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 study combines the effects of prolonged postremission chemotherapy with that of very early intensification. 900 adult patients at all ages with newly diagnosed AML uniformly received TAD for induction and consolidation followed by monthly myelosuppressive maintenance for 3 years. In patients of 60+ years with persistent bone marrow blasts a second TAD course was given. In all patients of less than 60 years a second induction course started on day 21 even in aplasia with no blasts. Second induction was randomly either TAD or HAM. In the younger age group 69% attained CR and similar in the two arms the CR rate after 5 years is 35%. Including the 50% patients attaining CR in the higher age group the CR rate after 5 years is 32%. In 40 patients receiving allogeneic BMT and 21 patients receiving autologous BMT in first CR relapse free survival is similar to that from chemotherapy alone in a matched pair analysis. We conclude that age adapted very early intensification followed by prolonged postremission chemotherapy represents a therapeutic progress.
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PMID:Combined effect of very early intensification and prolonged post-remission chemotherapy in patients with AML. 143 38

In 1990, 4,234 BMT were performed in Europe; 2,097 autologous BMT (388 AML) and 2,137 allogeneic BMT (494 AML). Although an established therapy with leukemia free survival (LFS) at five years of 41% +/- 5% (EBMT results) its value compared to alternative therapies remains controversial. During the year 1985, the EBMT conducted a prospective evaluation study. In 12 centres 168 patients with AML were registered at the time of HLA-typing. Basic patient data and treatment intention were recorded. 79 patients were HLA-typed at diagnosis. 68 patients in 1st CR and 21 at other stages. Follow-up of these patients was obtained as of January 1, 1991. Three-year LFS is 44% for patients with an HLA-identical donor and 21% for those without (p = 0.02). Of the 68 patients HLA-typed in first CR, 40 had an HLA-identical donor and 28 no donor. Three-year LFS is 42% and 35%. resp. (n.s.). The difference in results between patients typed at diagnosis and first CR patients illustrates the problem of selection. We conclude that patient registration early in the disease can give insight into the process of selection. Allogeneic BMT incorporated prospectively at diagnosis into therapy offers a survival advantage for patients in this age category compared to alternative therapies.
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PMID:Bone marrow transplantation for acute myeloid leukemia: the EBMT experience. A prospective analysis from HLA-typing. The EMBT Leukemia Working Party. 157 8

From 1987 to 1990, intensive postremission chemotherapy was compared to autologous bone marrow transplant in previously untreated children with AML who received identical induction therapy with two courses of Daunorubicin (DNR) and conventional dose ARA-C (protocol AIEOP LAM 87). Overall, 121 of the 155 eligible patients achieved complete remission (CR) (78%). Patients in CR who lacked HLA-MLC compatible donor were randomized to receive either autologous BMT (Auto-BMT) or further sequential postremission therapy. Patients with HLA-MLC compatible donor were assigned to allogeneic BMT (Allo-BMT). Projected 3-years disease free survival (DFS) are 58% for Allo-BMT group, 24% for Auto-BMT group, 26% for chemotherapy group and 30% for a group of not randomized patients (intention to treat analysis). On March 1990 a pilot study LAM 87M was initiated. Patients in CR after induction therapy (identical to the previous protocol) receive a single intensification course consisting of high dose ARA-C plus DNR. The study continues to accrue patients.
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PMID:Therapeutic strategies for postremission treatment in childhood acute myeloid leukemia (AML). The AIEOP experience 1987-1991. 157 40

In order to further improve the cure rate in AML we investigated the effect of more chemotherapy--in terms of its intensity and its duration--in 2 studies. In our 1981 study patients received TAD 1-2 courses for induction, 1 course for consolidation and randomly no further treatment or monthly myelosuppressive maintenance for 3 years. Evaluating 213 responders remission duration was clearly longer in the maintenance group with 24% CCR after 5 and 10 years. In our 1985 study the same successful strategy was further intensified by a second induction course given regardless of response to the first course to all patients up to 60 years of age while older patients received standard induction as before. This age-adapted concept resulted in a further increase of 5 years CCR in the 461 responders to as much as 34% not achieved for unselected patients in other multicenter trials. 20 patients receiving auto-BMT in first CR show the same relapse free survival as their counterparts receiving chemotherapy according to the 1985 protocol in a matched-pair analysis. We conclude that both very early intensification and prolonged maintenance contribute to a higher cure rate that is not further improved even by a maximum intensity short-term treatment. The limits of chemotherapy in AML may be overcome by modulating its myelotoxicity and antileukemic potency using GM-CSF as shown in 2 studies of our group.
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PMID:Longterm effects of prolonged maintenance and of very early intensification chemotherapy in AML: data from AMLCG. 157 46

