Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.1.1.69 (BMT)
2,655 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Allogeneic BMT and IFN-A-based therapy have undoubtedly changed the natural history of CML. Despite these advances, many patients still die from their disease. Most patients do not qualify for an allogeneic BMT either because of age or lack of an appropriate donor, and only a fraction of patients achieve a complete cytogenetic remission with IFN-A-based therapy. The timing of BMT and treatment sequences of IFN-A and BMT have been discussed. Prior treatment with IFN-A does not seem to affect transplant outcome; however, delaying transplantation has been reported to impact adversely on transplant results. Until controlled trials are performed, the issue of optimal timing of allogeneic BMT will remain controversial. The use of alternative donors may extend the option of allogeneic BMT to younger patients; however, for older patients this therapeutic modality still has an unacceptably high incidence of morbidity and mortality with current BMT regimens and other alternative treatments are needed. Investigational strategies searching for ways of improving the proportion of patients achieving complete cytogenetic remissions with IFN-A therapy need to be actively explored. These include new agents (eg, HHT) or new modalities such as intensive chemotherapy with autologous stem cell transplantation with in vitro purging. Investigators in the field must decide whether to continue randomized trials of IFN-A versus conventional chemotherapy, or to explore strategies that may enhance the effect of IFN-A-based therapy. Only when the durable cytogenetic response rates with IFN-A combinations increase to 40% or 50% will it be of value to proceed to phase III trials. Further understanding in the basic biology of CML and the effect of IFN-A in this disease will also provide clues to improving therapy with the goal of obtaining long-term disease control and cures in the majority of patients with the least burden of therapy.
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PMID:Treatment of chronic myelogenous leukemia. 763 36

Based on our understanding of CML, we recommend that patients age 65 or less with newly diagnosed CML should be evaluated to determine the stage of their disease and should be human lymphocyte antigen-typed along with their siblings. Patients age 55 years and younger who have matched or single antigen mismatched siblings should be advised to undergo BMT as soon as possible and patients up to age 65 should be considered for BMT early in their disease course if in good health. Patients age 55 years or younger without appropriately matched family member donors should have a search for an unrelated donor initiated and should be offered BMT if an appropriate donor is found. Patients for whom no donor is found and older patients without family matches can be considered for entry onto clinical trials evaluating autologous BMT or other experimental approaches.
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PMID:Bone marrow transplantation for chronic myelogenous leukemia. 763 37

Unrelated donor bone marrow transplantation is increasingly used to treat haemopoietic disorders where no HLA-identical sibling is available. The International Marrow Unrelated Search and Transplant Study has collected core data on consecutive unrelated donor BMT (UD-BMT) and HLA-identical sibling donor BMT (ID-BMT) performed in 46 participating centres world-wide between March 1989 and February 1993. Eighteen UD-BMT were performed in the first 6-month period in 14 participating centres, while in the last period there were 103 UD-BMT in 46 centres. The percentage of BMT recipients with the following diagnoses were: bone marrow failure UD-BMT 15% and ID-BMT 11%; AML 13% and 27%; ALL 18% and 17%; CML 48% and 31%; and other diseases 7% and 14%. Thirty-eight per cent of UD-BMT recipients had advanced disease compared with only 23% of ID-BMT recipients. Thirty six per cent of UD-BMT compared with 21% of ID-BMT recipients were under 16 years old. More extreme differences in pre-transplant clinical characteristics between UD and ID-BMT recipients were found when diagnosis and stage of disease were considered together. This survey indicates how UD and ID-BMT are currently used in the treatment of haematological disease; however, longer follow-up is required to assess the value of UD-BMT in the management of patients with bone marrow disorders.
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PMID:A survey of use of unrelated volunteer donor bone marrow transplantation at 46 centres worldwide, 1989-93. International Marrow Unrelated Search and Transplant (IMUST) Study. 765 72

