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)

We report a 33-year-old man with Ph chromosome-positive CML who underwent an allogeneic BMT from an unrelated donor. DNA microsatellite studies showed complete donor chimaerism immediately after BMT followed by mixed chimaerism; by day + 45 haematopoiesis was exclusively of recipient origin. Throughout the first year post-transplant all marrow metaphases were Ph negative but with non-clonal rearrangements consistent with autologous recovery. Cytogenetic relapse of leukaemia was first detected 15 months post-transplant. This case is unusual in that non-malignant stem cells of recipient origin survived the transplant and reconstituted haematopoiesis very early after BMT. Later the leukaemic cells reasserted their 'proliferative' advantage.
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PMID:Reconstitution with Philadelphia chromosome-negative recipient haematopoiesis early after allogeneic BMT for CML. 870 6

Twenty-five patients with hematologic malignancies were treated with busulfan (16 mg/kg) and cyclophosphamide (50 mg/kg x 3 days) as conditioning for bone marrow transplantation using marrow from serologically matched, DR locus genotypically identical unrelated donors. Previous studies of BuCy2 as conditioning for UD-BMT have reported a graft failure rate of up to 21% suggesting it may be insufficiently immunosuppressive in this setting. We elected not to use BuCy4 as it may have a higher incidence of extramedullary toxicity. In addition the patients received GM-CSF (500 mg/m2) from day 0, cyclosporine and short-course methotrexate (15 mg/m2 x 1, then 10 mg/m2 x 3) as GVHD prophylaxis and prophylactic ganciclovir at engraftment if either they or their donor were CMV antibody positive. The median age of the 25 patients was 41 years and the most common diagnosis was CML (76%). Seven patients were considered poor risk and eight males were recipients of marrow from female donors. Sixteen patients survive at a median of 435 days from transplant. The actuarial overall and disease-free survivals at 1 year in this group of older patients were 62 +/- 20% and 57 +/- 20% and 100-day survival was 70%. The engraftment rate was 100%; there have been no instances of secondary graft failure. Fifteen patients (60%) developed grade II-IV GVHD and 12 of 16 (75%) developed some chronic GVHD but only half of these were extensive. The performance status of survivors is good (median of 90); seven of 12 eligible patients are back at work. This study demonstrates that UD-BMT can be successfully performed in very closely HLA-matched older patients using a chemotherapy-only protocol and that low rates of severe acute GVHD can be achieved without T cell depletion.
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PMID:Unrelated donor bone marrow transplantation without T cell depletion using a chemotherapy only condition regimen. Low incidence of failed engraftment and severe acute GVHD. 872 53

In a retrospective analysis we assessed occurrence, contributing factors and outcome of patients experiencing granulocytic sarcoma as a localized extramedullary relapse after allogeneic BMT. EBMT members were asked to report the number of patients transplanted for leukemia between January 1981 and December 1992 and the number of patients with granulocytic sarcoma. Of a total of 5824 patients transplanted for AML, CML or MDS by 86 teams, granulocytic sarcoma was observed in 26 patients (0.45% occurring 4-56 months after BMT. Granulocytic sarcoma occurred after allogeneic BMT in 20 out of 3071 patients grafted for AML (0.65%), and in the CML/MDS subgroup in six out of 2753 grafted patients (0.22%). Granulocytic sarcoma can involve any site of the body, presenting as a soft tissue mass; it occurred in body cavities (eg pleural cavity, abdominal cavity, spinal canal, stomach and bladder), the head and neck region (orbit, ear, skull base, peripheral nerves), the trunk and limbs, and mammary and sex glands. Granulocytic sarcoma predicts an additional hazard to outcome after BMT. Nine of 26 patients (33%) were alive 15-151 months after the onset of granulocytic sarcoma. Advanced disease stage at grafting adversely affected survival and all patients died. The best treatment option still needs to be defined.
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PMID:Granulocytic sarcoma after allogeneic bone marrow transplantation: a retrospective European multicenter survey. Acute and Chronic Leukemia Working Parties of the European Group for Blood and Marrow Transplantation. 873 1

