OBJECTIVETo evaluate the effectiveness of chemotherapy (CT) and autologous hematopoietic stem cell transplantation (ASCT) as post-remission treatment for adult acute lymphoblastic leukemia (AL) patients.

METHODSSeventy-four ALL patients achieved first complete remission (CR(1)) with induction therapy, and then received early-stage sequential intensive consolidation chemotherapy. After that, 40 patients received chemotherapy (CT group) and 34 received ASCT (ASCT group) as post-remission treatment. The median follow-up was 20.5 months. The rates of leukemia free survival (LFS), overall survival (OS) and relapse were compared between the two groups.

RESULTS(1) The median LFS and OS were 14.0 and 20.6 months respectively for CT group and both were more than 53.5 months for ASCT groups. (2) Relapse occurred in 28 patients (70%) in CT group in a median time of 8.5 months (range, 1-72 months) and 20 of them (71.43%) relapsed within 1 year. Eleven patients (32.35%) relapsed in ASCT group, in a median time of 6 (2-30) months after transplantation. (3) There was no statistic difference in LFS, OS and relapse rate at 1 year between CT and ASCT groups (P > 0.05), whereas both LFS and OS at 3 and 5 years for ASCT group were significantly better than those for CT group (P < 0.05). Relapse rate for ASCT group was lower than that for CT group. (4) Higher LFS and OS and lower relapse rate were found for those who received monoclonal antibody purged autografts followed by immunotherapy and (or) maintenance therapy after ASCT (P < 0.05).

CONCLUSIONSEarly sequential intensive consolidation chemotherapy followed by auto-HSCT could significantly reduce late relapse rate for adult ALL patients, and those received ex vivo purged autografts and immunotherapy and (or) maintenance therapy after ASCT have lower late relapse rate and superior survival.

Adolescent ; Adult ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Female ; Follow-Up Studies ; Hematopoietic Stem Cell Transplantation ; Humans ; Male ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy ; surgery ; Retrospective Studies ; Transplantation, Autologous ; Treatment Outcome

OBJECTIVETo evaluate the treatment outcome of HLA-identical sibling allogeneic hematopoietic stem cell transplantation (allo-HSCT) for chronic myelogenous leukemia (CML) patients in first chronic phase (CP(1)).

METHODSFifty-one patients with CML-CP(1) received HLA-identical sibling allo-HSCT with conditioning regimens of TBI plus Cy or Bu plus Cy. Allogeneic peripheral blood stem cell transplantation (PBSCT) and bone marrow transplantation (BMT) were performed for 28 and 23 patients, respectively. The median follow-up duration was 1434 (60 - 4062) days.

RESULTSFifty (98.0%) patients were successfully engrafted. Transplant-related mortality occurred in 8 (15.7%) patients. Acute graft-versus-host disease (aGVHD) occurred in 35 (68.6%) patients and 11 (21.6%) patients were grade II-IV, while chronic GVHD (cGVHD) did in 17 (37.8%) patients. Five (7.4%) patients relapsed. The 5-year probability of disease-free survival (DFS) was (79.2 +/- 6.4)%. There was no significant difference in 5-year DFS, death rate and treatment related syndromes between the two conditioning regimens (P > 0.05), and in 5-year DFS, relapse rate and death rate between two transplant choices (P > 0.05). However, the rate of relapse was lower in Bu/Cy group (P < 0.01) and the rate of cGVHD was higher in allo-PBSCT group (P < 0.05).

CONCLUSIONSAllo-HSCT can cure a significant proportion of patients with CML-CP(1). There was no significant difference in DFS between the two different conditioning regimens and between the different transplant choices. Donor lymphocyte infusion is a therapeutic alternative for CML patients relapsed after transplantation.

