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)

Between June 1988 and May 1996, 428 patients underwent allogeneic BMT (288 related donor (RD) and 140 unrelated donor (UD)) at the Vancouver General Hospital. Eight patients (UD six and RD two) developed a post-transplant lymphoproliferative disorder (PTLD). Median age at BMT was 38 years (range 22-51). Five of the six UD allografts were T cell depleted. Cyclosporine+/-methotrexate was used for GVHD prophylaxis. All eight patients developed GVHD; in six this was refractory to treatment with corticosteroids. Rabbit antithymocyte globulin (ATG) or an anti-CD5-ricin A chain immunotoxin (Xomazyme) was used as second-line therapy for GVHD. Presentation with PTLD occurred at median day 90.5 (range 34-282) post BMT. Five of the eight patients had a rapidly progressive course characterized by fever, lymphadenopathy, lung and liver involvement and died within 3-8 days. PTLD was an incidental finding at post mortem examination in two patients. The remaining patient had localized disease and recovered. Pathological analysis revealed two morphological patterns; diffuse large B cell lymphoma (DLBC lymphoma, five patients) and polymorphous B cell hyperplasia (PBCH, three patients). EBV expression was positive in all eight cases and monoclonality was demonstrated in seven cases. In multivariate analysis, T cell depletion of the allograft (P=0.0001, relative risk (RR)=30.5), anti-T cell therapy for GVHD (P=0.006, RR=12.7) and acute GVHD grades 3-4 (P=0.04, RR=7.7) were the significant factors for development of PTLD. In conclusion, we have identified two forms of PTLD after BMT: one is characterized by disseminated disease with a rapidly progressive and often fulminant course and the other by localized, relatively indolent disease. Morphology, EBV positivity and clonality do not appear to correlate with the clinical course. The major risk factors for development of PTLD after BMT are ex vivo T cell depletion of the allograft and in vivo anti-T cell therapy for GVHD.
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PMID:Lymphoproliferative disorders following allogeneic bone marrow transplantation: the Vancouver experience. 984 95

In autologous bone marrow transplantation, immunologic effector cells such as lymphokine activated killer (LAK) cells may be useful for purging of bone marrow since these cells might have an additional in vivo effect on tumor cells in contrast to other purging protocols. Recently, immunologic effector cells termed cytokine-induced killer (CIK) cells have been shown to be more useful than LAK cells for purging of autologous BM in the context of autologous BMT. Here, we show that the expression of bcr/abl in CIK cells generated from patients with CML correlates with progression of disease in individual patients. In addition, progression of disease from chronic phase to accelerated phase could be predicted in two patients by studying the expression of bcr/abl in CIK cells generated from CML patients. Thus, it might be possible to use CIK cell generation for the prediction of progression of disease in CML patients.
Leuk Lymphoma 1998 Oct
PMID:Potential of autologous immunologic effector cells for prediction of progression of disease in patients with chronic myelogenous leukemia. 986 97

Between February 1993 and November 1997, 62 patients with severe aplastic anaemia (SAA), acute myeloid (AML), acute lymphoid (ALL), or chronic myeloid leukaemia (CML) as well as two patients with NHL underwent allogeneic marrow transplantation (BMT) from HLA-identical or one-antigen mismatched sibling or unrelated donors. Patients received preparative regimens according to the baseline disease. Patients with SAA were conditioned with ATG/Cy (2 cases) and TAI/Cy (3 cases), AML, ALL and NHL with TBI/Cy (21 cases including two retransplantations) and CML with Mitobronitol/Ara-C/Cy except two patients conditioned traditionally with Bu/Cy. For GVHD prevention, patients received cyclosporin-A (CsA) with short course methotheraxe according to the Seattle protocol. Significantly better overall survival rates were associated with the Mitobronitol (DBM)/Ara-C/Cy conditioning regarded the patients as a whole. Autologous stem cell transplantation (bone marrow and/or peripheral blood) were performed in ten cases including 2 AML, 4 non-Hodgkin's lymphoma (NHL), 3 Hodgkin's disease (HD) and 1 patient with multiple myeloma (MM). Patients with AML and two patients with NHL were conditioned with TBI/Cy and the others with BEAM combined chemotherapy. Eight out of ten patients are leukaemia- or lymphoma-free survivors. One patient relapsed having conventional chemotherapy and interferon maintenance therapy. One patient died in a rapid relapse five months post-BMT.
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PMID:Haemopoietic cell transplantation activity and results: a single institution experience. 991 38

