Lactobacillus casei was selected as an antigen delivery vehicle for the development of oral vaccine to express recombinant LTB and porcine parvovirus (PPV) VP2 protein. The fusion protein gene encoding PPV VP2 protein and LTB, was cloned into the surface expression vector pPG, and then the recombinant expression vector pPG-VP2-LTB was electrotransformed into Lactobacillus casei 393, generating recombinant strain pPG-VP2-LTB/L. casei 393. After induced by 2% Lactose in MRS broth, an about 78 kD protein was detected in the recombinant Lactobacillus casei by SDS-PAGE. The result of Western blot indicated that the protein possessed the antigenic specificity same as the native virus protein. The result of the whole bacteria cell ELISA indicated that the LTB protein was expressed at the same time. The results of indirect immunofluorescence test and immuno-gold electron microscopy showed that the interest protein was expressed on the surface of L. casei 393. The results provide potential for the development of lactic acid bacteria oral vaccine of PPV, which used LTB as mucosal adjuvant.

Adult ; Aged ; Carcinoma, Hepatocellular ; metabolism ; Female ; Humans ; Liver Neoplasms ; metabolism ; Male ; Middle Aged ; RNA, Messenger ; biosynthesis ; genetics ; Receptor, ErbB-2 ; biosynthesis ; genetics ; Receptor, ErbB-3 ; biosynthesis ; genetics

BACKGROUNDWide application of umbilical cord blood transplantation (UCBT) in adult patients is limited by low cell-dose available in one umbilical cord blood (UCB) unit. The aim of this study was to investigate the safety and long-term outcomes of UCBT from unrelated donors in adult and adolescent patients with leukemia.

METHODSThirteen patients with leukemia received double-unit UCBT with human leukocyte antigen (HLA) mismatched at 0 - 2 loci. We analyzed the engraftment, graft-versus-host disease (GVHD) and survival.

RESULTSTwelve evaluable patients (92.3%) had neutrophil and platelet engraftment at a median of 21 days (range, 16-38 days) and 34 days (range, 25 - 51 days), respectively. At day 30, engraftment was derived from one donor in 8 patients (66.7%, 95%CI 40.0% - 93.4%), and from both donors in 4 patients (33.3%, 95%CI 6.7% - 60.0%) with 1 unit predominated. Unit with larger nucleated cell (NC) dose would predominate in engraftment (P = 0.039), whereas CD34(+) cell dose or HLA-match failed to demonstrate any relationship with unit predominance. Only one patient developed grade II acute graft-versus-host disease (aGVHD). Chronic GVHD (cGVHD) was observed in 2 of 11 patients who survived more than 100 days, and both were limited. The median follow-up after transplantation for the 13 patients was 45 months (range 1.5 - 121.0 months) and 72 months (range 41.0 - 121.0 months) for the 8 alive and with full donor chimerism. The 5-year cumulative disease free survival (DFS) was (61.5 ± 13.5)%. Of the 13 patients, 5 patients died in 1 year and 1-year transplantation related mortality (TRM) was 23.1% (95%CI 0.2% - 46.0%).

CONCLUSIONDouble-unit UCBT from unrelated donors with HLA-mismatched at 0-2 loci may overcome the cell-dose barrier and be feasible for adults and adolescents with leukemia.

Adolescent ; Adult ; Cord Blood Stem Cell Transplantation ; adverse effects ; methods ; Disease-Free Survival ; Female ; Graft vs Host Disease ; etiology ; Humans ; Leukemia ; immunology ; mortality ; therapy ; Male ; Treatment Outcome ; Young Adult

