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)

A 40-year-old man with non-Hodgkin's lymphoma developed severe ascending sensorimotor neuropathy 10 days after treatment with high dose chemotherapy and autologous bone marrow rescue. The neuropathy had axonal plus demyelinating features on electrophysiological studies. Sural nerve biopsy showed heavy infiltration of the epineurium and endoneurium with mononuclear cells. The patient had no other evidence of graft-versus-host disease. He failed to respond to plasmapheresis but responded to high dose steroids.
Bone Marrow Transplant 1992 Sep
PMID:Inflammatory peripheral neuropathy following high dose chemotherapy and autologous bone marrow transplantation. 133 Jan 51

Lymphocytes in formalin-fixed skin biopsies from patients with cutaneous acute graft-versus-host disease (aGVHD) were studied with HECA-452 (an antibody recognizing lymphocytes with skin-homing properties) and a panel of antibodies recognizing pan-B (L26 [CD20]), pan-T (L60 [CD43] and A6 [CD45RA]), and T-helper subset (OPD4) antigens in paraffin sections. Biopsies from patients with erythema multiforme (EM) were similarly studied for comparison. In both conditions, T lymphocytes stained by OPD4 were predominantly confined to the dermis, whereas those stained by HECA-452 were concentrated in the epidermis; however, there was considerable variation between cases, and overlap between findings in the dermis and epidermis. Lymphocytes similarly studied in paraffin sections of liver, salivary gland, and gut affected by aGVHD were essentially unreactive with HECA-452, although they were largely stained by pan-T markers and showed some comparable reactivity with OPD4. The findings suggest that aGVHD of the skin is mediated by a different set of lymphocytes than in gut organs, and may have a similar immunologic mechanism to EM.
Am J Pathol 1992 Sep
PMID:T lymphocytes expressing HECA-452 epitope are present in cutaneous acute graft-versus-host disease and erythema multiforme, but not in acute graft-versus-host disease in gut organs. 138 61

Under FK 506-based immunosuppression, the entire cadaver small bowel except for a few proximal and distal centimeters was translated to 17 randomly matched patients, of whom two had antigraft cytotoxic antibodies (positive cross-match). Eight patients received the intestine only, eight had intestine in continuity with the liver, and one received a full multivisceral graft that included the liver, stomach, and pancreas. One liver-intestine recipient died after an intestinal anastomotic leak, sepsis, and graft-versus-host disease. The other 16 patients are alive after 1 to 23 months, in one case after chronic rejection, graft removal, and retransplantation. Twelve of the patients have been liberated from total parenteral nutrition, including all whose transplantation was 2 months or longer ago. The grafts have supported good nutrition, and in children, have allowed growth and weight gain. Management of these patients has been difficult and often complicated, but the end result has been satisfactory in most cases, justifying further clinical trials. The convalescence of the eight patients receiving intestine only has been faster and more trouble free than after liver-intestine or multivisceral transplantation, with no greater difficulty in the control of rejection.
Ann Surg 1992 Sep
PMID:Intestinal transplantation in composite visceral grafts or alone. 138 43

Participation of IE antigens (Ag) in immune response as the transplantation Ag was examined. IE- B10.A(4R)(4R; Kk, IAk, IE-, Db) mice could not reject skin graft from IE Ag alone-disparate B10.A(2R) (2R; Kk, IAk, IEk, Db) mice despite intravenous (iv) injection of 2R spleen cells (SC) before or after skin grafting, indicating that graft rejection could not be caused across IE Ag-barrier alone. Furthermore, 4R SC could not induce lethal graft-versus-host disease (GVHD) in supralethally (950 rad) irradiated 2R mice. On the other hand, infiltration of lymphoid cells was observed at the site of transplanted 2R skin in 4R mice. SC of 4R mice unprimed or primed with 2R skin or 2R SC showed the capability to proliferate in vitro in response to 2R Ag. In immunofluorescence analysis of lymph node cells (LNC) of 4R mice injected iv with 2R SC 7 days earlier, IE-reactive CD4+Vbeta 11+ T cells did not change in number, but slightly increased the expression of interleukin-2 receptor (IL-2R). In 2R mice irradiated with 670 rad and injected iv with 4R SC 7 days earlier, 4R-derived CD4+V beta 11+ T cells proliferated, changed to blastoid form, and showed a markedly increased expression of IL-2R. To further investigate the influence of IE alloantigens on transplantation immunity, IL-2 production and anti-class I CTL activity were assayed. The 4R SC capable of recognizing IEk and Dk Ag of B10.BR (Kk, IAk, IEk, Dk) generated levels of both IL-2 and CTL activities higher than those of 2R SC capable of recognizing Dk Ag alone. These results strongly suggest that IE alloantigens indirectly act as the transplantation Ag by the stimulation of IE-reactive CD4+ helper T cells resulting in the differentiation of class I-restricted CD8+ T cells.
Cell Immunol 1992 Sep
PMID:Alloreactivity against IE-encoded antigens: evidence of the discrepancy between graft rejection and reactivity of IE-reactive T cells. 138 50

