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

Immunocompetent donor-derived T lymphocytes play a crucial role in the elimination of residual leukemic cells post allogeneic bone marrow transplantation. Because this graft versus leukemia (GVL) effects is absent after autologous stem cell transplantation (ASCT), a high rate of relapse ensues. We introduced cell-mediated immunotherapy at the stage of minimal residual disease in lymphoma patients to help effect a GVL-like reaction by adoptive transfer of immunocompetent human leukocyte antigen-matched donor peripheral blood lymphocytes (PBL). Thirteen consecutive patients with high-risk lymphoma were treated with allogeneic cell therapy (AlloCT) after having undergone ASCT. In the absence of graft-versus-host disease, cell therapy-induced graft-versus-lymphoma reaction was amplified by human recombinant interleukin 2 (rIL-2) during 3 days to activate donor PBL in vivo, followed by infusion of in vitro rIL-2 activated donor lymphocytes combined with 3-day rIL-2 therapy. Nine of the patients underwent the treatment protocol well. In the four other patients, in whom the AlloCT resulted in marrow aplasia due to elimination of host hematopoietic cells, treatment with donor marrow cell infusion without further conditioning was performed. Adoptive cell therapy in the form of AlloCT may turn out to be an effective therapeutic modality for the treatment of resistant residual disease in lymphoma patients.
 ...
PMID:Allogeneic cell-mediated and cytokine-activated immunotherapy for malignant lymphoma at the stage of minimal residual disease after autologous stem cell transplantation. 980 40

Patients with advanced acute leukemia (AL) have a poor prognosis with death due to disease or complications of therapy. High-dose chemoradiotherapy followed by allogeneic marrow transplantation (BMT) has been used to overcome resistance of the leukemic clone resulting in long-term survival of up to 20%. Due to lack of suitable related donors BMT from an HLA-compatible unrelated donor (MUD) has been increasingly applied in these patients during the last years. Between January 1991 and August 1997 twenty five patients with advanced acute myeloid (n=19) or lymphoid (n=6) leukemia, 11 males and 14 females, age 22 to 41 (median 32) years received MUD (n=22) or 1-antigen mismatched unrelated donor (n=3) grafts. In four patients an autologous BMT had been performed previously. For conditioning all patients were given total body irradiation containing regimens. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine (CSA) and methotrexate (n=24) or CSA and methylprednisone (n=1). In 23 patients (92%) class II region compatibility was assessed by DRB1, DRB3, DRB5, and DQB1 allele typing by hybridization of amplified DNA with ligation based typing. In 2 patients HLA-DR typing was performed by two colour fluorescence cytotoxicity test and mixed lymphocyte cultures. As of November 1997 10/25 patients (40%) are surviving leukemia-free after a median observation time of 17 (range, 3 to 38) months. Transplant-related mortality was an overall of 36% and 28% in patients receiving their first BMT. In 6/25 patients (24%) relapse occurred 2 to 26 months after BMT. Incidence of acute GVHD grade I to IV was 85%. The probability of relapse projected at 3 years was 35%. High-dose chemoradiotherapy followed by MUD marrow infusion has a curative potential for patients with advanced acute leukemia and offers the chance of long-term leukemia-free survival. Currently, up to 80% of patients with acute myelogenous leukemia (AML) and acute lymphoid leukemia (ALL) under the age of 50 years achieve complete hematological remission (CR) with conventional dose chemotherapy. However, in patients who are refractory to induction chemotherapy or relapse prognosis is still poor. There, high-dose chemoradiotherapy followed by allogeneic marrow infusion has been used to overcome resistance of the refractory leukemic clone and has resulted in long-term survival. For selected patients lacking a human leukocyte antigen (HLA) compatible family donor marrow transplantation (BMT) with a suitable unrelated marrow donor (MUD) has become a feasible and effective treatment. Here, we report our experience in patients with advanced acute leukemia given marrow grafts from unrelated donors.
 ...
PMID:Matched unrelated donor marrow transplantation in patients with advanced acute leukemia. 991 36