With the rationale that a significant reduction of the malignant clone in CML might prolong time to metamorphosis, intensive treatment was given to patients < or = 55 years. Six months of hydroxyurea and high dose interferon-alpha (IFN-alpha) was followed by one to three courses of intensive chemotherapy. Patients who had a donor were allotransplanted and patients who became Ph-negative in bone marrow were autotransplanted. On 1 May 1995, 160 patients were registered in the study. Fifty-one percent of the patients who received six months IFN-alpha and hydroxyurea had a significant Ph-reduction and 5% became Ph-negative. The corresponding figures after two intensive chemotherapy courses were 47 and 28%, respectively. Twenty-seven of 30 autotransplanted patients have been analysed for Ph. Seventeen have relapsed cytogenetically, while ten are Ph-negative 1-64 + months after ABMT. BMT was performed in 59 patients. The actuarial 6-year survival from diagnosis of all 160 registered patients is 68%, which seems to be better than for age-matched historical controls.
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PMID:Intensive treatment in order to minimize the Ph-positive clone in CML. Danish-Swedish CML Group. 876 5

Allogeneic BMT provides potential life-saving therapy for a variety of inherited and acquired diseases of the hemopoietic and the immune systems, including malignancies. At the University of Essen more than 800 transplants have been performed during the past 20 years. CML was the most frequent indication for BMT in Essen. Patients transplanted in first chronic phase had a high probability of disease-free survival, whereas patients transplanted with more advanced disease had long-term remission only in a minority of cases. With AML, optimal timing for transplantation remains undetermined. Patients at high risk of chemotherapy failure and relapse may have a better overall chance of long-term disease-free survival and cure if transplanted in first remission. BMT for patients with ALL are generally reserved for patients failing chemotherapy or in first remission with prognostic factors predicting a high risk of failure with chemotherapy alone. Compared with conventional bone marrow harvest, the advantages of mononuclear-blood-cell apheresis will probably change the standard procedure for bone marrow harvest in the future. Since 1995, an increasing number of blood stem cell transplants have been successfully performed in allogeneic transplants at the University of Essen.
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PMID:Twenty years of bone marrow transplantation in Essen - 1995 update. 879 76

Whether or not peripheral stem cells have an unlimited capacity for self renewal is debated. However, everyday haematopoietic requirements are met by progenitors; and it seems that few "real' stem cells are needed. Although we may not yet have identified these "true' stem cells, for practical purposes the long term culture-initiating cells (LTC-ICs) are a close approximation. To date, experience in peripheral blood progenitor cell (PBPC) transplantation is largely confined to non-ablative regimens. It is therefore difficult to determine the number of PBPCs needed to effect long-term reconstitution. The number of tumour cells present among mobilised PBPCs can be reduced using the CD34 affinity column and by positive purging methods. The ex vivo expansion of CD34 cells also has the effect of diluting tumour cell concentration. In clinical use, PBPC transplantation has a proven role in support of high dose chemotherapy in certain haematological and oncological malignancies but the concept of dose intensification is not universally accepted. With the exception of leukaemia, lymphoma, myeloma or relapsed testicular cancer and possibly some subgroups of breast cancer; high dose chemotherapy does not demonstrate a survival benefit. For patients with CML, autografting with Ph- cells appears to become a useful alternative to allogeneic BMT. Allogeneic PBPC transplantation may have potential, though work is preliminary. Cord blood transplantation between matched siblings is viable, but it is not yet clear whether this source will increase the donor pool for adults needing allogeneic transplantation. For gene therapy using haematopoietic cells to be effective, a greatly increased rate of transduction will be needed. Meeting in Paris in September 1995, a European School of Oncology Task Force considered a number of important questions relating to peripheral blood progenitor cell (PBPC) physiology and transplantation. This review is a brief account of their conclusions.
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PMID:Peripheral blood progenitor cell transplantation: where do we stand? Chairman's Summary of the European School of Oncology Task Force meeting Peripheral Blood progenitor cell's held September 29-30, 1995. 880 40

A patient, who was treated twice with donor lymphocyte infusions for relapse of CML after an allogeneic BMT was given lymphoblastoid human alpha-IFN after a third relapse. Further donor lymphocyte infusions were followed by repeated courses of 30 days treatment with a low dosage of IL-2 subcutaneously, alternately with alpha-IFN. This treatment resulted in a hematologic and cytogenetic remission. He also developed a limited degree of chronic GVHD. At the latest follow-up at 20 months after the third course of lymphocyte infusions he is in continuous hematologic and cytogenetic remission. Furthermore, a qualitative PCR analysis for the bcr/abl translocation is negative.
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PMID:Lymphoblastoid human interferon and low dose IL-2 combined with donor lymphocyte infusion as therapy of a third relapse of CML--a case report. 883 27

