Necroptosis as a potential therapeutic target in multiple organ dysfunction syndrome.

PURPOSE: To investigate how necroptosisis, i.e. programmed necrosis, is involved in MODS, and to examine whether Nec-1, a specific necroptosis inhibitor, ameliorates multiorgan injury in MODS. EXPERIMENTAL DESIGN: A model of MODS was established in six-week old SD rats using fracture trauma followed by hemorrhage. Control animals received sham surgery. Cell death form and necrosome formation were measured by fluorescence-activated cell sorting and western blotting. MODS rats were randomly assigned to receive Nec-1 or saline with pretreatment and once daily. The first end-point was 72 hours survival. Organ injury and dysfunction, inflammatory cytokine levels, and necroptotic execution protein expression were also recorded. RESULTS: Organ injury and dysfunction were significantly more severe in the MODS group than the sham group (all p<0.01). Furthermore, MODS-induced liver, lung and kidney tissue injury was characterized by necroptosis rather than apoptosis, and accompanied by necrosome formation. Compared to MODS group, Nec-1 administration significantly improved 72 hours survival (p<0.01). Nec-1 administration significantly reduced necroptosis-induced liver, lung and kidney injury and dysfunction, inhibited inflammatory cytokines production, inhibited release of necroptotic execution proteins such as high-mobility group box 1 and mixed-lineage kinase domain-like protein pseudokinase in MODS rats (all p<0.01). CONCLUSIONS: These results suggest that necroptosis is involved the pathology of MODS. Further, a necroptotic inhibitor Nec-1 may be considered as an adjunct treatment for MODS.

Overexpression of Pygopus-2 is required for canonical Wnt activation in human lung cancer.

Lung cancer is the most common cause of cancer-related mortality worldwide. It is necessary to improve the understanding of the molecular mechanisms involved in lung cancer in order to develop more effective therapeutics for the treatment of this fatal disease. The canonical Wnt signaling pathway has been known to be important in a number of cancer types, including lung cancer. Pygopus (Pygo) is a recently identified downstream component of the Wnt signaling pathway required for ß-catenin/T-cell factor (TCF)-dependent transcription. However, the role of Pygo in lung cancer remains to be elucidated. The present study showed that Pygo2 is overexpressed in human lung cancer tissue samples and cell lines. Expression levels of Pygo2 were found to correlate with cytosolic ß-catenin protein levels in the samples examined. Co-immunofluorescent staining showed that Pygo2 protein accumulated in the nuclei and colocalized with nuclear ß-catenin in lung cancer cell lines expressing Pygo2. To investigate the functional importance of the Pygo2 overexpression in lung cancer, short hairpin RNA (shRNA) was used to knockdown Pygo2 mRNA in lung cancer cells expressing the gene. Pygo2 shRNA was observed to inhibit cell proliferation and decrease ß-catenin/TCF-dependent transcriptional activity in vitro. Furthermore, Pygo2 shRNA significantly suppressed lung cancer xenograft models in vivo (P<0.05). These results suggested that Pygo2 is a putative therapeutic target for human lung cancer and overexpression of Pygo2 may be important for aberrant Wnt activation in lung cancer.

[Expression and prognostic value of regulatory T cells and M2 macrophages in diffuse large B-cell lymphoma tissues].

OBJECTIVE: To explore the prognostic value of regulatory T cells (Tregs) and M2 macrophages in diffuse large B-cell lymphoma (DLBCL) tissues. METHODS: The expression of CD163 and Foxp3 was detected by immunohistochemistry in 92 cases of DLBCL, and it was statistically analyzed whether their expressions correlate with clinical data and prognosis in patients with DLBCL. RESULTS: The density of M2 macrophage and regulatory T cells in DLBCL tumor tissues was significantly higher than that in the adjacent tissues (P = 0.02, P = 0.04). The expression of M2 macrophages was significantly positively correlated with regulatory T cells expression (r = 2.012, P < 0.05). High density of M2 or Tregs had a relationship with extranodal involvement (P < 0.05). Cox regression analysis showed that the expressions of CD163 and Foxp3 were independent prognostic factors of DLBCL (P < 0.05). CONCLUSIONS: Combined detection of the expression of CD163 and Foxp3 proteins and then evaluation of the amount of M2 macrophages and Tregs can be used to more closely predict the prognosis for DLBCL patients.

