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)

Fifty-one children between 26 and 214 months of age (median, 100 months) with acute lymphoblastic leukemia (ALL) were grafted in second remission from HLA-identical sibling donors (except for two patients who were grafted with a marrow with 1 antigen-mismatch). Initial treatment and relapse therapy were similar in all patients according to the BFM- and CoALL-protocols (front line: 38 patients according to BFM-protocols and 13 patients according to CoALL-protocols; relapse: 12 patients in study ALL-REZ-BFM 83, 17 in ALL-REZ-BFM 85, 20 in ALL-REZ-BFM 87, and two in ALL-REZ-BFM 90). The conditioning regimens were different, consisting of cyclophosphamide (CY) total body irradiation (TBI) plus (n = 27), VP-16-TBI (n = 23), and CY-TBI and ARA-C (n = 1). Three patients had a second graft after conditioning with CY-TBI for the first transplantation. The second ablative regimen consisted of CY plus VP-16 in the first patient and CY plus busulfan in the two other patients, one of whom relapsed again. All patients but three had bone marrow (BM), either isolated or combined, relapses. Twenty-nine of the patients are in continuous complete remission (CCR), ranging from 1 to 67 months after transplantation with a median time of 30 months. One patient was lost to follow-up in continuous remission. Nine patients died from treatment-related complications (infections and graft-versus-host disease) and 12 patients suffered a leukemic relapse; three of them received a second graft and two are in CCR. Kaplan-Meier analysis yields an event-free survival (EFS) of 0.52 +/- 0.08. The probability of a 7-year relapse-free interval (RFI) is 0.68 +/- 0.08. EFS for patients with late relapses is 0.47 +/- 0.12 and for patients with early relapses 0.56 +/- 0.1. The RFI for patients with late relapses is 0.65 +/- 0.12 and for patients with early relapses 0.69 +/- 0.11. There is a nonsignificant trend towards superior results for patients grafted after conditioning with VP-16 plus TBI. When all patients who are not in CCR at day +125 (which is the median interval between relapse diagnosis and BM transplantation [BMT]) are excluded from the chemotherapy results, there is no significant difference between the results of BMT and chemotherapy for late relapses. On the other hand, there is a significant advantage between chemotherapy and BMT for early relapses over chemotherapy (P less than or equal to .01).
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PMID:Allogeneic bone marrow transplantation for childhood acute lymphoblastic leukemia in second remission after intensive primary and relapse therapy according to the BFM- and CoALL-protocols: results of the German Cooperative Study. 182 71

An artificial mixture of breast cancer cell line cells (T-47D) and normal human marrow cells was used to investigate optimal approaches for autologous BMT. The experiments were designed to test the applicability of chemocytotoxic agents, a dye-mediated photolytic agent and SBA for in vitro purging in autologous BMT of patients with advanced malignancies. Treatment with high concentration of etoposide (VP-16) (10 to 80 micrograms/ml) resulted in a maximal depletion of 1.5 log, whereas more efficient tumor cell eradication (2.5 log) was achieved by 30-min incubation with 100 micrograms/ml4HC. Photosensitization by exposure for 90 min to daylight in the presence of MC-540 could remove only 1 log of T-47D cells. The chemocytotoxic treatment with 4HC was chosen to follow initial tumor cell separation by SBA bound to polystyrene magnetic beads that had previously been shown to bind to several cancer cell types while sparing marrow progenitor cells. Artificial mixtures containing 10 to 14% T-47D cells in fresh normal BM cells were subjected to SBA-magnetic beads, and the SBA-negative fraction was further treated with 4HC. The combined two-step procedure resulted in a consistent tumor cell depletion of greater than 4 logs. The purging procedure appears acceptable for clinical marrow purging prior to cyropreservation and autotransplantation in patients with documented BM involvement of neoplastic cells sensitive to 4HC with positive binding to SBA such as breast cancer.
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PMID:Combination of magnetic and chemocytotoxic cancer cell depletion for autologous bone marrow transplantation. 306 Apr 42

Between 1983 and 1993, 42 patients with acute lymphoblastic leukemia (ALL) in second complete remission (CR) underwent an allogeneic HLA-identical bone marrow transplant (BMT; there was one family mismatched graft). The conditioning regimens varied, consisting of cyclophosphamide (CY) and total body irradiation (TBI; n = 10); CY, TBI, Ara C, VP-16 (n = 11); TBI, Ara C, melphalan (n = 20) (TAM) or other (n = 1). Cyclosporine A (CsA) (n = 15) or CsA and methotrexate (MTX) (n = 24) were the main regimens for prophylaxis of graft-versus-host disease (GVHD). Nineteen of 42 patients are alive in CR ranging from 1 to 72 months after BMT with a median follow-up of 36 months. The 4-year actuarial survival rate was 53%. The actuarial relapse rate was 17%. Twenty three patients died: 4 patients of leukemic relapse, 9 of infection, 2 of acute GVHD, 2 of multiorgan failure after chronic GVHD, 2 of a secondary tumour and 4 patients died of other causes. Several pre- and post-transplant characteristics were analyzed to determine predictive factors for survival, relapse and GVHD. The relapse rate was significantly influenced by the type of conditioning regimen with no relapse in the TBI, Ara C, melphalan group. The analysis of long-term sequelae shows that there are no severe complications in this last group. Our results confirm that allogeneic BMT can lead to long-term survival for children with ALL in second CR and suggest an advantage of using the TAM conditioning regimen in the eradication of the leukemic disease.
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PMID:Allogeneic bone marrow transplantation for childhood acute lymphoblastic leukemia in second remission: factors predictive of survival, relapse and graft-versus-host disease. 758 Oct 95

