Analysis of related factors of prognosis after surgical treatment of patients with non-metastatic colorectal cancer and construction of a normagram prediction model / 中华肿瘤杂志

Objective: To investigate the postoperative prognostic factors of non-metastatic colorectal cancer (non-mCRC), and construct a prognostic prediction model. Methods: A total of 846 patients with colorectal cancer who were admitted to the Cancer Hospital, Chinese Academy of Medical Sciences from July 1, 2014 to December 31, 2016 were included in the study. There were 314 patients in the metastatic colorectal cancer (mCRC) group and 532 patients in the non-mCRC group. The data of clinical characteristics, preoperative blood routine and common serum tumor markers for CRC tests were collected retrospectively. The disease-free survival time (DFS) data of patients in non-mCRC group were obtained by follow-up. Univariate and multivariate Cox regression analyses were used to clarify the independent risk factors of DFS, and then these factors were included to construct a nomogram prediction model. The concordance index (C index), receiver operating characteristic curve (ROC) and calibration curve were used to evaluate the performance of the model. Results: Platelet/lymphocyte ratio (PLR), neutrophil/lymphocyte ratio (NLR), carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9) and carbohydrate antigen 242 (CA242) in the mCRC group were higher than those of the non-mCRC group, while the lymphocyte/monocyte ratio (LMR) was lower than that of the non-mCRC group (P<0.05). ROC analysis showed that the area under curve (AUC) of CEA, CA19-9, CA242, NLR, LMR and PLR for the diagnosis of mCRC were 0.775, 0.716, 0.712, 0.607, 0.591 and 0.556, respectively. Multivariate Cox regression analysis demonstrated that age, perineural invasion, pN stage and preoperative CA242 level were independent risk factors for DFS of non-mCRC patients (P<0.05). Based on this, a nomogram prediction model predicting 3 years of DFS for non-mCRC patients was constructed, its C index and AUC for non-CRC prognostic prediction were 0.710 and 0.733, respectively, higher than 0.696 and 0.701 of AJCC 7th edition TNM staging system. The calibration curve of nomogram showed that the predicted DFS rate was consistent with the actual DFS rate. Conclusions: Age, perineural invasion, pN stage and preoperative CA242 level are independent risk factors for 3-year DFS of non-mCRC patients. The nomogram prediction model constructed based on these four indictors has a good predictive performance and may provide prognosis evaluation reference for the patients with non-mCRC.

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.

Ifosfamide, Cisplatin or Carboplatin, and Etoposide (ICE)-based Chemotherapy for Mobilization of Autologous Peripheral Blood Stem Cells in Patients with Lymphomas / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is a promising approach for lymphomas. This study aimed to evaluate the effect of ifosfamide, cisplatin or carboplatin, and etoposide (ICE)-based regimen as a mobilization regimen on relapsed, refractory, or high-risk aggressive lymphoma.</p><p><b>METHODS</b>From June 2001 to May 2013, patients with lymphomas who mobilized by ICE-based regimen for ASCT were analyzed in this retrospective study. The results of the autologous peripheral blood stem cells collection, toxicity, engraftment after ICE-based mobilization regimen were analyzed in this study. Furthermore, risk factors for overall survival (OS) and progression free survival (PFS) were evaluated by univariate analysis.</p><p><b>RESULTS</b>The stem cells were mobilized using ICE-based regimen plus rituximab or ICE-based regimen alone in 12 patients and 54 patients, respectively. The results of stem cell mobilization were excellent. Ninety-seven percentages of the patients had the stem cell collection of at least 2.0 × 10 6 CD34 + cells/kg and 68% had at least 5 × 10 6 CD34 + cells/kg. Fifty-eight percentage of the patients experienced Grade 4 neutropenia, 20% developed febrile neutropenia, and only 12% had Grade 4 thrombocytopenia. At a median follow-up of 63.8 months, the 5-year PFS and OS were 64.4% and 75.3%, respectively.</p><p><b>CONCLUSION</b>ICE is a powerful regimen for stem cell mobilization in patients with lymphomas.</p>

Effect of progesterone on expression of brain tissue damage factors and anti damage factors in neonatal rats with hypoxic-ischemic brain damage / 中华实用儿科临床杂志

