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 efficacy of graft-vs.-leukemia induction to treat relapses after allogeneic progenitor cell transplant in a variety of hematologic malignancies suggest that it may be possible to use the graft versus leukemia as primary therapy for these malignancies without the need of myeloablative therapy. This type of strategy should be explored initially in patients considered ineligible for conventional myeloablative therapies either because of age or concurrent medical conditions. GVHD remains a major obstacle that needs to be overcome. Although a potentially lower level of inflammatory cytokines may be present after non-myeloablative therapies, fatal GVHD still occurs. Methods to diminish GVHD after allogeneic transplant include selective T-cell depletion (39-43) and transduction of donor T-cells with Herpes simplex virus thymidine kinase which renders these cells sensitive to ganciclovir treatment (see chapter 16). We and others have demonstrated that nonablative chemotherapy using fludarabine combinations is sufficiently immunosuppressive to allow engraftment of allogeneic blood progenitor cells. Patients could then receive graded doses of donor lymphocytes without rejection, to mediate GVL. Ideally, this therapy could be titrated to levels of residual malignant cells using sensitive detection techniques. This novel approach to therapy would reduce the toxicity of the transplant procedure, allow it to be administered more safely to debilitated patients and possibly extend the use of transplantation to older patients who are not presently eligible for BMT procedures. Other possible indications include treatment of non-malignant disorders and induction of tolerance for solid organ transplantation.
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PMID:Non myeloablative "mini transplants". 1080 Jun 46

A 45-year-old matched unrelated BMT recipient had sequential mucocutaneous herpes simplex virus (HSV) type 2 infections. Five months after BMT, a penile lesion occurred and was cured using acyclovir, as expected from in vitro susceptibility results. The same lesion recurred 1 month later but worsened with acyclovir. The HSV isolate was resistant to acyclovir (IC(50) = 105 microM), and a nucleotide (G) was added to the thymidine kinase gene leading to a premature stop codon. The lesion improved markedly with foscarnet. During this treatment a second HSV infection occurred on the buttocks 2 weeks after the first one and healed completely with acyclovir. This course correlated with in vitro results of the buttock HSV isolate which was foscarnet-resistant (IC(50) = 300 microg/ml) and acyclovir-sensitive. Surprisingly, no mutation gene of the foscarnet-resistant isolate was detected in the DNA polymerase gene. This case shows that an HSV acyclovir-resistant infection may be followed by an acyclovir-sensitive one. Determination of antiviral susceptibility is needed to monitor the treatment of various HSV infections in immunocompromised BMT recipients.
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PMID:Multiple herpes simplex virus infections with various resistance patterns in a matched unrelated donor transplant recipient. 1178 35

Administration of herpes simplex thymidine kinase (HSV-tk)-expressing, gene-modified T cells (GMCs) with T cell-depleted bone marrow transplantation (TCD-BMT) can allow modulation of posttransplantation alloreactivity. Twelve patients received 2 x 10(5) to 2 x 10(6) CD3+ donor GMCs per kilogram with HLA-identical sibling TCD-BMT. Despite extensive T cell depletion of bone marrow, an intensive conditioning regimen, and immunosuppressive graft-versus-host disease (GvHD) prophylaxis, infusion at the time of TCD-BMT of this low number of GMCs sufficed to induce a rapid GMC-specific immune response, as detected by interferon- enzyme- linked immunospot assay in six of eight patients, preferentially targeting HSV-tk. Maximal responses were reached early (median time, 49 [35-68] days post-BMT), with a subsequent rapid and significant decrease in five of six evaluable patients. Immune responses were negatively correlated with the maximal circulating GMC counts. However, such immune response did not result in the elimination of circulating GMCs and was not associated with measurable ex vivo cytotoxic activity against GMCs. Furthermore, alloreactive GMCs still could induce GCV-sensitive GvHD in one patient despite an ongoing immune response. Overall, infusion of HSV-tk-expressing GMCs at the time of BMT results in an early immune response. Such immune response may be altered and may not prevent persistent GCV-sensitive alloreactivity.
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PMID:Early immune response against retrovirally transduced herpes simplex virus thymidine kinase-expressing gene-modified T cells coinfused with a T cell-depleted marrow graft: an altered immune response? 1881 Jul 97

A 28-year-old female presented with an isolated extramedullary relapse in the breast following an unrelated allogeneic bone marrow transplantation(UBMT)for acute lymphoblastic leukemia. She complained of a tumor in her right breast with hematological complete remission 23 months after her first UBMT. The extramedullary lesion resolved with chemotherapy, and she then received a second UBMT. Although there had been no relapse of leukemia in the bone marrow and extramedullary sites, she died from a herpes simplex virus infection in the central nervous system. Extramedullary relapses in the so-called 'sanctuary'sites after hematopoietic stem cell transplantation are unusual, and breast recurrences are even more rare. A treatment strategy for unusual sites of relapse after BMT should be established.
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PMID:[Extramedullary relapse of acute lymphoblastic leukemia in the breast after unrelated allogeneic bone marrow transplantation]. 2279 47


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