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)

Among patients included in the multicentric trial ALL87, 95 patients were randomly allocated to purged ABMT arm for post-remission therapy. Immunological phenotyping performed in patients at diagnosis allowed to assigned 51 patients (54%) to the B lineage and 34 patients (36%) to the T lineage. Only 64 patients (67%) actually received ABMT mainly because of early relapses. Fifty-two patients were depleted according to the protocol: 25 B-ALL were depleted with CD10+CD19 mAbs, 19 T-ALL with CD2+CD5+CD7 mAbs and 8 patients received an Asta-Z purged BMT. Among the 12 remaining patients, 4 received Asta-Z purged BMT and 8 an unpurged one. Using an intention to treat analysis, overall survival and event free survival were similar to results observed in chemotherapy group. This study emphasizes the importance of a precise phenotyping at ALL diagnosis which allows specific immunologic bone marrow purging for ABMT.
Leuk Lymphoma 1994
PMID:Autologous BMT for post-remission therapy in adult ALL: an immunological approach. For The French Group of Therapy of Adult ALL. 807 89

Infections by herpesviruses are common phenomena in patients being treated for acute leukemia and those undergoing bone marrow transplantation. Reactivation of endogenous latent virus caused by the immunosuppressive and cytotoxic effects of cytoreductive therapies is a common mechanism of infection. With cytomegalovirus (CMV), acquisition of exogenous virus by transfusion of blood products containing virus and from the bone marrow graft in the case of bone marrow transplantation can occur. Serious morbidity can result and occasional mortality. CMV infections in allogeneic BMT recipients have high case fatality rates. Treatment and preventive strategies for herpes simplex virus (HSV), CMV, and varicella zoster virus (VZV) have been developed to reduce morbidity. Acyclovir, either given prophylactically or as treatment of active infection, has been highly successful in reducing illness from HSV and VZV infection. For CMV, provision of CMV-seronegative blood products is the mainstay of prevention of morbidity in seronegative patients and is especially important in the care of patients undergoing allogeneic BMT. Ganciclovir given either prophylactically or as early therapy for patients detected to be shedding CMV appears to be a promising strategy. Bolstering host immunity through augmentation of anti-CMV cytotoxic T-cell responses appears to be an exciting candidate therapy under development.
Leuk Lymphoma 1993
PMID:Viral infections in leukemia and bone marrow transplant patients. 812 23

Emergence of drug resistance with conventional cytotoxic therapy is a major challenge towards the curability of many cancers, especially in patients undergoing autologous BMT with ex-vivo purged hematopoietic support. We have explored the potential role of photoradiation therapy in purging hematopoietic stem cells of various hematological malignancies. Benzoporphyrin derivative, monoacid ring A (BPD-MA), dihematoporphyrin ether (DHE), and MC-540 were evaluated for the "ex-vivo" purging of residual tumor cells from autologous bone marrow (BM) grafts. BPD-MA and DHE photosensitizing activity was tested against two human large cell lymphoma cell lines and colony forming-unit leukemia (CFU-L) derived from patients with acute myelogenous leukemia (AML). In mixing experiments four log elimination of tumor cell lines was observed after 1 hr of incubation with BPD-MA or DHE followed by white light exposure. By comparison, using the same concentration of BPD-MA or DHE, the mean recovery of normal BM progenitors was 4-5.2% for granulocyte-macrophage colony forming unit (CFU-GM) and 5-9.8% for burst forming unit erythroid (BFU-E). The T lymphoblastic leukemia cell line CEM and its vinblastine (VBL)-resistant subline CEM/VBL100, along with the acute promyelocyte leukemia cell line HL-60 and its vincristine (VCR)-resistant subline HL-60/VCR, were also tested. Our results demonstrated the preferential cytotoxicity of BPD-MA and DHE toward neoplastic cell lines and CFU-L from AML patients. In addition, DHE was slightly more effective in purging tumor cells expressing the p-170 glycoprotein.(ABSTRACT TRUNCATED AT 250 WORDS)
Leuk Lymphoma 1994 Feb
PMID:Newer options for treating drug-resistant (MDR+) cancer cells using photoradiation therapy. 818 Jun 6