Objective To study the effect of progesterone on tumor necrosis factor (TNF-α),interleukin-1β (IL-1β),nerve growth factor(NGF) and brain derived neurotrophic factor(BDNF) expression in the cortex and hippocampus tissue in newborn rats with hypoxic-ischemic brain damage (HIBD),and to discuss the protective molecular mechanism of progesterone on HIBD in neonatal rats.Methods Forty-eight 7-day-old neonatal rats were randomly divided into 3 groups:sham-operated group,hypoxic-ischemic group and pretreatment group.Rats in hypoxic-ischemic group and pretreatment group were subjected to left common carotid artery ligation,then they were exposed to 80 mL/L oxygen and 920 mL/L nitrogen gas in the closed container at 37 ℃ for up to 2.5 h to establish HIBD models.Progesterone was injected intraperitoneally into the rats in the pretreatment group 30 min before hypoxia,and solution was injected into the first 2 groups.All the rats were killed at the 24 h after operation.The levels of TNF-α,IL-1β,NGF,BDNF were measured by enzyme linked immunosorbent assay and the expressions of TNF-α,IL-13,NGF,BDNF mRNA were analyzed by reverse transcription-polymerase chain reaction.Results The contents of TNF-α,IL-1β,NGF,BDNF and their mRNA expressions in hypoxic-ischemic group were significantly higher than those in the sham-operated group.In pretreatment groups,the levels of TNF-α,IL-1β and their mRNA expressions were significantly lower than those in hypoxic-ischemic group.The levels of NGF,BDNF and their mRNA expressions in pretreatment group were significantly higher than those in hypoxic-ischemic group (all P ＜ 0.05).Conclusions Progesterone exerts neuroprotective effect on hypoxic-ischemic encephalopathy-induced brain damage,and the action mechanism is related to down-regulate the expression of damage factor and up-regulate the expression of anti damage factor.

Influence of arsenic exposure on menstruation / 中国地方病学杂志

Objective To study the influence of arsenic exposure on menstruation.Methods A cluster sampling method was applied to select the subjects of women aged 10 to 65 from Linhe,Hangjinhouqi and Wuyuan counties in Inner Mongolia in 2004.Drinking water samples were collected to detect arsenic levels,and menstrual related situation was surveyed.The subjects were divided into four groups according to drinking water arsenic concentration:control(≤0.01 mg/L),low(＞ 0.01-0.10 mg/L),moderate(＞ 0.10-0.20 mg/L) and high(＞ 0.20mag/L).Results A total of 602 women were surveyed.There were 83 subjects exposed to arsenic before menarche and their menarche age was (14.37 ± 1.54) years old.There were 90 people exposed to arsenic before menopause and the menopause age was (48.13-0.41) years old.The age of menarche and menopause were positively related to the years of arsenic exposure,and correlation coefficients were 0.268 and 0.278 (all P ＜ 0.05).Compared to control group(14.0％,16/112),menstrual abnormality rate decreased in low(12.1％,21/173) and high dose groups(10.2％,19/186),while increased in the moderate dose group(18.2％,16/88),but the differences were not statistically significant(x2 =3.664,P ＞ 0.05).Conclusions Long-term arsenic exposure delays the menarche and menopause age,suggesting that arsenic has certain endocrine disruption or estrogen-like effects.

Effects of chronic arsenic exposure on estrogen receptor-binding fragment-associated gene 9 and estrogen-responsive finger protein mRNA expression in female rat's myocardium / 中国地方病学杂志

Objective To observe the effects of chronic arsenic exposure on estrogen receptor-binding fragment-associated gene 9 (Ebag9) and estrogen-responsive finger protein (efp) mRNA expression in female rat' s myocardium.Methods Fifty female Wistar rats were randomly divided into five groups according to arsenic (As2O3) concentrations in drinking-water:0.00(control),0.05,0.10,0.20,0.40 mg/L groups and RT-PCR was used to detect Ebag9 and efp mRNA expression of myocardium at the 32 weeks of experiment.Results Ebag9 and efp mRNA expression levels in 0.00,0.05,0.10,0.20,0.40 mg/L groups were respectively as follows:0.54 ±0.14,0.52 ± 0.10,0.48 ± 0.24,0.58 ± 0.13,0.45 ± 0.19 and 0.85 ± 0.14,0.86 ± 0.12,0.87 ± 0.09,0.99 ±0.10,0.86 ± 0.19.Compared to the control group,Ebag9 mRNA level of the 0.20 mg/L group was increased,and decreased in other groups,but the difference between two groups was not significant(all P ＞ 0.05).Compared to control group,the efp mRNA level of 0.20 mg/L group increased significantly(P ＜ 0.05),and showed increased tendency in other arsenic groups,but the difference between two groups was not significant (all P ＞ 0.05).Conclusions Ebag9 and efp mRNA expression have changed in myocardium of rats exposed to chronic arsenic.Arsenic may has endocrine disruptor effect to female rat's myocardium.