The aim of this study was to investigate the incidence, risk factors of acute renal failure (ARF) after allogeneic hematopoietic stem cell transplantation (allo-HSCT), and evaluate its effect on the prognosis of patients after allo-HSCT. A retrospective analysis was performed in 86 patients undergoing allo-HSCT at Peking University First Hospital from June 2003 to April 2007. ARF is defined as a doubling of baseline serum creatinine at any time during the first 100 days post-transplant. The risks of ARF and mortality after ARF were examined using univariate analysis and multivariate unconditional logistic regression. The correlation of ARF and survival was examined using Cox regression. The results indicated that 27 patients (31.40%) developed ARF at a median of 59.5 days after transplant (range 1 to 93 days). The univariate analysis showed that elevated risks were severe acute GVHD (OR 6.196; 95% CI 1.121 - 34.249, p = 0.033), sepsis or septic shock (OR 4.184; 95% CI 1.314 - 13.325, p = 0.018) and hyperbilirubinemia (OR 3.709; 95% CI 1.428 - 9.635, p = 0.006). Renal disease before transplant (OR 6.711; 95% CI 1.199 - 37.564, p = 0.027), hypertension (OR 2.067; 95% CI 0.739 - 5.782, p = 0.165), the use of vancomycin (OR 2.133; 95% CI 0.844 - 5.392, p = 0.106) or foscarnet sodium (OR 2.133; 95% CI 0.844 - 5.392, p = 0.106) may be potential risks. Multivariate logistic regression analysis showed that renal disease before transplant (OR 6.288; 95% CI 1.218 - 32.455, p = 0.028), sepsis or septic shock (OR 3.614; 95% CI 1.040 - 12.544, p = 0.043) and hyperbilirubinemia (OR 4.448; 95% CI 1.563 - 12.665, p = 0.005) appear to be independently associated with an increased risk of ARF. Age, gender, baseline serum creatinine level, advanced malignant disease, unrelated-donor, total body irradiation (TBI) and cyclosporine levels were not associated with the development of ARF. Cox regression showed that ARF (RR 2.124; 95% CI 1.016 - 4.441, p = 0.045) was independently associated with survival of patients after allo-HSCT. The mortality of patients with ARF within 6 months post-transplant was significantly higher than that of those without ARF (44.4% vs 8.47%, p < 0.001). It is concluded that the cumulative incidence of ARF after allo-HSCT remains high. Renal disease before transplant, hyperbilirubinemia and sepsis or septic shock are all related factors which can increase the risk of ARF. ARF appears to be independent factor influencing survival of patients after allo-HSCT.
Acute Kidney Injury ; etiology ; Adolescent ; Adult ; Child ; Child, Preschool ; Female ; Graft vs Host Disease ; etiology ; Hematopoietic Stem Cell Transplantation ; adverse effects ; methods ; Humans ; Incidence ; Male ; Middle Aged ; Retrospective Studies ; Risk Factors ; Transplantation, Homologous ; Young Adult

OBJECTIVETo explore the therapeutic feasibility of allogeneic hematopoietic stem cell transplantation (allo-HSCT) from partially HLA-mismatched related donors for hematologic diseases.

METHODSThirty patients with hematologic diseases received allo-HSCT from 1 - 3 loci mismatched related donors conditioning regimen consisting of ATG (thymoglobulin, total dose of 10 mg/kg, intravenously on - 4 d to - 1 d), and only 5 (18%) of 28 recipients from HLA-identical sibling donors were treated with regimen containing ATG. Donors were given G-CSF prior to hematopoietic stem cell harvest and CsA, short-term MTX and mycophenolate mofetil (MMF) were used for GVHD prophylaxis in both group.

RESULTSAll patients were successfully engrafted. There was no significant difference in the incidence of grade II to IV acute graft-versus-host disease (aGVHD) and grade III to IV aGVHD between the mismatched and matched groups (34% vs 32%, and 13% vs 11%, respectively). 3-year overall survival (OS) and disease-free survival (DFS) in mismatched and matched groups were 57% vs 77% (P = 0.14) and 57% vs 69% (P = 0.28), respectively. Multivariate analysis showed that advanced disease pre-transplant (P = 0.006) and CMV infection (P = 0.04) were risk factors for OS. OS for patients with stable disease in mismatched and matched groups were 87% vs 81% (P = 0.65) respectively, and for those with advanced disease were 21% vs 71% (P = 0.02).

CONCLUSIONSIt is feasible to perform allo-HSCT from 1 -3 loci HLA-mismatched related donors for patients with stable disease who lack HLA-identical sibling donors. Nevertheless, for patients with advanced disease optimized conditioning regimen and intensive supporting therapy should be administered to obtain better clinical outcomes.

Graft vs Host Disease ; prevention & control ; HLA Antigens ; Hematopoietic Stem Cell Transplantation ; methods ; Humans ; Siblings ; Tissue Donors ; Transplantation Conditioning

OBJECTIVEDrug-induced liver damage is a potential complication from using many drugs. The aim of our study was to analyze the etiology and clinical features of drug-induced liver damage, in order to draw more attention to this problem.

METHODSTwo hundred and seventy-six cases over a 5-year period in Jiangsu Province Hospital were retrospectively analyzed.

RESULTSA variety of drugs, including traditional Chinese medicines (26.1% of our total cases) and anticancer drugs (17%) caused liver damage. The main clinical manifestations of it were fatigue, nausea, vomiting and jaundice. In 88% of our cases the symptoms were relieved or completely disappeared, but there was still a 5.1% mortality rate.

