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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.
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Humanos , Anticorpos , Doença Enxerto-Hospedeiro , Antígenos HLA , Transplante de Células-Tronco Hematopoéticas , Doadores de Tecidos , Condicionamento Pré-TransplanteRESUMO
<p><b>BACKGROUND</b>The postremission therapies for adult patients generally contain consolidation chemotherapy, allogeneic hematopoietic stem cell transplantation and autologous hematopoietic stem cell transplantation (auto-HSCT). Because of the various results from different centers, the optimal therapy for adult acute lymphoblastic leukemia (ALL) patients is still uncertain. This study aimed to better understand predictive factors and role of auto-HSCT in the postremission therapy for adult ALL patients.</p><p><b>METHODS</b>The outcomes of 135 adult patients with ALL, who received the first auto-HSCT in Hematopoietic Stem Cell Transplantation Center of Blood Diseases Hospital, Chinese Academy of Medical Sciences from January 1, 1994 to February 28, 2014, were retrospectively analyzed. Survival curves were estimated using the Kaplan-Meier method and simultaneous effects of multiple covariates were estimated with the Cox model.</p><p><b>RESULTS</b>Overall survival (OS) and disease-free survival (DFS) at 5 years for the whole cohort were 59.1 ± 4.5% and 59.0 ± 4.4%, respectively. The cumulative nonrelapse mortality and relapse rate at 5 years were 4.5 ± 0.03% and 36.6 ± 0.19%. For both OS and DFS, acute T-cell lymphoblastic leukemia, high lactate dehydrogenase (LDH) at diagnosis, blast cell proportion ≥5% on the 15 th day of induction therapy, and extramedullary infiltration before HSCT were the poor prognosis factors. In addition, age ≥35 years predicted poor DFS. Only T-ALL and high LDH were the independent undesirable factors associated with OS and DFS in Cox regression model. For 44 patients who had results of pretransplantation minimal residual disease (MRD), positive MRD (MRD ≥0.01%) indicated poor OS (P = 0.044) and DFS (P = 0.008). Furthermore, for the standard risk group, the patients with negative MRD (MRD <0.01%) had better results (OS at 18 months was 90.0 ± 9.5%, while for the patients with positive MRD OS was 50.0 ± 35.4%, P = 0.003; DFS at 18 months was 90.0 ± 9.5%, while for the positive MRD group DFS was 0%, P < 0.001).</p><p><b>CONCLUSIONS</b>This study confirmed that auto-HSCT combined with posttransplantation maintenance chemotherapy could be an option for adult ALL patients and pretransplantation MRD may play a significant role in the direction of therapy for adult ALL patients.</p>
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Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , China , Intervalo Livre de Doença , Transplante de Células-Tronco Hematopoéticas , Estimativa de Kaplan-Meier , Neoplasia Residual , Mortalidade , Terapêutica , Leucemia-Linfoma Linfoblástico de Células Precursoras , Mortalidade , Terapêutica , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Transplante HomólogoRESUMO
<p><b>OBJECTIVE</b>To investigate mesenchymal stem cells (MSCs) immunosuppressive activity in the presence of interferon-gamma (IFN-γ) to reveal synergistic immunomodulatory effects of IFN-γ and MSCs.</p><p><b>METHODS</b>① MSCs were cultured in the presence or absence of IFN-γ(100 ng/ml), the supernatants were collected for measurements of PGE2、HGF and TGF-β1 by ELISA kits. ② MSCs were cultured in the presence or absence of IFN-γ (100 ng/ml)for 48 h. The cDNA was analysed for the expression of human indoleamine 2, 3-dioxygenase(IDO)mRNA by semiquantitative RT-PCR. ③ Mononuclear cells (MNCs) were extracted from peripheral blood of healthy donors. The T cell proliferation was tested in the co-culture system added with MSCs, recombinant human IFN-γ (100 ng/ml) and anti-IFN-γ mAb (5 μg/ml) by BrdU ELISA kit.</p><p><b>RESULTS</b>①The immunosuppressive cytokines PGE2、HGF and TGF-β1 were detectable within 24-48 h in the supernatants. Their expressions were significantly up-regulated in the presence of IFN-γ. Concentrations of these cytokines were as of (1715.5±628.6) pg/ml vs (1344.5±709.4) pg/ml (P=0.001);(4031.8±1496.8) pg/ml vs (2452.4±1375.3) pg/ml(P=0.011);(1753.5±413.8) pg/ml vs (1026.6±450.5) pg/ml(P<0.001),respectively. ②The expression of IDO mRNA was undetectable when MSCs were cultured alone. In contrast, The IDO mRNA expression was remarkably enhanced in the presence of IFN-γ. ③Bone marrow-derived MSCs remarkably suppressed allogeneic T cell proliferation in vitro. Addition of exogenous IFN-γ had no significant effect on the inhibitory capacity of MSCs, the inhibitory ratios of T cell proliferation were (40.4±10.9)% vs(36.7±7.4)% (P=0.272). By contrast, the inhibitory ratio of T cell proliferation was significantly decreased in the presence of anti-IFN-γ mAb[(40.4±10.9)% vs (23.9±7.6)%,P=0.002].