The results of rapid tapering of Cyclosporin therapy in 7 patients with Philadelphia chromosome-positive chronic myeloid leukemia (CML) in relapse after allogeneic bone marrow transplantation are reported. All patients had cytogenetically-documented relapse within 6 months of transplant, and were on oral Cyclosporin therapy. Rapid tapering of Cyclosporin resulted in moderately severe acute GVHD in 2 cases, and in extensive chronic GVHD in a further 2 patients (fatal in 1 case). An antileukemic effect was observed in 6 patients, with complete haematological and cytogenetic remission observed in all cases. The seventh patient did not respond, and died after infusion of donor leucocytes. Four of the responders remain in complete remission of CML 30 to 120 months after BMT. One patient died in remission of chronic GVHD, and one patient had a complete response lasting 5 months, but relapsed and died 13 months post transplant. Rapid withdrawal of Cyclosporin therapy appears to be an effective means of treatment of early relapse of CML after transplant, and is an alternative to the use of donor leucocyte infusions for those patients still receiving Cyclosporin at the time of relapse.
Leuk Lymphoma 1998 Nov
PMID:Antileukemic effects of rapid cyclosporin withdrawal in patients with relapsed chronic myeloid leukemia after allogeneic bone marrow transplantation. 992 44

We conducted a double retroviral vector (RV) gene marking trial to test for the possible contribution to relapse of follicular non-Hodgkin's lymphoma (FNHL) cells present in bone marrow (BM) and peripheral blood (PB) grafts used for hematopoietic reconstitution of patients undergoing myelaoblative chemotherapy and autologous transplant. CD34 positive selection using the CellPro Ceprate CD34 column was performed on PB mononuclear cells obtained after cyclophosphamide/G-CSF mobilization. CD34 positive cells were exposed for 4-6 hours to the LNL6 or G1 Na RV in the absence of growth factors or stromal monolayers. One week later, BM mononuclear cells were similarly processed. Patients then received total body irradiation (TBI), cyclophosphamide, and etoposide followed by infusion of both PB and BM CD34 positive cells. Semiquantitative Southern blot analysis of DNA t(14;18) amplification products showed approximately a three log reduction in t(14;18) positive cells after CD34 positive selection. The first patient showed evidence of engraftment with RV positive BM and PB cells for 9 months. He relapsed one year after transplant. At relapse, one year after transplant, he had lost evidence of RV positive cells in ficolled mononuclear BM and PB cells as well as in CD19 positive cells. The second and third patients showed evidence of engraftment with RV positive cells up to 9 and 6 months post BMT respectively. The second and third patients are still in clinical remission. Our results demonstrate engraftment of RV transduced hematopoietic cells in the PB and BM for up to 9 months.
Leuk Lymphoma 1999 Jan
PMID:Hematopoietic retroviral gene marking in patients with follicular non-Hodgkin's lymphoma. 1003 25

Donor leukocyte infusions (DLI) from the original marrow donor have been shown to induce remission in patients with relapse after BMT. We analyzed factors that were associated with remission. Twenty-six patients with a relapse after T cell depleted BMT received DLI. The following pre-DLI factors were analyzed: sex and age of the patients and donors, GVHD after BMT, indication for DLI, percentage of donor T lymphocytes in the patient at the time of DLI, interval between relapse and DLI, and number of T lymphocytes infused. Remission was achieved in 11 of 15 patients (73%) treated for relapsed CML and in one of 11 patients (9%) treated for relapsed AML, ALL or RAEB-t (P = .002). Two of 13 patients (15%) with < or =40% of T lymphocytes from donor origin attained remission compared with 10 of 13 patients (77%) with >40% (P = .002). Two of 13 patients (15%) with an interval of < or =18 months between BMT and first DLI entered remission compared with 10 of 13 patients (77%) with an interval of >18 months (P = .002). Multivariate analysis demonstrated that indication for DLI (CML versus AML/ALL and RAEB-t) and the percentage T lymphocytes from donor origin (< or =40 versus >40) were significantly correlated with remission (P = .03). The occurrence of GVHD post DLI was highly associated with achievement of remission (P = .0001). DLI res ults in remission in a high percentage of patients with relapsed CML after BMT. The percentage of T lymphocytes from donor origin still present in the patient at the time of DLI is highly correlated with achievement of remission.
Leuk Lymphoma 1999 Jan
PMID:In relapsed patients after lymphocyte depleted bone marrow transplantation the percentage of donor T lymphocytes correlates well with the outcome of donor leukocyte infusion. 1003 29

