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)

4 patients (3 female, 1 male) bone marrow transplanted for severe aplastic anemia (3 allogeneic, 1 syngeneic) became pregnant or parented children 19, 37, 81, and 34, 52 months, respectively, after BMT. Conditioning regimen consisted of 200 mg/kg Cyclophosphamide. Donor buffy coat cells were used for rejection prophylaxis, and methotrexate was used as GVHD prophylaxis. 1 female patient developed a mild chronic graft versus host disease with vaginal sclerosis which made a cesarean section necessary. 3 out of 5 pregnancies were uneventful. 1 patient had mumps in the 14th week, another patient had a late abortion in the 25th week of unknown cause. A high incidence of offspring complications was noticed including 1) persistence of fetal circulation syndrome, 2) erythroblastosis fetalis, and 3) prolonged newborn-icterus. These observations confirm previous reports on resumed fertility after BMT for SAA. A relation between the unexpected high incidence of pre-, peri-, and postpartal complications and the BMT procedure can neither be proved nor excluded.
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PMID:[Pregnancy and fetal complications after bone marrow transplantation]. 194 50

Bone marrow transplant has proved to be an effective treatment in some hereditary metabolic diseases and, especially, in mucopolysdaccharidosis (MPS). A 9-year-old girl, of consanguineous parents, with MPS Type I, Hurler-Scheie syndrome, received a BMT from her heterozygous, HLA-compatible mother. -L-iduronidase activity in leukocytes and fibroblasts was undetectable and glycosaminoglycans (GAG) excretion in urine was very high. BMT conditioning treatment consisted of Busulfan (16 mg/kg) and Cyclophosphamide (120 mg/kg); clinical course was uneventful. Sixty days post-BMT iduronidase activity in leukocytes was similar to that of the donor and GAG levels were normal at 12 months. Echocardiography showed regression in hypertrophic myocardiopathy. Previously enlarged and vacuole-filled skin fibroblasts became reduced in size and vacuole content. The most notable clinical effects were: improved facial features, increased height, disappearance of visceromegalies, gradual clearing of corneal opacities with improved vision and reduced joint stiffness. It is concluded that the gradual deterioration in patients with MPS-I may be arrested and many clinical features improved by BMT.
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PMID:[Bone marrow transplantation in mucopolysaccharidosis type I, Hurler-Scheie variety. Metabolic correction and clinical results]. 212 72

Thirty patients with malignant hematological disease underwent allogeneic bone marrow transplantation following Busulphan (Bu) and Cyclophosphamide (Cy). The diseases were chronic myelogenous leukemia, acute lymphoblastic and non lymphoblastic leukemia, myelofibrosis and multiple myeloma in complete remission and in relapse. A sustained disease-free survival (DFS) was achieved in 0/5 acute leukemia patients transplanted in relapse, in 5/7 acute leukemia patients transplanted in remission (600-1550 days) and in 6/9 CML patients transplanted in the chronic phase of the disease (500-950 days). A sustained DFS was also achieved in one 2nd BMT for relapsed CML. The data suggest that the Bu-Cy protocol combines high tumor ablative capability with toxicity comparable to previously described conditioning regimens for allogeneic BMT, particularly in diseases involving a great expansion of the bone marrow.
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PMID:Allogeneic bone marrow transplantation for hematological malignancies following therapy with high doses of busulphan and cyclophosphamide. 251 Nov 15

In the literature 63 patients with myelodysplastic syndromes (MDS) are reported who were treated with syngeneic or allogeneic bone marrow transplantation. 62 patients were prepared for BMT with TBI containing regimens or Busulfan/Cyclophosphamide. GvHD prophylaxis was heterogenous. 33/63 patients are alive and well between 4 and 132 months after BMT. 23/63 patients died due to GvHD (n = 6), interstitial pneumonitis (n = 6), other infections (n = 4), toxicity of the preparative regimen (n = 5) or graft failure (n = 2). 9/63 patients relapsed between 2 and 98 (in median 6) months after BMT. There seems to be a correlation between the subtype of the MDS and the relapse rate: only 1/18 patients with RA/RARS relapsed compared to 7/42 patients with RAEB/RAEB-T. These results indicate that marrow transplantation can induce long term survival and may result in cure of patients with MDS.
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PMID:Allogeneic bone marrow transplantation for myelodysplastic syndromes (MDS). 269 17

The SAA Registry of the EBMT now contains data on 171 children younger than 15 years of age with acquired SAA and undergoing BMT between 1970 and 1988. The overall actuarial survival is 63% at 10 years. In a multivariate Cox analysis, the year of transplant was the most important prognostic factor with a significant advantage for children grafted in 1984-88 (81%) vs 1981-83 (67%) and 1970-80 (41%) (p = 0.02). Cyclosporine A given for GVHD prophylaxis, no treatment before transplant and an interval less than 90 days from diagnosis to BMT were all favourable variables in univariate analysis. As regard to transplant procedures, the better results were obtained using Cyclophosphamide and Cyclosporine A (78%) followed by Cyclophosphamide plus irradiation plus Cyclosporine A (77%). Sex, etiology and the severity of the aplasia had no impact on survival in both uni and multivariate analysis.
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PMID:Allogeneic bone marrow transplantation (BMT) for acquired severe aplastic anaemia (SAA) in children. 269 23