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

The activation of autologous cytotoxic cells by interleukin-2 (IL-2) may be a promising tool for elimination of minimal residual blast populations in patients with acute myelocytic leukemia (AML) to prolong disease-free survival. Here, we report the results of a phase II study using IL-2 for consolidation therapy in patients with second remission of de novo AML. All patients in 1st relapse of AML received a uniform induction therapy consisting of intermediate high-dose AraC (iHDAraC) 2 x 600 mg/m2 d1-4 and VP-16 100 mg/m2 d1-7. Patients achieving 2nd remission were treated with 4 cycles recombinant IL-2 (rIL-2) 9 x 10(6) IU/m2 administered on d1-5 and 8-12/cycle as 1h infusion every six weeks. In 37/66 (56%) evaluable patients, complete remission (CR) was achieved. So far, 21/37 patients (4 after additional autologous bone marrow transplantation (ABMT) received rIL-2 consolidation. Three patients are too early for evaluation, 4 received allogeneic BMT, 6 relapsed before IL-2 was scheduled and 4 refused treatment with rIL-2. The median disease-free survival (DFS) was 11 (4-49+) months. Up to now, in 5/21 (24%) patients the duration of 2nd remission exceeded that of 1st remission 7/21 (33%) are in ongoing 2nd remission (7+ to 49+ months). The side effects of rIL-2 were generally moderate and manageable. Only in two patients, previously treated with ABMT, severe side effects occurred; septicaemia and pneumonia in one patient and desquamative erythrodermia in the second one. In accordance with other studies rebound lymphocytosis with a marked increase of CD56(+)-cells and release of secondary cytokines such as TNF-alpha, IFN-gamma and IL-6 was observed. The schedule is feasible and the data suggest a possible benefit for DFS, which, however has to be confirmed by randomized trials.
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PMID:Interleukin-2 bolus infusion as late consolidation therapy in 2nd remission of acute myeloblastic leukemia. 771 35

In 1983, we began a series of clinical trials with the goal of reducing the relapse rate following allogeneic BMT for hematologic malignancies. Because of its anti-leukemic activity, the drug VP-16 was chosen and combined with total body irradiation (TBI). The first series (trial I) consisted of patients who had advanced leukemia. This trial showed a relapse rate of 32% and a disease-free survival rate of 43%. Thereafter, this regimen was tested in a randomized trial (trial II) under the auspices of the Southwest Oncology Group (SWOG study 8612). The FTBI/VP-16 regimen was compared with the combination of busulfan and cyclophosphamide (BU/CY). A recent analysis indicates a disease-free advantage for patients prepared with FTBI/VP-16; however this difference is not statistically significant. In another trial (trial III), patients in their first remission of leukemia were prepared with the FTBI/VP-16 regimen and long-term disease-free survival was found to be 60-70% with a relapse rate of approximately 10%. These results compare favorably with data obtained with alternative preparatory regimens. The FTBI/VP-16 regimen is currently being compared to the 'standard' regimen, FTBI/CY, in a prospective trial (trial IV). Since the regimen-related toxicity has been relatively low, we have added one dose of CY 60 mg/kg to the FTBI/VP-16 combination. This regimen (trial V) is currently being tested in patients with advanced leukemia. The preliminary results of this ongoing trial indicate further improvement in disease-free survival through a reduction of the post-transplant relapse rate.
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PMID:Role of etoposide (VP-16) in preparatory regimens for patients with leukemia or lymphoma undergoing allogeneic bone marrow transplantation. 772 33

The introduction of VP-16 into high-dose therapy regimens used for conditioning before BMT or PBSCT has resulted in higher remission rates and prolonged disease-free survival, even in high risk patients. VP-16 levels have been measured in plasma at the time of transplantation. The question is, is there a biological activity that corresponds with the risk of delayed engraftment or graft failure? We investigated the inhibitory effects of plasma samples obtained from patients under high-dose VP-16 therapy on the growth of human bone marrow progenitor cells. Bone marrow cells from healthy donors were exposed to the plasma samples and seeded into methylcellulose-culture (CFU-C-assay). We found a dose dependent CFU-C inhibition related to VP-16 plasma levels at the time of transplantation (k = 0.769, P < 0.01). There were signs of a correlation between CFU-C growth inhibition at the time of BMT and haematological recovery (k = 0.656, P < 0.05) between CFU-C inhibition and the time until leucocytes reached 0.2 x 10(9)/l. Patients with CFU-C growth inhibition at the time of BMT may show delayed engraftment of leucocytes and that there might be a correlation with VP-16 levels, but further investigation is necessary to determine the significance of the latter thesis and if VP-16 plasma levels could lead to failure of engraftment. We recommend a minimum time interval between VP-16 infusion and graft transplantation of 72 h.
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PMID:Inhibition of CFU-C growth by VP-16 containing plasma samples obtained from patients after conditioning therapy for bone marrow transplantation. 774 62

