%-81%) per Independent Review Committee (IRC) including 19% CR and 54% PR. With the follow-up period, the median DoR was 16.2 months by IRC and 13.4 months by investigator assessment; the median PFS was 18.6 months and 15.3 months, respectively. The most common non-hematologic adverse events (AEs) were gastrointestinal toxicity, pyrexia, and rash. Grade 3/4 neutropenia was reported in 76% of patients. Serious AEs were reported in 29 patients and five patients died during the study. Pharmacokinetic analysis indicated that the characteristics of bendamustine and its metabolites M3 and M4 were generally consistent with those reported for other ethnicities.@*CONCLUSION@#Bendamustine is an active and effective therapy in Chinese patients with relapsed, indolent B-cell NHL, with a comparable risk/benefit relationship to that reported in North American patients.@*CLINICAL TRIAL REGISTRATION@#ClinicalTrials.gov, No. NCT01596621; https://clinicaltrials.gov/ct2/show/NCT01596621.

Effects of the Aerobic Exercise on the AGE-RAGE Axis and NF-κB Pathway in T2DM Rats / 昆明医科大学学报

Objective The aim of this study was to evaluate the effects of aerobic exercise on AGE-RAGE axis and nuclear factor kappa B pathway in type 2 diabete rats and to discuss the rehabilitation function of aerobic exercise in type 2 diabetes mellitus (T2DM) . Methods After the 8-week-old male Wistar rats were fed with a high sugar and high fat for 4 weeks, type 2 diabetes rats were induced by streptozotocin way. 30 type 2 diabetes rats were allocated at random into 3 groups:type 2 diabetes mellitus (T2DM), low- and moderate- intensity exercise groups (T2DML, T2DMM) . Exercise group performed exercise protocol respectively. The AGEs, RAGE and NF-κB levels of the blood,muscle and heart were detected by ELISA method respectively. Results Compared with T2DM group, the NF-κB level of the blood, muscle and heart were decreased in T2DML group significantly (P<0.05);the AGEs, RAGE and NF-κB level of the blood, muscle and heart were decreased in T2DMM group significantly ( <0.05) . Compared with T2DML group, the NF-κB level of the blood, muscle and heart were decreased in T2DMM group significantly ( <0.05) . Conclusion Moderate intensity aerobic exercise inhibits AGE-RAGE axis and NF-κB pathway, which may decrease oxidative stress and inflammation, and so reduce tissue injure for the prevention and treatment of complications of the T2DM.

Clinical Characteristics and Outcome of 66 Cases of Mantle Cell Lymphomas / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To analyze the clinical features and prognostic factors of patients with mantle cell lymphoma(MCL).</p><p><b>METHODS</b>The clinical data of 66 MCL patients were collected from the Department of Hematology of Shanghai Ruijin Hospital, Shanghai Jiaotong University Medical School from January 2000 to December 2014. The clinical characteristics, treatment efficiency and survival rate were analyzed retrospectively.</p><p><b>RESULTS</b>The sex ratio of male to female in these 66 MCL patients was 3.71:1, the nosopoietic median age was 59 years old, and most cases were diagnosed as MCL in Ann Arbor stage III-IV(90.9%). "R-HperCVAD" regimen had the highest CR-rate reached to 55.6%, and CR rate of "R-CHOP" reached to 44.4%. The total prospective 5-year overall survival and progress-free survival rates were 35.5%±11.5% and 8.8%±5.6%, respectively. Leukocyte count abnormality(>10×10/L or <4×10/L), B symptom, LDH level, bone marrow involvement, Ki-67 and high risk group of MIPI scores, and therapy combined with or without rituximab were the independent prognostic factors.</p><p><b>CONCLUSION</b>The prognosis of MCL patients is poor, and the incidence is higher in men. The extranodal sites of bone marrow and gastrointestinal tract are involved more easily. The treatment combined with rituximab can increase survival rate for these patients.</p>

