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)

Gastrointestinal (GI) disease is frequent in all types of immunocompromised patients but occurs with greatest frequency in patients with acquired immunodeficiency syndrome (AIDS). Thus, much of this review deals with human immunodeficiency virus (HIV)-related GI diseases. Gastrointestinal diseases in other immunocompromised patients are compared with those in patients with AIDS. Conditions unique to transplant recipients, such as graft-versus-host disease (GVHD) and posttransplant lymphoproliferative disorders (PTLDs), are discussed separately. We have divided these GI diseases into four main categories: (1) HIV-related inflammatory conditions other than opportunistic infections (HIV-related enteropathy, proctocolitis, and CD8 lymphocytosis); (2) inflammatory conditions unrelated to HIV or opportunistic infections (neutropenic enterocolitis, regional enteritislike enteropathy, and GVHD); (3) opportunistic infections (illnesses caused by herpesvirus, cytomegalovirus, and miscellaneous other viruses; Mycobacterium, Candida, Histoplasma, Cryptococcus, Cryptosporidium, Microsporida, Isospora, Leishmania, Toxoplasma and Strongyloides organisms as well as Pneumocystitis carinii; and (4) neoplasias (Kaposi's sarcoma [KS], AIDS-related non-Hodgkin's lymphoma [NHL], HIV-related Hodgkin's disease [HD], PTLDs, and miscellaneous neoplasms). The prevalence, pathogenesis, clinical manifestations, gross pathological findings, and microscopic features of each disease entity are discussed.
 ...
PMID:Gastrointestinal disease in the immunocompromised patient. 795 57

High-dose therapy and bone marrow transplantation has been shown to be a potentially curative modality for patients with hematologic malignancies. Several obstacles to the use of this approach include the availability of histocompatible siblings and the increased toxicity even in HLA-matched patients owing to graft-versus-host disease and interstitial pneumonitis. The use of autologous marrow in support of high-dose therapy has lower toxicity; however, there is the issue that residual tumor cells may be reinfused into the patient. There are several laboratory studies demonstrating that residual tumor cells persist in the marrow despite histologic remission. In addition, case reports suggest that contaminated marrow has led to widespread early relapse owing to reinfusion of tumor cells. A variety of techniques have been developed that can deplete up to 5 logs of tumor cells from the marrow. These techniques include very specific immunologic as well as less specific pharmacologic purging. Both approaches have been refined so that normal hematopoietic stem cell reconstitution is relatively preserved. Although a large number of studies have been reported that have utilized ex vivo marrow purging, few have examined whether there has been an impact on disease-free survival. Although randomized studies have not been performed to date, several recent studies in ANLL and B-cell NHL strongly suggest that there is a relationship between the quality of elimination of the disease ex vivo in the marrow and disease-free survival. With further improvements in marrow treatment, whereby all detectable cells are depleted, as determined by highly sensitive molecular biologic techniques, and randomized trials involving purged and unpurged BM, the question of the impact of ex vivo marrow treatment can be better answered.
 ...
PMID:Developments in purging in autotransplantation. 834 86

The high relapse rate of hematologic malignancy treated with autologous bone marrow transplantation (ABMT) may reflect the absence of a graft-versus-leukemia (GVL) effect usually associated with graft-versus-host disease (GVHD). The purpose of this study was to determine whether administration of interleukin-2 (IL-2) early after ABMT might induce or exacerbate acute skin GVHD. Fourteen patients at high risk for post-transplant relapse, eight with NHL and six with AML > or = first relapse, were conditioned with chemotherapy and total body irradiation (13) or chemotherapy alone (1), and received purged (10) or unpurged (4) marrow. A median of 35 days (range 25-58) after ABMT, they received a 5-day induction course of Roche IL-2 (9 x 10(6) U/m2/day) followed by apheresis, reinfusion of LAK cells, and a 10-day maintenance course of IL-2 (0.9 x 10(6) U/m2/day), all by continuous i.v. infusion. Serial skin biopsies were obtained before and after IL-2 therapy and were read blindly. Patients were studied prospectively for the development of acute cutaneous GVHD as reflected by rash ( > or = 25% body surface area), skin biopsy ( > or = grade II histologic changes) and T cell infiltration as assessed by staining of the biopsy with antibodies UCHL-1 and TIA-1. No patient had a rash before IL-2 therapy, but 12 of 14 (85%) developed a rash during the IL-2 induction course. Before IL-2 therapy, biopsies from three of 10 patients (30%) revealed histologic GVHD; after induction IL-2, biopsies from 11 of 14 patients (79%) revealed grade II acute GVHD. Biopsies from all patients with histologic GVHD after IL-2 therapy contained TIA-1 positive T cells. HLA-DR was negative in the keratinocytes of these paraffin-embedded sections. One patient died early of sepsis, one patient required and responded to topical corticosteroids and 12 had spontaneous resolution of the rash. Six patients relapsed at 3-13 months, while seven remain in complete remission 32+ to 41+ months after ABMT. The results demonstrate that IL-2 therapy after ABMT can induce effects which histologically and clinically mimic cutaneous acute GVHD in most patients. Prospective, randomized trials of IL-2 vs observation after transplantation of autologous marrow or stem cells for high-risk NHL and AML have been initiated which may allow us to determine whether this phenomenon is associated with a clinical GVL effect as reflected by a decreased relapse rate.
 ...
PMID:Close simulation of acute graft-versus-host disease by interleukin-2 administered after autologous bone marrow transplantation for hematologic malignancy. 870 86

