Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018133 (graft-versus-host disease)
 18,032 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Murine graft versus host (GVH) disease takes two forms depending upon the parental/F1 strain combination employed. Acute lethal GVH disease is characterized by anemia, lymphopenia, hypogammaglobulinemia, profound anti-F1 cytotoxicity, and the loss of cytotoxic potential against third-party alloantigen. In contrast to this, chronic GVH disease is characterized by polyclonal B cell activation, autoantibody production, no anti-F1 cytotoxicity, and retained cytotoxicity against allotargets. We have previously reported that this marked disparity in disease expression results from a radiosensitive host cell which protects the F1 mouse from parental anti-F1 CTX in mice undergoing CGVH disease. Using an in vitro system to induce the host protective cell, we now demonstrate that two distinct Thy-1+ cells emerge which regulate CTX against the host. One cell is of host origin, radiation sensitive, and functionally resembles a veto cell. The second regulatory cell, of parental origin, is radiation resistant and restricted in its ability to suppress anti-F1 CTX. We further demonstrate that the emergence of these cells is modulated by competitive immunoregulatory influences mediated by T contrasuppressor and I-J+ cells.
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PMID:The host response in graft versus host disease. III. The in vitro induction of regulatory cells in chronic murine graft versus host disease. 763 39

A 23-year-old male suffering from severe aplastic anemia (SAA) weighing 60 kg was successfully treated by unrelated allo-CBSCT (cord blood stem cell transplantation). A six-loci HLA-identical umbilical cord blood (UCB) was infused after conditioning with low-dose cyclophosphamide (CTX) and antilymphocyte globulin (ALG). The prophylaxis of GVHD consisted of CsA and MTX. The infused cord blood provided 1.89 x 10(7) nucleated cells per kg, CD34-positive cells: 0.89%. Neutrophils >0.5 x 10(9)/l were reached 10 days after transplant, and platelets greater than 50.0 x 10(9)/l at day 26. RBC and platelet transfusion independence were reached on days 15 and 18. The patient developed grade 1 skin GVHD 10 months after engraftment of the donor cells. Microsatellite DNA fingerprinting indicated a stable and persistent donor-recipient mixed chimerism, whilst the circulating red cells remain of host origin.
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PMID:Umbilical cord blood transplantation from unrelated HLA-matched donor in an adult with severe aplastic anemia. 1110 15

Seventeen patients and their family donors HLA 2 - 3 antigen mismatched of 2 - 3 loci were enrolled in the study of haploidentical transplants from February 1999 to March 2001. Among patients with leukemia, most patients were classified as high risk. Eleven patients with ALL were all in more than second remission but one was in relapse. Patients with AML were one in CR1, one in CR2 while 4 patients with CML were two in CP and two in AP. The male-to-female ratio was 14:3 and the median age was 15 (range from 8 to 35). Conditioning regimens included Ara-C 3.0 g/m(2), 2 times per day x 3 d, on day 7, 6 and 5 pre-transplantation, CTX 45 mg/(kg per d) x 2 d on day 5 and 4 pretransplantation. TBI with 1000 cGy by 2 fractions on day 2 and 1 pretransplantation. The fresh and unmanipulated marrow was infused on day 0. Donors were received G-CSF (Lenograstim) at 3 - 4 microg/(kg per d) x 7 d. The BM cells were collected on eighth day. In GVHD prophylaxis, CSA, MTX, ATG (Antithymocyte globulin, Rabbit Fresenius S) and MMF (mycophenolate mofetic) were used in different periods. The dose of CSA was 1.5 mg/(kg per d) on day 7 to 1 pretransplantation, then 3 mg/(kg per d) from day 1 pretransplantation. MTX was 15 mg/m(2) on day 1 and 10 mg/m(2) on day 3, 6 and 11 posttransplantation. ATG was administered day 4 to 1 pretransplantation at 5 mg/(kg per d) and MMF dose was 1.0 g/d from day 7 posttransplantation. All patients established successful engraftment after initial transplantation. The median days of neutrophil exceeding 0.5 x 10(9)/L and platelet exceeding 20 x 10(9)/L were 18 (range 13 - 23) and 20 (range 16 - 32) days, respectively. Patients were monitored up to day 100 for the sign of aGVHD. The established grades II to IV aGVHD occurred in 5 out of 17 patients (29.4%). Eleven patients were surviving at a median follow-up of 13 months (range 3 - 27 months). Six out of the 17 patients died those 3 of them died of severe aGVHD, 2 of infection and 1 of leukemia relapse. Severe regimen-related toxicities were not experienced in all patients. The median follow-up period was 13 (range 3 - 27) months. Eleven patients were alive in disease-free situation with a Karnofsky performance status of 100%. This could be caused by the low overall incidence of aGVHD as a result of BM primed with G-CSF. The four-agent of immunosuppressive combined prophylaxis against GVHD in different periods may be highly effective.
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PMID:[Successful engraftment of T-cell undepleted haploidentical transplants by donor primed with G-CSF and additional use of ATG and MMF for recipients]. 1251 19