[Prognostic factors of nasal NK/T-cell lymphoma].

OBJECTIVE: To investigate the prognostic predictors of nasal NK/T cell lymphoma. METHODS: Records of 80 patients with nasal NK/T cell lymphoma were analyzed retrospectively. The correlation between clinical and haematological factors and prognosis was analyzed with univariate and multivariate analysis. RESULTS: After treatment, 33 of 80 patients achieved complete response, the 5-year overall survival and progression free survival were 52.5% and 32.5%, respectively. In univariate analysis, Eastern Cooperative Oncology Group performance status, Ann Arbor stage, local tumor invasion out of the nasal cavity, international prognostic index, complete response rate to the primary treatment, treatment model, lactate dehydrogenase (LDH),ß2-microglobulin level, globulin and white blood cell were found to be the prognostic factors. Multivariate analysis indicated that unfavorable prognostic factors included complete response rate to the primary treatment (χ(2) = 17.109, P < 0.01), LDH(χ(2) = 15.695, P < 0.01), and local tumor invasion out of the nasal cavity (χ(2) = 13.503, P < 0.01). CONCLUSION: Complete response rate to the primary treatment, elevated plasma LDH and tumor invasion out of the nasal cavity may be independent prognostic factors for NK/T cell lymphoma.

Evaluation of toxicity and single-dose pharmacokinetics of intravenous ursolic acid liposomes in healthy adult volunteers and patients with advanced solid tumors.

OBJECTIVE: The purpose of this study was to investigate the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), and pharmacokinetics of ursolic acid liposomes (UAL), as a new drug, in healthy adult volunteers and patients with advanced solid tumors. METHODS: All subjects received a single-dose of UAL (11, 22, 37, 56, 74, 98, and 130 mg/m(2)) administered as a 4-h intravenous infusion. Toxicity was assessed and plasma samples were analyzed using validated ultra-performance liquid chromatograph/tandem mass spectroscopy method. RESULTS: A total of 63 subjects including 4 patients and 35 healthy adult volunteers for toxicity study and 24 healthy adult volunteers for pharmacokinetic study were enrolled in this trial. The DLT was encountered at 74, 98, and 130 mg/m(2), and consisted of hepatotoxicity and diarrhea. Other adverse events included grade 1 nausea, grade 2 abdominal distention, grade 1 microscopic hematuria, grade 2 elevated serum sodium, grade 1 vascular stimulation, and grade 1 skin rash. The MTD was 98 mg/m(2). The single-dose pharmacokinetic parameters revealed a linear relationship between C(max), AUC(0→24 h), or AUC(0→∞) and escalated doses. CONCLUSIONS: The clinical data reported for the first time that UAL had manageable toxicities with MTD of 98 mg/m(2). The DLT were hepatotoxicity and diarrhea. Meanwhile, UAL had a linear pharmacokinetic profile. The registration number of this trial is ChiCTR-ONC-12002385.

[Efficacy and survival status of retuximab-NCE regimen treatment in patients with relapsed or refractory B cell non-Hodgkin's lymphoma].

OBJECTIVE: The aim of this study was to analyze the efficacy and toxicity of RNCE regimen in the treatment of relapsed or refractory B cell non-Hodgkin's lymphoma (NHL). METHODS: From January 2000 to December 2005, 46 patients with relapsed or refractory B cell NHL were treated by RNCE regimen with or without radiotherapy for the involved field. The clinical characteristics, response, toxicity and long-term survival results were analyzed retrospectively. RESULTS: A total of 46 patients were eligible. The complete response rate of second-line therapy was 52.17% (24/46), and the overall response rate was 82.61% (38/46). The median follow-up duration in this series was 69 months (range:6 to 102 months). The overall 1, 3, 5-year survival rate was 74.8%, 48.3%, 40.1%, respectively, with a median survival time of 30.2 months (5 to 65 months), and median progression free survival time of 10.9 months (2 to 31 months). The major toxicities were myelosuppression, GI toxicity, fatigue, fever and alopecia. CONCLUSION: Our data show that RNCE regimen treatment is effective and well tolerated in patients with relapsed or refractory B cell non-Hodgkin's lymphoma.

