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)

Bone marrow transplantation is the only treatment that can result in long-term disease-free survival and possible cure in a significant number of patients with CML. Several prognostic features influence relapse and survival following allogeneic BMT for CML. The most important factor is treatment of patients during chronic phase. The timing of BMT in chronic phase CML remains controversial, because the Seattle findings that BMT done within a shorter interval from diagnosis to transplant was associated with improved survival has not been confirmed by the IBMTR. No factor can predict in the individual patient the timing of transformation, even in patients with low-risk chronic phase CML, but we believe that allogeneic BMT should be offered as soon as possible for newly diagnosed patients who have histocompatible siblings. More widespread application of BMT in CML is possible because of effective methods for preventing GVHD, the major cause of morbidity after allogeneic BMT. However, in vitro techniques for the depletion of donor marrow T cells have resulted in higher graft failure and relapse rates. More precise understanding of the immune mechanisms involved may permit more selective depletion techniques which not only abrogate GVHD but also permit sustained engraftment and preserve GVL effect. This may extend application of BMT for patients with mismatched related or histocompatible unrelated donors. It is of interest that cytogenetic relapse after BMT is not invariably followed by hematologic relapse. It is likely that the use of polymerase chain reaction techniques which detect the bcr-abl rearrangement at a very low level will identify the persistence of the malignant clone after allogeneic BMT in even more patients. At present, the significance of such findings is unclear, but further study of the kinetics of disappearance of the CML clone post-BMT may increase our understanding of the immune mechanisms involved in suppression of the malignant clone and determine whether in fact CML can be cured using BMT approaches.
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PMID:The evolving role of bone marrow transplantation in the treatment of chronic myelogenous leukemia. 218 97

Multiple sclerosis is the most common demyelinating neurologic disease. Animal studies from three separate institutions suggest that BMT may be beneficial. Of paramount concern is the risk to benefit ratio. However, for patients with progressive disease at onset, survival is similar to patients with indolent lymphomas; while for patients with malignant MS, survival is roughly equivalent to chronic phase CML. In addition, for these patients, life may become intolerable due to progressive pain and disability. The fate of such individuals may justify, in carefully selected patients and in a controlled investigational protocol, the risk of early mortality from BMT.
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PMID:Bone marrow transplantation for multiple sclerosis. 758 Nov 7

In a patient undergoing allogeneic BMT for chronic phase CML, de novo chronic GVHD developed within 80 days after transplantation. Eighteen months post-BMT, high serum levels of neutralizing interferon-alpha (IFN-alpha) antibodies were detected, which persisted despite continuous immunosuppressive treatment. The antibodies were of oligoclonal or polyclonal origin, predominantly of the IgG1 type, and reacted broadly with various human IFN-alpha types, including the patients endogenous IFN-alpha, but failed to recognize natural IFN-beta and recombinant IFN-gamma. Pathogenesis and clinical impact of the IFN-alpha antibodies are unknown. Antibodies of cytokines are a novel class of autoantibodies that may develop after allogeneic BMT and interfere with cytokine homeostasis and immune regulation.
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PMID:High-titre interferon-alpha antibodies in a patient with chronic graft-versus-host disease after allogeneic bone marrow transplantation. 799 79

Between January 1985 and March 1992, 48 patients with chronic phase CML underwent BMT from volunteer unrelated donors (MUD) serologically identical at HLA-A, B and DR loci. 19 patients received donor marrow ex vivo T-cell depleted (EX-TCD) with Campath monoclonal antibodies. 29 patients received unmanipulated donor marrow with CsA/MTX GVHD prophylaxis; 28 received additional intravenous antilymphocyte therapy from day +1 to +5 (IN-TCD). Overall 26 patients survive at median follow up of 362 days; actuarial survival at 3 years is 50%. 3 patients have sustained haematological relapse; actuarial leukaemia-free survival is 38%. There is no difference in overall survival between the EX-TCD and IN-TCD groups, but primary graft failure (n = 4) occurred only in the EX-TCD group, while GVHD (grade II or greater) occurred more frequently in the IN-TCD group (61% vs. 29%, p = 0.084). The optimum method for GVHD prophylaxis in MUD BMT remains uncertain.
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PMID:Matched unrelated donor bone marrow transplantation for chronic myeloid leukaemia in chronic phase: comparison of ex vivo and in vivo T-cell depletion. 844 31