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

The relative importance of the effects of dose rate, dose fractionation, and prior exposure to Cytoxan on the recovery of cells in the bone marrow, following conditioning for BMT, remains controversial. Traditionally, bone marrow stem cells and leukemic cells have been considered as having a limited ability to repair radiation-induced damage following total body irradiation (TBI) compared to cells of the lung (the dose-limiting tissue for TBI). We examined the survival response of the bone marrow stem cells of mice (CFUs) at three TBI dose rates (0.47, 0.25 and 0.08 Gy/min). The radiation response of CFUs (compilation Do = 0.75 Gy) was independent of dose rate. One TBI dose fractionation was chosen: two fractions per day, separated by 6 hours, for 3 days. The radiation survival curve of CFUs showed a compilation Do of 1.09 Gy, compared to 0.75 Gy for the one-fraction case. The recovery of CFUs following 2 days of Cytoxan demonstrated an "overshoot," whereas recovery of CFUs was incomplete, even by day 23, following the initiation of the complete conditioning regimen of Cytoxan plus TBI. These data demonstrate no significant effect of dose rate, at least in the range 0.08 to 0.48 Gy/min, on the survival of CFUs following either single or six fractionated TBI doses. However, the statistically significant difference in the Do of CFUs in going from one to six fractions has direct application to bone marrow transplantation techniques. Moreover, Cytoxan, at least at 200 mg/kg for 2 days, prior to TBI, appears to have only a marginal modifying effect on the eventual recovery of CFUs.
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PMID:Modification of radiation-induced damage to bone marrow stem cells by dose rate, dose fractionation, and prior exposure to cytoxan as judged by the survival of CFUs: application to bone marrow transplantation (BMT). 327 33

Fanconi anaemia, an autosomal recessive constitutional aplastic anaemia, seems to be related to a DNA repair mechanism defect. Bone marrow transplantation is sthe only treatment which can cure these patients. Previous attempts at BMT have shown an increased sensitivity to Cyclophosphamide used for the conditioning. Such a sensitivity has also been observed in vitro when Fanconi anaemia cells were incubated with alkylating agents. We have tested the in vivo radiosensitivity and cell repair after skin contact radiotherapy to calculate the irradiation dose which could be tolerated by FA patients. Eight patients have been tested and the results confirmed the suspected increased radiosensitivity in the majority of patients. Following these results, four patients were conditioned with low dose Cyclophosphamide (20 mg/kg) associated with 5 Grays thoraco-abdominal irradiation. All had a take and no major complication of the conditioning regimen. All are alive in good condition from day 51 to day 330 after transplant. Oesophagitis was one major unexpected complication. This study confirms the possibility of curing FA patients with BMT when the conditioning regimen is modified according to the pathophysiology of the disease.
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PMID:Radiosensitivity in Fanconi anaemia: application to the conditioning regimen for bone marrow transplantation. 634 15

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

Mafosfamide (ASTA-Z) is a chemotherapeutic agent currently in use for in vitro purging of tumor-bearing human BM cells prior to autologous bone marrow transplantation (ABMT). We tested the efficacy of ASTA-Z against mouse plasmacytoma cells MOPC-315 (MOPC), a model of human multiple myeloma. BALB/c mice were injected intraperitoneally with different doses of MOPC preincubated with ASTA-Z. All control mice receiving > or = 10(4) MOPC intraperitoneally (ip) died within 23 days. All recipients of ASTA-Z pretreated MOPC remained healthy for > 180 days. To simulate the clinical situation, BALB/c mice received lethal doses of 10(3) MOPC ip prior to ABMT. Subsequently, mice were treated with cyclophosphamide 200 mg/kg one day prior to syngeneic BMT with 10(7) BMC containing 10(6) MOPC; 90% of the mice receiving unpurged syngeneic BMC died within 45 days whereas all mice transplanted with ASTA-Z-treated BMC/MOPC mixtures remained disease-free for > 100 days. Our results suggest that a similar approach may be successful in patients with multiple myeloma and residual disease prior to cryopreservation of their BM for ABMT. Bone marrow purging with ASTA-Z is effective and under certain conditions could be critical for prevention of relapse following ABMT, provided that effective elimination of residual disease in the host can be achieved by the conditioning regimen prior to ABMT.
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PMID:Successful purging of murine plasmacytoma by mafosfamide (ASTA-Z). 801 50


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