Adult ; Female ; HLA Antigens ; Hematopoietic Stem Cell Transplantation ; methods ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; surgery ; Male ; Middle Aged ; Recurrence ; Siblings ; Transplantation Conditioning ; Transplantation, Homologous ; Treatment Outcome

OBJECTIVECervical vertebra semidislocation was one of major pathological aspects of cervical spondylosis, and it was also the target of manipulation to treat cervical spondylosis. The aim of this study was to combine the technology of three dimensional finite element analysis to investigate the method to construct the cervical vertebra semidislocation model.

METHODSA cervical spondylosis patient (male, 28 years old,176 cm tall, weight 69 kg) was randomly chosen, who was diagnosed cervical vertebra semidislocation by dynamic and static palpation and X-ray,and CT scanned from C1 to C7 by 0.75 mm slice thickness. Based on the CT data, the software was used to construct the three dimensional finite element model of cervical vertebra semidislocation (C4-C6).

RESULTSThe model showed the three dimensional changes of vertebra semidislocation clearly. C5 had a three-dimensional abnormal position, which was downward translation for 0.9 mm and clockwise rotation for 4.5 degrees around X-axis. So C5 was diagnosed as hypokinesis-type semidislocation.

CONCLUSIONThe method to construct the three dimensional finite element model of cervical vertebra semidislocation is reliable, which provide a base study to analyse the mechanism of manipulation to treat vertebra semidislocation.

Adult ; Cervical Vertebrae ; Finite Element Analysis ; Humans ; Image Processing, Computer-Assisted ; Internet ; Joint Dislocations ; complications ; diagnostic imaging ; Male ; Models, Anatomic ; Spondylosis ; complications ; Tomography, X-Ray Computed

OBJECTIVETo evaluate the outcome of allogeneic hematopoietic stem cell transplantation (allo-HSCT) from HLA-matched sibling donor (MSD allo-HSCT) for severe aplastic anemia (SAA).

METHODSThe clinical data of 41 SAA patients received MSD allo-HSCT from May. 2003 to Aug. 2011 were analyzed retrospectively. 24 patients were male, 17 were female. Median age was 23 (5 - 43) years old. 28 patients had SAA-I, 9 had SAA-II, and 4 had post-hepatitis aplastic anemia. 17 patients received allogeneic bone marrow (BM) transplantation (allo-BMT), and 24 received allogeneic peripheral blood stem cell (PBSC) transplantation (allo-PBSCT). The conditioning regimens: 20 patients received cyclophosphamide (CY) + anti-thymocyte globulin (ATG) + fludarabine (Flu), 21 received CY + ATG + Flu+ cytarabine (Ara-C) ± busulfan (Bu)/melphalan (Mel). Prophylaxis for graft-versus-host disease (GVHD): 25 patients received cyclosporine (CSA) plus short-term methotrexate (MTX), 16 received tacrolimus (FK506) plus short-term MTX. The median number of infused CD34(+) cells were 3.48 (2.39 - 4.80)×10(6)/kg in allo-BMT and 2.95 (1.27 - 5.98)×10(6)/kg in allo-PBSCT, respectively.

RESULTSHematopoietic reconstitution was observed in all 41 patients (100%). The median time of neutrophils (ANC) reached to 0.5×10(9)/L and platelets (PLT) reached to 20×10(9)/L were 14 (10 - 23) days and 19 (8 - 38) days, respectively. 12 patients developed acute GVHD (aGVHD), out of which 11 developed grade I-II aGVHD, and one developed grade IV. 2 patients occurred chronic GVHD (cGVHD), out of which one with local cGVHD and the other with extensive. 4 patients occurred graft rejection (GR), all of them recovered haemopoiesis and survived after donor PBSC infusion. 5 patients (12.2%) died, out of which one died of extensive cGVHD, and 4 died of invasive fungal infections (IFI). Median follow-up time was 23 (3 - 79) months. 36 patients survived. 5-year estimated overall survival (OS), disease free survival (DFS), and transplant-related mortality (TRM) was (81.1 ± 9.0)%, (68.4 ± 11.0)%, and (18.9 ± 9.0)%, respectively. Univariate analysis showed that lover OS had significant correlation with receiving PBSCT, occurrence of aGVHD, the number of infused CD34(+) cells no more than 2.5×10(6)/kg, the number of red blood cell (RBC) transfusion before transplant more than 30 U and occurrence of IFI after transplantation (P = 0.034, 0.001, 0.006, 0.000, 0.001, respectively). Occurrence of aGVHD had significant correlation with the disparity between donor and recipient ABO blood groups, the number of PLT transfusion more than 100 U, and the number of RBC transfusion more than 30 U before transplantation, the number of infused CD34(+) cells no more than 2.5× 10(6)/kg (P = 0.019, 0.038, 0.005, 0.005, respectively). The occurrence of GR had significant correlation with the number of PLT transfusion more than 100 U before transplantation (P = 0.038).

