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)

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

The use of bone marrow transplantation is increasing in the management of advanced cancers. In autologous bone marrow transplantation (ABMT), many investigators have attempted to purge the graft of residual tumor cells because of concern that reinfused tumor cells might contribute to relapse. The feasibility of various methods (exposure to chemical agents, monoclonal antibodies (MoAbs), toxins, dye, magnetic microparticles ... ) has been confirmed. In allogeneic bone marrow transplantation, clinical studies have related the prevention of graft-versus-host disease reaction through the partial depletion of T lymphocytes in the donor graft limited to 1 log to maintain a graft-versus-leukemia (GVL) effect. Similarly, the feasibility of different assays (soybean agglutinin, Moabs and magnetic microparticles) have been shown. However, the clinical benefit of BM purging remains to be demonstrated. For ABMT, only recent data on B-cell lymphoma and leukemia strongly support the clinical usefulness of an ex-vivo purging. For allogeneic BMT, one question remains controversial: is T lymphocytes depletion the best method for GVHD prevention?
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PMID:[Ex-vivo treatment of a bone marrow graft]. 160 93

It is thought that natural killer cells may play a role in graft-vs.-host reactions after allogeneic bone marrow transplantation, but the use of NK cell-specific reagents has been limited. In this report, an NK allele-specific monoclonal antibody, anti-NK 1.1, was used to study the impact of in vivo donor NK cell depletion on GVH disease, graft-vs.-leukemia (GVL) reactivity and donor T cell chimerism after allogeneic murine BMT. AKR/J (H-2k) recipient mice were preconditioned with suboptimal irradiation (9 Gy = LD50) and transplanted with major histocompatibility complex-matched B10.BR (H-2k) BM cells with or without added spleen cells as a source of T cells. The addition of increasing numbers of spleen cells to the BM inoculum produced GVHD of varying intensities. The beneficial effect of NK depletion on GVHD was dependent on the intensity of the GVH reaction. Donor NK cell depletion had no effect on the survival of mice with severe GVHD after MHC-matched BMT (B10.BR into AKR) or after MHC-mismatched BMT (B10.BR into DBA/2; H-2k into H-2d). However, donor NK depletion increased survival of AKR hosts given sufficient B10.BR splenic T cells to induce mild-to-moderate GVHD. Ex vivo depletion of donor CD8+ T cells also reduced GVH-associated mortality, but the use of both CD8 and NK depletion offered no improvement over either alone, suggesting an interaction between CD8+ and NK 1.1+ cells. In contrast to CD8 depletion, donor NK depletion did not compromise the rapid and complete establishment of donor T cell chimerism nor the ability of chimeras to mount an effective GVL reaction. Thus, elimination of donor NK cells provides an alternate strategy for reducing GVHD without loss of GVL reactivity following MHC-matched allogeneic BMT.
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PMID:A decrease in graft-vs.-host disease without loss of graft-vs.-leukemia reactivity after MHC-matched bone marrow transplantation by selective depletion of donor NK cells in vivo. 163 18

As indications for BMT increase, so do variations in bone marrow processing and manipulation techniques. Many centers have their own unique methods of mononuclear cell purification, concentration and storage. This is particularly evident in the processing of bone marrow for autologous BMT to allow dose intensification as salvage therapy for malignant disease. Unique procedures have been developed to maximize yields, concentrate mononuclear cells necessary for engraftment, and reduce the likelihood of GVH disease. Graft rejection and disease relapse still remain a problem in some of these "manipulated" marrows. Newer procedures may allow titration of the optimum numbers of immune reconstituting cells; however, at this time, these techniques are not precise and the balance between preventing GVH disease at the expense of graft failure or relapse may still jeopardize disease-free survival. Innovative purging techniques that include pharmacologic and immunologic methods, continue to evolve, necessitating standards for bone marrow processing that are flexible yet practical. Quality control and viability assays are essential to verify the biologic proliferative potential of progenitor cells capable of marrow reconstitution. Although no standards are yet established, all centers should have criteria to monitor the quality of the processed marrow. Blood banks and transfusion services are well versed in regulations governing processing, labeling, storage, and quality control of blood components. Bone marrow is the ultimate blood component, and it stands to reason that methods outlined in this article be integrated into transfusion medicine.
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PMID:Bone marrow processing for transplantation. 168 56

