Graft vs Host Disease ; prevention & control ; Graft vs Leukemia Effect ; Hematopoietic Stem Cell Transplantation ; methods ; Humans ; Transplantation, Homologous ; methods

Hepatocyte growth factor (HGF) is a pleiotropic cytokine, its roles in the physiology and pathology of immune system, have been investigated thoroughly, great deal of data have been documented on its immunoregulatory activity. In this review, according to advance of study on HGF in recent years, the role of HGF in the immune regulation, such as immunoregulatory effects of HGF on T lymphocytes, B lymphocytes and dendritic cell, modulation of HGF on specific humoral and cellular immune response, control of acute GVHD and acceleration of myeloid and immunologic reconstitution in allogenetic bone marrow transplantation models, promotion of tissue repair and regeneration, and alleviation of immune rejection in allogeneic organ transplantation including the heart, liver and kidney transplantation, prevention of grafts from injury as well as applicably useful of HGF in the therapy of autoimmune disorders were summarized.
Animals ; Graft Rejection ; immunology ; prevention & control ; Graft vs Host Disease ; immunology ; prevention & control ; Graft vs Leukemia Effect ; immunology ; Hepatocyte Growth Factor ; physiology ; Humans ; Immunity, Cellular ; immunology

OBJECTIVETo evaluate the long-term outcome of 60 leukemia patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) prepared with busulphan-cyclophosphamide (BU-CTX(2)) conditioning regimen.

METHODSFrom April 1994 to August 2000, 60 leukemia patients (35 male, 25 female; median age 32 years old), including 20 acute myeloid leukemia (AML, CR(1) n = 19, CR(2) n = 1), 15 acute lymphocytic leukemia (ALL, CR(1) n = 8, CR(2) n = 6, CR(3) n = 1), and 25 chronic myeloid leukemia (CML, CP(1) n = 24, CP(2) n = 1) received allogeneic hematopoietic stem cells from HLA-identical siblings (n = 53), 1-locus mismatched siblings (n = 4), or HLA-identical unrelated donor (n = 3). BU-CTX(2) was used as conditioning regimen. All patients received cyclosporine A and either methotrexate (n = 54) or methylprednisolone (n = 6) for graft-versus-host disease (GVHD) prophylaxis.

RESULTSAll 60 patients got sustained engraftment. Acute GVHD (aGVHD) occurred in 22 patients (36.7%), while the incidence of aGVHD was 48.0% for the CML, 30.0% for the AML and 26.7% for the ALL patients. Thirty-eight patients are still alive in complete remission with a median follow-up of 30 (12 approximately 84) months and 22 died. The main causes of death were aGVHD in 3, CMV-IP in 7, and relapse in 11 patients. The remaining one died of pulmonary infection. Among 11 patients who died of relapse, 8 were ALL relapsed in the early posttransplant stage. All 4 long-term survivors of ALL developed chronic GVHD. The probability of DFS at 3 year for CML, AML and ALL patients was 80.0%, 70.0% and 26.7%, respectively.

CONCLUSIONBU-CTX(2) is an effective conditioning regimen for patients with AML and CML, resulting in a low relapse and high long-term survival rate. However, it is not effective enough for patients with ALL, because of a higher incidence of relapse.

Busulfan ; Graft vs Host Disease ; prevention & control ; Hematopoietic Stem Cell Transplantation ; Humans ; Transplantation Conditioning ; Transplantation, Homologous

Extracorporeal photochemotherapy, also called extracorporeal photopheresis, or ECP for short, is now an effective method to treat and prevent patients from graft-versus-host disease (GVHD). It is generally accepted that the mechanism of ECP is to induce immune tolerance. Further researches show that ECP acts on several stages of GVHD by means of many complex mechanisms. Firstly, ECP induces apoptosis of T lymphocytes, inhibiting T cells from differentiating and proliferating, and promoting regulatory T cells. Besides, it also adjusts the number and proportion of helper T cells. Secondly, ECP affects antigen presenting cells. It induces apoptosis and inhibits maturation of antigen presenting cells. At the same time it affects the ability to process and present antigens of antigen presenting cells. Thirdly, ECP adjusts the cytokine secretion, in order to inhibit inflammatory response. This review discusses why ECP can treat and prevent patients from GVHD via the three aspects mentioned above.
Apoptosis ; Graft vs Host Disease ; prevention & control ; therapy ; Humans ; Immune Tolerance ; Photopheresis ; methods

OBJECTIVETo study if methoxy polyethylene glycol modification (mPEG) affects grafts versus leukemia (GVL) when donor bone marrow mononuclear cells are camouflaged with mPEG in murine bone marrow transplantation (BMT).