Genomics research on roles of yishen kangxian compound in the TEMT process of HK-2 cells / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To study effects of Yishen Kangxian Compound (YKC) and benazepril containing serums on HK-2 cells (human renal proximal tubule epithelial cells) in the process of renal tubular epithelial cells to mesenchymal myofibroblasts transdifferentiation (TEMT) by gene chip.</p><p><b>METHODS</b>YKC and benazepril containing serums were prepared. Their inhibitory effects on HK-2 cells in the transforming growth factor-beta1 (TGF-beta1)-induced TEMT process were observed. HK-2 cells were randomly divided into four groups, i.e., the blank control group, the model group, the benazepril group, and the YKC group. The gross RNAs were extracted and purified by taking advantage of the HumanHT-12 v4 of IlluminaBeadChip. Differentially expressed genes were obtained after they were reversely transcribed to cDNA, incorporating biotin labeling probe, hybridized with GeneChip, picture signals of fluorescence in gene array scanned and compared with differential genes by computer analysis.</p><p><b>RESULTS</b>Differentially expressed genes were successfully identified by gene chip. Compared with the model group, there were 227 differentially expressed genes in the benazepril group, including 118 up-regulated genes and 109 downregulated genes. Compared with the model group, there were 97 differentially expressed genes in the YKC group, including 69 up-regulated genes and 28 down-regulated genes. The Gene Ontology (GO) analysis indicated that YKC was more actively involved in the regulatory process than benazepril in terms of cell damage, apoptosis, growth, NF-KB, protein kinase, neuron, and blood vessel growth.</p><p><b>CONCLUSIONS</b>YKC and benazepril could inhibit the TEMT process of HK-2 cells. But YKC also had taken part in cell damage, apoptosis, growth,and more pathways of early stage TEMT.</p>

Prognostic significance of EBMT score system for hematological malignancies with allogeneic hematopoietic stem cell transplantation / 中华血液学杂志

<p><b>OBJECTIVE</b>To evaluate the impact of EBMT score system in patients with hematological malignancies received allogeneic hematopoietic stem cell transplantation (allo-HSCT).</p><p><b>METHODS</b>A total of 144 consecutive patients were analyzed retrospectively. According to the EBMT score system, including age, disease status before transplantation, interval between diagnoses to transplantation, donor/recipient sex match and donor type, patients were divided into 3 risk groups: low risk (score 0-1), intermediate risk (score 2-3) and high risk (score 4-7).</p><p><b>RESULTS</b>The median follow-up duration were 413 (10-1827) days for all patients and 837 (166-1827) days for alive patients. The estimated 4-year overall survival (OS), transplant-related mortality (TRM) and relapse rate (RR) were (57.5±4.6)%, (21.6±3.7)% and (42.7±6.1)%, respectively. The 4-year OS, TRM and RR were (72.2±9.0)%, (8.1±4.5)% and (27.3±8.7)% in the low-risk group, significantly superior to both intermediate-risk group [(57.7±6.0)%, (23.1±5.1)% and (44.9±8.3)%] and high-risk group [(36.9±10.2)%, (33.5±9.2)% and (51.5±11.8)%] (P<0.01, 0.02 and 0.009 for OS, TRM and RR respectively).</p><p><b>CONCLUSION</b>The EBMT score system provides prognostic significance for OS, TRM and RR in patients with hematological malignancies received allo-HSCT.</p>

The retrospective study of serum aspergillus galactomannan (GM) antigen assay in invasive aspergillosis on hematological diseases / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the relationship between the optical density index of serum aspergillus galactomannan (GM) assay and invasive aspergillosis (IA).</p><p><b>METHODS</b>From Jan 2008 to Dec 2011, 825 hematological diseases patients with neutrophil count <0.5×10⁹/L⁹ by continuous blood count tests were admitted into our hospital. The optical density index of GM assay was ≥0.5 at least once. Of 825 patients, 247 cases were manifested as fever during hospitalization. The optical density index of GM antigen was detected by enzyme-linked immunosorbent assay, and the sensitivity and specificity of optical density ranged in 0.5-1.5.</p><p><b>RESULTS</b>In this study, the sensitivity and specificity of GM assay with continuous twice samples (73% and 93%, respectively) were higher than single sample (66% and 80%, respectively) when optical density index ≥1.0. 69 cases were diagnosed as proven IA with the incidence rate of 8.36%.</p><p><b>CONCLUSION</b>The cut-off level for serum GM antigen assay should be decided as optical density index in two continuous samples of ≥1.0.</p>