Cytomegalovirus (CMV) infection is common in patients who undergo allogeneic bone marrow transplantation. Gancyclovir is useful in treating CMV infections. Resistance to gancyclovir is rare and has, thus far, not been reported in the setting of BMT. Two patients with CMV infections unresponsive to gancyclovir were successfully treated with foscarnet. 10-15% of CMV infections are resistant initially or develop resistance to gancyclovir. Both patients had an adequate trial of gancyclovir and resistance developed over time. While we did not document resistance in the laboratory there was dramatic clinical improvement with foscarnet.
Leuk Lymphoma 1994 Feb
PMID:Treatment of gancyclovir resistant cytomegalovirus with foscarnet: a report of two cases occurring after bone marrow transplantation. 818 Jun 11

Myelodysplastic syndrome (MDS) is a complication of conventional antineoplastic therapy but has rarely been reported after autologous bone marrow transplantation (ABMT). We reviewed records of 206 patients who underwent ABMT for lymphoma at the University of Minnesota (Minneapolis, MN) between 1974 and 1993. Of 206 patients who underwent ABMT for non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD), 9 patients developed an MDS or secondary acute leukemia between 5 and 60 months (median 34 months) post-BMT. Two patients had relapsed after transplant and received additional therapy before the diagnosis of MDS. They were censored from the statistical analysis, resulting in a cumulative incidence of 14.5% +/- 11.6% (95% confidence interval) at 5 years. Three patients (15.2% +/- 18.0%) had HD, and four (14.0% +/- 14.7%) had NHL. In vitro BM purging had no affect on the incidence of MDS, although patients receiving peripheral blood stem cells had a projected MDS incidence of 31% +/- 33% versus 10.5% +/- 12% if BM cells were used (p = .0035). The patients had received a median of 14 cycles (range, 6 to 40) of chemotherapy before autologous transplantation; Five of nine patients received radiation therapy before BMT conditioning, and all patients received radiation before the diagnosis of MDS. No BM cytogenetic abnormalities were evident pretransplant in three of three patients studied, and all nine had normal pretransplant BM morphology. All patients had morphologic BM findings typical of MDS, and six of six studied had clonal cytogenetic abnormalities. At the diagnosis of MDS, all nine patients were without clinical, radiographic, or autopsy evidence of recurrent lymphoma; Three of the nine patients have died from complications of cytopenias at 23, 36, and 45 months after transplant (3 to 10 months after the diagnosis of MDS), whereas 6 survive 8 to 63 months after transplantation (1 to 34 months post-MDS). These data emphasize the cumulative leukemogenic potential of standard and salvage radiation and chemotherapy regimens and highlight treatment-induced MDS as an important and frequent late complication of potentially curative BM transplant therapy.
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PMID:Myelodysplastic syndrome after autologous bone marrow transplantation: an additional late complication of curative cancer therapy. 794 59

Autologous BMT performed in a 57-year-old woman with relapsed large cell lymphoma was complicated by two consecutive episodes of diffuse alveolar hemorrhage (DAH). The second episode occurred immediately after infusion of autologous BM. DAH is an increasingly recognized complication of autologous BMT and carries a high mortality. It is characterized by dyspnea, cough, bilateral pulmonary infiltrates and progressively bloodier aliquots of bronchoalveolar lavage fluid. The pathogenesis is probably multifactorial involving an initial insult to lung endothelium with inflammatory cells serving as the mediators of subsequent injury. The rapid development of DAH following marrow infusion strongly implicates DMSO as a potential cause in our patient.
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PMID:Diffuse alveolar hemorrhage following autologous bone marrow infusion. 824 90