CONCLUSIONSThe clinical features of drug-induced liver damage are of no specificity, and the mortality of it is not low. Liver function should be monitored when suspected drugs are prescribed.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Chemical and Drug Induced Liver Injury, Chronic ; classification ; diagnosis ; etiology ; Child ; Child, Preschool ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Young Adult

OBJECTIVETo observe the engraftment, survival and graft-versus-host disease (GVHD) after 2 units unrelated cord blood (UCB) transplantation for treatment of adult hematological malignancies.

METHODSAmong twelve patients with hematological malignancies, ten were in stable stage and 2 in advanced stage. Conditioning regimen was Bu/Cy or Cy/TBI in 11 cases, and 1 received nonmyeloablative regimen. Antithymocyte globulin (ATG) was administered in all patients. GVHD prophylaxis consisted of cyclosporine A (CsA), mycophenolate mofetil (MMF) and short course methotrexate (MTX). Each patient received 2 units UCB of HLA mismatched at 0 -2 loci. Median total nucleated cells (TNC) infused was 5.55 x 10(7)/kg [range (2.99 -8.18) x 10(7)/kg].

RESULTSOne patient showed primary graft failure. The other 11 patients showed neutrophil engraftment at a mean time of (21.6 +/- 5.1) days and platelet engraftment at (34.9 +/- 9.5) days. One patient showed secondary graft failure and died of leukemia relapse at 3 months after transplantation. Ten patients (83.3%) gained sustained engraftment. In 9 patients the UBC unit with larger TNC dose predominated engraftment, and only 1 patient showed the unit with smaller TNC predominated (P = 0.011). Acute GVHD was observed in 6 patients, including grade I in 5 and grade II in 1. Limited chronic GVHD was observed in 2 of 10 patients survived more than 100 days. Of the total 12 patients, eight were still alive in event-free status and 3-year event-free survival(EFS) was (66.7 +/- 13.6)%. Of the 10 patients in stable stage at the time of transplantation, the probability of EFS was (70.0 +/- 14.5 )%.

CONCLUSIONSTwo UBC units transplantation with HLA mismatched at 0 - 2 loci is feasible as a treatment modality for adult hematological malignancies, and the unit with larger TNC dose would predominate the engraftment.

Adolescent ; Adult ; Cord Blood Stem Cell Transplantation ; Female ; Follow-Up Studies ; Graft vs Host Disease ; prevention & control ; Hematologic Neoplasms ; drug therapy ; therapy ; Humans ; Male ; Survival Rate ; Transplantation Conditioning ; Young Adult

OBJECTIVETo observe whether rhIL-11 could accelerate the engraftment of platelets after unrelated cord blood transplantation (CBT).

METHODSNine patients (3 children and 6 adults) were enrolled in this study. The degree of HLA disparity was 0-2 loci. Cord blood was given two units for adults and one unit for children. Conditioning regimens were CY/TBI in 1 and BU/CY in 8 cases, both with antithymocyte globulin. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and short-term methotrexate. On day +1, rhIL-11 was used at 50 microg x kg(-1) x d(-1) and G-CSF at 5 microg x kg(-1) x d(-1) to accelerate hematopoiesis recovery.

RESULTSThe median age of the patients was 22.3 years and the median weight 52.3 kg. Among the 9 patients, 8 (88.9%) experienced engraftment. The median time to neutrophil > 0.5 x 10(9)/L was 21.3 (14-37) days and to platelet > 20 x 10(9)/L was 25 (18-36) days. 42.9% of the patients developed grade I aGVHD and 33.3% developed localized chronic GVHD. Six patients were alive and disease-free at a median follow-up of 7 months. Infection was the primary cause of death. The expected 1-year survival was 77.8%, 2-year survival was 52.2%. Five of 8 patients (62.5%) who received IL-11 presented leakage syndrome. On prophylaxis with drugs containing Arnebia root extract, all patients could tolerate the treatment.

CONCLUSIONrhIL-11 maybe helpful for accelerating the platelet recovery and reducing aGVHD severity in unrelated CBT. The major side effect is leakage syndrome. It is well tolerated on prophylaxis with drugs containing Arnebia root.

Adolescent ; Adult ; Blood Platelets ; drug effects ; Child ; Cord Blood Stem Cell Transplantation ; Female ; Follow-Up Studies ; Graft vs Host Disease ; prevention & control ; Humans ; Interleukin-11 ; pharmacology ; Male ; Recombinant Proteins ; pharmacology

OBJECTIVETo determine the role of Pre-S1 protein in diagnosing viral replication in patients with chronic hepatitis B.