Detection of epidermal growth factor receptor gene mutations in advanced non-small cell lung cancer / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the mutations of epidermal growth factor receptor (EGFR) in tumor tissue and pleural effusion in advanced non-small cell lung cancer (NSCLC) patients, and to analyze the relationship between EGFR mutations and the clinicopathologic characteristics.</p><p><b>METHODS</b>Two-hundred and forty-one cases of formalin-fixed, paraffin-embedded tumor tissues and 14 paired pleural effusions from advanced NSCLC patients were collected. Twenty-nine different EGFR mutations in exons 18-21 were assessed by scorpions and amplification refractory mutation system (scorpions ARMS) using real time PCR. The relationship between the EGFR mutations and clinical parameters was analyzed using statistical methods. EGFR mutation of 37 cases were detected with direct sequencing, and assessed the sensitivity, the specificity and the accuracy of scorpions ARMS.</p><p><b>RESULTS</b>EGFR somatic mutations were detected in 114 of 234 advanced NSCLC patients, with the mutation rate of 48.7%, including deletions in exon 19 in 65 patients and point mutation of L858R in exon 21 in 39 patients; both accounting for 91.2% (104/114) of all types of EGFR mutations. The test results of 14 paired pleural effusion specimens were entirely the same to the tissues. The concordance rate of 2 different detection methods was 94.6%. Mutation rate was higher in women (55.9%) than in men (42.2%), and there was no difference in mutation rates between smokers and non-smokers; patients in stage IIIB and stage IV; adenocarcinoma and non-adenocarcinoma.</p><p><b>CONCLUSIONS</b>EGFR somatic mutations appear to occur frequently in Chinese. Scorpions ARMS technology is a sensitive method to detect EGFR mutations and is suitable for screening patients who would likely respond to EGFR inhibitors therapy.</p>

Relationship between serum HER2 extracellular domain levels, tissue HER2 expression, and clinico-pathological parameters in early stage breast cancer / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Measurement of human epidermal growth factor receptor 2 (HER2) protein in the serum of metastatic breast cancer patients has previously been reported, but there are no consistent data to support the clinical utility of serum HER2 extracellular domain for patients with early stage breast cancer. We aimed to evaluate the correlation between serum extracellular domain levels and tissue HER2 expression, and analyzed their relationship with clinico-pathological parameters in patients with early stage disease.</p><p><b>METHODS</b>A prospective study was conducted on 232 breast cancer patients with stage I-III prior to treatment. Preoperative serum samples were measured by enzyme-linked immunosorbent assay. Tissue HER2 status was analyzed by immunohistochemistry and fluorescence in situ hybridization assays.</p><p><b>RESULTS</b>The median serum extracellular domain concentration was 6.8 ng/ml. The best diagnostic cut-off value was 7.4 ng/ml, with 62.9% sensitivity and 85.3% specificity. High serum extracellular domain levels were reported in 89 patients (38.3%), and HER2-positive expression was observed in 77 patients (33.2%). Multivariate analysis showed that elevated serum extracellular domain correlated with postmenopausal status (P < 0.001), high histological grade (P < 0.001), negativity of both estrogen (P = 0.012) and progesterone receptors (P < 0.001), and high levels of carcinoembryonic antigen 153 (P = 0.048).</p><p><b>CONCLUSIONS</b>We recommend that 7.4 ng/ml should be used as the cut-off value when evaluating serum extracellular domain levels in early stage of breast cancer. Patients with high serum extracellular domain levels have a certain clinico-pathological characteristics, may provide a basis for clinical practice.</p>