Nimotuzumab combined with gemcitabine and cisplatin as second-line chemotherapy for advanced non-small-cell lung cancer.

OBJECTIVE: To evaluate the efficacy and safety of nimotuzumab combined with gemcitabine and cisplatin as second-line chemotherapy for advanced non-small-cell lung cancer (NSCLC) and to investigate the association of the status of KRAS gene mutation and epidermal growth factor receptor (EGFR) genotype with clinical outcome. METHODS: Twenty-eight patients with advanced NSCLC were enrolled in this single center, uncontrolled pilot clinical study. All the patients developed drug resistance or disease progression after first-line chemotherapy of either a docetaxel + cisplatin regimen or a vinorelbine + cisplatin regimen and then received nimotuzumab combined with gemcitabine and cisplatin as second-line chemotherapy. Eight cases were stage IIIB and 20 were stage IV. An i.v. dosage regimen of 200 mg of nimotuzumab was given as a single dose, injected into the patient at days 1, 8 and 15; i.v. gemcitabine was injected at a dose of 1000 mg/m2 at days 1 and 8 and cisplatin (25 mg/m2 i.v.) at days 1, 2 and 3. Each patient received four or more therapeutic cycles. The efficacy and toxic reactions were evaluated, as well as time to progression and overall survival. RESULTS: In total, 28 patients with advanced NSCLC received 101 therapeutic cycles. The mean cycle number was 3.6. Median time to progression was 4.9 (2.5-6.5) months; median overall survival and 1-year survival rate were 9.8 months and 48.5%, respectively. There was one case of complete response, six cases of partial response, 11 cases of stable disease and 10 cases of progressive disease. Response rate was 25%, and clinical benefit rate was 64.3%. Major toxic reactions were bone marrow suppression and gastrointestinal reaction. Only one patient developed grade I acneiform eruption. CONCLUSION: Nimotuzumab combined with gemcitabine and cisplatin as second-line chemotherapy for advanced NSCLC was active and well-tolerated in this setting. Patients with EGFR amplification and KRAS gene wild type had a better prognosis. Prospective, randomized, controlled, large-scale clinical studies are needed to confirm the results.

[Expression of Cdc7 and mcm2 as a marker for proliferation and prognosis in diffuse large B cell lymphoma].

OBJECTIVE: The aim of this study was to assess the expression of cell division cycle 7 (Cdc7) kinase and minichromosome maintenance protein 2 (MCM2) in diffuse large B cell lymphoma (DLBCL) and explore their relationship with prognosis of DLBCL patients. METHODS: Clinical data of 60 DLBCL patients treated in our hospital from 2008.1 to 2010.1 were collected. The expression levels of Cdc7 and MCM2 in peripheral blood and bone marrow were determined by real-time PCR. A statistical analysis was carried out to evaluate their association with prognosis in DLBCL patients. RESULTS: The 2-year survival rate of patients with high expression of peripheral blood Cdc7 was 38.3% and those with low expression 65.4% (P = 0.001). The 2-year survival rate of patients with high expression of bone marrow Cdc7 was 37.2% and those with low expression was 75.5% (P = 0.032). The 2-year survival rate of patients with high expression of MCM2 in peripheral blood was 44.0% and those with low expression was 68.2% (P = 0.025). The 2-year survival rate of patients with high expression of MCM2 in bone marrow was 39.0% and those with low expression was 63.4% (P = 0.007). A poor disease specific survival was observed in DLBCL patients with high level expression of Cdc7 and MCM2. CONCLUSIONS: Cdc7 and MCM2 expression can be used to assess tumor proliferation and may be useful as an additional marker in combination with conventional markers in prediction of the outcome of DLBCL patients. Moreover, the Cdc7 and MCM2 signal pathway might be useful as a new approach in the treatment of refractory DLBCL lymphoma patients.

