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)

Prognosis of second marrow transplantation after leukemia relapse is usually gloomy. We report a patient with AML who was successfully treated by the second marrow transplant following high dose busulfan, etoposide, and Ara-C for the testicular relapse after the first marrow transplantation. A 24-year-old man was diagnosed as having acute myeloid leukemia (AML) in September, 1988. In December of 1989 when he was in early relapse after his 2nd remission, he received the first allogeneic BMT from his HLA identical brother after high dose busulfan and cyclophosphamide conditioning. His posttransplant course was uneventful and graft versus host disease was not observed. Three months after BMT, he noticed swelling on right testicle. Leukemic cell infiltration was confirmed by aspiration cytology. The testicular relapse was followed by marrow relapse. After successful remission induction chemotherapy, he received 17.5 Gy testicular irradiation and second marrow transplantation using high dose busulfan, etoposide, and Ara-C conditioning. Although his posttransplant period was complicated by severe mucositis, high fever and bronchopneumonia, hematologic recovery was obtained by 3 weeks after the second transplant. He is now continuing in complete remission 18 months after the second BMT. This case report suggests that the combination of high dose busulfan, etoposide, and Ara-C could be a choice as a conditioning regimen for resistant AML relapsing after BMT.
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PMID:[Second marrow transplantation following high dose busulfan, etoposide, and Ara-C after testicular relapse in a patient with AML]. 157 38

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

We treated a patient with chronic granulocytic leukemia (CGL), in the accelerated phase by intensive chemotherapy followed by the infusion of cryopreserved peripheral blood buffy-coat cells. The cells had been stored for 32 months. The chemotherapy consisted of daunorubicin 40 mg X 2 days, vincristine 2 mg X 1 day, cytosine arabinoside (Ara-C) 200 mg X 6 days and prednisolone 30 mg X 7 days in the first week, then Ara-C 3 g/m2 X 3 days and cyclophosphamide 60 mg/kg X 2 days in the second week, but reversion to the chronic phase was not achieved. Therefore, total body irradiation (TBI) was added to repeated intensive chemotherapy followed by infusion of the remaining cells. Marrow recovery was good. The patient is currently alive and has been in the chronic phase for 22 months. This preliminary result indicates that this therapy may be tried soon after transformation in CGL and that TBI is an important part of therapy in BMT in the accelerated or blastic phase of CGL.
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PMID:Treatment of chronic granulocytic leukemia in the accelerated phase by transfusion of autologous buffy-coat cells--a case report. 233 Aug 6

CSA toxicity includes renal impairment, microangiopathic hemolytic anemia (MAHA), thrombocytopenia (T), and consumptive coagulopathy (CC). We report five BMT patients who developed CSA-associated hematological toxicity. All were conditioned with Ara-C, Cyclophosphamide, Methylprednisolone, TBI, and in two cases busulfan. IV CSA was started the day after marrow infusion and, when practicable, changed to the enteral route. Five patients developed MAHA and T resulting in significantly increased transfusion requirements. All patients had renal impairment and red cell fragmentation. In all patients fragmentation was noted before renal impairment. All developed disproportionate increases in BUN relative to serum creatinine consistent with decreased renal perfusion. Hypertension followed renal impairment in four cases and occurred at the same time as the renal impairment in one case. Two developed CC, prolongation in APTT, and marked decreases in plasma fibrinogen. All patients improved on reduction of the CSA dose. BMT recipients receiving CSA at variable doses may develop evidence of a TTP-like syndrome and/or CC.
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PMID:Coagulation defects in cyclosporine A treated allogeneic bone marrow transplant patients. 304 63

Using T-depleted BM from HLA-identical sibling donors we have performed 36 BMTs since 5/83 in first remission (CR1) of acute leukaemia (AL). Standard conditioning for BMT consisted of Cy 60 mg/kg X 2 and 7.5 Gy single fraction TBI (n = 27). Six patients received Ara-C 3 g/m2 X 6, Cy 45 mg/kg X 2 and 7.5 Gy, while 3 received Cy 60 mg/kg X 2 and 8 Gy radiation. T lymphocytes were depleted in vitro with 2 murine McAbs (MBG6 + RFT8, n = 17; or RFT8 + RFT12, n = 13; or RFT2, RFT8 + RFT12, n = 6) plus rabbit C'-mediated lysis. No immunosuppressive therapy was given in the absence of graft-versus-host disease (GvHD). Of 34 patients evaluable for a GvHD, 4 had grade I, 2 grade II and 1 grade III. Chronic GvHD occurred in 3 of 22 evaluable patients (greater than 150 days). There have been 13 deaths but only 1 from leukaemic relapse (CNS). The mean KS of surviving patients is 86% and actuarial disease-free survival is 53% at 40 months or 65% in those having 'standard conditioning'. The previous major problems of GvHD and leukaemic relapse appear to have been largely overcome. The major risk factor now is infection, particularly pneumonitis, and this problem is surmountable.
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PMID:Bone marrow transplantation in acute or chronic leukaemia. 312 47