Evaluation of the role of rhIL-11 on hematological recovery in lymphoma patients after autologous hematopoietic stem cell transplantation / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the effect of recombinant human interleukin 11 (rhIL-11) on hematological recovery after autologous hematopoietic stem cell transplantation (AHSCT) in patients with lymphoma.</p><p><b>METHODS</b>A retrospective study was carried out on 73 patients with lymphoma after AHSCT. The patients were divided into two groups. The study group (n = 35) received rhIL-11 1.5 mg daily from the fifth day after AHSCT to the day when platelets recovering to 80.0×10⁹/L. The control group (n = 38) did not receive rhIL-11 after AHSCT.</p><p><b>RESULTS</b>All the 73 patients finished AHSCT from Mar 2003 to Dec 2008 in our department. Thirty-five patients received rhIL-11 and 38 patients did not. In the rhIL-11 group and control group, the nadir of platelet was (18.9 ± 5.0)×10⁹/L and (21.5 ± 6.0)×10⁹/L, respectively, with a significant difference (P = 0.04). The median time of platelet recovering to 50.0×10⁹/L was (14.3 ± 5.5) d and (13.2 ± 4.5) d (P = 0.37) in the two groups. There was no significant difference (P = 0.82) in the median numbers of platelet transfusion in the two groups. The curves of the mean of daily absolute platelet counts of the two groups were similar (P = 0.22). Adverse events related to rhIL-11 were not found in the rhIL-11 group.</p><p><b>CONCLUSION</b>The results of this study do not show obviously accelerating effect of rhIL-11 on the platelet recovery in lymphoma patients after AHSCT and obvious increase of adverse events after rhIL-11 administration.</p>

Efficacy of peripheral blood stem cell transplantation versus conventional chemotherapy on anaplastic large-cell lymphoma:a retrospective study of 64 patients from a single center / 癌症

Anaplastic large-cell lymphoma (ALCL) is characterized by frequently presenting adverse factors at diagnosis. Many groups believed aggressive treatment strategies such as autologous stem cell transplantation brought survival benefit for ALCL patients. However, few compared these approaches with conventional chemotherapy to validate their superiority. Here, we report a study comparing the efficacy of peripheral blood stem cell transplantation (PBSCT) and conventional chemotherapy on ALCL. A total of 64 patients with primary systemic ALCL were studied retrospectively. The median follow-up period was 51 months (range, 1-167 months). For 48 patients undergoing conventional chemotherapy only, the 4-year event-free survival (EFS) and overall survival (OS) rates were 70.7% and 88.3%, respectively. Altogether, 16 patients underwent PBSCT, including 11 at first remission (CR1/PR1), 3 at second remission, and 2 with disease progression during first-line chemotherapy. The 4-year EFS and OS rates for patients underwent PBSCT at first remission were 81.8% and 90.9%, respectively. Compared with conventional chemotherapy, PBSCT did not show superiority either in EFS (P = 0.240) or in OS (P = 0.580) when applied at first remission. Univariate analysis showed that patients with B symptoms (P = 0.001), stage III/IV disease (P = 0.008), bulky disease (P = 0.075), negative anaplastic lymphoma kinase (ALK) expression (P = 0.059), and age ≤ 60 years (P = 0.054) had lower EFS. Furthermore, PBSCT significantly improved EFS in patients with B symptoms (100% vs. 50.8%, P = 0.027) or bulky disease (100% vs. 52.8%, P = 0.045) when applied as an up-front strategy. Based on these results, we conclude that, for patients with specific adverse factors such as B symptoms and bulky disease, PBSCT was superior to conventional chemotherapy in terms of EFS.

Effect of mesenchymal stem cells on human Th1 cells by flow cytometry / 中国实验血液学杂志

This study was aimed to investigate the effect of fetal bone marrow-derived mesenchymal stem cells (FBM-MSC) on the development of human Th1 cells. FBM-MSC were isolated, cultured and expanded in vitro. The cells were identified by their phenotype profiles and differential capacity. Human CD4(+) T cells from healthy donors were cultured alone or co-cultured with FBM-MSC (FBM-MSC/CD4). In these two cultures, the quantities of Th1 cells (interferon-γ(+)) were analyzed by flow cytometry. The results indicated that the immunophenotype and multilineage differentiation of FBM-MSC satisfied the generally accepted criteria. FBM-MSC played an inhibitory role in the development of Th1 cells. Flow cytometry analysis showed that the percentage of Th1 cells in FBM-MSC/CD4 was significantly lower than that in CD4(+) T cells cultured alone. The protein level of IFN-γ in FBM-MSC/CD4 detected by ELISA was also lower than that in CD4(+) T cells cultured alone. It was also demonstrated that the expression level of IL-6 in FBM-MSC/CD4 was much higher than that in CD4(+) T cells cultured alone or FBM-MSC. The neutralizing antibody of IL-6 could increase the quantities of Th1 cells and the expression levels of IFN-γ. It is concluded that FBM-MSC may play an inhibitory role in the development of human Th1 cells, and the IL-6 pathway may be one of mechanisms involved in the inhibitory role.