Capecitabine combined with weekly docetaxel in Chinese patients > 65 years with anthracycline-resistant metastatic breast cancer.

BACKGROUND: There are no data on more tolerable capecitabine doses in elderly patients in Chinese population. The aim of this study was to evaluate the activity and safety of capecitabine combined with weekly docetaxel for the treatment of anthracycline-resistant metastatic breast cancer (MBC) in older Chinese patients. METHODS: MBC patients aged > 65 years pretreated with 1 - 5 prior chemotherapy regimens, including an anthracycline, received oral capecitabine 825 mg/m(2) twice daily, days 1 - 14, plus docetaxel 30 mg/m(2) on days 1 and 8 every 21 days. All 41 enrolled patients received at least 1 dose of treatment and were evaluable for safety; 38 received at least 2 cycles (median 4, range 2 - 8) and were evaluable for efficacy. RESULTS: The overall objective response rate was 47%, including complete responses in 8% of patients. Median time to progression was 8.9 months. Median overall survival was 17.6 months. The most common side effects were haematological and gastrointestinal toxicities and hand-foot syndrome. The only grade 3/4 adverse events were neutropenia (12%), alopecia (7%), grade 3 nausea and vomiting (2%) and grade 3 nail toxicity (2%). CONCLUSIONS: Capecitabine 825 mg/m(2) twice daily plus weekly docetaxel is active with an acceptable safety profile in Chinese women > 65 years with anthracycline-resistant MBC. Efficacy and tolerability compare favourably with previously reported trials evaluating higher capecitabine doses in combination with 3-weekly or weekly docetaxel.

Fine-tuned expression of programmed death 1 ligands in mature dendritic cells stimulated by CD40 ligand is critical for the induction of an efficient tumor specific immune response.

During maturation, murine myeloid dendritic cells (DCs) upregulated the expressions of CD11c, CD25, CD40, CD80, CD86, MHC II and programmed death 1 ligands 1 and 2 (PD-L1 and PD-L2). Differential expression patterns of PD-L1 and PD-L2 were found when DCs were triggered by CD40 ligand and TNF-alpha. PD-L1 expression was repressed and PD-L2 expression remained unchanged in mature CD40-ligated DCs, whereas TNF-alpha stimulated DCs kept high expression of PD-L1 and significantly enhanced PD-L2 expression on DCs. Proliferations of T lymphocytes stimulated by immature DCs were enhanced by blockade of the PD-1 and PD-1 ligand interaction. But inhibitive effects were found in T lymphocytes stimulated by CD40-ligated DCs. With the fine-tuned expressions of PD-L1 and PD-L2, CD40-ligated DCs could sustain a longer activation period and elicit a more efficient T lymphocyte activation.

[Construction of the transfected cell line expressing the human CXCR4 gene and study of its biological function].

AIM: To construct the tranfected cell line expressing the human CXCR4 gene and to study the biological function. METHODS: The total RNA was isolated from peripheral blood mononuclear cell (PBMC) with TRIzol, and the CXCR4 gene was amplified by RT-PCR, then digested with restriction endonuclease Pst I and EcoR I, and inserted into retrovirus vector pEGZ-Term. The recombinant vector together with its two helper virus vectors was co-transfected into the package cells 293T with LipofectAMINE 2000. Then the supernatant of the 293T cell culture was used to infect L929 cells, the cell clones stably expressing the CXCR4 molecule were screened in the presence of Zeocin (500 mg/L) after 72 h cultivation. RESULTS: It was found that the full-length of CXCR4 gene was successfully cloned, and the recombinant retrovirus vector carrying the CXCR4 gene was constructed. The CXCR4 cDNA transfected L929 cell could stably express the human CXCR4 on the cell membrane, and the migration ability of transfected cells was well evidenced in the transwell system induced by SDF-1alpha after the transfection with CXCR4. CONCLUSION: The CXCR4 transfected L929 cell line was successfully established, and it can make the basis for the further research.