Allogeneic BMT from histocompatible-related and -unrelated donors can provide curative therapy for a variety of hematologic, oncologic, immunologic and hereditary diseases. Obstacles to successful outcome of allogeneic BMT include GVHD, disease relapse, opportunistic infection and toxicity of the conditioning and GVHD prophylaxis regimens. As these problems are surmounted, the number of BMT survivors is expected to steadily increase and the QOL post-BMT will become as important as the duration of survival in evaluating the outcome of allogeneic BMT. High-dose chemotherapy or chemoradiotherapy, followed by ABMT or autologous peripheral blood stem cell transplant has been shown to produce long-term, disease-free survival in patients with relapsed, refractory and poor-risk HD and NHL. Despite the success of ABMT and PBSCT in treating these diseases, the short- and long-term transplant-related mortality continues to be a major concern and mandates exploration of new approaches to reduce acute and delayed fatal toxicities. ABMT as post-remission therapy for adult AML has yielded results similar to those achieved with allogeneic BMT. The role of bone marrow purging and posttransplant immunomodulation in preventing disease relapse after ABMT is being investigated.
 ...
PMID:Bone marrow transplantation: the City of Hope experience. 879 75

IL-10 plays an important role in the control of immune reactions during systemic infection. Here, IL-10 serum levels were investigated in patients after BMT. The IL-10 levels correlated with the clinical course of the patients and with serum levels of C-reactive protein (CRP) and neopterin (NP). A total of 26 patients with AML (7), ALL (12), CML (2), NHL (3) and multifocal Ewing's sarcoma (2) had received autologous (10) or allogeneic (16) BMT from related (9) or unrelated donors (7). Routine serum samples were obtained prior to BMT and at days 46 and 100 after BMT. However, in patients with severe complications additional samples were drawn at individual points in time. Prior to BMT, IL-10 serum levels were not detectable in 24/24 patients. Post-BMT, 11 patients developed elevated IL-10 levels, of these eight died of complications (DOC), whereas only one of 15 patients with undetectable IL-10 died of complications, indicating that high IL-10 levels were significantly correlated with severe life-threatening complications (chi2, P < 0.01). To determine the pathomechanism and role of the increased IL-10 levels, they were correlated to the respective NP and CRP serum concentrations. CRP and NP concentrations were found significantly elevated in patients with detectable IL-10, indicating a severe acute phase reaction associated with macrophage activation. In conclusion, high IL-10 serum levels in patients after BMT were significantly associated with fatal outcome. Since IL-10 is a strong suppressor of T cell immunity, high IL-10 production in patients with severe complications such as septic shock or GVHD > grade II after BMT might lead to functional immunodeficiency contributing to the poor prognosis of these patients.
 ...
PMID:High interleukin-10 serum levels are associated with fatal outcome in patients after bone marrow transplantation. 933 50