We report a case of a 19-year-old male with congenital aplastic anemia and multiple abnormalities; short stature, hypoplastic thumb, skin pigmentation and mental retardation. He was admitted to our hospital because of severe pancytopenia. Bone marrow aspiration showed markedly hypocellular marrow with 42% myeloblasts. He was diagnosed as AML (M2) transformed from Fanconi's anemia and underwent allo-BMT from an HLA-identical father. The conditioning regimen consisted of high dose Ara-C, high dose etoposide and 12Gy fractionated total body irradiation. Severe toxicity associated with the conditioning regimen was not observed. Cyclosporin A and short-term methotrexate were administered for prophylaxis of acute GVHD. Neither acute nor chronic GVHD were observed. He is well and free of disease for 15 months since BMT. Very few cases of Fanconi's anemia with leukemic transformation treated by BMT have been reported. Long-term observation will be necessary to evaluate our conditioning regimen for Fanconi's anemia with leukemic transformation.
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PMID:[Allogenic bone marrow transplantation for Fanconi's anemia with leukemic transformation from an HLA identical father]. 764 54

Conditioning regimens for BMT are important in determining transplant outcome. A radiation-free protocol containing Mitobronitol (DBM), Cytarabine (Ara-C) and Cyclophosphamide (Cy) was used for conditioning of patients with chronic granulocytic leukemia (CGL). Using this conditioning treatment, fewer transplant related complications, including acute GVHD, VOD and severe infections, were observed. Acute GVHD did not develop, but chronic GVHD, accompanied with graft-versus leukemia, was present in half of the cases. To determine the clinical effect of the DBM/Ara-C/Cy conditioning, the recovery of peripheral blood lymphocytes was examined after allogeneic BMT for patients with CGL in comparison with TBI/Cy conditioning. The lymphocyte subsets of 11 DBM patients were followed and analyzed periodically (30-90 days, 4-12 months and > 13 months) using ten monoclonal antibodies and flow cytometry. Decreased percentage of total T cells as well as CD4+ and CD8+ subpopulations, significantly decreased T cell activation and increased proportion of TCR gamma delta + cells were found to be characteristic in the early post-transplant period in the DBM group. Early recovery and consistently higher percentage of B cells were observed for the whole follow-up period of patients receiving DBM conditioning. A high proportion of NK cells was observed in all transplant recipients. These findings suggest that the characteristic pattern of recovering lymphocytes is associated with the lack of severe transplant-related clinical complications following DBM/Ara-C/Cy conditioning.
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PMID:Lymphocyte subset reconstitution after allogeneic bone marrow transplantation using radiation-free conditioning regimen for patients with chronic granulocytic leukemia. 767 5

Allogeneic BMT is the treatment of choice for patients with MDS or sAML, offering a good chance of long-term disease-free survival if the transplant is performed in an early stage of disease or if the patient receives the transplant in complete remission after polychemotherapy. The transplant is limited to a minority of relatively young patients (aged below 55 years) with an HLA-identical sibling. Allogeneic BMT may also be considered when a closely- or fully-matched unrelated donor has been identified for a young and fit patient. All patients, including those without an excess of blasts, should be conditioned with bone marrow ablative therapy rather than an immune suppressive regime, such as cyclophosphamide alone. For the majority of patients there is no standard therapy other than appropriate supportive care. Relatively young patients below the age of 60 years with poor risk features can be considered for treatment with combination chemotherapy. Maintaining remission after remission-induction chemotherapy is a difficult issue. Patients not eligible for allogeneic BMT could be treated with post-remission chemotherapy or autologous BMT in the framework of prospective studies. Older patients can be considered for treatment with haematopoietic growth factors alone or in combination with differentiating agents such as low-dose Ara-C. This treatment should be delivered within the context of carefully designed and conducted trials.
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PMID:New treatment approaches for myelodysplastic syndrome and secondary leukaemias. 807 47

