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)

We conclude that the most common secondary cancers which develop after marrow transplantation are lympho-proliferative disorders and solid tumors. The consequences of the secondary malignancies are serious, with more than 90% of the patients with non-Hodgkin lymphomas associated with EBV infection and more than 75% of the patients with solid tumors dying despite treatment. Secondary leukemia developing in donor T-s is rare, but was fatal in all cases. EBV infection plays a major role in leading to the non-Hodgkin lymphomas in a setting of immune dysregulation from ATG or anti-T-cell monoclonal antibody treatment of acute GVHD. Other factors are also important for development of non-Hodgkin lymphoma and include T-cell depletion of donor marrow and HLA-mismatching between donor and recipient, known to lead to dysregulation of T-lymphocyte function. These factors set up an environment of proliferative stimuli which cannot be controlled by the recovering immune system, setting the stage for a secondary cancer. The role of irradiation is becoming more prominent in association with solid tumors, particularly in aplastic anemia patients conditioned with irradiation. The final event of tumor expression is most likely the result of a cascade of events, perhaps initiated with the conditioning regimen or with stimuli to proliferation, which, after later signals, leads to malignant transformation. For lymphoproliferative disorders, the time of latency is shorter than for solid tumors, suggesting a different molecular mechanism. The incidence of oncogene expression or mutation in tumor suppressor genes in these solid tumor patients has not been investigated.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Secondary malignancies after marrow transplantation for leukemia or aplastic anemia. 780 95

Recent preclinical and clinical investigations indicate that phototherapy and photochemotherapy may have applications that go far beyond their "traditional" roles in the treatment of skin disorders, selected solid tumors, and neonatal hyperbilirubinemia. Bone marrow transplantation is one area that may benefit substantially from these new developments. This review focuses on new applications of phototherapy and photochemotherapy that pertain to the inactivation of tumor cells in autologous bone marrow grafts, the prevention and treatment of acute and chronic graft-versus-host disease, the prevention of transfusion-induced allosensitization and graft rejection, and the inactivation of pathogenic viruses and parasites in bone marrow grafts and blood products.
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PMID:Phototherapy, photochemotherapy, and bone marrow transplantation. 792 66

The prevention of graft-versus-host disease by T-lymphocyte depletion of allografts prior to bone marrow transplantation has resulted in an increase in graft failure/rejection and relapse of disease. Evidence for the selective roles of specific T-lymphocyte subsets in each of the engraftment, graft-versus-host disease, and disease relapse processes has been presented, but sufficient clinical verification to support any hypothesis in this regard is lacking. In this paper we describe a convenient and highly flexible clinical laboratory method for depletion of specific T-lymphocytes in controllable quantities by the use of select monoclonal antibodies. Almost 3 log10 removal of CD2+ and CD8+ cells without significant loss of hematopoietic progenitors (CFU-GM, BFU-E, and CD34+ cells) can be reproducibly achieved. This method, employing soybean agglutination and immunomagnetic beads, is potentially adaptable to depletion of any cell subset or any tumor cell for which unique cell-surface antigen characteristics have been defined. In addition, our protocol is equally suited to the positive selection of stem cells and hematopoietic progenitors bearing the CD34 surface antigen.
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PMID:The combined use of soybean agglutinin and immunomagnetic beads for T lymphocyte subset depletion of bone marrow allografts: a laboratory analysis. 792 14

A case control study was performed to investigate the potential advantage of allogeneic bone marrow transplantation in advanced or poorly responding neuroblastoma first remission patients using the European BMT Solid Tumor Registry. Seventeen allogeneic and 34 autologous bone marrow transplantation (BMT) cases were matched based on a number of prognostic factors including age, sex, prior treatment duration, pre-graft response status and bone and BM involvement before BMT. Only single BMT procedures are included. The median age at diagnosis was 47 months (range 18-113 months). The median follow-up time since BMT is 58 months (range 13-133 months). The only significant prognostic factor within the allogeneic BMT (p = 0.012) and autologous BMT groups (p = 0.025) was residual skeletal disease before BMT, detected by mIBG in 86% of the cases. However, the progression-free survival was not significantly different: 35% and 41% at 2 years, respectively. Only half of the allogeneic BMT patients had developed graft-versus-host disease (GVHD): 7 of 9 grade I-II and only 2 of 9 grade IV. The median donor age was very young with 74 months (range 20-240 months) and 10 of 17 were sex matched. Thus absence of GVHD risk factors in young children could be the major obstacle in achieving an anti-tumor effect with allogeneic BMT in neuroblastoma.
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PMID:Comparison of auto versus allografting as consolidation of primary treatments in advanced neuroblastoma over one year of age at diagnosis: report from the European Group for Bone Marrow Transplantation. 795 Nov 19