Prognostic analysis of non-cytogenetic factors in elderly adults with acute myeloid leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To analyze the prognostic factors in elderly patients with acute myeloid leukemia (AML).</p><p><b>METHODS</b>The clinical data of 211 AML patients with age 55 years or over and treated in Shanghai Jiaotong University Medical School affiliated Ruijin Hospital from 2007 to 2011 were collected and analyzed. Multivariate and univariate analysis of clinical data were performed using a Cox regression model and log-rank test, including age, subtype, performance status, white blood cell count, serum LDH and albumin level, and treatment strategy.</p><p><b>RESULTS</b>Acute promyelocytic leukemia (APL) patients had longer survival than other subtypes. To rule out the impact of APL on the prognostic analysis, we conducted multivariate and univariate analysis excluding APL patients. The significant parameters of the univariate analysis were age (P = 0.003), achieving remission (P < 0.01), performance status (P < 0.01), organ dysfunction (P < 0.01), increased WBC counts (P = 0.022), increased LDH level (P = 0.006) and low albumin level (P < 0.01). Multivariate analysis showed that only failure of achieving remission (P < 0.01), poor performance status (ECOG 3-4) (P < 0.01) and increased WBC counts (P < 0.01) were independent prognostic factors. The patients aged 70 years or over had poor overall survival, and no significant difference of OS was observed among patients with age between 55 and 69 years. For patients aged 55 - 69 years received either DA/IA or CAG treatments had longer survival than those with palliative treatments. For those aged 70 years or over, only patients with CAG treatment had significantly longer survival than palliative treatment. For the patients with age less than 70 years and achieving complete remission after induction, intermediate-dose cytarabine consolidation might not improve survival.</p><p><b>CONCLUSION</b>Elderly AML patients should be treated individually. The intermediate-dose cytarabine consolidation might not improve survival of elderly AML patients.</p>

Preliminary comparison of efficacy and safety of dasatinib and imatinib in newly diagnosed chronic myeloid leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To compare the efficacy and safety of dasatinib and imatinib in patients with newly diagnosed chronic phase chronic myeloid leukemia (CML-CP).</p><p><b>METHODS</b>37 CML-CP patients were randomized to receive dasatinib 100 mg orally daily or imatinib 400 mg orally daily. The efficacy and safety data were collected and compared.</p><p><b>RESULTS</b>Of 37 CML-CP patients, 18 received dasatinib and 19 received imatinib. The both of median duration of drug therapy and follow-up were 38 months. (1) The rate of complete cytogenetic response (CCyR) at 12 months was higher in dasatinib group than in imatinib group (89% vs 68%), but there was no significantly statistic significance between two groups (P = 0.232). The cumulative CCyR rate by 36 months was 89% in both arms. The major molecular response (MMR) at 18 months was 76% in dasatinib arm, being significantly higher than that in imatinib arm (37%) (P = 0.017). The cumulative MMR rate by 36 months was 82% versus 68% in dasatinib or imatinib (P = 0.694). The median time to CCyR and MMR was significantly faster for dasatinib than for imatinib (3 months vs. 6 months, and 14 months vs. 34 months, respectively). (2) The drug-related adverse events were mostly grade 1/2 and were well-tolerated. Increase of serum glutamic pyruvic transaminase, pleural effusion and thrombocytopenia were more common in dasatinib arm, while hypophosphatemia, edema and neutropenia were more common in imatinib arm.</p><p><b>CONCLUSION</b>Dasatinib is an effective and safe therapy option and can be used as first-line therapy for newly diagnosed CML-CP patients.</p>