Between 1978 and 1988 (median follow up 5 1/2 years), 396 newly diagnosed adults with AML (age range 14-59 years, median 44) received STT comprising daily Adriamycin: 25mg/m2 for 3 days, Cytosine arabinoside (ara-C): 100mg/m2 bd and 6-thioguanine: 100mg/m2 bd, each for 7 days. A maximum of 6 cycles was administered with as short an intercycle time as possible. No further treatment was given. Complete remission (CR) was achieved in 243/396 patients (62%), 71 patients (18%) having resistant leukaemia and 82 (21%) dying within 6 weeks. Antecedent myelodysplasia and advanced age correlated unfavourably with achievement of CR (p = less than 0.001 and 0.005 respectively). Sixty nine patients continue in first remission between 2 1/2 and 12 years; the median duration of remission was 1 year. M3 morphology (p = 0.005) and absence of hepatosplenomegaly (p = 0.001) correlated favourably with duration of remission. Ninety one patients remain alive with an actuarial survival of 22% at 5 years. More recently, additional consolidation comprising high-dose ara-C and total body irradiation (TBI) with autologous bone marrow transplantation (ABMT) has been evaluated in an open study. CR has been achieved in 41/66 patients under the age of 50 but only 19/41 have proceeded to ara-C + TBI + ABMT. Twenty two have not (early recurrence 10, allogeneic BMT 4, debility 6, refusal 2). 11/19 who proceeded to ablative therapy continue in remission (4 treatment related deaths, 4 recurrences) as compared to 9/22 who did not. Currently the overall median duration of remission for the 41 patients intended to proceed is identical to that of age-matched historical controls illustrating the difficulties inherent in demonstrating benefit for the use of myeloablative therapy and ABMT in patients with AML in first remission.
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PMID:Short term therapy (STT) for acute myelogenous leukaemia (AML). 157 52

Thirty-four consecutive patients with either relapsed (n = 28) or primary refractory AML (n = 6) were treated with one or two cycles of intermediate-dose (ID) cytosine arabinoside (Ara-C) (1 g/m2 i.v. q 12 h days 1-6) and amsacrine (m-AMSA) (120 mg/m2 i.v. days 5-7). Patients reaching complete remission (CR) were consolidated with one cycle of Ara-C 3 g/m2 i.v. q 12 h days 1-4 and m-AMSA 120 mg/m2 i.v. day 5. The median duration of the preceding remission was 8 months and median time from last chemotherapy until relapse 3.1 months. Of the relapsed patients, 22/28 (79%) achieved CR regardless of the type of prior intensive maintenance (HD Ara-C/m-AMSA/5-azacytidine) (AZA) or daunorubicin (DNR/CD-Ara-C). Three of the 28 (11%) patients died during hypoplasia; 3/28 (11%) were refractory to 2x ID-Ara-C/m-AMSA. Three of the 28 patients died in CR during hypoplasia after intensive consolidation with HD-Ara-C. Predictive factors for remission were duration of preceding remission and the time from last chemotherapy to relapse. Three patients were transplanted in second CR. One of the six refractory patients reached CR, two remained refractory, and three died during hypoplasia. The median duration of disease-free survival (DFS) of relapsed patients was 3.3 months without further treatment; median survival of responding patients (20 relapsed patients, 1 refractory patient) was 4.5 months, overall survival (n = 29) was 4.8 months. Patients receiving BMT were censored at the time of BMT. Seven patients experienced lung toxicity due to Ara-C, four of whom died.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Intermediate-dose Ara-C/m-AMSA for remission induction and high-dose Ara-C/m-AMSA for intensive consolidation in relapsed and refractory adult acute myelogeneous leukemia. 169 Nov 34

Fifty seven patients entered the cooperative study AML II/87 of the working group "Pediatric Hematology and Oncology" of East Germany. Two patients with initial hyperleukocytosis died prior therapy. 13 patients died within the first 4 weeks of therapy, 3 patients did not respond to therapy, and one patient is not yet in remission. 38 patients (70%) attained a complete remission. 15 patients get a bone marrow transplantation in first CR (10 autologous BMT without purging, 5 allogenous BMT). 12 of them are living and well 3 to 34 months after BMT. 9 of the 23 patients under chemotherapy relapsed, one patient is lost to follow up. 13 patients are living in continuous complete remission. The life table probabilities 48 months after the start of the protocol are 0.43 for disease free survival (DFS) and 0.60 for event free interval (EFI). The respective results of the former protocol AML I/82 were 0.34 for DFS and 0.47 for EFI.
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PMID:[Therapy of acute myeloid leukemia in children--results of the AML II/87 multicenter study]. 175 35

