Hematopoietic Stem Cell Transplantation ; Humans ; Societies, Medical ; United States

0.05);in treating gradeⅢto IV aGVHD,the effectiveness of FK506 with MP was significantly better than that of CsA with MP(P

Background: Acute graft?versus?host disease (aGVHD) is a common and severe complication of allogeneic hematopoietic stem cell transplantation (allo?HSCT). Some studies have found that the presence of certain specific human leukocyte antigen (HLA) loci could affect the occurrence of aGVHD. Meanwhile, the impact of HLA haplotypes on aGVHD has been rarely studied. This study aimed to investigate the effects of HLA loci and haplotypes on intestinal aGVHD. Methods: Totally, 345 consecutive patients undergoing first HLA?matched sibling peripheral blood stem cell transplantation (PBSCT) from February 2004 to June 2013 at Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, were enrolled in this study. HLA loci and haplotypes of recipients with frequency over 5% were searched and their effects on intestinal aGVHD were investigated. Other important factors including donor age, recipient age, donor?recipient sex combinations, and conditioning regimens were also evaluated using logistic regression. Pure upper gastrointestinal tract aGVHD without diarrhea was excluded because the histological proof was unavailable. The follow?up end?point was 6 months after HSCT. Results:The cumulative incidence of intestinal aGVHD was 19.4%,with 18.0%of the patients classified as classic aGVHD and 1.4% aspersistent, recurrent,or late aGVHD.Multivariate analysis showed that HLA?A31 locus(odds ratio[OR]2.893,95% confidence interval[CI][1.054,7.935], P = 0.039), HLAB40?DR15 (OR 3.133, 95% CI [1.250, 7.857], P = 0.015), and HLAB46?DR9 haplotypes (OR 2.580, 95% CI [1.070, 6.220], P = 0.035), female donor for male recipient (OR 2.434, 95% CI [1.319, 4.493], P = 0.004) were risk factors for intestinal aGVHD. Conclusion: The presence of certain HLA loci and haplotypes may influence the occurrence of intestinal aGVHD in PBSCT with HLA?identical sibling donors.

OBJECTIVETo investigate the risk factors of intestinal acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).

METHODSThe clinical data of 534 cases of 533 patients undergoing allo-HSCT during Jan 2004 and Sep 2012 were retrospectively analyzed. The effects of donor-recipient HLA mismatching, recipient age, donor age, donor-recipient sex combination, donor-recipient relationship, HSC source, conditioning regimen with or without total body irradiation (TBI) and HLA loci on intestinal aGVHD with different severity were analyzed by Logistic regression.

RESULTSIntestinal aGVHD occurred in 123(23.0%) cases, with 86(16.1%) cases of stage 1 intestinal aGVHD(16.1%) and 37(6.9%) cases of stage 2 to 4 intestinal aGVHD. Multivariate analysis showed that donor-recipient HLA mismatching (OR=2.519, P=0.002), increasing donor age (OR=1.034, P=0.003), female donor for male recipient (OR=1.855, P=0.007) were risk factors for intestinal aGVHD, HLA-B38 (OR=0.256, P=0.032) was its protective factor. Donor-recipient HLA mismatching (OR=2.799, P=0.011), increasing donor age (OR=1.045, P=0.012), HLA-A1 (OR=4.157, P=0.002), A30 (OR=3.143, P=0.005) were risk factors for stage 2 to 4 intestinal aGVHD.

CONCLUSIONOccurrence of intestinal aGVHD and its severity are associated with donor-recipient HLA mismatching, donor age, donor-recipient sex relationships and some HLA loci.

Adolescent ; Adult ; Child ; Child, Preschool ; Female ; Graft vs Host Disease ; epidemiology ; Hematopoietic Stem Cell Transplantation ; adverse effects ; Humans ; Intestinal Diseases ; epidemiology ; Male ; Middle Aged ; Retrospective Studies ; Risk Factors ; Tissue Donors ; Transplantation, Homologous ; adverse effects ; Young Adult

OBJECTIVEThis 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.