Study on norcantharidin-induced apoptosis in SMMC-7721 cells through mitochondrial pathways / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the mechanism of norcantharidin (NCTD)-induced SMMC-7721 hepatoma cell apoptosis.</p><p><b>METHODS</b>SMMC-7721 cell growth inhibition was measured by the MTT method. Apoptosis was detected by Annexin V/propidium iodide staining. The mitochondrial membrane potential was measured by flow cytometry. Western blot analysis was used to evaluate the level of cytochrome c, caspase-3, AIF, Bcl-2 and Bax expression.</p><p><b>RESULTS</b>NCTD inhibited SMMC-7721 cell growth in a time- and dose-dependent manner. The cells treated with NCTD showed the loss of mitochondrial membrane potential. The activities of caspase-3, cytochrome c, AIF, and Bax were up-regulated after NCTD treatment at different doses. The expression of Bcl-2 was decreased after treatment with NCTD.</p><p><b>CONCLUSIONS</b>NCTD could induce SMMC-7721 cell apoptosis. The activation of the mitochondrial pathway was involved in the process of NCTD-induced SMMC-7721 cell apoptosis.</p>

Clinical features and prognostic factors of angioimmunoblastic T cell lymphoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To retrospectively analyze the clinical features and prognostic factors of patients with angioimmunoblastic T-cell lymphoma (AITL).</p><p><b>METHODS</b>The clinicopathological and follow-up data of 18 AITL patients undergoing integrated treatment from Feb. 1998 to April 2009 in our department were retrospectively analyzed. All of the patients received CHOP-like regimens as initial chemotherapy, including 4 once treated with radiotherapy and 1 with high dose therapy followed by autologous stem cell transplantation (HDT-ASCT) as upfront consolidation therapy. B-cell, T-cell and NK-cell subgroup proportions in the peripheral blood were tested by flow cytometry in 6 patients.</p><p><b>RESULTS</b>The median age of the 18 patients was 55 years, male and female ratio was 2.6:1. Seventy-two percent of the patients were in an advanced stage. 72% of them had B symptoms, 69% hypergammaglobulinemia, 60% elevated LDH and 47% anemia. Forty-four percent achieved CR after initial treatment with CHOP-like regimens. With the median follow-up of 26 months, the overall 2-year survival and disease free survival (DFS) rates were 62.2% and 44.4%, respectively. In the univariate analysis, only age > 30 years and primary refractory disease adversely affected overall survival (OS); age > 30 years, advanced stage, B symptoms and splenomegaly adversely affected DFS. Four patients suffered from severe pneumonia during treatment, 2 of them died of respiratory failure. Flow cytometry of peripheral blood lymphocytes showed that 5 of the 6 tested cases had decreasing proportion of CD3(+)CD4(+) T cells, B cells and NK cells but elevated CD3(+)CD8(+) T cells. Two heavily treated patients achieved partial and complete response by thalidomide therapy, with a progression free survival (PFS) of 2 and 6+ months, respectively.</p><p><b>CONCLUSION</b>AITL patients do not response well to CHOP-like regimens chemotherapy. Age < 30 years and sensitive to initial chemotherapy are associated with prolonged OS. Effectiveness of thalidomide in the treatment of AITL deserves further investigation. Peripheral blood lymphocytes test indicates that AITL patients suffered from both natural and acquired immune defects.</p>