Bone marrow transplantation (BMT) is a valuable measure for treatment of leukemia. In order to reduce, even to eliminate, the graft versus host disease after allogenic BMT and prevent the reinfusion of tumor cells during autologous BMT, the cryopreservation of human BM after purging T-cells with immunotoxin or purging tumor cells with monoclonal antibody 55 (McAb55) was studied. Results demonstrated that: (1) treatment with McAb55 and rabbit complement (RC) did not affect the GM-CFU of BM, but treatment with immunotoxin slightly decreased the GM-CFU of BM; (2) a freeze-thawing procedure obviously decreased the GM-CFU number of BM, the GM-CFU numbers of frozen BM samples were lower than those of the nonfrozen samples; (3) there were no differences in GM-CFU numbers between normal BM and BM treated with McAb55 and RC when the cooling rate used was the same; (4) there was a negative linear correlation between cooling rates and GM-CFU numbers of BM in the cooling rate range used and the optimal cooling rate for the cryopreservation of normal BM and BM treated with McAb55 and RC or immunotoxin was the same, namely, 0.5 degrees C/min.
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PMID:Cryopreservation of human bone marrow after purging T-cells or tumor cells. 798 57

In our preceding paper, we demonstrated that both human and rat lymphocytes possess saturable high-affinity binding sites for the new sigma ligand SR 31747. Here we investigate the potential activity of this ligand on immune responses. In vitro, our study shows that SR 31747 exerts a concentration- and time-dependent inhibition of proliferative response to mitogens on mouse and human lymphocytes without affecting cell viability. This suppressive effect elicited by SR 31747 occurs over a concentration range which correlates with the pharmacological profile of the molecule in binding assays, strongly suggesting that SR 31747 acts through a receptor-mediated process. We showed that the SR 31747 effect, which was observed on purified T lymphocytes, affects a late event in the activation process which occurs after the G1 during the S phase of the cell cycle. Interestingly, no anti-proliferative effect was observed in a variety of tumor cell lines, supporting a specific effect limited to normal immune cells. In vivo, in mice, treatment with SR 31747 prevented both graft-versus-host disease and delayed-type hypersensitivity granuloma formation, while antibody response to sheep red blood cells was not affected. These results strongly suggest that the sigma-related receptor recognized by SR 31747 is very likely coupled to a biological function of lymphocytes.
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PMID:Immunopharmacological profile of SR 31747: in vitro and in vivo studies on humoral and cellular responses. 803 58

Relationship between blood transfusion and cancer is considered from five points of view: 1) The cancer patient as a blood donor. Cancer must remain a cause of exclusion from blood donation. 2) Autologous blood transfusion for cancer patients. Predeposited autologous blood transfusion is only possible for a small number of patients. Intraoperative blood salvage carries with it the risk of disseminating tumor cells. 3) History of blood transfusion and the risk of having a cancer: a) the persistence of immune alterations following blood transfusion for years might expose the patient to an increased risk of having a cancer; b) blood transfusion might carry immunosuppressive viruses, and hepatitis viruses are related to the risk of liver cancer. 4) Cancer recurrence and blood transfusion. Conclusion of most of the published studies is that blood transfusion is associated with an increased risk of recurrence of colorectal cancer. The only realistic randomized study would compare different transfusion strategies (allogenic, leukocyte poor allogenic and autologous blood transfusion) to determine which is the best for cancer patients. 5) Post-transfusion GVH in cancer patients. Some cases have recently been published. They all can be explained by a particular HLA compatibility between the recipient and one of the blood donors.
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PMID:[Transfusion and cancer]. 804 22