Alloreactive T lymphocytes that respond directly to foreign major histocompatibility complex (MHC) molecules and bound peptide are known to be central mediators of graft-versus-host disease (GVHD) and allograft rejection. We have recently identified a peptide from the human protein, cytochrome P450 (isotypes IIC9, 10, or 18), that is recognized in association with human leukocyte antigen (HLA) B*3501 by alloreactive cytotoxic T lymphocytes (CTLs). These CTLs with this specificity were isolated from several unrelated individuals and were found to express a common T-cell receptor (TCR). Synthetic analogs of the cytochrome P450 peptide were generated by introducing single amino acid substitutions at putative TCR contact positions. Four altered peptide ligands were powerful competitive antagonists of these CTL clones, reducing lysis levels of target cells expressing the alloantigen HLA B*3501 by over 80%. This first demonstration that it is possible to suppress CTL alloreactivity with structural variants of allodeterminants raises the prospect that such TCR antagonists could be exploited within the clinical arena to specifically modulate GVHD and allograft rejection.
 ...
PMID:Direct alloreactivity by human cytotoxic T lymphocytes can Be inhibited by altered peptide ligand antagonism. 992 Aug 51

To detect the effect of the stem cell source, allogeneic peripheral blood stem cell transplantations (alloPBSCTs) performed between 1995 and 1997 from human leukocyte antigen (HLA)-identical siblings in 40 patients with acute and chronic hematological disorders were compared with a historical group of 40 patients with similar variables who had received allogeneic bone marrow transplants (alloBMTs) between 1993 and 1995. Patients in both groups were identical except that both the recipient and the donor ages were, on average, higher in the alloPBSCT group (26 vs. 36 [p = 0.005] and 27 vs. 32 [p = 0.024], respectively). Patients received similar therapy excluding posttransplant granulocyte colony-stimulating factor administration (97% in alloBMT vs. 12.5% in alloPBSCT). The median time to reach neutrophil counts >0.5 x 10(9)/L and platelet counts >20 x 10(9)/L was 13 and 14 days, respectively, in patients receiving alloPBSCTs compared with 19 and 27 days in patients receiving alloBMTs (p = 0.0014 and p = 0.0002). The alloPBSCT group required similar transfusions of red blood cells or platelets. The incidence of grade II-IV acute graft-vs.-host disease (aGVHD) was similar in both groups. However, chronic GVHD (cGVHD) of all grades developed in 78.1% of patients in the alloPBSCT group after a median follow-up period of 12.5 (range 0.5-34) months. In alloBMT recipients, cGVHD of all grades developed in 21.4% after a median follow-up period of 38 (range 0.5-62) months (p = 0.00001). Day 100 transplant-related mortality was also similar: 20% (8 of 40) in the alloBMT patients and 17.5% (7 of 40) in the alloPBSCT group. Although not statistically significant, a relatively higher relapse rate occurred in the alloBMT group (21.4 vs. 10.7%). The estimated disease-free survival in month 24 was 51.3% for alloBMT and 54.6% for alloPBSCT, and the estimated overall survival in month 24 was 56.1% for alloBMT and 64.6% for alloPBSCT. In conclusion, this retrospective comparison suggests that alloPBSCT from HLA-identical donors is associated with faster engraftment, fewer transfusions, and no greater incidence of aGVHD, but a high incidence of cGVHD.
 ...
PMID:A retrospective comparison of allogeneic peripheral blood stem cell and bone marrow transplantation results from a single center: a focus on the incidence of graft-vs.-host disease and relapse. 1023 38

Human immunodeficiency virus (HIV-1) associated immune deficiency has the characteristics of chronic graft versus host disease (GVHD) caused by human leukocyte antigen (HLA) class 2 incompatibility. The envelope glycoprotein fragment TKAKRRVVEREKR mimics HLA class 1 C molecules serologically, and also mimics an immune regulatory T cell epitope, in the region of amino acids 67 to 71, within the HLA DR beta chain. This beta chain alloepitopic region (between amino acids 67 to 80) furnishes peptides predicted to bind optimally to HLA class 1 B alleles. The hypothesis predicts that viral parameters, such as viral load, and clinical parameters, such as rate of progress to acquired immune deficiency syndrome (AIDS) and severity of the associated immune deficient state, are linked to the HLA B and HLA DR beta chain haplotype in infected patients. Immune suppression is caused by HLA class 1 B restricted CD8+ T cells which normally regulate HLA class 2 DR restricted antigen specific responses. The hypothesis further predicts the severity of immune deficiency to be linked to those HLA DR beta chain allotypes which express the amino-acid glutamine (Q) in position 70.
 ...
PMID:How HIV-1 lentivirus causes immune deficiency disease. 1034 73