[Role of alloreactive natural killer cell in mouse MHC haploidentical bone marrow transplantation].

OBJECTIVE: To study the effect of alloreactive natural killer (NK) cells used in conditioning regimen on elimination of recipient-type T cell and granulocyte, reconstitution of hematopoiesis, engraftment and graft-versus-host disease (GVHD) in murine major histocompatibility complex (MHC) haploidentical bone marrow transplantation (BMT). METHODS: The murine model of MHC haploidentical BMT was established by using (C57BL/6 x BALB/c) BCF(1) (H-2(d/b)) mouse as the donor, and BALB/c (H-2(d)) mouse as the recipient. Recipient mice were divided into 8.5 Gy control group and 7, 6 and 5 Gy experimental groups according to different irradiation dose and different kinds of NK cell treatment. The control group was further subdivided into untreated and BMT groups, while each experimental group was subdivided respectively into untreated group, BMT group, non-allo-reactive NK cells (non-allo NK) group and alloreactive NK cells (allo NK) group. The effect of adding alloreactive NK cell to conditioning regimen was assessed by peripheral white blood cell and platelet counts, recipient type H-2(d+) T cells and granulocytes counts, expression of H-2(d/b+) cells and pathohistological examination. RESULTS: Survival time was (6.00 +/- 0.82) days for 8.5 Gy untreated group, and beyond 60 days for all the other groups. No clinical and histopathological evidence of GVHD was observed in all the groups. The reconstitution of hematopoiesis was faster in allo NK groups than in other groups (P < 0.05). On day 1 after BMT, in allo NK groups with different irradiation dose, bone marrow and spleen recipient type H-2(d+) granulocytes and T cells were significantly decreased compared with identical BMT groups and non-allo NK groups (P < 0.05). The engraftment rates of H-2(d/b+) cells were significantly higher in 7, 6 and 5 Gy allo NK groups than in identical BMT groups and non-allo NK groups (P < 0.05, respectively). CONCLUSIONS: In mouse MHC haploidentical BMT, alloreactive NK cell can eliminate recipient-type T cell and granulocyte, promote reconstitution of hematopoiesis, enhance engraftment while not induce GVHD.

[Influence of G-CSF mobilization on functions of donor T lymphocyte subpopulation and acute graft-versus-host disease].

To investigate the influence of G-CSF mobilization on functions of donor T lymphocyte subpopulation and acute graft-versus-host disease, peripheral blood samples of 20 healthy donors were collected before and after G-CSF mobilization. The whole blood was diluted with IMDM in ratio of 1:1 and then incubated with PMA + ionomycin + monensin at 37 degrees C, 5% CO2 for 4 hours. After being mobilized and stained, the IL-4, IFN-gamma and IL-2 positive cells were counted with three-color flow cytometry. The results showed that before G-CSF mobilization, the percentages of donor's CD3(+)IFN-gamma(+), CD4(+)IFN-gamma(+), CD8(+)IFN-gamma(+) T cells were 3.2% (0% - 45.9%), 1.3% (0% - 23.8%) and 1.5% (0% - 22.2%) respectively. The percentage of above mentioned cells in donor increased to 19.2% (0% - 53.9%), 9.5% (0% - 49.5%), 7.5% (0% - 38.1%) respectively after G-CSF mobilization. The IL-2 positive CD3(+), CD4(+) and CD8(+) T cell percentage in pre-G-CSF mobilized donors was 1.5% (0% - 31%), 0.8% (0% - 30.0%) and 0% (0% - 5.3%) respectively and subsequently increased to 25.7% (0% - 51%), 19.8% (0% - 39.7%), 4.6% (0% - 20.9%) respectively after G-CSF mobilization. The IL-4 positive T subpopulation did not increased significantly after G-CSF mobilization. In the early stage after peripheral blood stem cell transplantation, donor's Tc1 percentage in aGVHD group was significantly higher than that in non-aGVHD group. The morbidity of severe aGVHD in high Tc2 percentage group was significantly lower than that in low Tc2 percentage group. It is concluded that the donor's type I T cells increase after G-CSF mobilization, the Tc1 percentage of G-CSF mobilized donor is correlated with the occurrence of aGVHD in the early stage after HSCT, the percentage of Tc2 in donor is negatively correlated with aGVHD morbidity in recipients.