CONCLUSIONMSD allo-HSCT is an effective therapy for patients with SAA. Lower number of blood transfusion before transplantation, use of BMT, more number of infused CD34(+) cells can effectively prevent and treat aGVHD and IFI after transplantation, which may improve the efficacy of MSD allo-HSCT for SAA.

Adolescent ; Adult ; Anemia, Aplastic ; therapy ; Child ; Child, Preschool ; Female ; HLA Antigens ; Hematopoietic Stem Cell Transplantation ; Humans ; Male ; Retrospective Studies ; Siblings ; Tissue Donors ; Treatment Outcome ; Young Adult

OBJECTIVETo explore the efficacy of autologous or allogeneic stem cell transplantation in adult patients with acute lymphoblastic leukemia (ALL) and investigate its relevant prognostic factors.

METHODSA total of 96 adult patients with ALL who had admitted to our hospital from November 1986 to June 2004 were followed up till February 28, 2005. They were divided into autologous stem cell transplantation (Auto-SCT) group (n = 56) and allogeneic stem cell transplantation (Allo-SCT) group (n = 40). Auto-SCT group was further divided to treated subgroup, in which patients received graft-purified transplantation and (or) maintenance immunotherapy or chemotherapy after transplantation (n = 26), and non-treated subgroup (n = 30). Clinical characteristics of these groups were retrospectively analyzed. Survival date were analyzed by the Kaplan-Meier method and the prognostic factors were analyzed with the COX regression model.

RESULTSThe 1-, 3-, and 5-year leukemia-free-survival (LFS) were not significantly different between the auto-SCT group and the allo-SCT group. The 3-and 5-year LFS of auto-SCT treated subgroup, auto-SCT non-treated subgroup and allo-SCT group were [(73.0 +/- 8.7)%, (69.2 +/- 9.0)%], [(42.2 +/- 10.1)%, (35.1 +/- 10.0)%], and [(50.9 +/- 8.2)%, (50.9 +/- 8.2)%], respectively, which showed statistical significance (P < 0.05).

CONCLUSIONSThe long-term LFS is similar after auto-SCT and after allo-SCT. Purified graft and maintain immunotherapy or chemotherapy post-transplantation may decrease the relapse rate after auto-SCT and improve survival.

Adolescent ; Adult ; Female ; Follow-Up Studies ; Hematopoietic Stem Cell Transplantation ; methods ; Humans ; Male ; Middle Aged ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; surgery ; Retrospective Studies ; Transplantation, Autologous ; Transplantation, Homologous

BACKGROUNDThis study was aim to explore the characteristics of phenotypic resistance of resistant strains of HIV type-1 (HIV-1) subtype B and to compare the concordance between the phenotypic resistance and genotypic resistance.

METHODSThe genotypic resistance assay for the HIV-1 clinical isolates was performed. One isolate without resistance mutation was chosen as a drug-sensitive reference strain and seven subtype B isolates with resistance mutations were phenotypically tested. Fifty percent inhibitory concentrations (IC50) between resistant and sensitive viruses were compared. The resistance extent was determined by the folds of the increased IC50. The concordance between the phenotypic resistance and genotypic resistance was also analyzed.