The results of unrelated donor bone marrow transplantation are continually improving. These improved results are due to a better understanding of the complications of the procedure and the devising of strategies to avoid them. Nonetheless, many problems remain. This review will address some of the major controversies of the field including the indications for UD-BMT, infection, GVHD prophylaxis and treatment and whether UD-BMT should only be performed in specialist centres. Conclusions will be supported by evidence from the limited published literature and the authors' experience in 3 major transplant centres.
Leuk Lymphoma 1999 Feb
PMID:Unrelated donor bone marrow transplantation in adults: some current controversies. 1004 18

The spectrum of pediatric bone marrow transplantation has changed in recent years. Mismatched and unrelated donor transplants are common, demanding an increased vigilance to detect incipient graft failure, secondary lymphoma as well as relapse and other problems, which now are potentially treatable. To diagnose these complications it may be important to know whether blood and marrow cells are of recipient or donor origin. To evaluate the role of mixed donor-recipient chimerism in relation to clinical problems we adapted a polymerase chain-reaction technique, using fluorescent primers analyzing DNA fragment length polymorphisms, to follow prospectively 17 bone marrow grafted children. To increase the precision of chimerism analysis, immunomagnetically isolated leukocyte populations were assayed in selected cases. Five patients encountered clinical problems related to chimerism. One infant with adenosine deaminase deficiency failed to engraft stem cells, yet succumbed to graft-versus-host disease, mediated by mature donor T-cells. Three children developed significant mixed chimerism. One of these three patients died in relapse of leukemia, while the two other patients who had received T-cell depleted grafts had persistent recipient T-cells, in spite of engraftment. After 5 months, these were displaced by donor T-cells in one of the patients. In the fifth patient, also after T-cell depleted BMT, a fatal donor cell lymphoma occurred. Twelve children had stable full chimerism or in one case a low grade mixed chimerism and remain disease-free throughout follow up (median 9 months). In conclusion, the analysis of chimerism, particularly of separated leukocyte populations, offers an almost indispensable insight and a basis for therapeutic decisions in complicated situations such as grafting involving unrelated or mismatched donors, graft manipulation, adoptive immunotherapy and in immunodeficiency patients.
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PMID:Engraftment and chimerism, particularly of T- and B-cells, in children undergoing allogeneic bone marrow transplantation. 1008 48

Patients receiving intensive cytotoxic therapy are traditionally supported with parenteral nutrition (PN), although it is unclear whether all patients benefit from PN. This study aimed to identify regimen-associated differences in PN requirements, to reveal discrepancies between the number of PN indications and the frequency with which PN was actually given, and to describe characteristics of patients who met nutritional goals without PN. PN indications were defined as: (1) severe malnutrition at admission; (2) a prolonged period (7-10 days) of minimal oral intake; or (3) clinical weight loss >10%. PN was found to be needed in only 35% of consolidation courses, compared with 80% during remission induction and 55% during BMT. Significant differences were also seen between BMT protocols: PN was required in only 37% of autologous BMT recipients conditioned without total body irradiation (for lymphoma) vs 92% of recipients of a mismatched graft. A high body mass index was the only significant characteristic of patients who could do without PN. In conclusion, PN is not required for all patients undergoing intensive cytotoxic therapy. Screening of nutritional status at the start of therapy and monitoring oral intake following cytotoxic treatment may allow more appropriate identification of patients requiring PN.
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PMID:Parenteral nutrition following intensive cytotoxic therapy: an exploratory study on the need for parenteral nutrition after various treatment approaches for haematological malignancies. 1033 50

Patients with refractory malignant lymphoma (RML) have a poor prognosis when treated with conventional chemotherapy, as less than 20% remain alive and free of disease after 5 years. The use of myeloablative chemotherapy followed by BMT has improved the complete remission (CR) rate. Nevertheless, relapse rates remain unchanged, and only a few patients remain alive and free of disease for more than 3 years. For this reason, we began a prospective randomized clinical trial to determine if IFN-alpha2B (5.0 MU three times a week for 1 year) can improve the prognosis in RML. Ninety-six patients with high or high-intermediate clinical risk RML and in CR after intensive chemotherapy were randomly assigned to receive or not to receive IFN as maintenance therapy. A median follow-up of 48.1 months, the time to treatment failure and survival were similar in both groups. Toxicity secondary to IFN administration was mild, and all patients received the planned doses of IFN. We conclude that IFN is not recommended at this dose and schedule as maintenance therapy in patients with RML who achieve CR. Different therapeutic approaches may be developed to improve outcomes for these patients.
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PMID:Interferon as maintenance therapy in refractory malignant lymphoma. 1041 49


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