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51.
Levels of soluble FasL and FasL gene expression during the development of graft-versus-host disease in DLT-treated patients 总被引:2,自引:0,他引:2
Das H Imoto S Murayama T Kajimoto K Sugimoto T Isobe T Nakagawa T Nishimura R Koizumi T 《British journal of haematology》1999,104(4):795-800
Three patients with different clinical symptoms of graft-versus-host disease (GVHD) who had received donor lymphocyte transfusion (DLT) for the treatment of relapsed leukaemia after an allogeneic bone marrow transplantation (BMT) from HLA-matched sibling donors were analysed for the presence of soluble FasL (sFasL) in the sera and for the expression of the Fas ligand (FasL) gene in the peripheral blood mononuclear cells (PBMNC). Two patients who demonstrated liver damage with increased levels of serum bilirubin showed significantly increased levels of serum sFasL. The increase in the sFasL level was observed prior to the increase in the bilirubin during the clinical courses of both patients. The high dose of methyl predonisolone administered to one of these patients greatly reduced the levels of sFasL in the serum. The bilirubin levels were also reduced thereafter. The third patient (without liver damage) did not show any increase in the serum sFasL level. The expression of the FasL gene in the PBMNC of these three patients was examined. All three patients showed increased levels of the FasL gene expression during their clinical courses. However, only one patient showed a parallel alteration of FasL gene expression with sFasL in the serum. These cases provide evidence that the Fas/FasL system is closely associated with human GVHD, especially in the development of liver GVHD. 相似文献
52.
Long-term follow-up of patients after related- and unrelated-donor bone marrow transplantation for chronic myelogenous leukemia 总被引:1,自引:0,他引:1
Reiter E Greinix HT Keil F Brugger S Rabitsch W Schulenburg A Mannhalter C Schwarzinger I Worel N Volc-Platzer B Fischer G Dieckmann K Hinterberger W Schneider B Haas OA Geissler K Kalhs P 《Annals of hematology》1999,78(11):507-513
Between January 1983 and December 1997, 88 patients (36 female, 52 male, median age 37 years, range 19–57) with chronic myelogenous
leukemia (CML) underwent allogeneic bone marrow transplantation (BMT) at the University Hospital of Vienna. Sixty patients
were in chronic phase, 18 in accelerated phase, and ten in blast crisis. Marrow donors were HLA-identical siblings for 64
patients (BM 58, PBSC 6), 2-antigen-mismatched related donors (RD) for two, HLA-identical unrelated donors (URD) for 17, and
1-antigen-mismatched URD for five. The median time from diagnosis to BMT was 22 months (range 2–91), and 63 patients had received
prior interferon (IFN)-alpha therapy, 46 (73%) for more than 6 months. Conditioning therapy consisted of cyclophosphamide
(CY) and total body irradiation (TBI) in 71 patients and CY and busulfan (BU) in 16. One patient received etoposide and TBI.
For graft-versus-host disease (GVHD) prophylaxis methotrexate (MTX) was given to 12 patients, MTX and cyclosporin A (CSA)
to 67, CSA alone to four, and CSA and methylprednisolone to five. Durable engraftment was documented in 80 of 82 patients
(98%). As of December 31, 1997, 52 patients (59%) were alive, 38 (58%) after sibling transplantation with a median observation
time of 73 months and 14 (64%) after URD transplantation with a median observation time of 12 months. Probability of overall
survival is 59%, for patients undergoing transplantation in chronic phase and 44% for patients undergoing transplantation
in advanced stage CML. Probability of disease-free survival (DFS) after sibling and URD BMT is 55% and 59%, respectively.
Ten patients (12%) experienced relapse of CML. Transplant-related mortality was 32% both after RD and after URD transplantation.
Acute GVHD occurred in 53 of 80 evaluable patients (66%), consisting of grade III or IV in 14 patients (18%). Chronic GVHD
developed in 40 of 63 eligible patients (63%), including extensive disease in 26 patients (41%). Thus, sibling and URD BMT
offer high cure rates with acceptable toxicity to patients with CML.
Received: October 27, 1998 / Accepted: May 25, 1999 相似文献
53.
