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

After bone marrow transplantation many T-lymphocyte functions, including the production of cytokines (CK), such as interleukin 2, are severely depressed for months. The monocyte-derived cytokines tumor necrosis factor alpha and interleukin 6 are molecules central to immune functions. Moreover, they may be involved in graft-versus-host disease and in graft-versus-leukemia reaction. Hence, we have studied the reappearance of these CKs after BMT by analyzing whole blood cultures stimulated in vitro with lipopolysaccharide for 6 hr, followed by testing for the secretion of TNF in the WEHI 164/actinomycin D cytotoxicity bioassay and for IL-6 in the 7 TD 1 proliferation assay. We performed sequential studies in 6 children who were transplanted for aplastic anemia or leukemia with allogeneic bone marrow. We found that the production of both CKs can be induced as early as 10-14 days post BMT at the very beginning of engraftment, indicating that the regenerating monocyte system is recovering rapidly after BMT. Depletion and neutralization experiments confirmed that monocytes are the cellular source of the LPS-induced CK secretion after BMT. Control levels were reached 3 to 4 weeks post BMT. When analyzing the endotoxin-induced CK production in a larger panel of BMT patients after complete reconstitution, we could not detect any impact of acute or chronic GvHD, or of allogeneic or autologous BMT, nor did treatment with cyclosporine A (CsA) show any suppressive effect. Thus, our data show that the CK production of the monocyte/macrophage lineage is quite resistant to factors that do influence other cell lineages of the immune system during BMT. The coincident appearance of monocyte-derived cytokines and of GvHD suggests a role for these cytokines in GvHD in man.
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PMID:Recovery of monocytes after bone marrow transplantation--rapid reappearance of tumor necrosis factor alpha and interleukin 6 production. 192 48

A modified two-step polymerase chain reaction (PCR) was used for the amplification of BCR/ABL mRNA in 16 patients with Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML) following allogeneic bone marrow transplantation (BMT). At different intervals after BMT, patient cells were assessed for the presence of BCR/ABL mRNA by two subsequent rounds of PCR amplification; this procedure increased the sensitivity for the detection of one Ph+ cell in 10(4-5) to one cell in 10(5-6). Eight of 16 patients were negative by two-step PCR 1-39 months after BMT, suggesting an elimination of Ph-positive cells or a decrease below the threshold of detection. Although five patients showed negative results by the one-step PCR only, they were tested positive when nested primers were used, indicating a substantial decrease in the amount of BCR/ABL target mRNA compared with earlier pre- or post-transplant analyses. One patient who was still PCR positive 27 months after BMT became negative 12 months later. Persistence of BCR/ABL mRNA-expressing cells correlated with subsequent clinical relapse only when the transplantation was performed during blast crisis. All patients who underwent transplantation in chronic phase, including those with BCR rearrangement by PCR, are in clinical and hematological remission between 24 and 95 months after BMT. We conclude that aggressive chemotherapy combined with total body irradiation is unable to completely eradicate the malignant clone in all CML patients, and it might be speculated that other mechanisms (e.g., graft versus host reaction [GVHD] or graft versus leukemia effect [GVL]) may effectively eliminate residual leukemic cells.
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PMID:Apparent decrease and elimination of BCR/ABL mRNA-expressing residual cells in patients with chronic myelogenous leukemia after allogeneic bone marrow transplantation. 193 96

Seventeen bone marrow transplants were undertaken on 15 patients with leukemia or aplastic anemia using marrow from closely matched (phenotypic or five out of six HLA-A, B and DR antigen matched related and unrelated) donors. Donors were siblings (four), parents (seven), aunt (one), great aunt (one) or matched unrelated (two). When compared with transplants using matched sibling donors, survival was not different (51.4 +/- 13.4% vs. 48.1 +/- 9.6%; p = 0.87) but transplant-related complications and morbidity were higher as follows: graft-versus-host disease (GVHD) (87% vs. 15%; p less than 0.001), interstitial pneumonitis (59% vs. 14%; p less than 0.003), days in hospital (51 vs. 26; p less than 0.001), and chronic transplant related morbidity 50% vs. 11%; p + 0.033). The age of donors who were closely matched was significantly greater than that of their recipients (29.7 +/- 13.9 years vs. 8.1 +/- 3.1 years; p less than 0.001) and was associated with poorer transplant outcome. Median transplant-related complication-free survival for patients receiving transplants from age non-disparate donors was 53 months (range 18-86 months) compared with 12 months (range 2-42 months) for age disparate donors (p = 0.028). Transplants from closely matched donors were undertaken in the ratio of one to every three matched donors, indicating the importance of this source of marrow in a transplant program.
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PMID:Bone marrow transplantation in children using closely matched related and unrelated donors. 193 63