[Difference between FOXP3 gene expressions in donor grafts with or without acute graft-versus-host disease].

The study was aimed to investigate the association of FOXP3 gene expression in donor grafts with acute graft-versus-host disease after HLA-identical sibling allogeneic hematopoietic stem cell transplantation. Twenty-six donor grafts (peripheral blood or bone marrow) and their respective clinical characteristics were evaluated. Flow cytometry analysis was performed to assess the percentage of CD4+CD25+ and CD4+CD25(high) T cells in cord blood, healthy controls' peripheral blood and donor grafts. Relative transcripts of FOXP3 mRNA were determined by real-time quantitative reverse transcription -polymerase chain reaction with beta2-MG as the internal control gene. The specificity of FOXP3 and beta2-MG amplifications was confirmed by analyzing the dissociation curves and electrophoresis of the target amplicon. The results showed that the CD4+CD25+ T cells in peripheral blood, peripheral blood stem cell (PBSC) or BM grafts exhibited a continuous and primarily low expression of CD25 and the frequencies of CD4+CD25+ T and CD4+CD25(high) T in CD4+ T cells were (48.5 +/- 16.3)% and (9.6 +/- 2.5)%, (42.1 +/- 14.7)% and (13.1 +/- 4.2)%, (43.4 +/- 9.6)% and (14.6 +/- 4.5)%, respectively. There was no significant difference in the frequencies and absolute numbers of CD4+CD25(high) T cells between patients with aGVHD and patients without aGVHD (P > 0.05). The plot of log transfused cDNA amount versus DeltaCt had a slope of 0.0826 which indicated approximately equal efficiency of FOXP3 and beta2-MG amplifications in real-time PCR. The specificities of amplification were confirmed by analyzing the dissociation curves and electrophoresis of PCR products with the values of Tm 86.5 degrees C and 82.3 degrees C, respectively. The relative transcripts of FOXP3 in PBSC grafts of recipients without aGVHD were 318%high as those with aGVHD (median of 41.0 x 10(-5) and 12.9 x 10(-5), respectively) (P = 0.03). No significant difference was found in other related variables for GVHD. It is concluded that coexpression of CD4 and CD25 may be insufficient to identify regulatory T cells; FOXP3 mRNA expression may be specifically quantified with real-time quantitative RT-PCR using SYBR Green I chemistry. FOXP3 mRNA expression in donor grafts is significantly low in patients with aGVHD compared with patients without aGVHD. It indicated that the expression level of FOXP3 mRNA may be one of the useful indicators for in predicting aGVHD.

[Effects of mesenchymal stem cells on expansion potential and adhesion molecules expression of cord blood CD34+ cells].

OBJECTIVE: To explore the effects of bone marrow mesenchymal stem cells (MSCs) on in vitro expansion potential, the adherent molecules expression of cord blood (CB) CD34(+) cells. METHODS: MSCs were obtained from human bone marrow and their differentiation function and phenotype were identified. CB CD34(+) cells were expanded in culture systems with or without MSC layer. Hematopoietic progenitor cells and adhesion molecules expression were assessed by semisolid culture assay and flow cytometry. RESULTS: Thy-1, SH2, SB10, CD44, CD13, CD49e and CD29 were highly expressed on MSCs with no expressions of CD34, CD45, HLA-DR, CD14 and CD31. The MSCs could differentiate into adipocytes and osteoblasts under specific induction conditions. After culturing on MSCs layer with supplement of cytokines for 8 days, the absolute numbers of nuclear cells, CD34(+), CD34(+)CD38(-), CD34(+)CD62L(+) cells and CFU-Cs were increased by 145.57 +/- 17.89, 37.47 +/- 13.78, 69.78 +/- 50.07, 10.74 +/- 5.89 and 20.73 +/- 5.54-folds, respectively, being significantly higher than that cultured with cytokines alone. The expression of ALCAM, VLA-alpha4, VLA-alpha5, VLA-beta1, HCAM, PECAM and LFA-1 on CD34(+) cells remained unaffected. The expressions of ICAM-1 and L-selectin were downregulated during expansion, while the absolute numbers of CD34(+)CD62L(+) and CD34(+)CD54(+) cells were increased. CONCLUSIONS: MSCs layer improves expansion of CB CD34(+) cells while inhibiting their differentiation and retaining their homing ability.