METHODS104 consecutive patients with chronic hepatitis B were included in the study, liver biopsy were performed in all patients. Serial serum samples were studied with the quantitative determination of HBV-DNA by a quantitative PCR assay, determination of Pre-S1 protein by ELISA.

RESULTSThe positive rates of HBV-DNA and Pre-S1 protein in patients with HBsAg HBeAg anti-HBc (+) both were 96.5%. The positive rates of HBV-DNA and Pre-S1 protein in patients with HBsAg anti-HBe anti-HBc (+) were 81.5%, 72.3%, respectively. The positive rates of HBV-DNA and Pre-S1 protein in patients with HBsAg anti-HBc (+) were 87.5%, 75.0%, respectively. It represented some patients with HBeAg (-) anti-HBe (+/-) still had viral replication. HBV-DNA>10(3) copy/ml as positive criteria for diagnosing viral replication, the positive rate of HBeAg, Pre-S1 were 31.5% (28/89), 80.9% (72/89) in patients with HBV-DNA>10(3) copy/ml, respectively. The concordance rates of HBeAg, Pre-S1 with HBV-DNA were 40.0% (42/104), 82.0% (85/104), respectively.

CONCLUSIONIt showed that Pre-S1 was more sensitive than HBeAg in diagnosing viral replication in patients with chronic hepatitis B.

Adult ; DNA, Viral ; blood ; Female ; Hepatitis B Surface Antigens ; blood ; Hepatitis B e Antigens ; blood ; Hepatitis B virus ; physiology ; Hepatitis B, Chronic ; virology ; Humans ; Male ; Middle Aged ; Protein Precursors ; blood ; Virus Replication

OBJECTIVETo investigate the efficacy and treatment outcome of different induction regimens, and different post-remission therapies for adult acute promyelocytic leukemia (APL).

METHODSThe outcome of 73 patients with newly diagnosed APL were retrospectively analyzed. According to the induction regimens, the patients were divided into three groups: chemotherapy-only (14 cases group I), all-trans retinoic acid (ATRA) or combined with chemotherapy (33 cases group II), and ATRA combined with arsenic trioxide (As(2)O(3)) (26 cases group III). The complete remission (CR) rate and the time to CR (TTC) were analyzed. After CR, the patients were divided into 2 groups for post-remission therapies: one with sequential treatment of chemotherapy/ATRA/As(2)O(3) and the other with alternative treatment of chemotherapy/ATRA. The overall survival (OS), disease free survival (DFS) and relapse rate were compared between these two groups. Patients induced CR with both ATRA and As(2)O(3), and then sequentially treated with chemotherapy/ATRA/As(2)O(3) (group A), and those induced CR with ATRA or As(2)O(3) alone and then with non-chemotherapy/ATRA/As(2)O(3) sequentially (group B) were also analyzed and compared for CR, OS and DFS.

RESULTS(1) For induction treatment, the CR rate in ATRA and As(2)O(3) combination group was 100%, in ATRA combined with chemotherapy group was 78.8%, and in chemotherapy-only group was 57.1% (P = 0.030). The median TTC in ATRA with As(2)O(3) combination group was 26 (13 - 40) days being the shortest among the three groups. (2) For the post-remission treatment, 3-year OS rates in group I and group II were (95.7 ± 4.3)% and (68.6 ± 11.2)% (P < 0.05), and 3-year DFS rates were (79.0 ± 9.5)%, and (32.9 ± 15.5)%, respectively (P < 0.01). The relapse rate was 14.8% in group I, and 50.0% in group II (P = 0.011). (3) The CR, 3-year OS and DFS rates in group A were all 100%. The CR rate in ATRA or As(2)O(3) alone induced group was 72.9%, and 3-year OS was (72.3 ± 9.1)% (P < 0.05).

CONCLUSIONSFor adult APL induction with ATRA and As(2)O(3) combination can obtain a higher CR rate, and shorter TTC. The post-remission treatment with sequential chemotherapy, ATRA and As(2)O(3) results in a lower relapse rate, and significantly improves OS and DFS. The ATRA and As(2)O(3) combination induction with the sequential post-remission therapy is the best strategy for APL treatment.

Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Disease-Free Survival ; Humans ; Leukemia, Promyelocytic, Acute ; drug therapy ; Remission Induction ; Tretinoin ; therapeutic use