We reviewed the medical records of 97 patients undergoing T cell-depleted allogeneic bone marrow transplantation at our institution from 1984 to 1990 to determine the incidence of hepatic dysfunction, including venoocclusive disease of the liver following BMT. All patients received allogeneic marrow that had been purged with monoclonal antibody to the CD6 surface antigen (T12) and rabbit complement as the sole method of graft-versus-host disease prophylaxis. No additional immunosuppressive agents were routinely administered to these patients. Overall, 55% of patients in our series developed two-fold elevations in serum bilirubin, SGOT, or alkaline phosphatase within the first 30 days following BMT. A five-fold elevation in any liver function test was noted in only 19% of patients. Logistic regression analysis revealed that the presence of GVHD, female sex, and administration of amphotericin B all were independently associated with laboratory evidence of hepatic dysfunction. While LFT abnormalities were common in our series, they were generally mild, and the development of VOD was rare. Only three patients (3.1%) fulfilled clinical criteria sufficient to establish a diagnosis of VOD. Among the 86 patients whose ablative regimen consisted of cyclophosphamide (60 mg/kg x2) and total-body irradiation (1200-1400 cGy in 200 cGy fractions), only 1 patient (1.2%) developed VOD. Our experience suggests that patients undergoing allogeneic BMT are at low risk for VOD and other serious hepatic complications when they receive high-dose cyclophosphamide, fractionated TBI, and T cell-depleted marrow without hepatotoxic medications for GVHD prophylaxis.
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PMID:Hepatic dysfunction following T-cell-depleted allogeneic bone marrow transplantation. 175 63

This report presents the analysis of leukemic relapse of 52 patients who received allogeneic bone marrow transplantation between July 1984 and May 1990. Conditioning regimen consisted of TBI + CY and GVHD prophylaxis consisted of cyclosporin-A and methotrexate. The relapse ratios of chronic myelogenous leukemia (CML) (21 in chronic phase, 1 in accelerated phase, 1 in blastic crisis), acute nonlymphocytic leukemia (ANLL) (all 17 in 1st CR), acute lymphocytic leukemia (ALL) (all 12 in 1st CR) were 13%, 18%, 25%, respectively, and 3 year disease free survival (DFS) was as follows, CML 68%, ANLL 72%, ALL 49%. Regarding acute GVHD grading and chronic GVHD presence, 3 year DFS was as follows, acute GVHD 0 degree: 59%, I degree: 78%, II degree-IV degree: 53%, chronic GVHD (+): 82% GVHD (-): 77%. In our center leukemic relapse has been the major cause of death after BMT since 1984. Among 9 relapsed cases, one recurred more than 3 years after BMT, and another one got recurrent leukemia of donor origin.
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PMID:[The analysis of leukemic relapse after allogeneic bone marrow transplantation]. 175 50

Thirty-one patients with acute non-lymphocytic leukemia (18 patients) or with high-risk refractory acute lymphocytic leukemia (13 patients) underwent bone marrow transplantation between March 1980 and March 1990. The high-dose conditioning regimen employed included cyclophosphamide followed by fractionated total body irradiation (12 GY). Fourteen patients who had an HLA-identical sibling donor received allogeneic bone marrow transplantation (allo-BMT); the other 17 patients received autologous bone marrow transplantation (auto-BMT) purged with 4-hydroperoxycyclophosphamide (4HC). Four of the 14 allo-graft recipients died of leukemic relapse and 2 others died of graft-versus-host disease. Three of the 17 auto-graft recipients died of relapse and 1 suffered relapse in the testes. The actuarial risk of relapse was 29% for the allo-BMT patients and 24% for the auto-BMT patients (P less than 0.05). The event-free survival rate at five years was 57% and 74% respectively (P less than 0.05). Although there was no difference between them, a trend toward a higher survival rate and a lower mortality and morbidity was observed in the auto-BMT group. These results suggest that autologous bone marrow transplantation purged with 4HC is an effective and useful treatment for children with acute non-lymphocytic and lymphocytic leukemia who have no HLA-identical donor.
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PMID:Comparison of autologous and allogeneic bone marrow transplantation in children with acute leukemia. 179 16