Sixteen patients with relapse after allogeneic BMT were treated with donor leukocyte infusions (DLI) from the original donor. The diagnoses at relapse were: CML in chronic phase (CP) (two patients), CML in accelerated phase (AP) (four patients), AML (four patients), MDS (one patient), ALL (four patients) and relapse of Hodgkin's disease (one patient). The patients received a mean of 5.2 x 10(8) leukocytes/kg with a range of 1.4-12.3 x 10(8) leukocytes/kg. Six patients obtained complete remission (CR), one with CML in CP, three with CML in AP, one MDS and one ALL. Partial remission (PR) was seen in three patients, one patient with CML in AP, one with AML and one with Hodgkin's disease. Seven patients had no response (NR) to the infusions, including one patient with CML in CP transplanted with a syngeneic donor. Four patients developed marrow hypoplasia after DLI (three CR and one PR) and two patients (ALL with CR and MDS with CR) were hypoplastic at relapse and marrow hypoplasia continued after DLI. GVHD occurred without GVL, but GVL only occurred in one patient with absence of GVHD. Eleven patients died of leukemia, six patients are alive. Three patients with CML are in CR 12, 12 and 32 months after DLI and one patient with ALL is in CR 15 months after DLI.
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PMID:Treatment of relapse after allogeneic BMT with donor leukocyte infusions in 16 patients. 886 54

Cytogenetic analysis is the gold standard for the follow-up of CML patients. The sensitivity of cytogenetics is fairly similar to that of Southern detection of M-BCR rearrangement (5%); this last technique has the potential advantage of being independent of cell division and yield of metaphases. IFN alpha treatment can induce lack of growth of hemopoietic precursors and poor yield of metaphases has been observed. For this reason we decided to study the grade of concordance and complementarity between analysis of karyotype and detection of M-BCR rearrangement of Southern blot. We studied 43 Ph1 positive, M-BCR positive pre-BMT CML patients (48 samples) treated with IFN alpha 2a. Karyotype was done on bone marrow cells by direct method, culture, and banding. Southern technique was performed onto DNA from peripheral blood leukocytes treated with BgIII (and Xbal if necessary) and hybridized with the universal probe (Ph1/bcr-3, Transprobe 1) labelled with dCTP32. A highly significant association between both tests was obtained. Of 48 samples analyzed, 34 were evaluable by both methods and 28 gave the same result for both tests. The concordance between the tests was good (kappa index: 0.63). Of total samples 27.1% was not evaluable by cytogenetics; this figure was 31.2% in samples from patients who were previously in complete cytogenetic response. All of the specimens not evaluable by karyotyping were evaluable by Southern. One sample was not analyzable by Southern but it was evaluable by cytogenetic analysis. The information obtained by Southern technique was clinically relevant, and decisions were made according to its results. We conclude that both tests show a significant association and a good concordance, although they are not interchangeable. Cytogenetic and molecular studies are complementary and must be employed together in CML patients treated with alpha-interferon.
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PMID:Southern technique and cytogenetics are complementary and must be used together in the evaluation of Ph1, M-BCR positive chronic myeloid leukemia (CML) patients treated with alpha interferon (IFN-alpha). 889 87

From 1987 to 1991, 26 patients with CML and a median age of 31 years received allogeneic BMT from a partially mismatched related donor (PMRD) who shared at least one haplotype with the recipient. Nine patients were in accelerated phase (AP), and 11 patients were in blast crisis (BC) at the time of BMT. Patients were mismatched either in graft-versus-host or host-versus-graft directions for one antigen in 3 patients, two antigens in 14 patients, and three antigens in 9 patients. All patients were prepared with a regimen consisting of total body irradiation, etoposide, cytosine arabinoside, cyclophosphamide and methylprednisolone. All marrows were treated ex vivo with T10B91.A-31, a monoclonal antibody directed toward the alpha beta heterodimer of the CD3 receptor, and rabbit complement. Additional GVHD prophylaxis included either the anti-CD5 immunoconjugate XomaZyme-H65, cyclosporine, or both in combination with methylprednisolone. Eight patients did not have sustained engraftment. The 100-day survival was 42%. The incidence of > or = grade II acute GVHD was 29%. The incidence of chronic GVHD was 50% and was limited in all cases. The median survival at 4 years for all 26 patients was 27%. Seven patients (CP 1, AP 3, BC 3) remain in hematologic remission 1297-2241+ days after transplantation. AlloBMT from a PMRD may be considered for patients with advanced CML who lack a matched sibling or unrelated donor.
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PMID:Long-term survival in advanced chronic myelogenous leukemia following bone marrow transplantation from haploidentical related donors. 889 90


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