Donor mononuclear cell (MNC) infusions provide a very potent and effective anti-leukemic therapy. For patient's with CML who relapse after allogeneic BMT, the administration of donor MNC can result in a direct GVL effect and re-establish sustained remissions, even when assessed by very sensitive PCR-based techniques. The GVL reaction appears to be most prominent in patients with chronic phase CML. It is less apparent for patients with more advanced stages of CML or for patients with relapsed acute leukemia and myelodysplasia, although only small numbers of these patients have been treated. While the majority of patients tolerate this therapy very well, treatment related morbidity and mortality is still quite significant, and efforts to limit the severity of GVHD, and to recognize and treat marrow aplasia early may be useful. Longer follow-up of patients who have achieved complete remission will be required to determine if this therapy will have an impact on long term disease free survival, but at the current time, it would seem to be a very acceptable alternative to a second BMT.
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PMID:Adoptive immunotherapy for relapsed leukemia following allogeneic bone marrow transplantation. 858 Jul 87

Thirty-two adults (median age 36 years) with leukemia (15 AML, eight CML, six ALL, three CLL) persisting or relapsing 1-40 months (median 4) after allogeneic BMT (20 matched siblings, eight unrelated, four family mismatch) underwent immunotherapy to elicit GVHD. This comprised one or more of: infusion of donor cells (n = 22), stopping cyclosporine (n = 14), and administration of interferon-alpha2b (n = 15) or interleukin-2 (n = 4). Eight acute leukemia patients received chemotherapy as well. The time from relapse to immunotherapy was 0-1344 days (median 4). Acute and/or chronic GVHD developed in 17 patients. Response was not evaluable in three patients due to early toxic death. There was no response in 10 patients, whereas 19 showed objective response. Nine patients died due to toxicity and 10 due to progressive disease. Thirteen patients are alive 4-58 months (median 14) after immunotherapy; 12 in remission (five AML, four chronic phase CML, one ALL, one accelerated phase CML, one CLL) and one with progressive disease (accelerated phase CML). Eleven of 13 patients who are alive had GVHD compared with six of 19 who died (P = 0.005, Fisher's exact test). We conclude that with the exception of CML in myeloid blast crisis, immunotherapy is active in most types of acute and chronic leukemia relapsing after allogeneic BMT. It is associated with considerable toxicity. Clinically obvious GVHD, especially chronic GVHD, results in a higher probability of survival.
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PMID:Induction of graft-versus-host disease as immunotherapy of leukemia relapsing after allogeneic transplantation: single-center experience of 32 adult patients. 924 16

Timing of transplantation in the chronic phase of chronic myeloid leukemia (CML) and previous treatment with interferon remains controversial. We have tried to discover what influence pretreatment with interferon alpha (IFN-A) has on the results of allogeneic bone marrow transplantation for CML patients treated in a single institution. Fifty-one consecutive patients with chronic phase Ph-positive CML who received an allogeneic bone marrow transplantation from a HLA-identical familial donor were evaluated. Thirty had been treated with IFN-A (IFN+ group) prior to BMT and twenty-one had not (IFN- group). Both groups were homogeneous for clinical characteristics such as age, sex, previous chemotherapy, disease status, and time from diagnosis to transplant. No difference was found in neutrophil and platelet count recovery between the IFN+ and IFN- group. The incidence of acute and chronic GVHD, VOD and severe mucositis was not significantly different. Relapse and both overall survival and DFS were similar for both groups. No adverse effects of prior IFN exposure on the outcome of HLA-identical sibling donor BMT for chronic phase CML patients were found in this study.
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PMID:Absence of influence of prior treatment with interferon on the outcome of allogeneic bone marrow transplantation for chronic myeloid leukemia. 967 95

Five years after the diagnosis of Ph chromosome-positive chronic myeloid leukemia (CML) a 31-year-old patient developed malignant nephrosclerosis with renal failure. He then underwent an allogeneic unrelated BMT in first chronic phase CML. The preparative regimen consisted of fractionated total body irradiation (TBI) and cyclophosphamide (CY). We studied the pharmacokinetics of cyclophosphamide on hemodialysis and compared clinical parameters including time to engraftment and toxicity with parameters of a patient with normal renal function who also received an unrelated marrow as treatment for CML in first chronic phase. Our results suggest that TBI/CY is a suitable conditioning regimen for allogeneic transplantation in patients with hematological malignancy and renal failure on hemodialysis.
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PMID:Total body irradiation and cyclophosphamide is a conditioning regimen for unrelated bone marrow transplantation in a patient with chronic myelogenous leukemia and renal failure on hemodialysis. 975 50