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)

The activation of autologous cytotoxic cells by interleukin-2 (IL-2) may be a promising tool for elimination of minimal residual blast populations in patients with acute myelocytic leukemia (AML) to prolong disease-free survival. Here, we report the results of a phase II study using IL-2 for consolidation therapy in patients with second remission of de novo AML. All patients in 1st relapse of AML received a uniform induction therapy consisting of intermediate high-dose AraC (iHDAraC) 2 x 600 mg/m2 d1-4 and VP-16 100 mg/m2 d1-7. Patients achieving 2nd remission were treated with 4 cycles recombinant IL-2 (rIL-2) 9 x 10(6) IU/m2 administered on d1-5 and 8-12/cycle as 1h infusion every six weeks. In 37/66 (56%) evaluable patients, complete remission (CR) was achieved. So far, 21/37 patients (4 after additional autologous bone marrow transplantation (ABMT) received rIL-2 consolidation. Three patients are too early for evaluation, 4 received allogeneic BMT, 6 relapsed before IL-2 was scheduled and 4 refused treatment with rIL-2. The median disease-free survival (DFS) was 11 (4-49+) months. Up to now, in 5/21 (24%) patients the duration of 2nd remission exceeded that of 1st remission 7/21 (33%) are in ongoing 2nd remission (7+ to 49+ months). The side effects of rIL-2 were generally moderate and manageable. Only in two patients, previously treated with ABMT, severe side effects occurred; septicaemia and pneumonia in one patient and desquamative erythrodermia in the second one. In accordance with other studies rebound lymphocytosis with a marked increase of CD56(+)-cells and release of secondary cytokines such as TNF-alpha, IFN-gamma and IL-6 was observed. The schedule is feasible and the data suggest a possible benefit for DFS, which, however has to be confirmed by randomized trials.
Leuk Lymphoma 1995 Jan
PMID:Interleukin-2 bolus infusion as late consolidation therapy in 2nd remission of acute myeloblastic leukemia. 771 35

We studied 23 consecutive patients, median age 34 years, with relapsed or resistant aggressive lymphoma who underwent allogeneic BMT at the UCLA Medical Center Bone Marrow Transplantation Unit from 1 November 1984 to 30 March 1993. All patients were < 50 years of age and had sibling donors who were matched at the HLA-A, B and DR loci. Nine patients had Hodgkin's disease (HD) and 14 had non-Hodgkin's lymphoma (NHL); three of these had low grade histology and 11 had intermediate or high grade lymphoma histology. After a median follow-up of 34 months, eight patients are alive, seven without recurrent lymphoma. Five patients had early deaths. The disease-free survival for the entire group is 26% with an overall survival of 29%. There was no difference in survival rate on the basis of disease or histology. Comparing preparative regimens containing TBI to those without there was no difference in survival rate (P = 0.35). Neither age nor sex was a significant determinant of outcome (P = 0.63 and 0.36, respectively). Disease status at the time of transplantation proved to be the important determinant of outcome. Patients transplanted with chemotherapy sensitive disease (n = 9), defined as a partial or complete response to salvage chemotherapy, had a survival rate of 42%, which was significantly better than those who had refractory disease at transplantation (n = 14), who had a survival rate of 21% (P = 0.006). However, this small, but significant fraction of patients with refractory disease was curable. Thus, our data demonstrate that allogeneic bone marrow transplantation is an effective means of treatment for relapsed or aggressive Hodgkin's and non-Hodgkin's lymphoma.
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PMID:Allogeneic bone marrow transplantation for Hodgkin's and non-Hodgkin's lymphoma. 777 22

Cytokines produced by T lymphocytes, monocytes/macrophages, and fibroblasts play a central role in the immune response and in the development of graft-versus-host disease (GVHD). Also, it has been reported that dysregulated production of cytokines maybe the primary mediator of clinical manifestation of acute GVHD. Regarding cytokine gene expression after human allogeneic bone marrow transplantation (allo BMT), we have demonstrated increased IL-1 beta, IL-6, and TNF-alpha mRNA expression in peripheral blood mononuclear cells during the development of acute and chronic GVHD and that the degree of the increase was dependent on the severity of the disease. Furthermore, overexpression of these cytokine mRNAs could be detected before the clinical manifestations of GVHD developed. In contrast, IL-2 mRNA expression was not detected in peripheral blood mononuclear cells in GVHD patients. On the other hand, we have reported that increased mRNA expression and protein product of IL-2 and IFN-gamma were evident in the mixed lymphocyte culture of the cases who developed severe lethal transplantation-related complications. Therefore, the detection of increased IL-2 and IFN-gamma gene expression in MLC appeared to be useful for predicting transplantation-related complications in BMT patients. Furthermore, we found increased IL-2 receptor alpha subunit mRNA expression in the peripheral blood mononuclear cells during GVHD. These findings may indicate the important role of inflammatory cytokines such as IL-1 beta, IL-6 and TNF-alpha in the development of the clinical manifestation of GVHD and also may be indicative of the important role of IL-2 and the IL-2 receptor in allo response perhaps mainly as an autocrine effect.(ABSTRACT TRUNCATED AT 250 WORDS)
Leuk Lymphoma 1995 Feb
PMID:Cytokine gene expression after allogeneic bone marrow transplantation. 778 51

