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)

We here report a male patient with an additional t(3;21)(q26;q22) in Philadelphia positive chronic myelogenous leukemia (Ph + CML). In spite of the presence of this progression of disease marker and probably related to alpha-interferon therapy, this case entered into remission as a second chronic phase. At that time, he underwent allogeneic bone marrow transplantation. One year after BMT he showed a disappearance of leukemic clones at the cytogenetic and molecular levels. At present the patient has 21 months of clinical and hematologic remission. It is of interest to note that the association of alpha-interferon-hydroxyurea and bone marrow transplantation might produce a negative selection pressure against the leukemic clone in this patient.
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PMID:Remission of Philadelphia positive chronic myelogenous leukemia associated with t(3;21) after bone marrow transplantation. 835 3

A male patient with CML received a BMT from his sister and developed chronic GVHD. The host-origin normal karyotype (46,XY) was identified for the first time in the 60th month after BMT. Detection of Y-chromosome-specific DNA in BM and peripheral blood (PB) showed that all BM samples obtained 6 months from BMT were positive for Y-specific DNA, while PB became positive in the 60th month after BMT. The BCR-ABL mRNA derived from leukemic cells was detected in the 36th month post-BMT, but not in the 60th month or thereafter. Fluorescence in situ hybridization revealed that 1.5% and 0.6% in BM and PB cells were Y-positive in the 70th month post-BMT, respectively. DNA analysis of hematopoietic progenitor colonies revealed 1 of 42 erythroid colonies to be host derived. These results indicate that host-origin hematopoietic cells survive chronic GVHD, while the Ph1 clone was eliminated.
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PMID:Hematopoietic recovery from host progenitors with normal karyotype devoid of Philadelphia chromosome in a patient with CML after allogeneic BMT. 837 40

Data from 311 patients with hematological malignancies who received an autologous, allogeneic or syngeneic BMT in a single institution were analyzed. Interstitial pneumonia (IPn) was observed in 58 patients. Two years actuarial probability of IPn was 26.8%. In 50% of cases CMV was detected. In 23 patients (39.7%) IPn was considered idiopathic. The median time from BMT to IPn was 63.5 (range 7-720) days. Patients submitted to allogeneic BMT had a significantly higher risk of developing IPn than patients receiving syngeneic or autologous BMT (34.1% vs 16.7% and 4.9%, respectively; p = 0.0006). Among 230 patients receiving allogeneic transplant, factors with a higher risk for IPn in univariate analysis were: age over 20 years, CML, alloimmunized donor, previous splenectomy, acute and chronic GVHD. When the analysis was restricted to patients with a CMV-associated IPn, all factors except alloimmunization maintained their significance. Multivariate analysis showed that only acute GVHD (p < 0.0001) and a diagnosis of CML (p < 0.001) in the whole group of allogeneic transplants, and acute GVHD (p < 0.001) and splenectomy (p < 0.003) in CMV-associated IPn, maintained their significance. These results are discussed within the frame work of the clinical application of BMT.
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PMID:Interstitial pneumonitis after BMT: 15 years experience in a single institution. 839 85

The role of mixed hematopoietic chimerism in engraftment and relapse after allogeneic BMT remains unclear. To better evaluate post-transplant chimerism we used polymerase chain reaction (PCR) in vitro amplification of four single locus simple repetitive DNA sequences, all of which vary extensively in their repeat number among different individuals: variable number of tandem repeats D1S80, APOB and D17S5, and the tetranucleotide repeat F8VWF. We tested 13 cases of CML, four of multiple myeloma (MM), three of ANLL and one of B-CLL. In a sequential analysis protocol with the different loci, the donor could be distinguished from the recipient in 14 of 20 (70%) pairs with the first marker used (D1S80). When a donor of opposite sex was involved, karyotyping and Y chromosome-specific PCR were also used. With the use of the four markers, chimerism was identified in all the pairs. Mixed chimerism was present in 5 patients, and complete chimerism in 15. No patients relapsed. The application of PCR for documenting post-transplant chimerism has several advantages over Southern blotting: increased sensitivity, use of small amounts of sample, ease of preparation of DNA, elimination of restriction enzyme analysis and of radioisotopes, and speed.
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PMID:In vitro amplification of hypervariable DNA regions for the evaluation of chimerism after allogeneic BMT. 840 55

Allogeneic BMT is the treatment of choice for juvenile CML (JCML). This has been successful following conditioning with cyclophosphamide (120 mg/kg) and total body irradiation (TBI) (10-15.75 Gy). However, busulphan (16 mg/kg) and cyclophosphamide (200 mg/kg) (Bu/Cy) conditioning has been reported to be insufficient to eradicate the malignant clone in JCML. We report successful BMT and eradication of the disease at 18 months follow-up in a child 15 months old at presentation, who was conditioned with busulphan 20 mg/kg and cyclophosphamide 200 mg/kg, with the addition of splenic irradiation. Despite using higher than conventional doses of busulphan, pharmacokinetic analysis revealed very low busulphan peak levels and rapid excretion. As a possible consequence, only partial chimerism was achieved, but full engraftment ensued following the discontinuation of cyclosporin A, rebound donor lymphocytosis and the onset of acute GVHD. We suggest that host resistance to engraftment and tumour elimination was overcome by removing a suppressive effect on donor lymphocytes, allowing a graft-versus-leukaemia effect.
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PMID:Successful allogeneic bone marrow transplantation in juvenile CML: conditioning or graft-versus-leukaemia effect? 846 91