This study was undertaken to establish a murine model for unrelated allogeneic umbilical cord blood transplantation (UCBT). The characteristics and percentage of hematopoietic stem/progenitor cells between near-term fetal and neonatal murine peripheral blood (FNPB) and bone marrow (BM) were evaluated by flow cytometry and semisolid methylcellulose culture. BABL/c (H-2(d)) recipient mice conditioned with high dose CTX were transplanted with FNPB form C57BL/6 (H-2(b)) mice and the survival rate, hematopoietic and immunological reconstruction, graft versus host disease (GVHD) and engraftment level were observed. The results showed that the numbers of day 14 CFU-GM and CFU-GEMM in FNPB (176.40 +/- 78.39)% and (141.40 +/- 56.57)%, respectively were much higher than those in BM (75.20 +/- 26.41)% and (68.80 +/- 23.95)%, respectively. Moreover the percentage of Sca-1(+) CD34(+) cell subsets in FNPB (3.63 +/- 1.13)% was also higher than that in BM (1.41 +/- 0.8 7)%. FNPB transplantation improved survival rate and reconstituted hematopoietic and immune function in recipients. There was no evidence of GVHD. Chimeric analysis showed that the proportion of donor cells in BM of recipients was 27.94% at 21 days after transplantation. It was concluded that FNPB contains more hematopoietic stem and progenitor cells with high expansion ability and weak allogeneic immunity, which was similar to human UCB. The murine model for allogeneic UCBT (C57BL/6-->BALB/c) was established successfully.
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PMID:[Establishment of a murine model for allogeneic umbilical cord blood transplantation]. 1251 23

Allo-CBSCT (cord blood stem cell transplant) has been applied in six adult patients with severe aplastic anemia (SAA). Anti-lymphocyte globulin (ALG) 40 mg kg(-1) d(-1) x 3 days combined with cyclophosphamide (CTX) 20 mg kg(-1) d(-1) x 3 days constituted a lower intensive conditioning regimen. The prophylaxis of GVHD consisted of standard CsA and MTX. Patients are all male having a mean age of 26.5 years (range 22-38), and a median weight of 55.6 kg (range 52-60 kg). Cord blood searches were all conducted at Guangzhou Cord Blood Bank. Three of six patients in our study received one unit of cord blood in a procedure, whereas for another three patients, two units of cord blood (double units) were infused at the same time in a transplant protocol. The nine units of umbilical cord blood (UCB) infused contained 1.6-10.7 x 10(7) nucleated cells/kg body weight of the recipient after thawing. HLA antigens were identical in one unit, 1 antigen mismatched in seven, 2 antigens mismatched in 1. As of February 2003, after a median follow up of 20 months (range 7-50), four patients are alive and disease free. Five patients engrafted with molecular biology analyses showing donor-recipient mixed chimerism post transplant which is stable and persistent. One patient died of severe infection in the third month from transplant and another patient died in the early stage post transplant of serious aspergillus infection without evidence of engraftment.
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PMID:Umbilical cord blood transplant for adult patients with severe aplastic anemia using anti-lymphocyte globulin and cyclophosphamide as conditioning therapy. 1470 55