METHODSSixty (BALB/c(H-2d) x 615(H-2k))F(1) mice were divided into four groups randomly. Mice in group A were only irradiated with 8.0 Gy (60)Cogamma, and mice in the other groups were inoculated intraperitoneally with 1 x 10(6) L615 cells 3 days before irradiation with the same dose (60)Cogamma. BALB/c(H-2d) mice were sacrificed and bone marrow cells and spleen cells were collected. The bone marrow cells (1 x 10(7)) were mixed with the spleen cells (1 x 10(7)), which were camouflaged or not camouflaged with mPEG, were transplanted into irradiated leukemia mice in C and D groups. GVL effects were assessed by L615 cells proportion in peripheral blood, histopathological changes and survival time.

RESULTSSevere GVHD was observed in group C (without mPEG modification), and the mice rapidly died, the mean survival time was 6.9 days. The mice in irradiated group (group B) with leukemia cell died of leukemia. The average survival time of group D (with mPEG modification) was 24.2 days, which was longer than that of the other groups (P < 0.05), and the survival rate of group D (27%) was significantly higher than that of the others (P < 0.05), 11 mice (11/15) died of leukemia and the others were still alive.

CONCLUSIONThe camouflage with mPEG modification is capable of preserving GVL effect and preventing GVHD in mice BMT.

Animals ; Bone Marrow Transplantation ; Female ; Graft vs Host Disease ; prevention & control ; Graft vs Leukemia Effect ; Male ; Mice ; Mice, Inbred BALB C ; Polyethylene Glycols ; pharmacology

Child, Preschool ; Graft vs Host Disease ; prevention & control ; Hematopoietic Stem Cell Transplantation ; Humans ; Male ; Niemann-Pick Diseases ; therapy ; Transplantation, Homologous

Blood transfusion leads to leucocyte-mediated adverse reactions related to the transfusion of leucocytes in allogeneic blood and blood products. The leucocytes are also capable of transmitting virus infection. Leucocyte depletion of homologous blood products can effectively reduce the immunosuppressive effect as well as minimize the likelihood of transmitting virus. Blood component transfusion is generally "buffy-coat-poor", which removes about two thirds of the leucocytes present in whole blood. Using special filters, blood component can be filtrated 99.9% of the leucocytes. Leucocyte-depletion using filter should significantly lessen the leucocyte-mediated transfusion adverse reactions, such as febrile non-hemolytic transfusion reactions and graft versus host disease. At the same time, leucocyte filtration can decrease the risk of transmitting virus. Otherwise, leucocyte-depletion plays very important role in the treatment of cardiac surgical patients to attenuate leukocyte-mediated inflammation and organ reperfusion injury, the treatment of ulcerative colitis, and the treatment intractable diseases such as autoimmune and neurologic diseases.
Blood Component Removal ; Blood Transfusion ; Cardiopulmonary Bypass ; Filtration ; Graft vs Host Disease ; prevention & control ; HLA Antigens ; immunology ; Humans ; Leukocytes

OBJECTIVETo explore the prophylaxis effect of pretreatment of allograft with methoxypolyethylene glycol-succinimidyl-propionic acid ester (mPEG-SPA) and anti-OX40L monoclonal antibody (McAb) on acute graft-versus-host disease (aGVHD) after allogeneic bone marrow transplantation (allo-BMT) in mice.

METHODSResponder splenocytes from C57BL/6 donor mice (H-2(b)) were co-cultured with stimulator splenocytes from BALB/c recipient mice (H-2(d)) for 7 days in the presence or absence of anti-OX40L McAb followed by mPEG-SPA chemical modification. Donor bone marrow cells plus the mixed culture of T-cells were then transplanted into lethally irradiated BALB/c mice. The BALB/c recipient mice were divided into four groups: group A (allo-BMT control group), group B(mPEG-SPA modification group), group C (anti-OX40L McAb pretreated group) and group D (mPEG-SPA and anti-OX40L McAb dual-treated group). Survival time and survival rate of the recipients were observed after allo-BMT. GVHD was assessed by clinical signs and histological changes of skin, liver and small intestines. Enzyme-linked immunosorbent assay (ELISA) was used to detect cytokines (IL-4, IL-10 and INF-gamma) production. Flow cytometry (FCM) analysis was used to detect allogeneic chimerism.

RESULTS(1) The mice in group A developed typical clinical signs of aGVHD and all mice died within 17 days after BMT with an average survival time (AST) of (12.1 +/- 5.5) days. The signs of aGVHD were less evident in mice of groups B, C and D, and their AST (36.2 +/- 24.9, 32.0 +/- 24.8 and 44.3 +/- 23.2 days, respectively) were all longer than that in group A (P < 0.05). AST of group D being the longest (P < 0.05). The survival rates at day 60 post-BMT in groups B, C and D were 50%, 41.7% and 66.7%, respectively. (2) Serum IFN-gamma level was increased after BMT in group A, and peaked in day 10 to day 15 post-BMT, while the level was decreased in groups B, C and D, reached the nadir on the day 10 post-BMT, with the lowest in group D (P < 0.01). After BMT, IL-4 and IL-10 levels were slightly decreased in group A, their levels were elevated in groups B and C (P < 0.05) and even more significantly increased in group D (P < 0.01). IL-4 and IL-10 levels peaked between day 10 and 15 post-BMT. (3) The average proportion of H-2(b) positive cells in recipient mice was 95% - 100% on day 60 post-BMT, with complete donor-type implantation.