Clinical features and prognostic analysis of mantle cell lymphoma / 中华血液学杂志

<p><b>OBJECTIVE</b>To study the clinical features, therapeutic effects, survival time and prognostic factors of patents with mantle cell lymphoma (MCL).</p><p><b>METHODS</b>Clinical data of 47 MCL patients admitted from January 2002 to December 2011 were retrospectively analyzed.</p><p><b>RESULTS</b>Of all patients, median age was 58 year-old and male to female ratio was 3.3:1. Forty-two cases (89.4%) were in Ann Arbor stage III-IV, 13 cases (27.7%) with bone marrow involvement, 6 cases (12.8%) with lymphocytosis, 18 cases (38.3%) with elevated LDH, and 28 cases (59.6%) with elevated β(2)-MG. Age, bone marrow involvement, increased LDH level and treatment without rituximab were poor prognostic factors. The efficiency and complete remission rate of rituximab combined with chemotherapy were 91.4% and 48.6%, which were superior to those of CHOP regimen (41.7% and 16.7%). As compared to CHOP regimen, rituximab combined with chemotherapy induced longer progression-free survival and overall survival.</p><p><b>CONCLUSION</b>Most patients with MCL were older adults with a male predominance and usually had bone marrow involvement and poor prognosis. Rituximab combined with chemotherapy could significantly improve patient outcome.</p>

Analysis of plasma trough level of imatinib in Chinese CML patients / 中华血液学杂志

<p><b>OBJECTIVE</b>To evaluate the relationship between plasma trough level of imatinib and clinical outcomes in Chinese CML patients.</p><p><b>METHODS</b>Plasma trough levels in 416 CML patients who received imatinib orally in six general hospitals were assessed. The correlations of imatinib plasma trough level with baseline characteristics including age, weight and BSA, and clinical response were evaluated.</p><p><b>RESULTS</b>(1) Effects of age, body weight and BSA on imatinib plasma trough levels were not to be clinically significant. (2) Median imatinib plasma trough levels was 1271 (109-4329). Imatinib plasma trough level was related to dose of imatinib administration. Plasma trough levels at imatinib of dose < 400, 400 and > 400 mg were (969 ± 585), (1341 ± 595) and (1740 ± 748) µg/L (P < 0.01), respectively. (3) There was no statistic difference in imatinib plasma trough level with complete cytogenetic response [CCyR (1337 ± 571) µg/L vs no CCyR (1354 ± 689) µg/L, P = 0.255]. (4) Imatinib plasma trough level might be important for a good clinical response in some CML patients.</p><p><b>CONCLUSION</b>There was a large interpatient variability in imatinib plasma concentration in Chinese CML patients. No correlation of imatinib plasma trough level with CCyR was observed. However, higher doses of imatinib were shown to attain greater trough plasma concentration, suggesting that imatinib plasma trough level might be important for a good clinical response in some CML patients.</p>

Study on efficiency and safety of dasatinib in Chinese patients with chronic myelogenous leukemia who are resistant or intolerant to imatinib / 中华血液学杂志