METHODSA 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.

RESULTSOutcomes 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.

CONCLUSIONASCT was a choice for adult ALL patients when suitable donors were unavailable.

Adolescent ; Adult ; Female ; Follow-Up Studies ; Hematopoietic Stem Cell Transplantation ; Humans ; Male ; Middle Aged ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; therapy ; Prognosis ; Retrospective Studies ; Risk Factors ; Transplantation, Autologous ; Young Adult

To explore the difference of biological characteristics between two subpopulations of adult bone marrow mesenchymal stem cells (MSC), this study was designed to observe the morphological feature and immunophenotype of the adult MSC in the ex vivo culture, the mononuclear cells isolated from normal adult bone marrow were cultured in DMEM with 10% fetal bovine serum. Cell morphology, immunophenotype and cell cycle of two different subgroups were investigated. Cells from 80% confluence were passed through a 10 microm filter, then the fillered cells were cultured in the semisolid methylcellulose medium. The results showed that (1) two different subpopulations were observed in the ex vivo culture. The fibro-like cell was called mature MSC (mMSC) and the smaller round cell was defined rapidly as MSC self-renewing cells (RS cells); (2) the average proportion of cells in G(0)/G(1) of RS cells was approximately 99%, but that of mMSCs was 90%; (3) both of the two populations were negative on the lineage-committed antigen (such as CD34, CD45, CD3, CD19, CD33, HLA-DR, CD38), while positive on the expression of CD90, CD105, C166, CD29, CD44, CD49e, CD54, CD13. However, the expression of these antigens on RS cells was weaker than that on mMSC, but CD117 and KDR were higher expressed when compared with the mMSC; (4) after 4 to 5 week semisolid culture, no hematopoietic progenitor cell colonies were observed. It is concluded that adult MSCs are heterogeneous in that distinct morphological populations exist. The RS cells appear to be the more primitive with greater potential for self-renewal and multilineage differentiation.
Adult ; Antigens, CD ; analysis ; Bone Marrow Cells ; cytology ; immunology ; Cell Cycle ; Cell Differentiation ; immunology ; Cell Lineage ; immunology ; Cell Size ; Cells, Cultured ; Humans ; Immunophenotyping ; Leukocytes, Mononuclear ; cytology ; immunology ; Mesenchymal Stromal Cells ; cytology ; immunology

OBJECTIVETo evaluate the method for expanding Valpha24 natural killer T (NKT) cells with alpha-galactosylceramide (alpha-GalCer) ex vivo.

METHODSMononuclear cells (MNCs) isolated from adult peripheral blood or umbilical cord blood (UCB) were divided into three groups. In Group A1 (n = 5), CD34+ progenitorderived dendritic cells were differentiated in a cytokine-supplemented culture system from cord blood and acted as antigen presenting cells (APC) to induce the expansion of cord blood Valpha24 NKT cells in presence of alpha-GalCer; in Group A2 (n = 5), adult peripheral monocyte-derived dendritic cells (Mo-DC) were used as APC to induce the expansion of adult peripheral NKT cells in presence of alpha-GalCer; whereas in Group B (n = 16), alpha-GalCer was added into adult peripheral MNCs culture system without additional DCs. Cytokine-produce were measured by ELISA, and NKT cells' proliferation ability, cytotoxicity, and suppressive effect on mixed lymphocyte reaction (MLR) were examined by MTT assays.

RESULTSValpha24 NKT cells in Group A1, A2, and B were expanded up to 128 (95-207), 250.5 (179.6-790.6), and 326 (101-2 136) -fold by day 12, respectively. Adult NKT cells expanded in Group B were markedly better than those in Group A1 (P = 0.038). When stimulating by PMA, the NKT cells had a 3-day stimulate index of 1.80 +/- 0.41; and the secretion ratio of IL-4 to IFN-gamma of UCB or adult peripheral blood NKT cells were 0.30 +/- 0.13 and 0.28 +/- 0.18; and the ex vivo antitumor effect of expanded NKT cells were found in cell line HL60, KG1a, and Raji except for K562; and the suppressive effect of expanded NKT cells or the culture supernatant on MLR were confirmed.