</p><p><b>CONCLUSION</b>①Human MSCs constitutively expressed immunosuppressive concentrations of PGE2, HGF and TGF-β1, and their expressions were significantly up-regulated by IFN-γ. ②IFN-γ-induced expression of IDO on MSCs involved in tryptophan catabolism. ③MSCs notably suppressed allogeneic T cell proliferation in vitro. IFN-γ promoted the immunosuppressive capacity of human MSCs, indicating the synergistic immunomodulatory effect of IFN-γ and MSCs.</p>
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Humanos , Células da Medula Óssea , Alergia e Imunologia , Proliferação de Células , Células Cultivadas , Técnicas de Cocultura , Citocinas , Alergia e Imunologia , Tolerância Imunológica , Interferon gama , Farmacologia , Células-Tronco Mesenquimais , Alergia e Imunologia , Linfócitos T , Biologia CelularRESUMO
Objective To investigate the treatment effects of operation and nerve growth factor on adult multisegmental cervical spinal cord injury without fracture dislocation.Methods Sixty-eight patients with multiple segmental cervical spinal cord injury without fracture dislocation,admitted to our hospital from January 2004 to May 2011,were chosen in our study; according to the will of the patients,18 patients received conservative treatment (group A),25 patients were treated by posterior single open-door laminoplasty (group B) and the other 25 patients were treated with posterior single open-door laminoplasty combined with nerve growth factor (group C,once daily for 4 weeks); their clinical data were retrospectively analyzed.Follow up was performed at 3,6 and 12 months after the treatments;Japanese Orthopaedic Association (JOA) scale was employed to evaluate the clinical efficacy.Results Three,6,12 months after the treatments,the JOA scale scores were statistically different among the three groups (P<0.05); the scores in group B and C were significantly higher than those in group A at all time points (P<0.05); 6 and 12 months after the treatmemts,the JOA scale scores in group C were significantly higher than those in group B (P<0.05).Conclusion To patients with multisegmental cervical spinal cord injury without fracture dislocation,conservative treatment can make the spinal cord function partially restored,but the effect is limited; exogenous nerve growth factor has good repairing effect on spinal cord injury.
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<p><b>OBJECTIVE</b>This study was aimed to observe the efficacy of autologous stem cell transplantation (ASCT) for adult patients with acute lymphoblastic leukemia (ALL), and investigate related prognostic factors.</p><p><b>METHODS</b>A total of 86 adult ALL patients underwent ASCT in Institute of Hematology and Blood Disease Hospital from November 2001 to January 2012 were followed up. Clinical characteristics and outcomes of all patients were retrospectively analyzed. Survival and univariate prognosis were analyzed by the Kaplan-Meier method and multivariate analysis by COX regression model.</p><p><b>RESULTS</b>Outcomes were assessed in 81 cases, including 47 standard-risk and 34 high-risk patients. 1-, 3-, 5-, and 10-year leukemia-free survival (LFS) of standard-risk patients were (82.3±5.7)%, (76.9±6.5)%, (74.1±6.8)%, (67.4±8.9)% respectively,and relapse rates (RR) were as of (13.6±5.2)%, (21.6±6.4)%, (24.5±6.8)%, (31.3±9.0)% respectively. 1-, 3-, 5-, and 10-year LFS of high-risk patients were (55.8±8.9)%, (39.8±9.3)%, (39.8±9.3)%, (39.8±9.3)% respectively, and relapse rates (RR) were (38.8±9.2)%, (56.4±10.0)%, (56.4±10.0)%, (56.4±10.0)% respectively. T-ALL, white blood cell count(WBC) more than 30×109/L when first visited, increased LDH, positive fusion gene of TCR and bone marrow transplantation were the adverse prognostic factors. Multivariate analysis showed bone marrow transplantation was an independent adverse prognostic factor.</p><p><b>CONCLUSION</b>ASCT was a choice for adult ALL patients when suitable donors were unavailable.</p>