Erythroderma as a manifestation of graft-versus-host disease after cardiac operations with blood transfusion may occur more frequently in Japan than in other countries. We have seen this problem in five patients who, after heart operations, died with symptoms and signs characteristic of graft-versus-host disease: cutaneous eruption, fever, diarrhea, leukopenia associated with agranulocytosis, and liver dysfunction. In the three patients seen most recently, skin biopsy showed findings similar to those of graft-versus-host disease after bone marrow transplantation. In addition, immunologic investigation showed remarkable differences in the findings in these patients and in those who did not have a graft-versus-host disease-like syndrome after cardiac operations. In particular, interleukin-2 production in response to mitogen stimulation was markedly diminished after operation in our patients, and the ratio of OKT4+ cells to OKT8+ cells in peripheral blood was low, reflecting increased numbers of OKT8+ cells after the occurrence of symptoms. The results raise the possibility that transient depression of cellular immunity after cardiac operations with blood transfusion may contribute to the occurrence of postoperative acute graft-versus-host disease.
J Thorac Cardiovasc Surg 1992 Sep
PMID:Postoperative erythroderma after cardiac operations. The possible role of depressed cell-mediated immunity. 138 38

The potential involvement of cytokines in acute graft-versus-host disease led us to analyze interleukin-6 in serial serum sets from 22 allogeneic marrow recipients who developed either grade 3 or 4 GVHD (n = 10), grade 2 GVHD (n = 6), or grade 1 or no diagnosed GVHD (n = 6). A total of 279 serial serum samples taken three times weekly before day 35 were analyzed. Maximum IL-6 levels were greater than 40 U/ml (range, 40-1536 U/ml), 11-40 U/ml, and less than or equal to 10 U/ml for six, eleven, and five patients, respectively. Serum IL-6 peaks were temporally related to onset of GVHD, onset of a syndrome of hepatorenal dysfunction (HRD), or bilateral lung infiltration. Eight of ten patients who developed grade 3 or 4 GVHD overall had IL-6 maxima of greater than 10 U/ml an average of 1.5 +/- 1.8 days before the clinical onset. Fifteen of 17 patients with peak IL-6 levels greater than 10 U/ml developed symptoms of hepatic and renal dysfunction within three days of the peak, while none of five patients with less than or equal to 10 U/ml of Il-6 developed HRD. Regression analysis demonstrated a linkage between the log magnitudes of the serum IL-6 peaks and onset of either GVHD or HRD within three days (P = 0.001). Furthermore, IL-6 peaks tended to precede GVHD onset for the 10 patients whose GVHD onset and IL-6 peak were within three days of each other (P = 0.02). These results, confirmed by both specific bioassay and by IL-6 ELISA, support the idea that acute GVHD in humans involves a cytokine cascade that includes production of IL-6 in addition to the previously reported involvement of tumor necrosis factor alpha and interferon-gamma.
Transplantation 1992 Sep
PMID:The relationship of serum IL-6 levels to acute graft-versus-host disease and hepatorenal disease after human bone marrow transplantation. 141 27