Comparison of the efficiency of CHOP-based regimen with or without high dose consolidation treatment combined with hematopoietic stem cell transplantation in 63 lymphoblastic lymphoma patients / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To retrospectively analyze and compare the treatment efficiency of CHOP-based regimens with or without high-dose consolidation treatment combined with hematopoietic stem cell transplantation (HDT-HSCT) in the patients with lymphoblastic lymphoma (LBL).</p><p><b>METHODS</b>From 1989 to 2004, totally 63 patients with LBL were initially treated with a standard CHOP-based regimen. Forty-two of the 63 patients achieved complete response (CR), 26 of those subsequently received consolidation HDT-HSCT, while the other 16 had 6-8 cycles of standard CHOP-based treatment only.</p><p><b>RESULTS</b>Of the 63 patients, 57 had a T-LBL and 6 B-LBL, with a median age of 20 years, 19 (30.2%) had a stage I-II diseases and 44 (69.8%) stage III-IV diseases, 61.9% presented with a mediastinal mass. Bone marrow involvement presented in 28.6% of the patients. Fourteen percent had central nervous system involvement. The median follow-up period was 24 months, and the estimated 5-year overall survival and disease-free survival of this series was 31.2% and 29.3%, respectively. Of the 42 patients who achieved CR, the 5-year OS rate of the patients who received HDT-HSCT as a consolidation therapy was 59.8% versus 14.6% of the patients treated by CHOP-based regimens alone (P=0.004). Bone marrow involvement, age > or =20 years, short response duration and primary refractory disease were factors significantly associated with poor outcome. Among the 18 patients with bone marrow involvement, 3 received allogeneic HSCT and were all still alive at the follow up time of 22, 32 and 37 months, respectively, while another 4 received auto-HSCT and all died of the disease within 14 months.</p><p><b>CONCLUSION</b>Short term treatment with a CHOP-based regimen is not sufficient for the patients with lymphoblastic lymphoma. High-dose consolidation treatment and hematopoietic stem cell transplantation may improve overall survival and disease free survival. Bone marrow involvement, age >20 years, and short response duration and primary refractory disease are all the factors significantly associated with poor outcome. For the patients with bone marrow involvement, allohematopoietic stem cell transplantation is superior to auto-hematopoietic stem cell transplantation.</p>

A prospective multicenter study of rituximab combined with high-dose chemotherapy and autologous peripheral blood stem cell transplantation for aggressive B-cell lymphoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the feasibility and efficacy of rituximab combined with high-dose chemotherapy supported by autologous peripheral blood stem cell transplantation (ASCT) in patients with aggressive B-cell non-Hodgkin lymphoma (NHL).</p><p><b>METHODS</b>Twenty-eight patients with aggressive B-cell NHL (22 newly diagnosed, 6 relapsed) were enrolled in this study. The high-dose chemotherapy included CHOP regimen (CTX + ADM + VCR + PDN) for the newly diagnosed patients and DICE (DEX + IFO + DDP + VP-16) or EPOCH (VP-16 + PDN + VCR + CTX + ADM) for the relapsed patients. Each patient received infusion of rituximab at a dose of 375 mg/m(2) for four times, on D1 before and on D7 of peripheral blood stem cell mobilization, and on D1 before and D8 after stem cell reinfusion.</p><p><b>RESULTS</b>Complete remission was achieved in all patients after high dose chemotherapy and ASCT. At a median follow-up of 37 months, the estimated overall 4-year survival and progression-free survival rate for all patients were 75.0% and 70.3%, respectively, while both were 72.7% for the previously untreated patients. The therapy was generally well tolerated with few side-effects attributable to rituximab.</p><p><b>CONCLUSION</b>These results suggest that adding rituximab to high-dose chemotherapy with peripheral blood stem cell transplantation is feasible and may be beneficial for patients with aggressive B-cell non-Hodgkin lymphoma.</p>

Efficacy of once-per-cycle administration pegylated recombinant human granulocyte colony-stimulating factor in chemotherapy-induced neutropenia in a phase I trial / 中国医学科学院学报

<p><b>OBJECTIVE</b>To explore the efficacy of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in the prophylaxis of chemotherapy-induced neutropenia.</p><p><b>METHODS</b>Patients with previously untreated non-small cell lung cancer or breast cancer and with normal bone marrow function were eligible for the trial. In the phase I trial, patients were to treated with two cycles of paclitaxel/carboplatin chemotherapy every 21 days. In cycle 1, if absolute neutrophil count (ANC) dropped below 1.0 x 10(9)/ L with fever and/or ANC dropped below 0.5 x 10(9)/L, rhG-CSF 150 microg/d was administrated until WBC > or = 10 x 10(9)/L or ANC > or = 5.0 x 10(9)/L. In cycle 2, patients were to receive a single injection of PEG-rhG-CSF (30, 60, 100, or 200 microg/kg) 48 hours after chemotherapy. Pharmacodynamic analyses were performed.</p><p><b>RESULTS</b>All the 16 patients enrolled (4 in each group) were eligible for efficacy evaluation. In cycle 1, 7 patients received rhG-CSF administration because of grade 4 neutropenia, while in cycle 2, there was only 1 episode of grade 4 neutropenia, which were in the 30 microg/kg group. In cycle 1, the mean ANC nadir of 1.37 x 10(9)/L occurred on day 13 in the 9 patients who received no rhG-CSF administration. In cycle 2, the mean ANC nadirs were 0.77 x 10(9)/L, 4.54 x 10(9)/L, 3.00 x 10(9)/L, and 5.56 x 10(9)/L, respectively, in 30, 60, 100, or 200 microg/kg group. The nadirs of the first two groups occurred on day 8 of cycle 2, while those of the other two groups appeared on day 7. After PEG-rhG-CSF administration, two mean ANC peaks were observed. The first one ranging from 20.87 x 10(9)/L to 33.61 x 10(9)/L in the 4 groups appeared on day 3 to day 4. In the 30 microg/ kg group, the mean ANC reached the second peak at 5.03 x 10(9)/L on day 14. The second peaks on day 10 in the other groups were 12.42 x 10(9)/L, 11.59 x 10(9)/L, and 18.92 x 10(9)/L, respectively. Pharmacodynamic analyses showed sustained serum concentrations of PEG-rhG-CSF during the period of neutropenia.</p><p><b>CONCLUSIONS</b>PEG-rhG-CSF administration may decrease the incidence of grade 4 neutopenia and result in earlier and higher nadir ANCs. PEG-rhG-CSF has a potential of once-per-cycle administration. The ANC and serum concentration of PEG-rhG-CSF are consistent with neutrophil receptor-mediated clearance.</p>