<p><b>OBJECTIVE</b>To evaluate the efficiency and safety of dasatinib in Chinese patients (pts) with chronic myelogenous leukemia (CML) in chronic phase (CP), accelerated-phase (AP) or blast-phase (BP) who are resistant or intolerant to imatinib (IM).</p><p><b>METHODS</b>119 CML pts received dasatinib 100 mg once daily for pts in CP or 70 mg twice daily for pts in AP/BP. The hematologic/cytogenetic response, progression-free-survival (PFS), overall survival (OS) and adverse effects (AE) of the pts were assessed.</p><p><b>RESULTS</b>59 pts in CP, 25 in AP and 35 in BP received dasatinib treatment. The median duration of dasatinib treatment were 19.32, 20.99 and 3.22 months respectively. Complete hematologic response (CHR), major cytogenetic response (MCyR) and complete cytogenetic response (CCyR) were achieved by 91.5%, 50.8% and 42.4% of pts in CP respectively. The median times to achieving MCyR was 12.1 weeks. None of the pts in CP achieved MCyR progressed or died till to last follow-up. CHR and major hematologic response (MaHR) were achieved by 52.0% and 84.0% of pts in AP, respectively. The median time to CHR and MaHR were 16.0 and 12.1 weeks, respectively. 10 pts in AP achieved MCyR and 9 of them were CCyR. The median duration of PFS was 25.7 months for pts in AP. For 35 pts in BP, the rates of CHR and MaHR were 17.1% and 31.4% respectively. Both of the median time to CHR and MaHR were 12.1 weeks and median time of duration of MaHR was 11.2 months. 8 pts in BP achieved MCyR and the median time of duration of MCyR was 13.2 months. The median duration of PFS and OS for the pts in BP were 4.3 and 16.7 months respectively. Grade 3-4 of hematologic AEs related to dasatinib were frequent but manageable by dose interruption/reduction or supportive care. 52.5% and 61.0% of pts in CP experienced grade 3-4 of neutropenia and thrombocytopenia. More than 80% pts in AP/BP occurred grade 3-4 cytopenia. The common non-hematologic AEs related to dasatinib were including grade 1-2 pleural effusion, headache, pneumonia and diarrhea. The frequency of non-hematologic AE was higher in pts with AP/BP than in pts with CP.</p><p><b>CONCLUSION</b>Chinese pts with CML resistant or intolerant to IM treated by dasatinib can achieve relatively sustained hematologic and even cytogenetic remission and are well tolerated.</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>

Treatment options and prognosis in newly diagnosed multiple myeloma patients / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the effect of treatment option on the response and outcomes in multiple myeloma (MM) patients suitable for autologous hematopoietic stem cell transplantation (auto-HSCT).</p><p><b>METHODS</b>A total of 71 newly-diagnosed MM patients less than 65 years admitted to RuiJin Hospital from June 2005 to December 2009 were analyzed retrospectively. Among them, 21 received auto-HSCT (HSCT group) with standard conditioning of melphalan 200 mg/m(2), 30 received conventional chemotherapy (conventional group) and 20 received Bortezomib-based therapy (Bortezomib group). The responses and outcomes of different treatments were analyzed.</p><p><b>RESULTS</b>The median follow-up duration for all patients was 18 (1 - 58) months with estimated 3-year overall survival (3-yr OS) of (79.8 ± 6.3)% and progression-free survival (3-yr PFS) of (54.8 ± 9.0)%. Thirty-four patients achieved complete remission (CR) or very good partial remission (VGPR) on induction therapy, which were 80% for the Bortezomib group, 33.3% for the conventional group and 38.3% for the HSCT group. After auto-HSCT the CR + VGPR rate was increased to 76.1% for the HSCT group. Overall, the 3-yr PFS was (26.3 ± 13.8)% (median 21 months), (40.5 ± 20.1)% (median 25 months) and (93.8 ± 6.1)%(median not reached, P = 0.025) for conventional, Bortezomib and HSCT groups respectively. Univariate analysis demonstrated that CR/VGPR after induction (P = 0.020), best response of CR/VGPR (P < 0.01), autoHSCT (P = 0.002) and maintenance therapy after CR/VGPR (P = 0.0005) were associated with improved PFS and that CR/VGPR after induction (P = 0.009), best response with CR/VGPR (P < 0.01), maintenance therapy for any patients (P = 0.035) and maintenance therapy for patients with CR/VGPR (P = 0.031) were associated with OS. In multivariate analysis, only auto-HSCT (P = 0.039) and best response of CR/VGPR (P = 0.009) were independent prognostic factors for PFS and the best response of CR/VGPR was the only independent prognostic factor for OS (P = 0.005). The estimated 3-yr OS was (62.4 ± 13.7)%, (94.1 ± 5.7)% and (87.9 ± 8.3)% respectively for 3 groups.</p><p><b>CONCLUSIONS</b>For newly-diagnosed MM younger than 65 are suitable for auto-HSCT, the best response of CR/VGPR was associated with OS and PFS. Auto-HSCT is also important prognostic factor for PFS. Induction therapy with Bortezomib can achieve rapid CR/VGPR while auto-HSCT as a crucial consolidation therapy and maintenance therapy maybe also important for improvement of long-term outcome.</p>