Carella A. M. Frassoni F. van Lint M. T. Gualandi F. Occhini D. Carlier P. Pollicardo N. Pungolino E. Fagioli F. Santini G. Congiu A. Nati S. Raffo M. R. Podesta M. Corvo R. Vitale V. Gallamini A. Pogliani E. M. Lanzi E. Bacigalupo A. Marmont A. M. 《Annals of hematology》1992,64(3):128-131
Summary In the attempt to evaluate the role of Autologous and Allogeneic Bone Marrow Transplantation, we have retrospectively analyzed 159 patients with Acute Myeloid Leukemia in first complete remission treated in our Unit, most of whom were referred from other Institutions. High-dose therapy was uniform and consisted of cyclophosphamide 60 mg/kg/d on two consecutive days and TBI in a single dose (10 Gy) for ABMT patients and in fractionated doses (3.3 Gy × 3 days) for BMT patients. Eight years actuarial survival was similar in two groups (52% for BMT and 49% for ABMT). The actuarial risk of relapse for BMT and ABMT was 29% and 43%, respectively. Considering that none of ABMT patients was purged with in vitro technique, this review seems to confirm the importance of in vivo purging with postremission intensification, immediately before the harvesting. Of course, more patients and a longer follow-up are needed to drow final conclusions. 相似文献
54.
Ting SS Tangye SG Wood J Ffrench RA Ziegler JB 《British journal of haematology》2001,112(4):1004-1011
X-linked severe combined immunodeficiency (XSCID) is a lethal disease resulting in death in infancy. In many instances, haploidentical bone marrow transplantation (BMT) offers reconstitution of T-cell immunity alone, with residual hypogammaglobulinaemia. The exact nature of B-cell dysfunction in these patients is unclear, although differentiation arrest of the B cells is a potential explanation. To ascertain the differentiation status of peripheral blood B lymphocytes from XSCID patients after BMT, the surface expression of CD19, CD10, CD34, CD5, serum immunoglogulin (sIg)M, sIgD, sIgG and CD27 on these B cells was investigated using three-colour flow cytometry. CD27 is a marker of memory B cells. Populations of CD19+IgM-D- B cells, CD19+IgM-only, CD19+IgG+CD27+ and CD19+IgM+ CD27+ B cells were found to be diminished in the XSCID patients after BMT with persistent hypogammaglobulinaemia, compared with both post-BMT patients with B-cell function and age-matched normal controls. This indicated the lack of CD19+IgM-D- B cells, which represent Ig isotype-switched B cells, as well as CD19+IgM-only and CD19+IgG+CD27+ or CD19+IgM+CD27+ memory B-cell populations. Interaction between CD27 and its ligand CD70 has been shown to induce IgG and IgM production by CD27+ B cells. Therefore, the lack of CD27/70 interaction is a probable explanation for the hypogammaglobulinaemia in these patients after BMT. 相似文献
55.
Veno-occlusive disease of the liver (VOD) was originally described in patients who drank infusions made with plants containing pyrrolizidine alkaloids [1]. This disease was characterized, histologically, by a progressive and concentric non-thrombotic narrowing of the lumina of small intrahepatic veins. Later, VOD was related to other pathogens such as alcohol, contraceptives, toxic oil, liver radiation and several antineoplastic drugs [2–3]. The first case of veno-occlusive disease following bone marrow transplantation (BMT) was reported in 1979 [4]. Since then, BMT has proved to be the main cause of VOD which is one of the leading causes of morbidity and mortality after transplant [5–7]. Clinical manifestations of VOD are very characteristic (jaundice, painful hepatomegaly and fluid retention) but indistinguishable from those produced by other regime-related morphological changes on zone 3 of the liver acinus. For this reason, the term “syndrome of veno-occlusive disease of the liver” has been adopted to designate the clinical manifestations of conditioning regimen toxicity on this zone [8]. This review focuses on the present knowledge of VOD syndrome after BMT. 相似文献
56.