To evaluate the safety and efficacy of marrow transplantation for older adults, the regimen-related mortality and event-free survival for patients > or = 40 years were compared with those for patients < 40 years. Of 148 consecutive patients receiving autotransplants for lymphoma or Hodgkin's disease, 70 were < 40 years and 78 were > or = 40 years at the time of transplant, including 40 who were > or = 50 years and 12 who were > or = 60 years. Eleven patients (16%) in the younger age group died from transplant-related complications compared with 4 (5%) in the older age group. The 4-year actuarial event-free survivals (EFS) for the younger and older age groups were 43% and 48%, respectively. After adjustment for covariates with prognostic significance, older age was marginally associated with improved event-free survival (P = 0.08). Of 92 consecutive patients undergoing allogeneic BMT during the same period, 62 patients were < 40 years and 30 patients were > or = 40 years, including 8 patients > or = 50 years, and 1 patient > 60 years. Non-relapse mortality (including deaths from GVHD) occurred in 28 of the younger patients (45%) and 9 of the older patients (30%). The 3-year actuarial EFS for the younger patients was 26% vs. 56% for the patients > or = 40 years (P = 0.057). However, this difference was mainly due to the higher proportion of patients with CML and early-stage leukemia in the older age group.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Patients > or = age 40 years undergoing autologous or allogeneic BMT have regimen-related mortality rates and event-free survivals comparable to patients < age 40 years. 765 76

Among 42 consecutive recipients of unrelated marrow were 39 HLA-A, -B, -DR identical, matched unrelated donors (MUD) and three with one HLA antigen mismatch. The majority were genomically typed for DRB, DQA, DQB and DPB. The recipients of MUD marrow were compared with 39 recipients of marrow from HLA-identical siblings with similar diagnoses, disease status and age. Each group included 24 patients with hematological malignancies, 6 with severe aplastic anemia and 9 inherited disorders. Immunosuppression consisted of anti-thymocyte globulin (ATG; pre-BMT mainly to recipients of unrelated marrow), CsA and four doses of MTX. Grade I acute GVHD was treated with prednisolone 2 mg/kg. In a comparison of MUD marrow recipients and HLA-identical siblings 34 of 39 and 36 of 39 of the patients engrafted, respectively. Recipients of MUD marrow and HLA-identical siblings achieved 0.2 x 10(9) WBC/l on day 16 (median) and 14, respectively (P = 0.03). Furthermore, the recipients of MUD marrow needed more platelet transfusions (P = 0.04). The incidence of acute GVHD grade II-III was 15% in the MUD marrow recipients compared with 11% among the HLA-identical siblings. The 2-4 year cumulative incidence of chronic GVHD was 29% and 22% in the two groups, respectively. The overall 2-year survival was 59 and 78%, respectively. Among patients with CML in chronic phase or accelerated phase (n = 26), 2-year relapse-free survival was 79% in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Similar incidence of graft-versus-host disease using HLA-A, -B and -DR identical unrelated bone marrow donors as with HLA-identical siblings. 765 90

Epstein-Barr-associated lymphoproliferative disorders have been described as complications of immunodeficiency states including allogeneic BMT. There is, however, only one report in the English language literature of such a disorder after autografting. We report a 56-year-old man undergoing autologous BMT for CML in whom a rapidly progressive lymphoproliferative disorder showing the histology of typical post-transplant lymphoproliferative disorder with latent EBV presence developed at approximately 30 days after BMT. Therapy with corticosteroids, acyclovir and alpha-interferon was instituted and led to prompt resolution of symptoms and signs. There was no evidence of lymphoproliferative disease at 7 months after BMT. It is concluded that EBV-associated lymphoproliferative disorders may be a complication, albeit a rare one, of intensive therapy with autologous stem cell support.
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PMID:Polyclonal Epstein-Barr virus-associated lymphoproliferative disorder following autografting for chronic myeloid leukemia. 765 94

