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)

Human granulocyte-macrophage colony-stimulating factor (hGM-CSF) secreted by a hepatoma cell line, HA22T/GVH, was purified and assessed for its effects in vivo on blood leukocytes and bone marrow granulocyte-macrophage progenitor cells (CFU-GM) in ICR mice pretreated with a sublethal dose of cyclophosphamide (cytoxan). The hGM-CSF preparations were natural and had no detectable endotoxin. Five days after the administration of 300 mg/kg cytoxan, severe leukopenia with marked myelopoietic suppression was induced. The cytoxan-treated mice were then injected intraperitoneally with 10,000 units of purified hGM-CSF/mouse daily for three days. Leukopenia was totally abrogated and the leukocyte number greatly increased to a level 2- to 3-fold higher than in GM-CSF-uninjected mice. Differential white cell count showed that the subpopulations of leukocytes responsive to hGM-CSF stimulation were mainly of neutrophils and monocytes, while the lymphocytes remained unaffected. Meanwhile, in the bone marrow, hGM-CSF administration induced an apparent (3-fold) increase in the number of myeloid progenitor cells, CFU-GM. However, the effect in vivo of a single hGM-CSF injection could only maintain for 48 hrs. In addition, the loss in body weight caused by cytoxan was less in the mice with subsequent hGM-CSF than those without CSF. These results suggest that injection of GM-CSF can effectively reconstitute the cytotoxic drug-damaged myelopoiesis without apparent in vivo toxic reaction.
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PMID:In vivo stimulation of myelopoiesis in cyclophosphamide-treated mice by purified human GM-CSF. 165 33

Femoral marrow, obtained at autopsy, was stained using immunohistological techniques, for T (CD2+) cells, B (CD19+) cells, helper/inducer (CD4+) T cells, suppressor/cytotoxic (CD8+) T cells and natural killer (HNK1+) cells. The numbers present in 13 recipients of allogeneic marrow, 14 to 140 days after transplantation, were compared with those in marrows from nine subjects with no haematological or malignant conditions. In marrow sections from non-transplant subjects, approximately 8% nucleated cells were CD2+ with CD4+ and CD8+ cells present in nearly equal numbers; 1-3% were CD19+ and generally less than 1% HNK1+. The percentages of CD19+ and CD4+ cells were significantly reduced after bone marrow transplantation but, if a correction factor for marrow cellularity was introduced, then CD2+ and CD8+ cell values were also low. The findings were compared with the number of cells transplanted, the time after transplantation, presence of graft-versus-host disease or infection and peripheral blood white cell count, but no correlation was found.
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PMID:Lymphocyte populations in autopsy bone marrow sections from recipients of allogeneic marrow and non-transplant sudden death cases. 197 75

The distribution of white cell subclasses in different lymphoid (bone marrow, spleen, and blood) and parenchymal (liver, skin, lungs, and gut) target organs was studied after bone marrow transplantation in the rat. BN rats were irradiated and transplanted with 60-80 X 10(6) Lew (allogeneic) or BN (syngeneic) bone marrow cells. The recovery of lymphocytes was somewhat elevated in the bone marrow and spleen, slightly decreased in the blood, and markedly higher in the liver and skin in the allograft compared with the syngeneic graft recipient. A mild lymphocytic bronchitis was present in the lungs of the allografted animal, and the gut was hypocellular throughout the observation period. The total recovery of different lymphocyte subclasses; pan T, T helper, T suppressor-killer, class-II-positive cells, and surface-Ig-positive B cells in the different lymphoid organs--i.e., bone marrow, spleen, and blood--was similar in allogeneic compared with syngeneic graft recipients. In the liver and skin, which are the major target organs of acute graft-versus-host disease (aGVHD) in the rat, there was a massive infiltration of different T cell subclasses; high numbers of B cells were also seen in the liver. There was no difference in the T helper/T suppressor-killer ratio in the lymphoid organs or the liver of allograft compared with syngeneic graft recipients; in the skin and lungs the ratio was reduced more in the allograft compared with syngeneic graft recipient, whereas in the gut the situation was the opposite. These observations emphasize regional differences in the structure of inflammation in the different parenchymal target organs of aGVHD in the rat.
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PMID:Bone marrow transplantation in the rat. V. Lymphoid cell subclasses in the target organs during acute graft-versus-host disease. 294 Jul 37