To explore the feasibility and potential advantages of PBSC in allogeneic transplantation, we grafted 24 patients (age 16-57, median 37) with different hematologic diseases (ALL = 10, AML = 5, MM = 4, NHL = 2, CML = 1, MDS = 1, AA = 1), 23 HLA-identical to their siblings and 1 partially matched. Cells were collected from donors by apheresis after G-CSF 10 to 16 mg/kg/day for 4 to 5 days, and stored at 4 degrees C until infusion. The patients were conditioned with chemotherapy regimens including busulfan and cyclophosphamide in the majority of cases and received GVHD prophylaxis with CSA-MTX in all but two. The graft consisted of PBSC alone, with a median of 143.5 (range 18.1-358.9) x 10(4)/kg CFU-GM, 9.0 (range 3.3-18.0) x 10(6)/kg CD34+ cells and 2.8 (range 1.2 to 8.6) x 10(8)/kg CD3+ and cells. An ANC >0.0.5 x 10(9)/L was recovered on (median) day 13 (range 11-17), and a platelet count >50 x 10(9)/L on (median) day 13 (range 12-55) post graft. There was no correlation between CD34+ cells or CFU-GM number in the inoculum and time to hematologic reconstitution. Acute GVHD (grade II-IV) occurred in 10 out of 22 (45%), chronic GVHD in 10 out of 18 evaluable (55%) patients. We found no relationship between occurrence of acute or chronic GVHD and number of CD3+ cells in the graft. Four patients relapsed and 7 died after transplantation. Fifteen patients are currently alive and disease-free 67 to 710 (median 286) days from the graft. Allogeneic transplantation with unmanipulated PBSC ensures a fast and stable engraftment. Acute GVHD incidence and severity seems comparable to that of bone marrow transplantation, but there may be an increase in chronic GVHD, mainly of the extensive form.
 ...
PMID:Transplantation of unmanipulated allogeneic PBSC: preliminary report on 24 patients. 957 Jun 80

Relapsed or very aggressive high-grade NHL and refractory low-grade NHL have a poor clinical outcome. Autologous BMT may be used but is of limited efficacy in these cases. Allogeneic BMT offers the advantage of tumour-free bone marrow and a possible GVL effect. Between 1987 and 1996, 13 patients (median age 31 years) suffering from lymphoid malignancies underwent allo-BMT. Four patients had low-grade NHL, three intermediate-grade and six high-grade NHL. Three patients were grafted with evolutive disease, four were in partial remission after several courses of chemotherapy, two were in CR2 and four were in CR1 after initial therapy. The mean number of prior treatments was 2.7 (1-6). Median time from diagnosis to BMT was 25 months (4-90). The conditioning regimen consisted of cyclophosphamide (120 mg/kg/day for all, plus VP16 in one case) and total body irradiation. Five out of the seven patients who were not in CR at the time of transplantation entered CR after BMT. Eight patients developed acute GVHD grade > or = II and four had chronic GVHD. Nine patients are alive, eight in CR with a median follow-up of 49.8 months post BMT (2-125). Overall survival is 67.3% and the median time for EFS is 102 months. Two patients with low-grade NHL relapsed 61 and 102 months post BMT and were treated with DLI. One patient with a stage IV SLL had a partial remission and one with multiple cutaneous localisation of FL entered CR after grade IV acute GVHD. Allo-BMT is a highly effective treatment for advanced poor prognosis lymphoid malignancies with acceptable toxicity. Moreover, DLI can be effective in relapsing patients.
 ...
PMID:Long-term follow-up of allogeneic bone marrow transplantation in patients with poor prognosis non-Hodgkin's lymphoma. 1010 May 76

Relapse is a serious complication following high-dose therapy and autologous bone marrow transplantation (ABMT) for malignant lymphoma (ML). Allogeneic transplantation (alloSCT) is a therapeutic option. However, it is associated with a high incidence of transplant-related organ toxicity and mortality. We recently reported fast engraftment and minimal transplant-related toxicity, using fludarabine-based conditioning with reduced amounts of chemotoxic drugs prior to alloSCT. We now present our experience with 23 heavily treated high risk ML patients who underwent matched alloSCT following the same low intensity conditioning. The patients (20 male, three female) were aged 13-63 years. Nineteen had NHL and four HD (resistant disease 12, partial remission 11). Five were post ABMT. Twenty-two patients had fully matched sibling donors, and one a fully matched unrelated donor. Engraftment was fast. There was no rejection or non-engraftment. Organ toxicity was moderate with no liver or renal toxicity >grade II. Four patients developed >grade II graft-versus-host disease (GVHD). Seven patients died - four of grade III-IV GVHD and severe infections, two of bacterial sepsis, one of pulmonary failure. Ten patients are alive after 22.5 (15-37) months. Survival and disease-free survival at 37 months are both 40%. Probability of relapse is 26%. These encouraging results suggest that alloSCT following fludarabine-based low intensity conditioning in high-risk patients merits further evaluation. Bone Marrow Transplantation (2000).
 ...
PMID:Allogeneic peripheral blood stem cell transplantation using a fludarabine-based low intensity conditioning regimen for malignant lymphoma. 1082 60