Expression of adhesion molecules on CD34+ cells of BM and PB stem cell samples during high-dose chemotherapy combined with transplantation of autologous PB stem cells / 中国实验血液学杂志

This study was aimed to investigate the expressions of adhesion molecules such as CD54, CD49d and CD62L by CD34(+) cells sampled from different stages of bone marrow (BM) and peripheral blood (PB) before/after G-CSF mobilization and after transplantation through the direct labeling with three colour-immunofluorescence and flow cytometry, and to explore the differences in expression of adhesion molecules on CD34(+) cells from different origins and their clinical significance. Mononuclear cells collected from BM and PB before mobilization, after collection of stem cells and hematopoietic recostruction of BM at the end of transplantation were marked with CD54-FITC, CD49d-FITC and CD62L-FITC separately, as well as CD34-PE and CD45PerCE. 3-color fluorescene analysis was carried out by FACS. The expression differences of CD34(+) and adhesion molecules between BM and APBSC were compared. The results showed that expression differences of CD54, CD49d and cd62Lon CD34(+) cells belore mobilization, after collection and reconstraction of transplantation were not statiscally significant, the difference of CD54, CD49d and CD62L on CD34(+) between 1st and 2nd collections of hematopoietic stem cells also were not statiscally significant. In the collected APBSC, the expression level of CD34(+) CD49d(+) was significantly lower than those in BM before mobilization (P = 0.001). It is concluded that the method of chemotherapy combined with G-CSF mobilization can down-regulate CD49d expression in BM CD34(+) cells, thus can mobilize and move theirs into peripheral blood. After the reconstitution by transplantation, the expression of CD49d on CD34(+) cells tends to normal, the clinical significance needs to be elucidated by accumulation of much more cases.

Mobilization of autologous peripheral blood stem cells with etoposide and recombinant human granulocyte colony stimulating factor in malignant tumor patients / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To observe the combined effect of etoposide (Vp-16) and recombinant human granulocyte colony-stimulating factor (rhG-CSF) on mobilization of autologous peripheral blood stem cells (APBSC) in malignant tumor patients and find out the suitable dose of Vp-16.</p><p><b>METHODS</b>Thirty patients were randomly divided into two groups, 15 in each group. In group A, Vp-16 1000 mg/m(2) was injected intravenously in six divided doses, for 2 hours every 12 hours on day 1, 2 and 3. In group B, Vp-16 1500 mg/m(2) was injected intravenously in six divided doses for 3 hours every 12 hours on day 1, 2 and 3. rhG-CSF was given as a single daily injection subcutaneously at the dose of 300 microg.body(-1).day(-1) from the day of the nadir of white blood cell (WBC) to the day before the end of APBCS harvest. APBSC harvest started when WBC > or = 5.0 x 10(9)/L and finished when accumulated mononuclear cells (MNC) > or = 5 x 10(8)/kg or CD34+ cells > or = 2 x 10(6)/kg.</p><p><b>RESULTS</b>There was no significant difference between the time of nadir, nadir of WBC, absolute neutrophil count (ANC), the beginning time and continuous time of rhG-CSF given, the beginning time and continuous time of APBSC harvest. When the blood volume, flow rate and continuous time of apheresis were similar in each apheresis in the two groups, the number of APBSC in each harvest and total number of APBSC were also not significantly different between the two groups. The side effects induced by Vp-16 were also not significant different between the two groups.</p><p><b>CONCLUSION</b>Vp-16 combined with rhG-CSF is a safe and highly effective method for APBSC mobilization, 1000 mg/m(2) and 1500 mg/m(2) of Vp-16 possess similar efficiency and side effects for APBSC mobilization.</p>