Advances in both allogeneic marrow transplantation and conventional therapy for acute leukaemia have complicated the choice between bone marrow transplantation (BMT) and other remission treatment options. Because older patients may be more susceptible to BMT-related complications, this study analysed the effect of age on clinical outcome for 149 patients with acute leukaemia in remission receiving allogeneic BMT. Overall projected relapse-free survival at 3 years post-transplant is equivalent for 48 adults (18 years or older) and 101 children (less than 18) at 45.4% (31.1-59.6; 95% confidence interval) and 39.9% (30.1-49.7; 95% C.I.), respectively. Among 73 patients with acute lymphocytic leukaemia (ALL) 35.3% of adults and 30.1% of children survive relapse-free at 3 years. Cox multiple regression analysis demonstrated that higher diagnostic white count, but not pre-transplant extramedullary leukaemia, remission number, or age, was important as an independent adverse clinical prognostic factor for patients with ALL. Overall outcome was better for 76 patients with acute myeloid leukaemia (AML) with 51.6% of adults and 52.9% of children surviving relapse-free at 3 years post-transplant. Cox multivariate regression analysis identified first remission status and lower white cell count, but not patient age, as independent predictors of improved relapse-free survival for AML patients. Adults had greater transplant morbidity, predominantly related to a higher incidence of acute graft-versus-host disease (GVHD), resulting in longer hospital stay. Survival at 100 d, long-term survival and clinical performance status were similar in both age groups. These data suggest that results of allogeneic BMT for adults with acute leukaemia compare favourably with those found in children and are superior to most reports of conventional chemotherapy. Allogeneic BMT remains a reasonable option for remission acute leukaemia patients up to the age of 45.
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PMID:Allogeneic bone marrow transplantation for acute leukaemia: comparative outcomes for adults and children. 304 39

Sixty-seven children with acute non-lymphocytic leukemia (ANLL) in first remission underwent HLA-identical sibling bone marrow transplants as part of a cooperative study by the Childrens Cancer Study Group. Three patients died of sepsis before marrow recovery. Sixty-four patients recovered marrow function and have been followed for a median of greater than 1300 days. Two-year actuarial survival is 59% (95% confidence interval (CI): 47-71%). The risk of relapse by 2 years is 16% (95% CI: 6-26). All relapses occurred among patients with single-dose irradiation (p = 0.07), but these patients also experienced a diminished risk of acute graft-versus-host disease (AGVHD) (p = 0.12) compared to patients conditioned with fractionated irradiation. Radiation technique (single-dose vs fractionated) did not affect survival or the risk of development of interstitial pneumonia. Significant AGVHD (greater than or equal to grade II) occurred in 27 patients (40%). Patients with AGVHD were at increased risk of death due to sepsis or interstitial pneumonia during the first year after transplant, but disease-free survival was unaffected by AGVHD, because all 10 relapses occurred in patients without significant AGVHD. Neither survival nor relapse risk were affected by patient age, sex, white cell count at diagnosis, or FAB classification. This collaborative transplant study has resulted in survival data comparable to those of single institutions and the best reported outcomes of conventional chemotherapy.
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PMID:Bone marrow transplantation for acute non-lymphocytic leukemia: a report from the Childrens Cancer Study Group of sixty-seven children transplanted in first remission. 333 84

Gamma irradiation of blood products is a standard practice recommended for the prevention of posttransfusion graft-versus-host disease in susceptible hosts. We studied the effects of irradiation on stored platelet concentrates and evaluated whether platelets could be stored for 5 days in the irradiated state without adverse effects on their viability. Using a pair-controlled design in which each of six normal subjects acted as his or her own control, we compared in vitro storage characteristics and in vivo kinetics of platelet concentrates exposed to 30 Gy and stored for 5 days with those of platelet concentrates simply stored for 5 days without irradiation. Irradiation had no significant effects on in vitro storage characteristics (platelet count, mean platelet volume, pH, and white cell count) or on in vivo kinetics, including initial recovery and mean platelet survival. Using the multiple-hit model, initial recovery was 49.6 +/- 10.8 percent, and mean platelet survival was 5.6 +/- 1.05 days for irradiated concentrates, compared with 51.3 +/- 13.0 percent and 5.9 +/- 0.50 days, respectively, for the unirradiated control concentrates. We conclude that irradiation of platelet concentrates with up to 30 Gy has no effect on their in vivo recovery or survival, and that irradiation administered before storage of platelet concentrates does not interfere with their clinical efficacy.
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PMID:Viability of platelets following storage in the irradiated state. A pair-controlled study. 342 Jun 72

