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)

The active immunization of bone marrow (BM) donors with myeloma immunoglobulin (Ig) results in an idiotypic T cell response that can be transferred to the recipient. Using a murine model we evaluated the effectiveness, side-effects and underlying mechanisms of this approach. Balb/c (H-2d) mice were given a dose of HOPC-1F myeloma cells secreting the monoclonal IgG2a followed by lethal total body irradiation (7.5 Gy) 2 days later and a subsequent transplantation of 2 x 10(7) allogeneic MHC-matched DBA/2-derived marrow cells. Donors were pre-immunized with three i.p. injections of HOPC(IgG2a) or control Ig given with incomplete Freund's adjuvants (IFA) spaced 1 week apart. In some experiments, donor-spleen cells were additionally transferred 2 h post transplant. Injection of HOPC-myeloma led to death of all animals after a median survival time (MST) of 42 days. A lethal dose of TBI followed by transfer of unmanipulated marrow grafts plus splenocytes resulted in moderate antimyeloma effects with 8% of mice achieving long-term survival. Nearly the same results were obtained after transplantation of BM immunized with the control Ig. In contrast, transplantation of marrow grafts from HOPC(IgG2a) immunized donors exerted a significant GVM effect with 63% long-term survival for more than 180 days. The additional transfer of 2 x 10(7) immune splenocytes derived from the same donor resulted in even stronger anti-myeloma effects (FFR 87%). No increase in the incidence of severe acute GVHD was observed. In vitro data suggest that allogeneic CD8+ idiotype-specific T cells may be the major effector cells. Our results demonstrate that active immunization of the donor with the myeloma-specific Ig can induce powerful graft-versus-myeloma effects after allogeneic BMT.
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PMID:Transfer of idiotypic protein primed allogeneic marrow grafts elicits potent graft-versus-myeloma effects in mice. 1127 75

Progress in allogeneic SCT will depend on several factors including the advances in the conventional treatment of diseases treated currently with allogeneic SCT, the expansion of the donor pool, the selective control of GVHD, the development of more effective and less toxic preparative regimens to eradicate the neoplastic cell population, the characterization of a new generation of hematopoietic growth factors and cytokines and the development of newer and safer techniques for ex-vivo manipulation of stem cells. The use of hematopoietic growth factor-mobilized donor progenitor cells collected from the peripheral blood has been associated with a rapid hematopoietic engraftment without an increase in the incidence of acute GVHD compared to allogeneic BMT, an increased donor acceptance, elimination of the risk of general anesthesia and a decreased cost. The use of nonmyeloablative conditioning regimens prior to SCT represents a novel treatment approach that may lead to reduced toxicity and an extended use of this treatment in older patients and those with co-morbid conditions and in the treatment of malignant and non-malignant disorders. This approach may play a role in inducing tolerance for solid organ transplantation and in utilizing the GVM effect to treat solid tumors that are not fully responsive to myeloablative cytotoxic regimens. The optimal intensity of cytoreduction and immunosuppression is not well defined. GVHD and disease recurrence remain a challenge. Promising results have been reported in patients with refractory hematologic malignancies as well as in metastatic renal cell cancer, but the ultimate role of this treatment modality remains to be defined pending prospective, well designed, randomized trials.
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PMID:Current concepts in allogeneic hematopoietic stem cell transplantation. 1498 67