Myelodysplastic syndromes (MDS) represent an acquired group of clonal disorders of the pleuripotent stem cells, resulting in progressive life-threatening cytopenias or transformation into acute leukemias. A major issue of using alloBMT in MDS is the criteria used for patient selection. Therapeutic trials of lesser intensity such as differentiating agents, and cytokines could be the preferable choice for patients with good prognostic features. On the other hand, patients with poor prognostic features may urgently need to establish a normal hematopoiesis through allogeneic bone marrow transplantation (alloBMT). Important prognostic indicators in MDS include FAB classification, presence of abnormal localization of immature precursors, degree of cytopenias and cytogenetic abnormalities. We used a novel preparative regimen--"BAC" consisting of the consecutive administration of 1 mg/kg of busulfan every 6 hours for 16 doses followed by 2 g/M2 of cytosine arabinoside (ara-C) given every 12 hours for four doses, and finally 60 mg/kg of cyclophosphamide daily for 2 days. Thirty two patients transplanted had a median age of 33 years. Nine of the patients had either RA or RARS, 21 had RAEB or RAEB-T and 2 were unclassified MDS. Twenty two of our patients had chromosomal abnormalities while 10 had a normal karyotype analysis. Nine of the 32 patients had documented leukemic transformation and received induction therapy prior to BMT. The median time from diagnosis to BMT was 5.6 months, ranging from 1.3 to 30.2 months. Nineteen out of 32 patients are alive without disease, with a median follow up of 24 months. The actuarial event-free survival for the entire group is 52%. Two patients have relapsed with an actuarial relapse rate of 12%. Only significant favorable prognostic indicator for the event-free survival was in the recipient of a genotypically matched graft (76%) compared to recipients of a non-genotypic graft (23%) (p = 0.02). "BAC" is a unique preparative regimen for alloBMT in MDS with excellent results.
Leuk Lymphoma 1994 Aug
PMID:Allogeneic bone marrow transplantation in patients with myelodysplastic syndromes. 781 96

Bone marrow transplantation procedure has emerged as an effective treatment for hematological malignancies. However, recurrence of leukemia is still the major cause of treatment failure. Subsequent treatment in this category of patients, generally considered incurable, has not been yet standardized. At our institution, 13 patients, 7 with acute non lymphoid leukemia (ANLL) and 6 with acute lymphoid leukemia (ALL), were treated at relapse after bone marrow transplantation either autologous or allogeneic (AuBMT 8, ABMT 4) performed in complete remission (CR). The interval between BMT and relapse was less than 9 months in 6 patients (2 ABMT and 4 AuBMT) and more than 9 months in 7 patients. Early relapsed patients showed no response to treatment and died at a median of 5.5 months (range 1-13) after relapse. Late relapse after BMT was characterized by a high percentage of response (5 CR and 1 PR), particularly after intensive chemotherapy and by a longer survival (median 14 months; range 2-36). Chemotherapy after transplantation should be carefully evaluated in patients relapsed after BMT in order to select a population that can achieve long term disease free survival.
Leuk Lymphoma 1994 Sep
PMID:Aggressive chemotherapy for acute leukemia relapsed after transplantation. 785 90

We investigated the proliferation and therapeutic utility of anti-CD3 activated splenocytes infused into mice following BMT. Using congenic mouse strains we demonstrated that splenocytes activated briefly ex vivo with anti-CD3 plus IL-2 (T-activated killer cells or T-AK) and infused intravenously following BMT had a greater expansion in blood, spleen and BM compared with splenocytes stimulated with IL-2 alone. T-AK cells recovered from blood, spleen and BM consisted predominantly of CD8+ T cells. A single infusion of T-AK cells given on day +1 post-syngeneic BMT and sustained in vivo with liposomal encapsulated IL-2, significantly increased survival of mice with BDL-2 lymphoma when compared with mice receiving saline and those treated with IL-2 liposomes alone. The anti-tumor effect of T-AK cells was significantly enhanced when IL-2 was given by continuous infusion compared with bolus injections. Depletion studies confirmed that the CD8+ T-AK cells were mainly responsible for the anti-tumor effect against BDL-2 lymphoma. Our findings demonstrate that brief ex vivo activation of splenocytes with anti-CD3 plus IL-2 results in in vivo proliferation of effector cells with potent anti-tumor activity following BMT.
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PMID:Short-term ex vivo activation of splenocytes with anti-CD3 plus IL-2 and infusion post-BMT into mice results in in vivo expansion of effector cells with potent anti-lymphoma activity. 785 30