Different dose combinations of bortezomib and dexamethasone in the treatment of relapsed or refractory myeloma: an open-label, observational, multi-center study in China / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Although previous clinical study revealed that bortezomib combined with dexamethasone had improved the outcomes of relapsed or refractory multiple myeloma (RRMM), the optimal dose combinations of bortezomib and dexamethasone remain unknown. This trial aimed to observe the efficacy and safety of different dose combinations of bortezomib and dexamethasone in the treatment of RRMM patients in China.</p><p><b>METHODS</b>A total of 168 patients with relapsed multiple myeloma (MM) who were refractory to at lest two prior treatments were enrolled in this multicenter, open-label, non-randomized, prospective clinical trial. Twenty patients received 1.3 mg/m(2) of bortezomib twice weekly for 2 weeks of a 3-week cycle for up to 8 cycles and oral or intravenous dexamethasone 20 mg on the day of and after each bortezomib dose (group 1); 66 patients received less than 1.3 mg/m(2) (0.7 - 1.0 mg/m(2)) of bortezomib and dexamethasone 20 mg on the same schedule (group 2); 37 patients received 1.3 mg/m(2)2 of bortezomib and dexamethasone 40 mg (group 3) and 45 patients received less than 1.3 mg/m(2) (0.7 - 1.0 mg/m(2)) of bortezomib and dexamethasone 40 mg (group 4). The response was evaluated according to the criteria of the European Group for Blood and Marrow Transplantation and confirmed by an independent review committee. Adverse events were graded according to the National Cancer Institute Common Toxicity Criteria, version 3.0.</p><p><b>RESULTS</b>The median age of groups 1 to 4 was 61, 62, 56, and 60 years, respectively. Most patients were in stages II/III of MM and the most common subtype was IgG. The rate of overall response to bortezomib and dexamethasone of group 1 to 4 was 72.2% (13/18), 73.8% (48/65), 78.8% (26/33) and 78.0% (32/41) (P = 0.91), including a complete response rate of 22.2% (4/18), 20.0% (13/65), 33.3% (11/33) and 29.3% (12/41) (P = 0.67), respectively. There was no statistical significance in time to progression and overall survival among these 4 groups (P > 0.05). The most commonly adverse events of any grade in the entire 4 groups were fatigue, gastrointestinal effects, peripheral neuropathy and thrombocytopenia, and there was no significance in the number of adverse events among the 4 groups (P > 0.05) except that peripheral neuropathy was reported more frequently in group 3 (36.3%) than in group 2 (13.8%, P < 0.05) and group 4 (14.6%, P < 0.05).</p><p><b>CONCLUSIONS</b>The combination of bortezomib and dexamethasone was associated with high responses in Chinese RRMM patients. No significant differences of efficacy were detected in different dose combinations of bortezomib and dexamethasone. Moreover, low dose of bortezomib reduced the incidence of peripheral neuropathy without affecting outcome in the treatment of patients with RRMM in China.</p>