The liver is a major parenchymal target organ of acute graft-versus-host disease (aGVHD) after bone marrow transplantation in the rat. The authors have analyzed the nature of cellular infiltrates in the liver using monoclonal antibodies against white cell subsets and investigated the anatomic distribution of the inflammatory cell subsets inside the liver parenchyma. Several types of white cells are present in a normal control liver: In the portal area the T-helper (Th) cells predominate, (surface) immunoglobulin-expressing B cells are present in ample numbers, and most of the phagocytes are Ia-positive. In the central vein area the T-suppressor/killer cells (Tsk) dominate, no B cells are present, and most of the phagocytes are Ia-negative. During aGVHD the number of T cells increases rapidly in the portal area; and after an initial strong increase, the Th/Tsk ratio decreases but remains still above 1. In the central vein area there is also an increase in the number of T cells, compared with that in the syngeneic recipient, but the Th/Tsk ratio rapidly decreases and remains uniformly below 1. During aGVHD the B cells entirely disappear from the portal area, whereas a small but distinct number of mature plasma cells with intracellular immunoglobulin appear in the central vein area. Following irradiation the Ia-positive phagocytic cells entirely disappear from the portal area and decrease distinctly in number in the central vein area. During aGVHD the number of Ia-positive phagocytes increases again in both locations. In the central vein area the positive phagocytes are seen over the background level, and, concomitantly, the Ia-negative phagocytes disappear.
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PMID:Bone marrow transplantation in the rat. III. Structure of the liver inflammatory lesion in acute graft-versus-host disease. 389 73

Prior to administration, leukocyte transfusions are commonly irradiated with up to 5,000 R to eliminate lymphocytes and thereby prevent graft-versus-host disease in the recipient. It has been widely believed that phagocytes are resistant to this irradiation. In a recent report, we noted that phagocyte oxidative metabolism was compromised during preparation of white cells for transfusion. As part of our effort to examine the basis for this inhibition of phagocyte function during white cell preparation, we assessed the effects of irradiation on the long-lived monocytes that have been shown to persist at inflammatory foci posttransfusion. Human monocytes were irradiated for up to 3 min, receiving 2,500-5,000 R. This irradiation damaged human monocytes, significantly decreasing their in vitro survival for the first 3 wk of culture (p less than 0.02, irradiated versus control survival), and growth as assessed by two-dimensional cell size measurements during the first 2 wk of culture (p less than 0.01, irradiated versus control growth). Despite smaller cell size, total cell protein was significantly increased over time in irradiated cultures (p less than 0.001, irradiated versus control total protein per cell). Extracellular release of lysozyme and beta-glucuronidase per cell was not affected by irradiation, but extracellular lactate dehydrogenase (LDH) release was significantly increased after irradiation (p less than 0.001, irradiated versus control LDH release). Irradiated monocytes killed Listeria monocytogenes at a slower rate than the nonirradiated controls (p less than 0.05, irradiated versus control rate of killing). Thus, the data indicate that irradiation in doses used to prevent graft-versus-host disease in leukocyte transfusion recipients has a deleterious effect on in vitro human monocyte survival and function.
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PMID:Radiation effects on cultured human monocytes and on monocyte-derived macrophages. 642 52

Two consecutive patients with acute myeloid leukaemia (AML) developed severe probable graft-versus-host disease (GVHD) following transfusion of blood products from normal donors. In one patient the AML had arisen de novo, while in the other it occurred four years after the patient developed non-Hodgkin's lymphoma (NHL) and was treated with radiotherapy and combination cytotoxic chemotherapy. Both patients received anti-leukaemic treatment with doxorubicin and cytosine arabinoside and intensive haematological supportive care with transfusions of red cell, white cell and platelet concentrates obtained from normal donors. Clinically the GVHD in each patient was manifest by a severe erythematous rash, intractable diarrhoea and abnormalities in the liver function tests. On pathological examination the skin in each case showed the typical changes of GVHD. Both patients died. There have been few previous reports of GVHD occurring after accidental engraftment of immunosuppressed patients undergoing therapy for acute leukaemia. Our experience suggests that it may occur more often than has hitherto been recognised. At present there is controversy concerning the possible anti-leukaemic effects of granulocyte transfusions. Until the relative importance of the benefits and deleterious effects of cells with the potential for engraftment is determined by further studies, we recommend the routine irradiation of all cellular blood products intended for administration to acute leukaemia patients undergoing intensive cytoreductive chemotherapy.
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PMID:Graft-versus-host disease in consecutive patients with acute myeloid leukaemia treated with blood cells from normal donors. 694 43

Peripheral blood lymphocyte subsets were enumerated at regular intervals during the first year after allogeneic bone marrow transplantation (BMT) in 21 Chinese patients. Eight of these patients had acute graft-versus-host disease (GVHD) while they were assessed at the time of engraftment. Our results show in patients receiving allogeneic BMT: (1) T and NK cells were the predominant lymphocyte subsets in the early reconstitution stage while B cells were severely depleted; (2) absolute numbers of the major lymphocyte subsets normalised in 4-5 months; (3) an increased percentage of T cells that expressed the activation antigen HLA-DR and a reversed CD4:CD8 ratio were observed throughout the first 12 months after BMT; (4) patients with acute GVHD had significantly higher white cell count and NK cell percentage than those not complicated by acute GVHD.
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PMID:Peripheral blood lymphocyte subsets after allogeneic bone marrow transplantation: reconstitution and correlation with the occurrence of acute graft-versus-host disease. 761 4


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