CONCLUSIONCombination of mPEG-SPA and anti-OX40L McAb can block T-cell activated antigens and co-stimulatory pathway, regulate the T cells differentiation and induce the immune shift of Th0 cells toward Th2 cells. The immune tolerance induced by this method can significantly relieve aGVHD after allo-BMT.

Animals ; Bone Marrow Transplantation ; Graft vs Host Disease ; prevention & control ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Transplantation, Homologous

OBJECTIVETo explore the therapeutic feasibility of allogeneic hematopoietic stem cell transplantation (allo-HSCT) from partially HLA-mismatched related donors for hematologic diseases.

METHODSThirty patients with hematologic diseases received allo-HSCT from 1 - 3 loci mismatched related donors conditioning regimen consisting of ATG (thymoglobulin, total dose of 10 mg/kg, intravenously on - 4 d to - 1 d), and only 5 (18%) of 28 recipients from HLA-identical sibling donors were treated with regimen containing ATG. Donors were given G-CSF prior to hematopoietic stem cell harvest and CsA, short-term MTX and mycophenolate mofetil (MMF) were used for GVHD prophylaxis in both group.

RESULTSAll patients were successfully engrafted. There was no significant difference in the incidence of grade II to IV acute graft-versus-host disease (aGVHD) and grade III to IV aGVHD between the mismatched and matched groups (34% vs 32%, and 13% vs 11%, respectively). 3-year overall survival (OS) and disease-free survival (DFS) in mismatched and matched groups were 57% vs 77% (P = 0.14) and 57% vs 69% (P = 0.28), respectively. Multivariate analysis showed that advanced disease pre-transplant (P = 0.006) and CMV infection (P = 0.04) were risk factors for OS. OS for patients with stable disease in mismatched and matched groups were 87% vs 81% (P = 0.65) respectively, and for those with advanced disease were 21% vs 71% (P = 0.02).

CONCLUSIONSIt is feasible to perform allo-HSCT from 1 -3 loci HLA-mismatched related donors for patients with stable disease who lack HLA-identical sibling donors. Nevertheless, for patients with advanced disease optimized conditioning regimen and intensive supporting therapy should be administered to obtain better clinical outcomes.

Graft vs Host Disease ; prevention & control ; HLA Antigens ; Hematopoietic Stem Cell Transplantation ; methods ; Humans ; Siblings ; Tissue Donors ; Transplantation Conditioning

OBJECTIVETo analyse the engraftment, transplant-related complications and survival after unrelated cord blood transplantation (UCBT) in patients with hematologic malignancies.

METHODSTwenty eight consecutive adult patients with hematological malignancies were treated with UCBT and 20 of them were advanced-stage diseases. Double or multiple UCB grafts were used for 18 patients, while single UCB graft for 10 patients. Myeloablative conditioning regimens were given to 26 cases and nonmyeloablative regimens to 2 cases. All patients were given a combination of cyclosporine (CsA) and mycophenolate mofetil (MMF) for graft-versus-host disease (GVHD) prophylaxis.

RESULTSMedian time to neutrophil engraftment (≥ 0.5 × 10(9)/L) in 26 patients was 18 (14 - 37) days and platelet engraftment (≥ 20 × 10(9)/L) in 22 patients was 30 (25 - 49) days. Chimerism was weekly assessed by PCR analysis of short tandem repeat (STR) sequences in whole blood or bone marrow and 22 cases were confirmed of fully donor chimeric from 7 to 21 days after transplantation. Eighteen cases developed acute GVHD, greater than grade II in 1, and 6 of 22 patients who survived more than 100 days developed limited chronic GVHD. Eighteen cases were alive in hematologic remission at a median follow-up of 9.5 (2.5 - 72.0) months. The probability of event-free survival at 3 years was 56.7%. Two cases relapsed and 8 of 10 cases died of transplant related complications.

CONCLUSIONSUCBT could be safely and effectively used for adult patients with hematologic malignancies. Use of double UCB units is a strategy extending the feasibility of UCBT.

Adult ; Fetal Blood ; Graft vs Host Disease ; prevention & control ; Hematologic Neoplasms ; therapy ; Hematopoietic Stem Cell Transplantation ; Humans ; Transplantation Conditioning