RESULTSIC50 of resistant isolates were 0.0006 - 0.1300 micromol/L for zidovudine (AZT), 0.0016 - 0.0390 micromol/L for lamivudine (3TC), 0.0104 - 0.4234 micromol/L for nevirapine (NVP), and 0.0163 - 0.1142 micromol/L for indinavir (IDV), respectively. Genotypic and phenotypic resistance assays indicated that the resistant strains were intermediately and highly resistant to nucleotide analog reverse transcriptase inhibitors and non-nucleotide analog reverse transcriptase inhibitors. The phenotypic assay was consistent with the genotypic assay. For measuring the potential resistance, the genotypic assay was more sensitive than the phenotypic. In evaluating the resistance to protease inhibitors, these two assays were discrepant.

CONCLUSIONSBoth the phenotypic and genotypic assays indicate that the resistant viruses exist in HIV-infected patients in China who have received treatment. Phenotypic and genotypic assays have high concordance, and the genotypic assay could replace the phenotypic assay to predict the HIV-1 resistance.

Anti-Retroviral Agents ; pharmacology ; China ; Drug Resistance, Viral ; genetics ; HIV-1 ; drug effects ; genetics ; Humans ; Mutation ; Phenotype

This study was aimed to explore the effect of autologous hematopoietic stem cell transplantation (auto-HSCT) and allogeneic hematopoietic stem cell transplantation (allo-HSCT) in adult patients with acute lymphoblastic leukemia and to analyze the related prognostic factors. Clinical data of 114 ALL patients receiving HSCT, including 70 auto-HSCT and 44 allo-HSCT, were retrospectively analyzed. Disease-free-survival (DFS), relapse-rate (RR) and transplantation-related-mortality (TRM) of patients receiving different HSCT were compared. The results showed that the eight-year OS and DFS in a total of 114 adult ALL patients were (40.89+/-5.27)% and (39.50+/-5.22)% respectively. The three-year DFS of ALL patients who received HSCT in phase CR1 and no CR1 were (47.63+/-5.63)% and (17.65+/-9.25)% (p=0.0034). The two-year DFS of patients who received allo-HSCT and had I/II aGVHD was (62.75+/-12.30)%, and the six-month DFS of patients who had III/IV aGVHD was 0, and the two-year DFS of patients without aGVHD was (29.35+/-9.70)% (p=0.005). The three-year DFS of patients with and without maintenance chemotherapy after transplantation were (55.12+/-7.89)% and (33.33+/-11.11)% respectively, there was significant difference between them (p=0.0499). The five-year DFS between patients received auto-HSCT and allo-HSCT in phase CR1 was not significantly different. The RR of patients received allo-HSCT was lower than that of patients received auto-HSCT, but there was no significant difference between them. The TRM of patients received allo-HSCT was higher than of patients received auto-HSCT (p=0.0313). Expression of myeloid antigen and higher LDH level in diagnosis were poor- prognostic factors. It is concluded that auto-HSCT and allo-HSCT completed in phase CR1 may improve prognosis of the patient with ALL as a method for consolidation chemotherapy, but no significant difference exists between the two HSCTs. Patients receiving allo-HSCT and having I/II aGVHD may achieve higher DFS. The maintaining chemotherapy for patients after auto-HSCT may improve therapeutic effect.
Adolescent ; Adult ; Disease-Free Survival ; Female ; Follow-Up Studies ; Hematopoietic Stem Cell Transplantation ; methods ; Humans ; Male ; Middle Aged ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; surgery ; Prognosis ; Retrospective Studies ; Transplantation Conditioning ; Transplantation, Homologous ; Young Adult

OBJECTIVETo investigate the prognosis and hepatitis B serologic marker changes in patients with HBV infection or with HBV infected donors after allogenic hematopoietic stem cell transplantation (allo-HSCT).

METHODSThe clinical outcomes of 79 patients receiving allo-HSCT, including 55 with HBV infection and 24 from HBV infected donors were analyzed retrospectively.