The authors present the organisation and preliminary experience with a comprehensive autologous bone marrow transplantation (ABMT) program in patients with malignant blood diseases. The procedure involves harvesting of bone marrow from patients in complete remission, purification of mononuclear cells and cryopreservation of these at -196 degrees C. After bone marrow cultures show that a sufficient number of hemopoietic progenitor cells (CFU-GM) are present in the marrow to reconstitute the patient, he/she is conditioned with chemo- (busulphan/cyclophosphamide (Bu + Cy)) or chemo/radiotherapy (total body radiation/cyclophosphamide (TBI + Cy)) in doses equal to those commonly used in allogeneic BMT. From February 1988 to July 1990 bone marrow (BM) was harvested from 24 patients. The median yield of mononuclear cells (MNC) was 1.2 x 10(8)/kg body weight (range 0.55-3.7). After buffy coat preparation, density gradient centrifugation, cryopreservation and thawing out, 0.60 x 10(8) MNC/kg (0.18-3.3) corresponding to 9.3 x 10(4) CFU-GM/kg (2.28-144) could be recovered. Twelve patients have received transplants, five with AML (after Bu + Cy conditioning), six with lymphoblastic lymphoma and one with Hodgkin's disease (with TBI + Cy conditioning). The median number of days to obtain greater than 1.0 x 10(9) leucocytes/l, greater than 0.5 x 10(9) neutrophils/l, greater than 50 x 10(9) thrombocytes/l and last requirement for erythrocyte transfusion were 21 (12-49), 28 (10-60), 55 (21-270) and 55 (12-129) days, respectively. Four patients had sepsis and the median duration of hospitalization was 39 (22-58) days. The most severe complications were seen in the AML patients, two of whom died during the posttransplant period (one of septicemia, one of thrombocytopenic bleeding).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Autologous bone marrow transplantation in malignant blood diseases]. 185 57

A combination of density flotation centrifugation and counterflow centrifugation (elutriation) allows the elimination of 98% of the T-lymphocytes, present in a marrow aspirate. This reduces substantially the occurrence of graft versus host disease (GvHD) after transplantation without loss of the repopulation capacity. A limitation of the traditional Beckman elutriator rotor is the relatively small size of the elutriation chamber, which makes five to six runs, of one hour each, necessary to process the whole bone marrow graft. We developed a new elutriator rotor, containing four disposable elutriator chamber (Dijkstra BV, Amsterdam, The Netherlands), which allows to complete the lymphocyte elimination from the bone marrow graft within 2 hours. Ninety-nine consecutive patients were transplanted with elutriated MLC-negative bone marrow grafts from histocompatible siblings. Indications for transplantation were: AML (n = 32), ALL (n = 34) and CML (n = 33). The grafts contained after counterflow centrifugation a mean of 12.1 (+/- 2.4)% of the nucleated cells, 1.9 (+/- 1.4)% of the T-lymphocytes, and 93.5 (+/- 59.4)% of the CFU-GM, originally present in the collected bone marrow. Immunoprophylaxis post grafting was given to 97 BMT recipients. Primary graft failure occurred in 5 of 95 evaluable patients (5%). The probability of acute GvHD greater than grade 1 at day 100 after BMT was 16%. The projected 3-year estimate of extensive chronic GvHD was 13%. The low incidence of GvHD was associated with a relatively low transplant related mortality in patients above the age of 40 years.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prevention of graft-versus-host disease by lymphocyte depletion of the bone marrow graft with use of counterflow centrifugation. 186 51

The AML model in the BN rat has contributed considerably to improved understanding of the various aspects of leukaemia growth, responses to chemotherapy, application of BMT as treatment modality and the possibilities and limitations for the detection of residual disease during the remission phase. Obviously, there are restrictions with regard to the extrapolation of the rat data to the human situation. Leukaemia growth in inbred rats is highly reproducible, while in humans it presents a high degree of individual variation. However, several characteristics are shared and the aim should be to identify the similarities as well as the dissimilarities between human and rat leukaemia. In that way progress may be envisaged with respect to reaching the final goal of curing human leukaemia.
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PMID:Minimal residual disease in acute leukaemia: preclinical studies in a relevant rat model (BNML). 195 83


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