CONCLUSIONSAlpha-GalCer can facilitate the rapid shorttime expansion of Valpha24 NKT cells in presence of IL-2 and IL-15. These expanded NKT cells, kill tumor cell lines, and inhibit can massively excret IL-4 and IFN-gamma allogeneic T-cell response.

Antigens, CD34 ; analysis ; immunology ; Cytotoxicity Tests, Immunologic ; Dendritic Cells ; immunology ; Galactosylceramides ; immunology ; HL-60 Cells ; pathology ; Humans ; K562 Cells ; pathology ; Killer Cells, Natural ; cytology ; immunology ; metabolism ; Lymphocyte Activation ; drug effects ; Receptors, Antigen, T-Cell, alpha-beta ; immunology ; T-Lymphocyte Subsets ; cytology ; immunology ; metabolism

The study was purposed to investigate the differentiation ability of mesenchymal stem cells (MSCs) into myocardial cells in vitro. Rat bone marrow-derived MSCs were labeled and co-cultured with neonatal rat cardiomyocytes (CM) for 5 - 7 days. The expression of cell surface antigens was detected by flow cytometry, and the expression of muscle-specific marker myosin and troponin T in labeled cells was detected by immunofluorescence. The results showed that in vitro cultured MSCs expressed CD90, CD44, CD105, CD54, not expressed CD34, CD45, CD31. After co-cultured with neonatal rat CM, labeled MSCs differentiated into cardiomyocyte-like cells expressing myosin and troponin T. It is concluded that MSCs can differentiate into cardiomyocyte-like cells when co-cultured with neonatal myocardial cells in vitro. In co-culture of two kind of cells in ratio of four to one showed obvious efficacy differentiating MSCs into CMs.
Animals ; Bone Marrow Cells ; cytology ; Cell Differentiation ; Cells, Cultured ; Coculture Techniques ; Mesenchymal Stromal Cells ; cytology ; Myocytes, Cardiac ; cytology ; Rats ; Rats, Wistar

OBJECTIVETo explore the incidence, pathogenesis, risk factors, prophylaxis and treatment of acute kidney injury (AKI) after myeloablative allogeneic hematopoietic stem cell transplantation (allo-HSCT).

METHODSClinical data of 120 patients received myeloablative allo-HSCT were retrospectively analyzed.

RESULTSSerum creatinine level in the patients showed significantly higher than baseline value at 28-60 days after transplantation (P<0.05). 73 patients (60.8%) developed AKI at a median of 33 days after allo-HSCT, including grade 2 in 32 patients (26.7%). Patients with grade 1 AKI showed significant higher serum cyclosporine A (CsA) levels (P<0.05). Hepatic veno-occlusive disease( HVOD), acute graft-versus-host disease (aGVHD) and total bilirubin > 40 micromol/L were high risk factors of occurring AKI (P<0.05). 19 patients died within 100 days after allo-HSCT, grade 2 AKI was a high risk factor of mortality (P< 0.05). 180-day survival rate was significantly lower in patients with grade 2 AKI after allo-HSCT (P<0.05).

CONCLUSIONAKI is one of the major complications after myeloablative allo-HSCT. Prophylaxis and treatment of AKI might reduce mortality in early stage of transplantation.

Acute Kidney Injury ; etiology ; prevention & control ; Adolescent ; Adult ; Female ; Hematopoietic Stem Cell Transplantation ; Humans ; Male ; Middle Aged ; Postoperative Complications ; prevention & control ; Retrospective Studies ; Risk Factors ; Transplantation Conditioning ; Transplantation, Homologous ; Young Adult