There is no doubt that the poor reputation of T-cell depleted bone marrow transplant arises from its use in CML patients, where an increase in graft rejection and, above all, in leukaemia relapse has been reported by almost all centres. Evidence suggests that the standard conditioning regimen (once thought to be sufficiently immunosuppressive and myeloablative in unmanipulated transplants) should no longer be considered adequate when the immunological balance has shifted in favour of unopposed host-versus-graft reactivity and the GvL effect is lacking. Since GvHD remains the major problem in BMT, we suggest T-cell depletion should be considered the most effective method for GvHD prophylaxis but the cytoreductive effect of the conditioning regimens and the anti-leukaemia immune reactivity should be enhanced.
Leuk Lymphoma 1993
PMID:Is there any future for T-cell depleted bone marrow transplantation in chronic myeloid leukaemia? 825 97

The management of CML patients with some evidence of disease after BMT depends on the molecular, cytogenetic and hematological findings of relapse. Presently, a number of technical and biological problems do not allow to draw any definitive conclusion on the prognostic significance of Minimal Residual Disease detected by PCR. A positive PCR, particularly if observed late after BMT, leads to increase the frequency of cytogenetic examinations, but a therapeutic intervention is not justified. The criteria to define the cytogenetic relapse are not still established. Therefore it is difficult to interpret the reappearance of Ph-1 chromosome after BMT as disease recurrence invariably progressing towards the hematological phase. However, alpha-Interferon, donor buffy-coat infusion or their association should be considered in the treatment of patients for whom the cytogenetic relapse has been confirmed. The therapeutic approach to patients with hematological relapse is mainly depending on the phase of disease. The single, sequential or combined use of chemotherapy, alpha-IFN, donor buffy-coat infusion and second transplant has been shown to be effective in restoring donor hematopoiesis in several patients who relapsed either in chronic or advanced phase. Prospective, randomized, multicentre trials on CML relapse after BMT should be planned.
Leuk Lymphoma 1993
PMID:What does one do for the CML patient in relapse after allogeneic bone marrow transplantation? 825 99

Immune mechanisms superimposed to the myeloablative conditioning regimens exert an additional powerful effect in eradicating leukemia and in achieving immunological control of minimal residual disease. The impact of GVHD-independent GVL has been evaluated to be absent, or near absent, in ALL, about 30% in AML and about 40% in CML. While until little time ago most of the evidence in favor of an immune antileukemia mechanism exerted by allo BMT in CML was indirect, based on the lack of GVL, there is now solid evidence of a positive type, based on the antileukemia effect of donor lymphocyte infusions in patients having relapsed after transplant. There are three lines of indirect clinical evidence for GVL in CML: they include the classical linkage between GVHD and reduced relapse rate, increased relapse rate after identical twin allografts, and increased relapse risk after effective GVHD prophylaxis, with T lymphocyte depletion in the foreground. The eradicating effects of donor lymphocyte infusions in relapsed patients are the ultimate demonstration that allogeneic immune competent cells are capable of recognizing and destroying the Ph-positive clone. However the frequency of irreversible aplasia indicates that donor lymphocytes act in the same way on residual host hematopoiesis, so that a second graft, without repeat conditioning, should be programmed for such cases.
Leuk Lymphoma 1993
PMID:The graft versus leukemia (GVL) effect after allogeneic bone marrow transplantation for chronic myelogenous leukemia (CML). 825

Two hundred and twenty-nine patients with chronic myeloid leukaemia in chronic phase awaiting bone marrow transplantation from an HLA-identical sibling donor were randomized as part of their conditioning, to receive splenic irradiation (SI+, 115 patients), or not (SI-, 114 patients). Both groups were identical in regard to age, sex, donor/recipient sex combination and disease activity. Survival, leukaemia-free survival, incidence of transplant-related mortality, acute and chronic graft versus host disease, incidence of rejection and probability of relapse were not different in either groups at a median follow-up time of 4.5 years (minimum follow-up 2 years). Recovery of peripheral white blood cell counts to 1 x 10(9)/l but not of platelet counts to 50 x 10(9)/l was significantly faster in patients with SI+ (21 vs 24 days). This small benefit does not justify routine splenic irradiation prior to BMT, in CML.
Leuk Lymphoma 1993
PMID:Splenic irradiation before bone marrow transplantation for chronic myeloid leukemia: update of a prospective randomized study. 825 1


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