RESULTS(1) HBV infection did not interfere with the clinical outcome of allo-HSCT. (2) In 20 HBsAg(+) patients, 13(65.0%) developed HBV reactivation between 0.5 and 10 months after transplantation, 9(45.0%) developed HBV-related hepatitis. (3) For the 35 HBsAg(-) and HBcAb/HBeAb positive patients, 4 (11.4%) occurred HBV seroconversion, 1 of the 4 complicated with severe chronic graft-versus-host disease (cGVHD). (4) There was a significant difference in HBV reactivation rate between the HBsAg(+) and HBsAg-groups (P < 0.01). The incidence of hepatitis occurred within 100 days after HSCT was high in HBsAg(+) patients (P < 0.05). (5) Clearance of HBsAg was observed in 2 HBsAg(+) patients, both of whom received graft from HBsAb positive donors.

CONCLUSIONSDonors or recipients infected with HBV is not considered an absolute contraindication for HSCT, but HBsAg positivity is a high risk factor for HBV reactivation and prophylactic lamivudine treatment may be helpful. For patients with HBcAb/HBeAb positivity, seroconversion can be observed, especially after immunosuppressant withdrawal. Adoptive immunity is effective in clearing HBV in these patients.

Hematopoietic Stem Cell Transplantation ; Hepatitis B ; epidemiology ; Hepatitis B Antibodies ; Hepatitis B Surface Antigens ; Hepatitis B virus ; Humans

OBJECTIVETo 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).

METHODSForty-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.

RESULTSMyeloid 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].

CONCLUSIONThe 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.

Acute Disease ; Adolescent ; Adult ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Bone Marrow Purging ; Child ; Combined Modality Therapy ; Female ; Hematopoietic Stem Cell Transplantation ; methods ; Humans ; Immunotherapy ; methods ; Kaplan-Meier Estimate ; Leukemia ; therapy ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; prevention & control ; Remission Induction ; Retrospective Studies ; Transplantation Conditioning ; methods ; Transplantation, Autologous ; Transplantation, Homologous ; Treatment Outcome

Objective: To investigate the effects of donor-specific HLA antibodies(DSA) for graft failure in un-manipulated haploidentical hematopoietic stem cell transplantation(haplo-HSCT) and the feasible treatment for DSA. Methods: HLA antibodies were examined using the Luminex-based single Ag assay for 92 patients who were going on haplo-SCT and the correlations of graft failure and DSA among the patients who had finished SCT were analyzed. Results: Of the total 92 patients who were going on haplo-HSCT, sixteen (17.4%) patients were HLA Ab-positive, including six (6.5%) patients with antibodies corresponding to donor HLA Ags (DSA-positive). Among the patients who had finished the haplo-HSCT with conventional myeloablative conditioning regimen, the engraftment rate was significantly higher in DSA (-) patients than that in DSA (+) patients [92.3% (24/26) vs 25.0%(1/4), χ²=8.433, P=0.004] and DSA was the only factor relevant with graft failure in multiple-factor analysis [OR=12.0(95% CI 1.39-103.5), P=0.024]. Strategies to decrease antibody levels were taken for 4 patients, two were their first transplantations, and the other two patients were their second haplo-HSCT. Three of the four patients were HLA-I-DSA positive and had gained donor engraftment by means of donor platelet transfusions to decreased the level of DSA, the fourth patient with both HLA-I and HLA-II DSA also gained engraftment with the treatments of TBI, rituximab and donor platelet transfusion. Conclusion: DSA is one of the key factors of graft failure in haplo-HSCT. Donors should be selected on the basis of an evaluation of HLA antibodies before transplantation. If haplo-HSCT from donors with DSA must be performed, then recipients should be treated for DSA to improve the chances of successful engraftment.
Antibodies ; Graft vs Host Disease ; HLA Antigens ; Hematopoietic Stem Cell Transplantation ; Humans ; Tissue Donors ; Transplantation Conditioning