Efficacy and safety of itraconazole as empirical antifungal therapy in febrile neutropenic patients with hematologic malignancies: an open-lable, multicenter, observational trial in a Chinese cohort / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Invasive fungal infection (IFI) is a common and fatal complication in neutropenic patients with hematological malignancy. Empirical antifungal therapy is widely used in practice due to the difficulty of pathogens determination and illness of the hosts. The aim of this study was to evaluate the efficacy and safety of itraconazole as empirical antifungal therapy for persistent fever in neutropenic patients with hematologic malignancies.</p><p><b>METHODS</b>Two hundred and seventy-four patients with hematologic malignancies who had suspected fungal infections were enrolled in 18 centers across China between April 2008 and April 2009. Empirical antifungal therapy with intravenous itraconazole 200 mg twice daily was given for the first two days, followed by 200 mg once daily for the next 12 days. Oral itraconazole solution was sequential for follow-up therapy if necessary. Five composite end points were evaluated for the response, which was more restrictive and adopted for the first time in such study in China.</p><p><b>RESULTS</b>The intent-to-treat analysis included data from 274 patients (full analysis set, FAS), of whom 248 were included as the per-protocol population (PPS). As the composite end point of five indices was concerned, the overall response rate was 43.4%. Seperately, defervescence was achieved in 90% of patients in which 55.5% occured during neutropenia. The mean time to defervescence was 2.71 days. Absence of breakthrough IFI during drug administration or within the first 7 days after study completion was observed in 71.5% of patients. Fifty-five point five percent patients with IFI at baseline was successfully treated. Ninety point five percent patients survived for at least 7 days after completing the study. PPS analysis revealed that the duration of neutropenia ≥ 10 days was a statistically significant negative predictor for the response. The withdrawal rate due to drug-related toxicity or lack of efficacy was 11.0%. The incidence of adverse events was 22.6%, in which 11.6% was study drug related. The most frequent adverse events were mild to moderate liver toxicity.</p><p><b>CONCLUSION</b>Itraconazole shows desirable efficacy and safety as empirical antifungal therapy for febrile neutropenic patients with hematologic malignancies.</p>

Nilotinib treatment for imatinib resistant or intolerant chronic myelogenous leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To evaluate the safety and efficacy of nilotinib in chronic myelogenous leukemia (CML) patients with resistance or intolerance to imatinib.</p><p><b>METHODS</b>Thirty-five CML patients after imatinib failure or intolerance received oral administration of 400 mg nilotinib twice daily. The overall survival, hematologic and cytogenetic responses, as well as adverse events were evaluated.</p><p><b>RESULTS</b>The median duration of nilotinib therapy was 11 (1 - 23) months, with a median follow-up of 19 months. Nonhematologic adverse events were mostly of grade 1-2. The most common ones possibly related to nilotinib were increase of bilirubin (76%) and rash (46%). Grade 3-4 hematologic adverse events includes thrombocytopenia (37%), neutropenia (26%) and anemia (26%). Nilotinib was proved to be well-tolerated in this study. Grade 3-4 hematologic adverse events happened more frequently in advanced phase CML. The rate of major cytogenetic response in chronic phase (CP) CML was much higher than those in advanced CML (38.5% vs 22.2%). The median time to major cytogenetic response was 3 months. The estimated overall survival at 18 months was (93.5 +/- 1.0)%.</p><p><b>CONCLUSION</b>Nilotinib is a more effective and safe treatment option for imatinib-resistant or -intolerant CML-CP patients.</p>

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>

Treatment outcome analysis of CTOP or CHOP regimen in newly diagnosed aggressive non-Hodgkin's lymphoma patients-results of a prospective, open, randomized, multicenter clinical trial / 中华血液学杂志

<p><b>OBJECTIVE</b>To compare the efficacy and toxicity of CTOP and CHOP regimen for newly diagnosed aggressive non-Hodgkin's lymphoma (NHL) patients.</p><p><b>METHOD</b>From Oct 2006 to Jun 2009, 196 patients enrolled into this clinical trial from 72 centers in China were randomized into CTOP or CHOP group.</p><p><b>RESULTS</b>Of 154 patients evaluated, 105 assigned in CTOP group and 49 in CHOP. Complete remission (CR) rate was 73.3%, and response rate (RR) was 87.6% in CTOP group and CR rate 71.4%, RR 86.2% in CHOP group, respectively (both P > 0.05). For B cell lymphomas, there was no difference in outcome between the two groups, but for T cell lymphomas, CR was 71.1% in CHOP, being significantly higher than that of 58.8% in CHOP group. There was no difference in hematological toxicity, GI reaction, liver and kidney function abnormality, but the occurrence of grade 3-4 alopecia in CTOP group (12.4%) was significantly lower than that in CHOP group (40.8%). The progress-free survival and overall survival (PFS and OS) at 1-, 2-, 3-year in CTOP group were 79%, 64.8%, 51.4% and 82.9%, 70.5%, 58.1%respectively; while in CTOP group were 77.6%, 61.2%, 49% and 81.6%, 67.3%, 55.1% respectively.</p><p><b>CONCLUSION</b>CTOP regimen has similar effectiveness to CHOP regimen in newly diagnosed aggressive NHL, but with less side effects, and better efficacy for T cell lymphomas.</p>