Between October 1988 and December 1990, 60 patients with leukaemia (25 with AML, 19 ALL and 16 CML) undergoing BMT were randomised in a double-blind clinical trial to receive prostaglandin E2 (PGE) (Prostin E2, 0.5 mg per tablet) or placebo for prophylaxis of oral mucositis. Patients had to dissolve tablets in the mouth three times daily starting 7 days before BMT and continuing until 21 days after BMT. The incidence of severe oral mucositis was similar for both groups, 55% in patients receiving PGE and 52% in patients receiving placebo. The duration of severe mucositis did not differ between PGE and placebo groups (chi-square 0.95, p = NS). The incidence of HSV infection was significantly higher in patients receiving PGE. Patients with HSV infection receiving PGE also had a higher incidence of severe oral mucositis. The results presented indicate that PGE is not effective for prophylaxis of oral mucositis in BMT recipients.
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PMID:Prostaglandin E2 for prophylaxis of oral mucositis following BMT. 850 71

We report the syndrome of inappropriate antidiuretic hormone secretion (SIADH) preceding the development of skin lesions of varicella zoster virus (VZV) infection in a patient with CML 5 months post-allogeneic BMT. This is the first report of SIADH complicating disseminated VZV infection in a BMT patient. SIADH is an unusual complication that may precede VZV infection post-BMT.
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PMID:Inappropriate antidiuretic hormone secretion (SIADH) preceding skin manifestations of disseminated varicella zoster virus infection post-BMT. 850 76

Alpha-interferon (alpha-IFN) has been used in relapsed CML post-BMT, cytogenetic responses being attained in a number of cases (33 to 42%). In first chronic phase-CML patients such cytogenetic response has been correlated with the disappearance of the bcr region rearrangement, as seen with Southern-blot, but when RT-PCR is used only a small number of patients maintain undetectable traces of the Ph1 clone. A case of CML in haematological and cytogenetic relapse after BMT is reported who showed criteria of "accelerated" phase and, after treatment with alpha-IFN achieved haematologic, cytogenetic and molecular remission (Southern-blot and PCR negative) and disappearance of the abnormal clone with recovery of the donor haemopoiesis. The duration of the alpha-IFN cytogenetic response is longer than that of BMT (5 vs 3.5 yr), which is noteworthy. Taking the low toxicity of alpha-IFN into account, as compared with that of the other choices (a second BMT, IL2), this treatment should be offered to all patients with cytogenetic relapse after BMT.
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PMID:[Alfa-2a interferon induces molecular remission in post-BMT relapse of chronic myelogenous leukaemia. Report of a case with loss of bcr-abl RNA]. 855 77

Donor mononuclear cell (MNC) infusions provide a very potent and effective anti-leukemic therapy. For patient's with CML who relapse after allogeneic BMT, the administration of donor MNC can result in a direct GVL effect and re-establish sustained remissions, even when assessed by very sensitive PCR-based techniques. The GVL reaction appears to be most prominent in patients with chronic phase CML. It is less apparent for patients with more advanced stages of CML or for patients with relapsed acute leukemia and myelodysplasia, although only small numbers of these patients have been treated. While the majority of patients tolerate this therapy very well, treatment related morbidity and mortality is still quite significant, and efforts to limit the severity of GVHD, and to recognize and treat marrow aplasia early may be useful. Longer follow-up of patients who have achieved complete remission will be required to determine if this therapy will have an impact on long term disease free survival, but at the current time, it would seem to be a very acceptable alternative to a second BMT.
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PMID:Adoptive immunotherapy for relapsed leukemia following allogeneic bone marrow transplantation. 858 Jul 87

The chronic myelogenous leukemia [CML] is a clonal disease of hematopoietic stem cells with unknown etiology. The incidence is around 2/100,000/year, the median age at diagnosis about 47 years. The course of CML is characterized by a chronic phase with few symptoms and good therapeutic response of about 4 to 5 years duration and by transition to a prognostically unfavourable blast phase of about 3 months duration. Therapy of choice, at present, is early allogenous bone marrow transplantation [BMT], which is curative in 40 to 80% of transplanted cases. In patients below 55 years, a donor search should be started at the earliest possible time after diagnosis. Drug therapy of choice are interferon alpha [IFN] and hydroxyurea, which are both superior to busulfan with regard to duration of chronic phase and survival. Complete cytogenetic remissions are observed in 5 to 9% of IFN-treated patients in randomized studies, but virtually all remain positive for bcr/abl by PCR. Whether and in how far IFN is superior to hydroxyurea appears, at least in part, to depend on the treatment intensity with hydroxyurea and on patients characteristics. In analyzing median survival times, the risk profiles of the patients have to be considered. In the future, intensive chemotherapy with or without autografting might play an important role in the therapy of chronic-phase CML. Forthcoming trials have to consider both, conventional and new experimental treatment modalities. An example is the treatment strategy of the ongoing randomized study of the German CML Study Group which compares allogenous BMT with the best available drug therapy and, in addition, analyses the influence of intensified drug therapy on survival.
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PMID:[Chronic myeloid leukemia]. 862 68


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