To circumvent aGVHD in the early phase after allogeneic stem cell transplantation but to provide GVL activity later on, we performed alloPBSCT with CD34+ selected grafts followed by delayed add-back of CD3+ T cells. Ten consecutive patients having an HLA-identical sibling donor were enrolled on to this trial. Four patients were in first CR of high-risk ALL, another four in first CR of AML, one was in second myeloid blast crisis of CML, and one was in PR of relapsed NHL. Conditioning consisted of 2 x 60 mg/kg CY plus 12 Gy TBI. G-CSF (Filgrastim) mobilized peripheral cells were CD34+ selected using the Isolex 300i system in nine patients and the CliniMacs system in one. Median CD34+ purity was 86%. A median of 2.8 x 10(6)/kg CD34+ cells were transplanted. The number of CD3+ cells in the allografts was 5.7 x 10(4)/kg (median) after Isolex 300i, and 0.2 x 10(4)/kg after CliniMacs. All patients received G-CSF (Filgrastim) and engrafted rapidly. Standard-dose CsA was administered, and until day +60 no aGVHD occurred. At that time point, seven patients received 2 x 10(6)/kg CD3+ cells while CsA had been tapered to 50% of the starting dose. One of these patients died after a second T cell boost given on day +90 without concomitant immunosuppression due to grade IV intestinal aGVHD. Three others developed cutaneous cGVHD. Taken together, T cell depletion by CD34+ selection does not impair rapid engraftment in the HLA-identical sibling donor setting. Using standard-dose CsA the risk for acute GVHD seems to be minimized. Add-back of 2 x 10(6)/kg CD3+ cells on day +60 with CsA protection is feasible. However, whether this is the optimal time point and number of T cells remain to be further elucidated.
 ...
PMID:CD34 selected alloPBSCT and adoptive immunotherapy. 1093 76

Peripheral blood stem cell transplants (PBSCT) from unrelated donors (n = 37) were compared with bone marrow transplants (BM, bone marrow group, n = 37) in a matched pair analysis. Ten patients (2, class 1) in the alloPBSCT group and seven patients (2, class 1) in the BM group had one HLA locus mismatch donor, respectively. The following factors were matched: HLA-compatibility, diagnosis, disease stage, age and gender. The median age in the PBSC group was 37 years (19-56, excluding one 6-year-old child) and in the BM group 37 years (18-53). The BM group consisted of 12 females and 25 males, 17 females and 20 males were in the PBSC group. Twelve patients in the BM and 11 patients in the PBSC group were diagnosed with AMI,; 7/7, ALL; 15/15, CML; 2/3, MDS; 1/1, NHL. Thirty-four (14/20) of the 74 patients (45%) were considered as high risk patients. The conditioning regimen was BU/CY for standard risk patients with myeloid diseases (31 patients) and TBI/CY for ALL and NHL patients (36 patients); six patients received intensified conditioning with VP16 (2 patients), thiotepa (2 patients) or melphalan (1 patient). The GVHD prophylaxis regimen was used according to the Seattle protocol. DFS was 51% (19 patients) with a median of 352 days and 59% (21 patients) with a median of 760 days, in PBSC and BM transplants, respectively. The median time to leukocyte engraftment in PBSC patients was 14 days (range 6-26 days) and in the BM group 19 days (range 9-29 days; P < 0.02). The time of platelet engraftment did not differ significantly between the groups. The incidence of grade II-IV acute GVHD was 40% (four patients died, 13%) in the PBSC group and 20)% (three patients died, 8%) in the BM group, respectively (P < 0.05, log-rank). No signs of aGVHD were found in 19% of the patients in the PBSC and 27% in the BM group. Our results indicate that allogeneic PBSCT does lead to a significantly faster leukocyte engraftment. The significant increase with regard to the incidence and shorter time of onset of severe aGVHD in PBSC patients, compared to marrow transplant patients, need to be confirmed in a randomised trial.
 ...
PMID:A comparative study of peripheral blood stem cell vs bone marrow transplantation from unrelated donors (MUD): a single center study. 1093 83


1 2 3 4 5 Next >>