To explore the effects of ABO incompatibility between recipient and donor on HLA-matched nonmyeloablative allogeneic peripheral blood stem cell transplantation (NAST), a retrospective, cohort study was performed. Among 24 HLA-matched NAST, 15 were major ABO-incompatible and 9 minor. Control group included 24 HLA-matched NAST with ABO-compatible grafts. Nonmyeloablative conditioning regimens consisted of CTX, Ara-C and ATG. The patients were given cyclosporine A and mycophenolate mofetile for prophylaxis of acute GVHD. The ABO-incompatible patients received grafts depleted erythrocytes by hydroxyethyl starch (HES) sedimentation. The results showed that successful and stable engraftment was established in 23 patients. No recipient developed clinically immediate hemolysis during graft infusion, but 2 recipients experienced delayed hemolysis attributable to the ABO incompatibility. The median time of granulocyte counts >0.5 x 10(9)/L and platelet >30 x 10(9)/L was 11 and 14.9 days, respectively. In ABO major incompatible group, the onset of erythropoiesis after NAST was delayed. One out of 10 recipients with blood group "O" in this group developed pure red cell aplasia (PRCA), lasting 5 months. The acute GVHD occurred in 7 out of the 24 patients. The chronic GVHD occurred in 5 of 21 cases. Relapse was observed in 2 patients with acute leukemia. The actuarial probability of disease-free survival at 2 years was 63.3%. In conclusion, ABO-incompatible grafts for NAST have no adverse effect on engraftment, recovery of platelets, incidence of GVHD, relapse rate or survival. ABO-incompatible NAST is fairly safe if there is indication, however, the onset of erythropoiesis is delayed when major ABO mismatched.
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PMID:[ABO-incompatible nonmyeloablative allogeneic peripheral blood stem cell transplantation]. 1574 33

We evaluated the engraftment of donor cells from unrelated cord blood into adult patients with severe aplastic anemia (SAA) and the outcome of allo-CBSCT (cord blood stem cell transplantation). Nine patients were conditioned with decreased dosage of immunosuppressive agents of CTX (60 mg/kg) and ALG (120 mg/kg). The prophylaxis of GVHD consisted of standard CsA and MTX. Patients have a media age of 25.3 yr (range: 15-37), and a median weight of 57.2 kg (range: 52.5-60) at the time of transplantation. Cord blood searches were all conducted at Guangzhou Cord Blood Bank. The engraftment state of the donor cells into recipients was confirmed by microsatellite DNA fingerprinting and fluorescent quantitative PCR analysis. Engrafted evidence has been found in seven patients involved by biomolecular analyses showing donor-recipient mixed chimerism post-transplant which was stable and persistent. After a median follow up of 32.2 months (range: 4-69), seven patients were alive and disease free. This study shows that durable donor-recipient stable mixed chimerism can be achieved by unrelated CBSCT in patients with SAA. Umbilical cord blood could be employed as a source of hematopoietic stem cell for adult transplantation.
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PMID:Sustained and stable hematopoietic donor-recipient mixed chimerism after unrelated cord blood transplantation for adult patients with severe aplastic anemia. 1619 Oct 94

Dendritic cells (DCs) are the most efficient antigen-presenting cells and play a role in immune reconstitution after autologous transplantation. Recent reports suggest that mobilization with granulocyte colony-stimulating factor (G-CSF) containing regimens polarizes DCs into pDC2, which could potentially result with increased Th2 response and decreased graft-versus-host disease (GVHD) in allogeneic transplantation and with decreased cytotoxic Th1 response and graft versus tumor effect, which in autologous transplantation could translate into increased relapse rate. Previously, we have shown that non-Hodgkin's lymphoma (NHL) patients receiving cyclophosphamide (CTX) plus granulocyte- macrophage (GM)-CSF, G-CSF or GM-CSF followed by G-CSF for stem cell collection, mobilize up to five-fold more mature CD80(+) DCs compared to CTX plus G-CSF mobilized patients. Here, we analyzed samples from the same study for the number of pDC1 and pDC2 subsets in blood and apheresis products obtained from these patients. Samples from 29 patients were collected. Patients mobilized with CTX plus G-CSF collected a mean of 1.2 +/- 0.4 x 10(6) pDC1/kg per day and 2.2 +/- 1 x 10(6) pDC2/kg per day, whereas patients mobilized with CTX plus GM-CSF collected a mean of 1.1 +/- 0.5 x 10(6) pDC1 and 1.5 +/- 0.9 x 10(6) pDC2/kg per day. Patients mobilized with CTX plus GM-CSF followed by G-CSF collected 2.5 +/- 1.1 x 10(6) pDC1 and 2 +/- 0.5 x 106 pDC2/kg per day, with significantly higher levels of pDC1 +/- pDC2 cells. No significant difference was observed in pDC1/pDC2 ratio between the three mobilization arms. Patients mobilized with the GM-CSFcontaining regimen had a higher probability for survival compared to patients receiving G-CSF alone (median of 55 months vs. 15 months; p = 0.02). These results support the hypothesis that higher levels of DCs in the graft might be associated with prolonged survival of autotransplanted NHL patients. Further similar studies are merited in a larger population of NHL patients.
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PMID:No polarization of type 1 or type 2 precursor dendritic cells in peripheral blood stem cell collections of non-hodgkin's lymphoma patients mobilized with cyclophosphamide plus G-CSF, GM-CSF, or GM-CSF followed by G-CSF. 1664 73