[T-bet gene expression in acute graft versus host disease].

OBJECTIVE: To study the role of T-bet [a T helper 1 (Th1) lymphocyte transcription factor] gene expression in predicting acute graft-versus-host disease (aGVHD) and evaluate the correlation between T-bet gene and aGVHD. METHODS: Twenty patients who underwent allogeneic stem cell transplantation (allo. HSCT) entered this study. The expression of T-bet gene was examined with reverse transcription (RT)-PCR in bone marrow samples collected from patients on the day before conditioning, and day 0, day 14, day 28, and day 42 after HSCT. RESULTS: The expression level of T-bet in patients developed aGVHD was increased compared with that before conditioning (P = 0.043). The incidence of aGVHD was 91.7% in patients whose T-bet expression level was increased on day 14 after transplant while was 12.5% in those whose T-bet gene expression level was not increased on that day (P < 0.001). CONCLUSION: Patients with increased expression levels of T-bet after allo-HSCT may have an increased possibility to develop aGVHD. T-bet expression level may serve as an advisable guide to the clinician in predicting aGVHD and monitoring treatment.

[Comparison of autologous and allogeneic hematopoietic stem cell transplantation for 140 patients with de novo acute leukemia in first complete remission].

OBJECTIVE: To evaluate the outcome of patients with de novo acute leukemia (AL, no AML-M(3)) in CR(1) undergone autologous hematopoietic stem cell transplantation (auto-HSCT) or HLA-identical sibling allogeneic HSCT (allo-HSCT). METHODS: Forty-six AL patients received allo-HSCT and 94 received auto-HSCT in CR(1). The conditioning regimens mainly consisted of TBICy, BuCy and MAC. Cyclosporine plus methotrexate, or cyclosporine alone, or FK506 alone was used for graft-versus-host disease (GVHD) prophylaxis. Among auto-HSCT group, 39 patients received purged autologous bone marrow and 38 received immunotherapy and/or maintenance chemotherapy after transplant. RESULTS: Myeloid reconstitution was achieved in all patients. After a median of 700 (range, 18 approximately 5563) days follow-up, the probabilities of leukemia-free survival (LFS) at 5 year were not significantly different in these two groups: (51.5 +/- 5.4)% for auto-HSCT group and (52.8 +/- 7.6)% for allo-HSCT group (P > 0.05). There was a lower cumulative relapse incidence (RI) [(26.3 +/- 6.9)% vs. (52.0 +/- 5.5)%, P > 0.05] but a significantly higher cumulative transplant-related mortality (TRM) [(37.6 +/- 7.8% vs. (14.4 +/- 4.1)%, P < 0.05] in the allo-HSCT group than in auto-HSCT group. Among auto-HSCT group, the patients received purged autografts and/or post-transplant therapy had significantly better LFS and lower RI (P < 0.05) than those received unpurged autografts or no post-transplant treatments [5-y LFS: (62.8 +/- 6.8)% and (38.4 +/- 8.4)%; RI: (37.7 +/- 6.8)% and (74.2 +/- 8.7)%, respectively]. CONCLUSION: The long-term LFS of auto-HSCT was comparable to that of allo-HSCT in the management of patients with AL in CR(1), because autograft purging and post-transplant treatment can significantly decrease relapse of auto-HSCT patients and auto-HSCT has lower therapy-related toxicities.