Allogeneic stem cell transplantation (allo-SCT) is the only treatment with curative potential for patients with myelodysplastic syndrome (MDS). From June 1986 to April 1997, we treated 12 patients with primary MDS (5 men, 7 women, median age, 36.5 years) by allo-SCT. All patients had one or more of the following poor prognostic factors: intermediate-2 or high-risk categories according to the International Prognostic Scoring System; disease progression during follow-up; heavy transfusion requirements and recurrent infections. The median duration from diagnosis of MDS to allo-SCT was 6 months. The preconditioning regimen included total body irradiation combined with either high-dose cytarabine (n = 6), high-dose cyclophosphamide (n = 4), or other regimens (n = 2). Ten patients received bone marrow transplantations and two patients received peripheral blood stem cell transplantations. Prophylaxis for graft-versus-host disease (GVHD) consisted of standard cyclosporin and short-course methotrexate. Acute GVHD of grade 2 or above occurred in 10 patients, while chronic GVHD occurred in seven of the nine patients who survived longer than 6 months after allo-SCT. With a median follow-up of 50 months, all nine patients with human leukocyte antigen (HLA)-matched sibling donors survived. One patient had a relapse 6 months after transplantation and achieved complete remission again with low-dose cytarabine therapy. The three patients receiving allo-SCT from unrelated or HLA-mismatched donors died of grade 3 to 4 acute GVHD and infection within 5 months after transplantation. The estimated disease-free survival at 4 years was 67% (95% confidence interval, 40-93%), and the overall survival was 75% (95% confidence interval, 50-99%). Our data suggest that allo-SCT should be considered early in the clinical course for young MDS patients with a poor prognosis and a matched sibling donor.
 ...
PMID:Allogeneic stem cell transplantation for patients with high-risk myelodysplastic syndrome. 1036 33

The transplantation of placental/umbilical cord blood (P/CB) has been used successfully to reconstitute bone marrow function in both related and unrelated recipients. We report here the experience of the New York Blood Center P/CB Program. Since its inception in 1992, over 400 unrelated transplants were supported between July 1993 and September 1997. Overall, event-free survival for all diagnoses and ages approached 0.45. Success and rapidity of engraftment correlated most strongly with the degree of human leukocyte antigen (HLA) disparity and cell dose/kg body weight recipient. Acute graft-versus-host disease (GVHD) was common in all patients but, surprisingly, did not differ between those patients who received grafts having one or more antigen mismatches. Chronic GVHD was uncommon and only rarely contributed to death. These results demonstrate the feasibility of large-scale P/CB banking for the provision of cryopreserved stem cell preparations for unrelated transplants. The degree of the program's success argues strongly for additional P/CB banks in order to increase the likelihood of finding a suitable stem cell preparation for patients for whom related matched donors do not exist.
 ...
PMID:The Placental/Umbilical Cord Blood Program of the New York Blood Center. A progress report. 1037 35

Peripheral mobilized parental CD34+ progenitors were isolated and used for the hematopoietic reconstitution after a myeloablative therapy in 23 pediatric patients with various diseases. Fourteen donors were human leukocyte antigen (HLA) three-loci mismatches, 6 donors were two-loci and 3 donors were one-locus mismatches. For depletion of T-lymphocytes, a positive selection of the mobilized peripheral CD34+ progenitors using the method of magnetic-activated cell sorting (MACS) was used. The purity of the CD34+ cells after MACS-sorting was 98-99%, the average number of transplanted CD34+ cells was 14.2 x 10(6)/kg (range 5.4-3.9 x 10(6)/kg) and the average number of infused T-lymphocytes was 1.4 x 10(4)/kg. Due to this low T cell number, only a short-term or no prophylaxis of graft-versus-host disease (GVHD) was necessary and no GVHD was seen. A significant GVHD was only seen in patients after add-back of donor T-lymphocytes, which was performed in some patients for prevention of relapse or in patients who showed a transient mixed chimerism. Since the B lymphocyte contamination of the isolated CD34+ cells was low in the range of 0.2%, no Epstein-Barr virus (EBV)-associated lymphoproliferative syndrome was observed. A primary engraftment was seen in 18 patients. Nonengraftment and rejection occurred in three and two patients, respectively. In four of these 5 patients, a second transplant using purified CD34+ cells from the same donor after an immunological reconditioning regimen resulted in a complete and sustained hematopoietic reconstitution. The speed of the immunological recovery was dependent on the number of transplanted CD34+ cells and was more rapid if this number was > 20 x 10(6)/kg. Eleven of the 23 patients are alive and disease free with a median follow-up of 12 months (range 2-30). The main cause of death was relapse (7 patients), and only one fatal infection was seen. Our data suggest that the transplantation of megadoses of haploidentical CD34+ cells is a realistic therapeutic option for patients who otherwise have no suitable donor, and an alternative to the use of unrelated cord blood.
 ...
PMID:Transplantation of megadoses of purified haploidentical stem cells. 1037 37