Allogeneic bone marrow transplantation (BMT) is associated with a severe complication--graft-versus-host disease (GVHD). Although effectively preventing GVHD, ex vivo T-lymphocyte marrow depletion unfortunately increases graft rejection and reduces the graft-versus-leukemia (GVL) effect. The ex vivo transfer of the herpes simplex thymidine kinase (HS-tk) suicide gene into T cells before their infusion with hematopoietic stem cells could allow for selective in vivo depletion of these T cells with ganciclovir (GCV) if subsequent GVHD was to occur. Thus, one could preserve the beneficial effects of the T cells on engraftment and tumor control in patients not experiencing severe GVHD. To obtain T cells specifically depleted by GCV, we transduced primary T cells with a retroviral vector containing the HS-tk and neomycin resistance (NeoR) genes. Gene transfer was performed by coculturing PHA +/- CD3- or alloantigen-stimulated purified T cells on an irradiated retroviral vector producer cell line or by incubating the T cells in supernatant from the producer. Subsequent culture in G418 for 1 week allowed for the selection of transduced cells. GCV treatment of interleukin-2-responding transduced and selected cells resulted in greater than 80% growth inhibition, whereas GCV treatment of control cells had no effect. Similarly, the allogeneic reactivity of HS-tk-transduced cells was specifically inhibited by GCV. Combining transduced and nontransduced T cells did not show a bystander effect, thus implying that all of the cells inhibited by GCV were indeed transduced. Lastly, studies involving the transduction of the HUT-78 (T-lymphoma) cell line suggest that stable expression of HS-tk can be maintained over 3 months in vitro in the absence of G418. In summary, we have established the feasibility of generating HS-tk-transduced T cells for subsequent in vivo transfer with hematopoietic stem cells and, if GVHD occurs, specific in vivo GCV-induced T-cell depletion in allogeneic BMT recipients.
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PMID:Ganciclovir treatment of herpes simplex thymidine kinase-transduced primary T lymphocytes: an approach for specific in vivo donor T-cell depletion after bone marrow transplantation? 804 49

Dose intensification of cytotoxic drugs is now being evaluated in several trials. Various methods are available to manage the hematopoietic toxicity. Hematopoietic growth factors can be used alone and/or in combination with hematopoietic stem cell rescue. Patients undergoing autologous stem cell transplantation (AuSCT) have their own bone marrow and/or peripheral blood used for hematopoietic engraftment. In several malignancies, the bone marrow is involved with tumor, and in such situations, the success of AuSCT may improve if hematopoietic elements are enriched (positive selection) or if contaminating cancer cells are purged by negative selection. In patients undergoing allogeneic bone marrow transplantation, T lymphocytes, from donor cells, contribute to the development of graft-versus-host disease (GVHD), which can result in major morbidity and mortality. The incidence of GVHD has decreased with selective purging of T lymphocytes, but further modifications are needed to improve hematopoietic engraftment. Methods for purging hematopoietic stem cells are discussed, with emphasis on the therapeutic role of purging. Growing stem cells from a small amount of bone marrow presents a new possibility. Furthermore, genetic engineering can enhance immune surveillance and decrease drug resistance. Analysis of the clinical trials utilizing various doses of cytotoxic therapy with proper methods of hematopoietic rescue will help avoid unnecessary dose escalation and help decide the optimum use of cancer treatment modalities.
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PMID:Improving the role of hematopoietic support for high-dose cytotoxic therapy. 809 59

Since the first successful attempt in 1985, peripheral blood stem cell transplants are increasingly performed worldwide and should now be considered as an essential therapeutic weapon against onco-hematological diseases. Their development has benefited greatly from a rapid concomitant advance of experimental knowledge regarding the nature of hematopoietic progenitor cells. For this reason and also for technical ones, until now these transplants generally have been autotransplants. Although one of the main reasons to use blood rather than bone marrow-derived stem cells was that they might carry less risk of relapse than autologous bone marrow cells, the lack of clinical randomized trials and/or the short follow-up make conclusions difficult so far in terms of disease-free and overall survival. Probably the risk of relapse also depends on the type of disease, on prior chemotherapies, on the type of peripheral stem cell mobilization regimen and on the number of blood-derived cells transplanted. Nevertheless, there are several major clinical indications for autologous blood stem cell transplant: acute nonlymphoblastic leukemias (ANLL), low-grade non-Hodgkin's lymphomas, multiple myeloma, some solid tumors, and even chronic myeloid leukemia. Now well-demonstrated advantages add a socioeconomic interest to this technique. The speed of post-transplant hematopoietic recovery induces a briefer hospitalization and a lower cost of the procedure, which represents "per se" important progress. Furthermore, the increasing use of hematopoietic growth factor(s) at time of blood-derived cell mobilization should increase the safety of the procedure. Also new trends are currently being developed: autotransplants with purified peripheral CD34+ cells; addition of adjuvant immunotherapy to induce graft-versus-tumor effect, which is lacking in autotransplant; and transplants using allogenic umbilical cord blood progenitors. Allogenic blood cell transplants might also be developed, provided that blood cells would be less likely to cause graft-versus-host disease (GVHD) than bone marrow, which is still not verified. Finally, the use of blood-derived cells as a vehicle for gene therapy should develop greatly in the near future.
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PMID:Peripheral blood stem cell transplantations: past, present and future. 810 Apr 62


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