Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.1.1.69 (BMT)
 2,655 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have investigated the response of unmanipulated and lymphocyte-depleted BM cells (BMC), pretreated with monoclonal rat antihuman lymphocyte (CD52) antibody (Campath-1G) used for prevention of GvHD, to incubation with rhIL-6 alone or in combination with rhGM-CSF, rhIL-3, or both. We investigated optimal conditions needed for incubation of human BMC under conditions that can be upscaled for clinical application prior to autologous (auto-BMT) and allogeneic blood or BM transplantation (allo-BMT). When used as a single agent, rhIL-6 showed no or a minimal effect in enhancing in vitro CFU-GM colony formation of human BMC. A potent additive effect was obtained when rhIL-6 was added to rhGM-CSF, rhIL-3, or a combination of both. Binding of the mAb Campath-1G, which is used for in vivo and in vitro depletion of immunocompetent lymphocytes to BMC, did not reduce the enhancing effect of a combination of rhGM-CSF and rhIL-3 on CFU-GM in the presence or absence of rhIL-6. Our present and previously published observations suggest that enhancement of hematopoiesis by rhIL-6 and other hematopoietic growth factors is T cell independent. Based on the present observations, pilot clinical studies to determine the potential benefit of in vitro activation of BMC prior to BMT with various cytokine combinations, including rhIL-6, seems justified. Our goal is to enhance hematopoietic reconstitution in vivo, focusing on possible enhancement of platelet reconstitution in vivo toward safer auto-BMT and more effective allo-BMT with better engraftment of T cell-depleted allografts while avoiding GvHD.
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PMID:Enhancement of hematopoietic reconstitution with recombinant cytokines: effect of rhIL-6 in combination with rhGM-CSF and rhIL-3 on unmodified or T cell-depleted bone marrow. 1041 47

The anti-CD52 (Campath-1) monoclonal antibodies (Mabs) have a substantial history of use for controlling graft-versus-host disease in allogeneic bone marrow transplantation. Now, with the availability of a humanised form, alemtuzumab (Campath-1H), and the demonstration that this agent can reduce the tumour burden in B-CLL, a new niche may be found - as a potentially curative agent in which its tumour purging ability in vivo combines with its role as a conditioning agent in nonmyeloablative transplantation. Review of the literature shows that alemtuzumab has unique advantages as a method of depleting malignant lymphocytes, including those in patients resistant to conventional chemotherapy. Alemtuzumab can also be used in BMT for depletion of normal T and B lymphocytes of both the recipient and donor for prevention of graft rejection and GVHD. It allows good stem cell recovery with resultant rapid engraftment, has a low risk of EBV-triggered secondary malignancy and does not interfere with blood stem cell mobilisation. As a method of eliminating the malignant clone in B-CLL, alemtuzumab has shown remarkable efficacy in heavily pre-treated patients, a number of whom have progressed to autologous or allogeneic transplantation. Efficacy data are shown within the context of other transplantation data for B-CLL. These results indicate that the combination of tumour-depleting and immunosuppressive properties of alemtuzumab should be explored, with the hope of providing improved treatment options for elderly patients with advanced B-CLL or indolent lymphoma whose prognosis is too poor currently to allow treatment with traditional regimens of high-dose myeloablative chemotherapy.
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PMID:Alemtuzumab (Campath-1H) for treatment of lymphoid malignancies in the age of nonmyeloablative conditioning? 1247 71