Fifty-one children between 26 and 214 months of age (median, 100 months) with acute lymphoblastic leukemia (ALL) were grafted in second remission from HLA-identical sibling donors (except for two patients who were grafted with a marrow with 1 antigen-mismatch). Initial treatment and relapse therapy were similar in all patients according to the BFM- and CoALL-protocols (front line: 38 patients according to BFM-protocols and 13 patients according to CoALL-protocols; relapse: 12 patients in study ALL-REZ-BFM 83, 17 in ALL-REZ-BFM 85, 20 in ALL-REZ-BFM 87, and two in ALL-REZ-BFM 90). The conditioning regimens were different, consisting of cyclophosphamide (CY) total body irradiation (TBI) plus (n = 27), VP-16-TBI (n = 23), and CY-TBI and ARA-C (n = 1). Three patients had a second graft after conditioning with CY-TBI for the first transplantation. The second ablative regimen consisted of CY plus VP-16 in the first patient and CY plus busulfan in the two other patients, one of whom relapsed again. All patients but three had bone marrow (BM), either isolated or combined, relapses. Twenty-nine of the patients are in continuous complete remission (CCR), ranging from 1 to 67 months after transplantation with a median time of 30 months. One patient was lost to follow-up in continuous remission. Nine patients died from treatment-related complications (infections and graft-versus-host disease) and 12 patients suffered a leukemic relapse; three of them received a second graft and two are in CCR. Kaplan-Meier analysis yields an event-free survival (EFS) of 0.52 +/- 0.08. The probability of a 7-year relapse-free interval (RFI) is 0.68 +/- 0.08. EFS for patients with late relapses is 0.47 +/- 0.12 and for patients with early relapses 0.56 +/- 0.1. The RFI for patients with late relapses is 0.65 +/- 0.12 and for patients with early relapses 0.69 +/- 0.11. There is a nonsignificant trend towards superior results for patients grafted after conditioning with VP-16 plus TBI. When all patients who are not in CCR at day +125 (which is the median interval between relapse diagnosis and BM transplantation [BMT]) are excluded from the chemotherapy results, there is no significant difference between the results of BMT and chemotherapy for late relapses. On the other hand, there is a significant advantage between chemotherapy and BMT for early relapses over chemotherapy (P less than or equal to .01).
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PMID:Allogeneic bone marrow transplantation for childhood acute lymphoblastic leukemia in second remission after intensive primary and relapse therapy according to the BFM- and CoALL-protocols: results of the German Cooperative Study. 182 71

The immunopathological appearances of skin and rectum in 64 autologous and allogeneic recipients were determined before and after bone marrow transplantation. Patients who developed acute graft-versus-host disease were biopsied as soon as a clinical diagnosis was made. At the same time peripheral blood samples were collected for comparative analysis. Immunohistological and morphometric techniques were employed using a panel of monoclonal antibodies to T lymphocytes and subsets, B lymphocytes, natural killer cells, macrophages, and Langerhans cells. A reduction in the CD4/CD8 ratio after BMT was seen in skin and rectal biopsies from both autologous and allogeneic recipients with or without GVHD. The same pattern was observed in blood samples taken at the same time. Langerhans cells were reduced in the skin in all patients after BMT, probably by the conditioning regimen. Only a few cells expressing activation or natural killer cell markers were present and there were no changes observed in the macrophage population. This study has provided no evidence to implicate either CD4- or CD8-positive T lymphocytes as the initiators of the cellular damage in acute GVHD. The distribution of lymphocyte subsets in the blood was similar to that in the tissues, suggesting that the tissue changes reflect the pattern of lymphocyte repopulation after BMT and may have little bearing on the pathogenesis of GVHD.
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PMID:Immunopathology of early graft-versus-host disease--a prospective study of skin, rectum, and peripheral blood in allogeneic and autologous bone marrow transplant recipients. 183 84

Autologous bone marrow transplantation (Auto-KMT) involves harvesting of a portion of a patient's bone marrow for subsequent reinfusion and restoration of marrow function following ablative doses of cytotoxic therapy, used in the treatment of various malignancies. The use of autologous rather than allogeneic marrow stem cells reduces the probability of acute graft-versus-host disease and reduces the need for obtaining HLA-matched marrow from limited donor pools. The greatest problem in Auto-KMT involves efficacy of the cytotoxic therapy and the obvious lack of graft-versus-leukemia effect. In addition, a theoretical limitation is that the marrow may contain clonogenic malignant cells, which may be the source of reestablished disease. In absence of phase III clinical trials directly comparing Auto-KMT with conventional therapies in the treatment of most malignancies, its role continues to be poorly defined. In an attempt to identify subsets of patients with leukemia or lymphoma who might benefit from transplantation, we performed this study of recent reports from the literature. It is concluded that the associated mortality is acceptable. At present the indications for Auto-KMT are lymphoma in relapse after conventional therapy and acute myeloblastic leukemia in second remission. It is probable that Auto-BMT will be used in earlier disease stages in the future (first remission).
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PMID:[Autologous bone marrow transplantation in malignant hematologic diseases]. 185 58


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