Organ toxicity in BMT may in part be due to free radical damage. Therefore the 'Total Radical-trapping Antioxidant Parameter of plasma' (TRAP), individual plasma antioxidants, serum iron and linoleic acid, a main substrate of lipid peroxidation, were monitored before and after BMT, and they were compared with values obtained from healthy controls. Seven patients (3 AML, 3 CML, 1 multiple myeloma) receiving 16 mg/kg busulfan, 30-45 mg VP-16 and 120 mg/kg cyclophosphamide were investigated. TRAP values declined during chemotherapy by about 40% (day -9: 1019 +/- 245 mumol/l, mean +/- s.d.; day 0: 660 +/- 164 mumol/l; P < 0.05). The concentration of uric acid, one of the main antioxidants in plasma, decreased markedly (day -9: 339 +/- 108 mumol/l, day 0: 148 +/- 61 mumol/l; P < 0.05) and paralleled TRAP values. Vitamin E and bilirubin did not change from day -9 to 0 whereas vitamin C increased (day -9: 46 +/- 16 mumol/l, day 0: 89 +/- 44 mumol/l; P < 0.05). Serum iron rapidly increased within the pre-transplantation period, reaching values normally seen only in iron overload (day -9: 11.8 +/- 5.2 mumol/l, day 0: 40.6 +/- 6.5 mumol/l; P < 0.05). Linoleic acid levels were normal at the start and decreased substantially (27.0 +/- 1.6 wt% at day -9; 15.7 +/- 4.9 wt% at day 0; P < 0.05), indicating possible lipid peroxidation during high-dose chemotherapy. In conclusion, complex monitoring of the antioxidant status before and after BMT revealed a breakdown of plasma antioxidant defence and of radical-vulnerable lipids, which was associated with high circulating levels of iron.
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PMID:Deteriorating free radical-trapping capacity and antioxidant status in plasma during bone marrow transplantation. 767 Apr 3

A 48-year-old woman underwent allogeneic BMT for CML in chronic phase. One day +180 she experienced fever (37.8 degrees C) and skin rash. Blood cultures from the Hickman catheter and peripheral veins were positive for Saccharomyces cerevisiae. The clinical course of this patient indicates that Saccharomyces should be considered as a possible cause of fever of otherwise unknown origin.
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PMID:Saccharomyces cerevisiae fungemia with granulomas in the bone marrow in a patient undergoing BMT. 767 Apr 7

A case of fulminant rhabdomyolysis occurring 4 months after allogeneic BMT for CML is reported. The patient developed rhabdomyolysis following the empiric institution of antibacterial and anti-tuberculous medication. His inpatient course was complicated by the development of acute anuric renal failure and a severe myopathy. With aggressive supportive care, both of these complications resolved, making this patient the only reported survivor of rhabdomyolysis occurring after BMT.
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PMID:Recovery from rhabdomyolysis after allogeneic BMT: report of a case with speculation on causation. 767 Apr 12

Twenty-five patients with CML (chronic phase (CP): 15 patients; accelerated phase (AP): 10 patients) at a median of 40 months after diagnosis and ineligible for allogeneic BMT, received an intensive chemotherapy regimen consisting of idarubicin, intermediate-dose ara-C and etoposide (ICE protocol). All patients had previously received alpha-interferon and only two patients had had partial cytogenetic response. During recovery from chemotherapy-induced aplasia, blood progenitors cells (BPC) were harvested by leukapheresis. All metaphases were found to be Ph-negative in the collection of 12 of 25 (48%) patients (CP: 9 of 15 (60%), AP: 3 of 10 (30%)) and a decrease of < 50% Ph-positive metaphases was seen in an additional five (CP: 4 patients; AP: 1 patient). The percentage of complete Ph-disappearance was 66% in patients receiving this procedure within the first 2 years of diagnosis and 30% in those treated after the second year of diagnosis. So far, the Ph-negative collections have been used in 9 patients (CP: 8 patients; AP: 1 patient) as autograft after conditioning with total body irradiation/etoposide/CY. Seven of 9 patients engrafted and 5 are alive and well, Ph-negative at 2+, 3+, 6+, 10+ and 18+ months.
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PMID:Collection of 'normal' blood repopulating cells during early hemopoietic recovery after intensive conventional chemotherapy in chronic myelogenous leukemia. 769 24


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