Three groups of patients with leukaemia and myelodysplasia were assessed with regard to the blood product support they required during their period of bone marrow hypoplasia following treatment. One group received myelo-ablative remission-induction chemotherapy followed by appropriate consolidation therapy (two courses in patients with acute myeloid leukaemia and one or two intensification courses in patients with acute lymphoblastic leukaemia); whilst the other two had 'conditioning' with chemotherapy and radiotherapy prior to autologous bone marrow transplantation (auto-BMT) or T cell depleted allogeneic bone marrow transplantation (allo-BMT). There was no statistically significant difference in blood product requirements between the three groups. However, platelet requirements during remission-induction chemotherapy alone were significantly less than for allo-BMT or auto-BMT. Platelet requirements for patients undergoing auto-BMT were also significantly higher than for patients receiving consolidation chemotherapy; and were required for a longer period than for patients receiving allogeneic-BMT. There was no difference in blood product support between ABO matched and mismatched transplants within the allogeneic group, but the presence of graft versus host disease and/or cytomegalovirus infection did significantly increase the requirements for blood product support.
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PMID:Blood product support in patients undergoing chemotherapy and autologous or allogeneic bone marrow transplantation for haematological malignancies. 193 21

Graft-versus-host disease (GVHD) is an immunologically mediated disease occurring most frequently after allogeneic bone marrow transplantation. The aim of this study was to evaluate the contribution of immunohistochemistry in the diagnosis of cutaneous GVHD. Patients transplanted for either leukemia or beta-thalassemia were included in the study. Skin lesions of acute and chronic GVHD were examined both by direct immunofluorescence to detect immunoglobulin deposits and by an avidin-biotin-peroxidase complex technique to evaluate the inflammatory cell infiltrate. Epidermal and dermal fluorescent bodies (IgG and IgM) were frequently found in both acute and chronic GVHD. Most of the infiltrating cells were CD3+ T lymphocytes, with CD8+ cells representing the major cell population invading the epidermis both in acute GVHD and in chronic lichenoid GVHD. A small proportion of the dermal cells were CD14+ macrophages; no B cells were detected. HLA-DR, but not HLA-DQ antigens, were variably expressed by keratinocytes in all cases of acute GVHD and in chronic lichenoid GVHD. KL-1, a monoclonal antikeratin antibody specific for the 56.5 KD acidic polypeptide usually present in suprabasal keratinocytes, stained all epidermal layers, including the basal layer. Langerhans cells were dramatically reduced in number in the epidermis of both acute and chronic lichenoid GVHD. It is concluded that immunohistologic analysis may be supportive in the diagnosis of acute and early chronic lichenoid cutaneous GVHD.
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PMID:Immunohistochemistry of cutaneous graft-versus-host disease after allogeneic bone marrow transplantation. 193 60

We reported the results of 6 allogenic bone marrow transplantation (BMT) and 3 autologous BMT for patients with Philadelphia chromosome (Ph1)-positive acute lymphoblastic leukemia (ALL) by Nagoya BMT group. Two of six patients who received allogenic BMT have continued complete remission (CR) on +639 days and +1,597 days. Four of six patients relapsed on +134, +203, +216, and +267 days. Two patients with a disease-free survival for a long time had both acute and chronic GVHD. It is suggested that graft-versus-leukemia (GVL) effect might prevent the relapse. On the contrary, one patient who received with monoclonal antibodies plus complement-treated autologous bone marrow is free of leukemia on +439 days. Our results suggest the follows. 1) We do chromosomal analysis at initial diagnosis in all cases to do BMT in first CR. 2) We intensify the conditioning regimen for BMT. 3) We study on application of GVL effect to prevent the relapse. 4) We establish the best purging method to eradicate residual leukemic cells for autologous BMT. 5) We do allogenic BMT using HLA-matched unrelated donor for patients without related donor.
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PMID:[Bone marrow transplantation for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia]. 194 24