《Expert opinion on biological therapy》2013,13(5):857-867
The lysosomal storage disorders (LSD) are monogenic inborn errors of metabolism with heterogeneous pathophysiology and clinical manifestations. In the last decades, these disorders have been models for the development of molecular and cellular therapies for inherited metabolic diseases. Studies in preclinical in vitro systems and animal models have allowed the successful development of bone marrow transplantation (BMT) and enzyme replacement therapy (ERT) as therapeutic options for several LSDs. However, BMT is limited by poor donor availability and high morbidity and mortality, and ERT is not a life-long cure. Moreover, the neuropathology present in many LSDs responded poorly, if at all, to these treatments. Therefore, gene therapy is an attractive therapeutic alternative. Gene therapy strategies for LSDs have employed ex vivo gene transduction of cellular targets with subsequent transplantation of the enzymatically corrected cells, or direct in vivo delivery of the viral vectors. Oncoretroviral vectors and more recently adeno associated vectors (AAV) and lentiviral vectors have been extensively tested, with some success. This review summarises the main gene therapy strategies which have been employed or are under development for both non-neurological and neuronopathic LSDs. Some of the in vitro and in vivo preclinical studies presented herein have provided the rationale for a gene therapy clinical trial for Gaucher disease Type I. 相似文献
57.
Anna Meo Annalisa Ruggeri Maria A. La Rosa Laura Zanghì Nancy Morabito Lorena Duca 《Hemoglobin》2013,37(1):131-137
In this retrospective study, we report the results of the association of a combined phlebotomy program and chelation in hereditary sideroblastic anemia (HSA) to reduce iron overload after bone marrow transplantation (BMT). A male HSA patient, not responding to pyridoxine treatment, was submitted to successful allogeneic BMT. As there was a persistence of a tissue iron overload, a regular phlebotomy program was started followed by chelation. A significant decrease of iron burden was obtained using a combined treatment with deferoxamine (DFO) and deferiprone (L1) in addition to the phlebotomy program. A 10-year follow-up shows a marked decrease in the concentration of serum ferritin, non-transferrin-bound iron (NTBI), liver iron and normal hemoglobin (Hb), which allows the patient to reach and maintain a good quality of life. 相似文献
58.
59.
The gastrointestinal and nutritional impact of congenital immunodeficiencies is varied and non-specific (serious refractory diarrhea, exsudative enteropathy, enterocolitis and chronic infections by Cryptosporidium, Giardia, rotavirus, Candida, etc.). Ulcerative colitis and autoimmune diseases are less frequent. Available therapeutic tools (immunoglobulins, implantable venous accesses and BMT) are reasonably effective. AIDS in children can be either rapidly or slowly progressive, and is usually due to maternofetal transmission. Gastrointestinal lesions are non-specific (candidiasis, chronic malabsorptive diarrhea, hepatitis, cryptosporidiosis, CMV, giardiasis, herpes) and cause overall malnutrition. Early nutritional support is indicated, but the modalities and results remain to be determined. 相似文献
60.
Laure Garin Dominique Rigal Gerard Souillet Janine Bernaud Yves Mrieux Noel Philippe 《European journal of haematology》1996,56(3):119-123
Abstract: Four children with acute lymphoblastic leukaemia had autologous bone marrow (BM) or peripheral stem cell (PSC) transplantation with low dose of cyclosporine (CsA, 1 mg/kg/d i.v. during the first 28 d) to induce an autologous GVHD (auto-GVHD). Two children did not have clinical auto-GVHD and they relapsed 3 and 4 months after treatment. The 2 other children had clinical signs of auto-GVHD (grade I and grade II): they both are in complete remission but after a first normal haematological recovery they had a prolonged period of aplasia until month 9 for 1 patient and still persistent at month 7 in the other case. We studied lymphocyte subsets reconstitution after transplantation in these patients. All patients had an important decrease in the CD4/CD8 ratio related both to a strong decrease in the CD4+ cells and a strong increase in the CD8+ cells. Most of the CD8+ cells were of the CD8bright+CD28- phenotype. These CD8bright+CD28- T-cells represented from 33% to 68% of the total lymphocytes. We discuss the role of these cells after autologous transplantation with CsA, and wonder if these cells could mediate cytotoxicity. In conclusion, among 4 children who received autologous BM or PBC transplantation with low dose of CsA, we observed a complete remission after an auto-GVHD and a prolonged period of aplasia in 2 patients and a relapse of leukaemia in 2 other patients. All these 4 patients had an increase in the CD8bright+CD28- T lymphocytes. 相似文献