Seven patients with relapsed acute leukemia (4 ANLL, 3 ALL) and one with juvenile chronic myelomonocytic leukemia (JCMML) received a second BMT (BMT2). Patients were conditioned with CY/TBI (n = 7) or BU/CY (n = 1) for the first BMT (BMT1), with adequate recovery in all and without the appearance of acute GVHD (n = 3) or with mild forms (grade I, n = 2; grade II, n = 3). Relapse after BMT1 occurred in < 6 months (n = 2), between 6 and 12 months (n = 5) and > 12 months (n = 1), and the interval from BMT1 to BMT2 was < 6 months (n = 1), from 6 to 12 months (n = 5) or > 12 months (n = 2). Conditioning for BMT2 was done in untreated relapse and included combinations of BU/CY (n = 2), CY/TBI (n = 1) or BU 1 mg/kg at intervals of 6 h by mouth on days -7 to -4 and melphalan 180 mg/m2 i.v. on day -2, with the addition of VP-16 in the patient with JCMML. Two patients died on day +11 with no evidence of residual leukemia at autopsy. Six patients engrafted, one of whom had an uneventful BMT2, but he relapsed 6 months later. The other five developed severe acute GVHD (grades III-IV), with a fatal outcome in three cases, while two responded to treatment and are currently alive in continuous CR at 12 and 36 months. All patients had received conventional prophylaxis against acute GVHD.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Second bone marrow transplantation for leukemia in untreated relapse. 785 33

From 1983 to 1994 two types of trials were performed. Between 1983 and 1987 a modified VAPA protocol (post-remission therapy with intensive sequential blocks for 12-16 months) was given to 40 patients from two institutions. CR was attained in 75% and 5-year EFS was 35%. In 1988 a post-remission protocol based on intensification chemotherapy (two high-dose Ara C treatments combined with mitoxantrone in the first and amsacrine in the second) followed by BMT was initiated. Remission induction was DAE combination (1 or 2). Patients in CR or PR with HLA-compatible donor received an allogeneic transplant (al-BMT) and those without an autologous transplant (ABMT) with "purged" marrow. Pre-BMT therapy was fractionated TBI and CYCLO in patients over 3 years and Busulfan + CYCLO + VP-16 in those under 3. Between April '88 and December '94, 51 patients (aged 3 months to 15 years) were enrolled. 80% attained CR, 14% were failures or partial responses and 6% died before the 30th day. During the intensification phase, 5 patients attained CR and one relapsed and died. 47 patients (45 in CR and 2 in PR) proceeded to the BMT phase. 16 patients (14 in CR and 2 in PR) received al-BMT and 31 (all in CR) ABMT. Both group characteristics were comparable.
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PMID:Allogeneic and autologous bone marrow transplantation in AML in first remission. The Spanish experience. 893

This report summarizes indications and results of autologous bone marrow transplantation (ABMT) performed in childhood acute myeloid leukemia (AML) in Italy since 1984. A total of 158 patients have been reported from 12 teams to the AIEOP-BMT Registry: 110 have been autografted in first complete remission (CR) and 48 in second remission. Several conditioning regimens have been utilized, mainly consisting of BAVC (an original polichemotherapy schedule, BCNU, mAMSA, VP-16 and Ara-C) (63 cases) and of total body irradiation (TBI) plus Melphalan (33 cases): other 28 patients received different TBI-including regimens, and 34 received various chemotherapy regimens (Busulfan plus cyclophosphamide +/- VP-16, Busulfan plus Melphalan, Melphalan alone). Projected event-free survival (EFS) for patients autografted in first CR is 41.4% (S.E. 5.5%) at 7 years, with a total of 53 patients in continuous CR. EFS is better in patients receiving a TBI-including regimen: 78.8% versus 27.2% (p = 0.0001). In particular, results obtained in a subgroup of 21 cases receiving TBI + melphalan and purged marrow are particularly encouraging, with a EFS > 85% projected a 7 years. The overall EFS in second CR is 41.5% at 7 years, and no difference have been observed after a TBI-including regimen or after a chemotherapy regimen, being EFS 43.1% and 39.3% for these 2 groups respectively. A total of 11 transplant-related deaths occurred, with 5 patients (4.5%) dead in first CR and 6 (12%) dead in second CR within 100 days from transplant. From these data, ABMT is confirmed to represent an effective treatment for AML after first relapse, while the encouraging results obtained in first CR with TBI-including regimens should be confirmed with a longer follow up and a larger number of patients.
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PMID:Autologous bone marrow transplantation in children with acute myeloblastic leukemia: report from the Italian National Pediatric Registry (AIEOP-BMT). 893 1


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