Bone marrow and/or peripheral blood of patients with chronic myeloid leukemia (CML) was investigated by the following three parameters: Ph' chromosome, bcr-abl expression in fresh blood and/or bone marrow, and bcr-abl expression in single hematopoietic progenitor colonies generated from blood and/or bone marrow. Expression of bcr-abl was proven by a reverse "nested primer" polymerase chain reaction (PCR) that is able to detect 1 pg of hybrid mRNA. We performed 108 investigations on 68 patients containing all three parameters: 12 on untreated patients, seven after interferon-alpha (IFN-alpha), seven after low-dose cytosine arabinoside (Ara-C), 22 after cyclic high-dose hydroxyurea (HU), 49 after allogeneic BMT, five before and three after stem cell mobilization, and three after autologous stem cell transplantation (ASCT). In 53 cases (49%), cytogenetics and PCR gave identical results. In 40 cases (37%), PCR from single colonies gave additional information compared to cytogenetics (e.g., mosaic in colonies when all metaphases were positive or negative). Most interesting were the results of one patient after IFN, one patient after ASCT, and 10 patients after BMT (14 investigations = 13%), showing only Ph'-negative mitoses accompanied by a negative nested primer PCR from fresh blood/bone marrow but single bcr-abl-positive progenitor colonies. False-positive results could be widely excluded by repeated insertion of negative controls into the experiments. One explanation for these results could be that CML, progenitors survive in the patient's body by being inactive and not proliferating. These cells express no or very little RNA and bcr-abl is not detectable by reverse PCR. When stimulated ex vivo in a colony assay by external growth factors, cells proliferate and produce detectable amounts of hybrid mRNA. The value of these observations is not clear. A follow-up of the patients will show if such sleeping progenitors can be activated in vivo. Concluding our observations, we can say that in special cases (therapy follow-up, detection of minimal residual disease) it could be useful to perform a PCR analysis of single progenitors in parallel with the routine investigations.
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PMID:Detection of bcr-abl mRNA in single progenitor colonies from patients with chronic myeloid leukemia by PCR: comparison with cytogenetics and PCR from uncultured cells. 854 60

Busulfan pharmacokinetics, specifically area under the concentration curve (AUC), have been correlated with the occurrence of veno-occlusive disease (VOD) following BMT. To evaluate the risk of VOD, we studied 66 patients who received pharmacotherapeutically monitored busulfan regimens in combination with CY, etoposide (VP16) and/or Ara-C in preparation for BMT. These patients received a total of 16 doses of busulfan dosed as 1 mg/kg/dose q 6 h beginning at 09.00 (n = 39), 18.00 (n = 2), 21.00 (n = 1) or 24.00 (n = 24) h. With the first dose, blood samples were obtained at baseline, every 15-30 min for 2 h, then every 1-2 h for 4 h. Blood was analyzed for busulfan concentration by high performance liquid chromatography and AUC calculated by the trapezoidal rule. Seventeen patients (25.8%) were not evaluable for AUC calculation due to slow absorption and/or elimination: 13 of 27 (48.1%) received the first dose between 18.00-24.00 vs four of 39 (10.2%) patients who received the first dose at 09.00 (P < 0.001). Eighteen of 51 (35.3%) evaluable patients had an AUC > 1500 mumol x min/l; 10 of whom received doses reduced proportionally to achieve an AUC = 1200 mumol x min/l starting with the 10th to 15th dose. Six of 18 (33.3%) patients with an initial AUC > 1500 mumol x min/l developed VOD vs one of 33 (3.0%) patients with an initial AUC < 1500 mumol x min/l (relative risk = 11.1; P = 0.0056). Other pharmacokinetic parameters, age, gender, type of BMT, previous therapy or pre-transplant liver function tests were not predictive of VOD. A higher incidence of VOD occurred in patients receiving BUCY (4 of 10) compared to those receiving BUCYAra-C (1 of 18) or BUCYVP16 (7 of 38), which could not be attributed to increased busulfan exposure in the BUCY patients. Routine pharmacotherapeutic monitoring of busulfan is recommended with further study to evaluate the impact of earlier and greater overall dose reduction in patients with high initial busulfan exposures.
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PMID:Association of busulfan area under the curve with veno-occlusive disease following BMT. 864 Jan 71


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