Peripheral gamma/delta+ T cells were studied in patients following allogeneic bone marrow transplantation (BMT) by indirect immunofluorescence utilizing two monoclonal antibodies (G1 and A13) able to recognize the two major subpopulations (V delta 2+ and V delta 1+, respectively) of these cells. We found that the relative percentage of 'total' (gamma/delta+ T lymphocytes) (V delta 2 + V delta 1 positive cells), and particularly of G1+ (V delta 2+) cells, in CD3+ lymphocytes was higher in transplanted patients, and especially in those presenting with acute graft-versus-host disease (aGVHD), than in normal controls. This finding was confirmed by the analysis of the V delta 2+/V delta 1+ cell ratio which was again significantly higher in patients with aGVHD as compared to controls. Similarly, the absolute number of 'total' gamma/delta+ and V delta 2+ cells was also significantly increased in patients with aGVHD. TCR gamma/delta+ T cells increased as a function of time after BMT reaching a plateau value at about day 60 post-BMT. When patients were stratified for the presence or absence of aGVHD this correlation was maintained only for patients with aGVHD. Finally, most V delta 2+ cells expressed surface T cell activation markers such as CD25 (IL-2 receptor) and DR (MHC class II) antigens. Our results suggest a possible involvement of gamma/delta+ T cells and particularly of V delta 2+ cells in the clinical and immunological events (aGVHD) occurring after allogeneic BMT.
Bone Marrow Transplant 1992 Sep
PMID:TCR gamma/delta positive lymphocytes after allogeneic bone marrow transplantation. 142 78

Pneumocystis carinii pneumonitis (PCP) can occur in immunocompromised hosts, especially AIDS and cancer patients. Although recent research has focused on PCP in AIDS patients, few studies have described the clinical presentation of PCP in recipients of bone marrow transplantation (BMT). Between 1976 and 1991, of 1454 BMT patients at the University of Minnesota, PCP was documented in only 19. Eighteen of these had not been receiving PCP prophylaxis. Patients presented with a brief period (2-10 days) of symptoms including dyspnea, cough, and fever in greater than 75% of patients, but had only scant abnormal physical findings. Chest X-rays showed bilateral infiltrates in 58% of all patients, though 15% had no or minimal X-ray findings. Bronchoscopic alveolar lavage confirmed the diagnosis most often, but 13% of lavages were negative and required biopsy for the diagnosis. High dose trimethoprim-sulfamethoxazole was the initial treatment for 84% of the patients though 25% of these patients were later switched to pentamidine due to poor response or hypersensitivity reactions. Despite prompt diagnosis and therapy, overall survival was poor, with only 37% of patients surviving pneumonitis. Patients developing PCP less than 6 months post-BMT had greater mortality (89%) versus only 40% in later onset PCP (p less than 0.0001). Despite this better survival in the late-onset PCP cohort, the development of pneumonitis in these patients underscores the necessity for continued PCP prophylaxis beyond 1 year in some patients. Ongoing immunocompromise and need for prophylaxis should be appreciated in patients with graft-versus-host disease.(ABSTRACT TRUNCATED AT 250 WORDS)
Bone Marrow Transplant 1992 Sep
PMID:Pneumocystis carinii pneumonitis following bone marrow transplantation. 142 81

Donor leukocyte infusions were administered to a patient who had relapsed with chronic myelogenous leukemia after having failed two successive HLA-matched allogeneic bone marrow transplants. Serial cytogenetic, restriction fragment length polymorphism, and polymerase chain reaction studies of the patient's marrow and blood after receiving donor leukocyte infusions revealed disappearance of the leukemic clone and the establishment of complete donor chimerism. An antileukemic response in this patient occurred initially in the absence of clinically evident graft-versus-host disease (GVHD), but complete eradication of the leukemic clone did not occur until after the onset of GVHD. The patient is now 48 weeks post infusion and remains in complete remission. This case demonstrates that leukocyte infusions are an effective form of adoptive immunotherapy which can result in a sustained molecular remission.
Bone Marrow Transplant 1992 Sep
PMID:Molecular remission occurring after donor leukocyte infusions for the treatment of relapsed chronic myelogenous leukemia after allogeneic bone marrow transplantation. 142 83

We report a patient who underwent two allogeneic bone marrow transplants for chronic myelogenous leukemia, initially in 1984 and again after relapse in 1990, who developed an identical pulmonary syndrome at a similar interval following each transplant. The patient presented with a non-productive cough, bilateral inspiratory crackles, and multiple patchy infiltrates on chest X-ray. Pulmonary function testing revealed a restrictive abnormality but no obstructive defects. The appearance of this pulmonary disorder after each transplant coincided with the development of chronic graft-versus-host disease. In both instances, this pulmonary syndrome completely reversed with corticosteroid therapy. The patient's chest computed tomographic scan and lung biopsy specimens were consistent with the diagnosis of bronchiolitis obliterans with organizing pneumonia (BOOP). While bronchiolitis obliterans has been reported following allogeneic transplant, BOOP has not previously been reported in this setting.
Bone Marrow Transplant 1992 Sep
PMID:Bronchiolitis obliterans organizing pneumonia as a complication of allogeneic bone marrow transplantation. 768 3


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