Analysis of outocome of pirarubicin-based combination chemotherapy regimen in the treatment of newly diagnosed acute myeloid leukemia-a prospective, open, randomized and multicenter clinical trial / 中华血液学杂志

<p><b>OBJECTIVE</b>To compare the effectiveness and side effects of two chemotherapy regimens [pirarubicin + cytarabine (TA) and daunorubicin + cytarabine (DA)] in patients with acute myeloid leukemia (AML).</p><p><b>METHODS</b>From Oct 2006 to Jul 2009, there were 207 newly diagnosed AML patients randomized into DA or TA group from 72 centers all over the country. The aim of this clinical trial is to observe and evaluate complete remission rate (CR), total remission rate (TRR), and side effect after one or two circles of therapy.</p><p><b>RESULTS</b>In 198 evaluable patients, 126 cases in TA group and 72 in DA group were evalvable, with a ratio of 1.75:1. CR was 69.8% and TRR (CR + PR) was 81.8% in TA group and 63.9%, 80.9% in DA group, correspondingly (P > 0.05). For patients with subtype M(2), CR (77.1%) in TA group was higher than that in DA (60%). There was no difference in side effect between the two groups.</p><p><b>CONCLUSION</b>There is no difference of the effect between TA and DA chemotherapy for newly diagnosed AML patients. But for subtype M(2), TA is more efficacy. And there is no difference in side effect between the two regimens.</p>

Synergistic effects of proteasome inhibitor and histone deacetylase inhibitor on apoptosis and aggresome formation in T lymphoma cells / 中国实验血液学杂志

The aim of the study was to explore the synergistic effect of the proteasome inhibitor bortezomib (bor) and the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) on apoptosis of T lymphoma cell lines Jurkat and Hut78, and on the formation of aggresome. Jurkat and Hut78 cells were treated with bor (10 nmol/L) or bor (10 nmol/L) combined with SAHA (2 micromol/L) respectively. Cell growth inhibition was estimated by trypan blue dye exclusion test. Cell morphology was evaluated by light microscopy with Wright's staining of cytocentrifuge preparations. Cell apoptosis was analyzed by flow cytometry. Ultrastructure of cell apoptosis and aggresome were observed by transmission electron microscopy. The results showed that proliferation of both Jurkat and Hut78 cells was significantly inhibited in the bor+SAHA group, as compared with the control group and the bor alone group. Flow cytometric analysis confirmed that the percentage of apoptosis in Jurkat and Hut78 cells in the bor+SAHA group (41.8+/-4.7% and 72.7+/-11.7% respectively) was remarkably higher than those in the control group (3.6+/-1.3% and 7.0+/-1.9% respectively) and the bor alone group (6.3+/-2.3% and 18.7+/-9.2% respectively) (p<0.01). Ultrastructure examination revealed that typical aggresomes in cells could be observed in bor alone group. The combination of bor and SAHA diminished both the amount and density of aggresomes, or even eliminated them, accompanied by the increased rate of apoptosis. It is concluded that proteasome inhibitor combined with histone deacetylase inhibitor synergically induces T lymphoma cell apoptosis. Bortezomib stimulates the formation of aggresome, while SAHA destroys this aggresome structure, which may be one of the mechanisms underlying the enhancement of bortezomib-induced apoptosis.