Manifestation of graft-versus-leukemia (GVL) effect in MHC-compatible and -incompatible, allogeneic bone marrow transplantation and the roles of T cell subsets contaminated in the donor bone marrow were studied using radiation-induced leukemia-bearing C3H mice maintained under specific-pathogen-free (SPF) condition. The results indicated that BMT from MHC-incompatible allogeneic (B10) donor significantly improved the survival of the treated mice as compared with that from syngeneic (C3H) donor. When donor (B10) bone marrow cells were treated with either anti-Thy 1.2 or anti-Lyt 2.2 antibody plus complement prior to BMT, a beneficial GVL effect was completely abolished. On the other hand, BMT from MHC-compatible allogeneic donors (B10.BR, CBA, AKR) failed to show an improvement in survival. However, intentional enhancement of GVH reaction by preimmunization of B10.BR donor mice with a relatively small number (10(4) approximately 10(5] of C3H spleen cells or by an addition of B10.BR lymph node cells to the donor bone marrow resulted in a significant improvement in survival. The depletion of all T cells completely abrogated the GVL effect, while the depletion of either Lyt 2+ or L3T4+ T cells from donor (B10.BR) bone marrow resulted in only partial, if any, abrogation of GVL effect. The results indicate that GVL effect observed in leukemic mice treated with allogeneic BMT from MHC-compatible (B10.BR) and -incompatible (B10) donors was totally dependent on T cells contaminated in the donor bone marrow, and suggest that the roles of T cell subsets in the induction of GVL effect were different between MHC-compatible (B10.BR) and -incompatible (B10), allogeneic BMT.
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PMID:Graft-versus-leukemia effect in MHC-compatible and -incompatible allogeneic bone marrow transplantation of radiation-induced, leukemia-bearing mice. 194 75

An overview about the recent state of the supportive therapy with blood components in the treatment of leukemia is given. The 1st part is devoted to the procurement of blood components and the techniques of preparation and storage are described. The 2nd part includes the side effects of blood components like alloimmunization, graft-versus-host disease and CMV-transmission and discusses the possibilities of prohibition. The 3rd part deals with the dosage of the single blood components and how to judge the efficacy of transfusion. In the last part the indications for the single blood donor components are described and therapeutical strategies are outlined.
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PMID:[Supportive therapy with blood components]. 194 46

Cyclosporin A is used to prevent graft-versus-host disease (GvHD) following bone marrow transplantation (BMT) and it has been implicated in reducing the time to engraftment for leukaemia and aplastic anaemia patients. To evaluate the effect of cyclosporin A on engraftment, the proliferative capacity of bone marrow progenitors (CFU-E, CFU-F and CFU-C) was assessed both in vitro and following treatment with cyclosporin A over a 9-week period using an animal model. Cyclosporin had a differential effect on the haemopoietic progenitors, with the myeloid series unaffected at therapeutic concentrations. Both erythroid and stromal progenitors were significantly inhibited at similar concentrations. The mechanism by which cyclosporin A enhances engraftment remains unclear; however, it is not mediated by enhancing any of the haemopoietic progenitors.
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PMID:Inhibitory effect of cyclosporin A on erythroid and stromal colonies. 195 87

In conclusion, lessons from the animal model of lymphoid leukaemia suggest that in the setting of allogeneic BMT, under certain conditions GVL effects may be separable from GVHD; more specifically, GVL effects may be induced despite development of tolerance of donor cells against allogeneic host alloantigens. The latter phenomenon suggests that either curative GVL effects may be inducible despite subclinical GVHD or alternatively that effector cells of GVL may recognize different tumour-associated targets different from cell surface determinants of 'normal' alloantigens. Alternatively, effector cells of GVL may be distinguished from effector cells of GVHD. It is tempting to suggest that NK and IL2-aspirated NK cells may play a major role as effector cells of GVL in an MHC non-restricted fashion, different from classical CD8+ cytotoxic cells that certainly play a major role in GVHD and GVL. Once proven, the latter hypothesis may help develop new and safer therapeutic approaches since NK cells and products of the NK cell family are unlikely to play a major role, if any, in GVHD. The feasibility of induction of GVL-like effects by MHC non-restricted effector cells, such as that observed by CMI, most likely through cytokine-activated NK cells, seems promising because such effector mechanisms may be utilized clinically through either adoptive transfer of in vitro-activated lymphocytes or activation of lymphocytes in vivo by administration of cytokines such as IL2 and alpha IFN. Similarly, induction of CCI following ABMT may permit establishment of GVL-like effects with no major risk of GVHD. Our animal models suggest that both approaches may be beneficial and perhaps even combined. From a practical standpoint, activation of antitumour effector cells in vivo is much more feasible, in comparison with the cumbersome and expensive technologies for large-scale in vitro manipulation of IL2-activated 'LAK' cells or tumour-infiltrating lymphocytes ('TIL') at dose ranges required for obtaining clinically meaningful responses. No less important is the fact that more potent immunotherapy may be inducible by cytokine combinations (such as IL2 and alpha IFN). We are currently investigating additional cytokine combinations in order to attempt to optimize antitumour effects inducible by allogeneic and syngeneic lymphocytes since it appears logical that amplifying in vivo antitumour responses by multiple cytokine combinations may yield better antitumour effects.
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PMID:Control of relapse due to minimal residual disease (MRD) by cell-mediated cytokine-activated immunotherapy in conjunction with bone marrow transplantation. 195 88


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