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 identify the side effect of all-trans retinoic acid (ATRA), and improve early therapeutic response in patients with acute promyelocytic leukemia (APL).

METHODThe first case of Sweet's syndrome (SS) developed in a APL patient treated with ATRA was reported in mainland of China, and reviewed correlative literature.

RESULTSOnly 14 cases of SS associated with ATRA therapy in APL have been reported in the literature, including the present case. The median age was 49.5 years (9 -84) and 10 were women and 4 men. Of them, SS was restricted to the skin in 10 case, the other 4 muscle, fascia, kidney, and lung were involved. SS appeared after a median of 18 days of ATRA therapy (6 - 34 days). The median WBC count was 7.05 (0.80 - 23.00) x 10(9)/L. Four patients continued with the ATRA therapy without interruption, 13 patients treated with steroids and 12 responded. One patient improved without any treatment. Two cases of SS developed retinoic acid syndromes after ATRA therapy.

CONCLUSIONSweet's syndrome is a rare adverse effect of ATRA, and has similar features with inflammatory or infective dermatosis. The corticosteroids treatment could improve the systemic and cutaneous symptoms. When ATRA therapy was restarted after SS subsided, no recurrence of rashes was observed.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Female ; Humans ; Leukemia, Promyelocytic, Acute ; drug therapy ; Male ; Middle Aged ; Sweet Syndrome ; chemically induced ; Tretinoin ; adverse effects ; therapeutic use

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

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

In order to analyze the incidence and high-risk factors of invasive fungal infections among recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT), 180 cases of allo-HSCT were enrolled in this study. The incidence and risk factors of IFI were analyzed by method of Kaplan-Meier and Cox regression model. The results showed that an incidence of IFI in 35 cases (19.5%) were detected, with 1 case proven and 34 cases probably diagnosed, which was composed of 18 cases (51.4%) of aspergillosis and 17 cases (48.6%) of candidosis. There was significant difference in one-year overall survival rate between patients with (34.3%) or without (53.8%) IFI. In univariate analysis, risk factors of IFI included: pretransplant fungal infection or colonization, unrelated donor (peripheral blood or bone marrow stem cell) transplantation, acute GVHD, extensive chronic GVHD and the use of methylprednisolone. In multi-variate analysis, the following risk factors of IFI were found:unrelated donor for allogeneic peripheral blood or bone marrow stem cell transplantation, acute GVHD and pretransplant fungal infection or colonization acute GVHD (RR: 2.399, 1.589, and 0.836). It is concluded that IFI is a frequent complication and one of the leading causes of mortality among recipients of allo-HSCT. As for patients with higher risk of IFI, early interventions should be taken.
Adolescent ; Adult ; Aspergillosis ; epidemiology ; etiology ; Candidiasis ; epidemiology ; etiology ; Child ; Child, Preschool ; China ; epidemiology ; Female ; Graft vs Host Disease ; complications ; Hematologic Neoplasms ; therapy ; Hematopoietic Stem Cell Transplantation ; adverse effects ; Humans ; Incidence ; Male ; Middle Aged ; Risk Factors ; Young Adult

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