The aim of this study was to investigate the effect of nonmyeloablative peripheral blood stem cell transplantation in treatment of chronic myeloid leukemia in chronic phase (CML-CP) and accelerated phase (CML-AP). 24 patients with CML including 16 in CML-CP and 8 in CML-AP were treated with nonmyeloablative conditioning regimen for peripheral blood stem cell transplantation (PBHSCT). The conditioning regimen included fludarabine (30 mg/m(2)x6 d), busulphan [4 mg/(kg.d)x2 d] and CTX [350 mg/(m2.d)x2 d] combined with or without Ara-C. The donors were HLA-identical (n=20) and 5/6 antigen-matched (n=4). The dynamic observation of hematopoietic recovery in all patients was carried out. The results indicated that all the patients were successfully engrafted. The mean time for increase of the number of neutrophils to more than 0.5x10(9)/L and platelet more than 20x10(9)/L were 13 days and 11.5 days respectively. Out of 12 patients, 9 patients showed complete donor chimerism and 3 patients showed mixed chimerism at 30 days after transplantation. At 180 days after transplantation, 18 survival patients showed complete donor chimerism. 18 patients remained alive after a median follow-up length of 24 months (4-48 months). 2 cases died of severe acute GVHD and 1 case died of chronic GVHD, 2 cases died of interstitial pneumonia and 1 case died of relapsed. In conclusions, nonmyeloablative peripheral blood stem cell transplantation is an effective therapeutic method for CML patients in chronic phase and accelerated phase.
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PMID:[Nonmyeloablative peripheral blood stem cell transplantation for chronic myeloid leukemia in chronic and accelerated phases]. 1842 68

This study was purposed to explore the efficacy of hematopoietic reconstitution and survival of patients with myelodysplastic syndrome (MDS) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Allo-HSCT without T lymphocyte depletion was used in 6 patients with MDS from November 1999 to June 2007. 4 cases out of them received allo-PBSCT from HLA matched sibling donors with conditioning regimen of cyclophosphamide (CTX) and Bu. Graft versus host disease (GVHD) was prevented by the administration of immunosuppressive drugs of cyclosporine A (CsA) and short-course MTX. 2 patients received haploidentical allogeneic bone marrow transplantation (hi-alloBMT) after preconditioning with cytosine arabinoside (Ara-C), CTX and total body irradiation (TBI) with a linear accelerator. GVHD was prevented by the administration of immunosuppressive drugs including CSA, short-course MTX, MMF, anti-CD25 monoclonal antibody and ATG. The results showed that all of the patients were engrafted successfully. The median time of granulocyte recovery exceeding 0.5 x 10(9)/L and platelets exceeding 20 x 10(9)/L were days 15 and 20.3 respectively, and 100% donor hematological cells were detected by cytogenetic analysis. All patients did not experience serious acute graft-versus-host disease (aGVHD). During 18 - 108 months of following-up, 2 cases died of pulmonary complication and of relapse; the other 4 cases survive in a disease-free situation. In conclusion, allo-HSCT was an effective approach for the treatment of MDS.
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PMID:[Allogeneic hematopoietic stem cell transplantation in 6 patients with myelodysplastic syndrome]. 1954 94


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