Kinetic study on the variety of lymphocytes and CD34+ cell subsets during autologous peripheral blood stem cell transplantation / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To monitor the variety of lymphocytes and CD34(+) cell subsets in peripheral blood (PB) and peripheral blood progenitor cell (PBPC) during mobilization and collection, and determine the optimal time for PBPC collection.</p><p><b>METHODS</b>Flow cytometry (FCM) was used to detect the concentration of lymphocyte subsets, such as CD3, CD4, CD8, NK and CD19, as well as CD34(+) cell subsets, such as CD34(+)CD38(-), CD34(+)Thy1(+) and AC133(+) in PB or PBPC during autologous peripheral blood stem cell transplantation (APBSCT) during high dose chemoradiotherapy (HDC) with recombinant human granulocyte colony-stimulating factor (rhG-CSF) in 47 consecutive patients with malignant solid tumor. Colony culture in vitro was performed when evaluating the clonogenic capacity of the PBPC.</p><p><b>RESULTS</b>After mobilization, the concentration of lymphocyte subsets in PB decreased to the level below the baseline with CD3 (P = 0.007) and CD8 (P = 0.016) decreased significantly. On the contrary, the total CD34(+) cell and the other CD34 subsets in PB increased significantly (P < 0.05). CD34(+) cell peak of the blood was observed with the median time of 16 d (15-17 d) from the mobilization. The concentration of progenitor cell was the highest in the first apheresis. There was no significant change in PBPC lymphocyte subsets, except CD4 and CD4/CD8 which decreased below PB (P < 0.000 5). There was a significant linear correlation between PB CD34(+) cells and PBPC CD34(+) cells, CD34(+)CD38(-), CFU-GM or BFU-E (P < 0.05), but none between PB CD34(+) cells and PBPC MNC, CD34(+)Thy1(+) or AC133(+) cells. There was a significant correlation between PBPC CD34(+) cells and PBPC CD34(+)CD38(-), CD34(+)Thy1(+), MNC, CFU-GM or BFU-E (P < 0.05), but none between PBPC CD34(+) cells and AC133(+) cells. After transplantation, the CD4/CD8 ratio decreased markedly and CD19 cells returned to the normal range rapidly.</p><p><b>CONCLUSION</b>PBPC increases significantly during mobilization by HDC and rhG-CSF. The immunosuppressed state exists after APBSCT. The peripheral blood CD34 cell count is able to predict autograft yield reliably and can be the best indicator for the clinical collection of PBPC.</p>

Autologous peripheral blood stem cell transplantation in the treatment of patients with primary large mediastinal B-cell lymphoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the therapeutic effectiveness and safety of high dose chemoradiotherapy (HDC) combined with autologous peripheral blood stem cell transplantation (APBSCT) in the treatment of patients with primary large mediastinal B-cell lymphoma (PMLBL).</p><p><b>METHODS</b>Among nine patients with PMLBL treated with APBSCT, high dose chemotherapy combined with total body irradiation (TBI) or total lymph node irradiation (TLI)/subtotal lymph node irradiation (STLI) were given to 7 patients and high dose chemotherapy only as pre-transplantation regimen in 2 patients. All patients received supplementary irradiation at the primary mediastinum after transplantation.</p><p><b>RESULTS</b>After a median follow-up of 24 (10 - 84) months, 5 patients achieved complete remission (CR) and 3 patients partial remission (PR) after induction chemotherapy. One patient developed progressive disease before transplantation. All 5 patients who achieved CR after induction chemotherapy became disease-free survivors (DFS). One of 3 patients who achieved PR after induction chemotherapy was DFS, the other two died in the third and fifth month, respectively. The patient who relapsed before transplantation died in the sixth month carrying the disease all along. According to the life table method, the cumulative probability of 7-year DFS and overall survival (OS) were both 66.7%. No transplant-related mortality was found.</p><p><b>CONCLUSION</b>High dose chemoradiotherapy combined with autologous peripheral blood stem cell transplantation is a highly potential therapeutic treatment for poor prognostic primary mediastinal large B-cell lymphoma.</p>