Bone Marrow Transplant (BMT) is a critical therapeutic intervention for a variety of diseases occurring in the pediatric patient. Complications of allogeneic BMT include graft-versus-host disease (GVHD), infection, drug toxicity, thrombotic microangiopathy, and veno-occlusive disease. With solid organ transplantation, chronic vascular rejection has emerged as a major factor limiting long-term survival of the graft. We present a vasculopathy of small muscular arteries in 6 patients after allogeneic BMT. Cases include 4 boys and 2 girls ranging in age from 4 months to 13 years with full or partial human leukocyte antigen matching. Five of the 6 transplants were from related donors. The vasculopathy occurred 13 to 418 days after transplant and was noted in surgical specimens (2) and at autopsy (4). It was seen in the gastrointestinal tract and lung in 3 cases each. Vascular changes in small muscular arteries include concentric intimal or medial hyperplasia with luminal narrowing, prominent myxoid change, extravasated red blood cells, and presence of some foamy histiocytes with no evidence of thrombotic microangiopathy. Vasculopathy contributed to intestinal compromise requiring surgical intervention 3 times in 1 patient, and diffuse alveolar damage with hemorrhage in another. All 6 patients are dead. The cause of this unusual vasculopathy present in patients after BMT is likely to be multifactorial, involving effects of irradiation, chemotherapy, cyclosporine, and GVHD. Together these may create a negative synergy which produces an obliterative arteriopathy that should be recognized as a pathological entity and may be a harbinger of a poor prognosis.
 ...
PMID:Vasculopathy of small muscular arteries in pediatric patients after bone marrow transplantation. 1041 90

We evaluated 18,014 patients who underwent allogeneic bone marrow transplantation (BMT) at 235 centers worldwide to examine the incidence of and risk factors for posttransplant lymphoproliferative disorders (PTLD). PTLD developed in 78 recipients, with 64 cases occurring less than 1 year after transplantation. The cumulative incidence of PTLD was 1.0% +/- 0.3% at 10 years. Incidence was highest 1 to 5 months posttransplant (120 cases/10,000 patients/yr) followed by a steep decline to less than 5/10,000/yr among >/=1-year survivors. In multivariate analyses, risk of early-onset PTLD (<1 year) was strongly associated (P <.0001) with unrelated or human leukocyte antigen (HLA) mismatched related donor (relative risk [RR] = 4.1), T-cell depletion of donor marrow (RR = 12.7), and use of antithymocyte globulin (RR = 6.4) or anti-CD3 monoclonal antibody (RR = 43.2) for prophylaxis or treatment of acute graft-versus-host disease (GVHD). There was a weaker association with the occurrence of acute GVHD grades II to IV (RR = 1.9, P =.02) and with conditioning regimens that included radiation (RR = 2.9, P =.02). Methods of T-cell depletion that selectively targeted T cells or T plus natural killer (NK) cells were associated with markedly higher risks of PTLD than methods that removed both T and B cells, such as the CAMPATH-1 monoclonal antibody or elutriation (P =.009). The only risk factor identified for late-onset PTLD was extensive chronic GVHD (RR = 4.0, P =.01). Rates of PTLD among patients with 2 or >/=3 major risk factors were 8.0% +/- 2.9% and 22% +/- 17.9%, respectively. We conclude that factors associated with altered immunity and T-cell regulatory mechanisms are predictors of both early- and late-onset PTLD.
 ...
PMID:Risk of lymphoproliferative disorders after bone marrow transplantation: a multi-institutional study. 1049 90


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>