Sixty-nine adolescents and adults 15-51 years of age with untreated acute lymphoblastic leukaemia (ALL, 54 patients) or lymphoblastic lymphoma (LL, 15 patients) were referred for intensive antileukaemic therapy. Patients were treated according to one of two protocols. Both included induction and consolidation with vincristine, prednisone, daunorubicin, cyclophosphamide, Ara C and asparaginase. Fifty-eight patients achieved complete remission within 8 weeks of chemotherapy. One additional patient entered remission after allogeneic BMT. Altogether 86% of the patients achieved CR. Thirty-three patients are alive, corresponding to an actuarial survival of 48 +/- 6% at 5 years after start of therapy. Survival from time of achievement of CR is 53 +/- 7% at 5 years and disease-free survival (DFS) is 52 +/- 7%. Consolidation treatment was given to all patients except one. An HLA-identical sibling was identified for 30 patients (45%). Twenty-two patients were scheduled to be transplanted with marrow from an HLA-identical sibling. The survival and DFS in these 22 patients was 58 +/- 11% at 5 years. DFS was not significantly different compared with the DFS of the eight patients who received an auto-BMT and the 26 patients treated with maintenance chemotherapy. DFS at 5 years was 63 +/- 17% and 40 +/- 10%, respectively. We also evaluated the influence of the presence of an HLA-identical sibling on the treatment outcome of all patients alive 12 weeks after initiation of remission-induction therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of allogenic bone marrow transplantation in adolescent or adult patients with acute lymphoblastic leukaemia or lymphoblastic lymphoma in first remission. 788 10

Seventy-three BMT procedures (42 allogeneic-BMT, 30 autologous-BMT, 1 syngeneic transplant) were undertaken at the Shariati Hospital in Tehran between March 1991 and November 1993. Allogeneic-BMT was performed for thalassaemia major (n = 23), AML in complete remission (n = 3), severe aplastic anaemia (n = 7), CML (n = 7), dyskeratosis congenita (n = 2) and Fanconi anaemia (n = 1). Conditioning regimens comprised busulphan (BU) plus cyclophosphamide (CY) or CY only. Thirty-two (78%) of the 43 patients remain alive 1-34 months after BMT. Twelve patients died: the causes of death were haemorrhagic cystitis (n = 1), CMV pneumonitis (n = 1), GVHD (n = 3), infection (n = 3), rejection (n = 1), VOD (n = 2) and hepatitis (n = 1). Autologous-BMT was performed for patients with AML in CR (n = 16), ALL in CR (n = 9), lymphoma in relapse (n = 3), Ewing sarcoma (n = 1) and multiple myeloma (n = 1). The median age was 18 years. Conditioning regimens were Ara C plus CY, etoposide plus CY and high-dose melphalan. Sixteen (54%) of the 30 patients survive, 14 in continuous complete remission. The causes of death were relapse (AML (n = 7), ALL (n = 4), lymphoma (n = 1)), VOD (n = 1) and infection (n = 1).
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PMID:Bone marrow transplantation in Iran. 792 Mar 8

Over a 6-year period, 275 patients were treated with autologous bone marrow transplantation (auto-BMT) for advanced-stage malignant lymphoma. After BMT, clonal chromosomal abnormalities were detected in hematopoietic cells from 10 patients. All 10 had morphologically and cytogenetically normal BMs at the time of stem cell harvest. The cytogenetic changes were first detected 1.8 to 6.5 years (mean, 3.9) after induction chemotherapy, and 0.5 to 3.1 years (mean, 1.4) after transplantation, and were characteristic of those reported for therapy-related myelodysplastic syndrome (MDS) in 9 of the patients: abnormalities of chromosome 5 or 7 (classical-form) were present in 4, 11q23 or 21q22 abnormalities (topoisomerase II-related form) were detected in 3, and a combination of both forms was seen in 2 patients. Clonal 2p abnormalities were found in the 1 remaining patient. The abnormal karyotypes were associated with morphologically recognizable MDS in 3 patients and with acute myeloid leukemia (AML) arising in MDS in 2. Four of these patients have died: 3 of AML and 1 of infection. One patient is still alive with cytopenia. The clonal cytogenetic abnormalities were not associated with MDS in 5 patients: 1 has died of recurrent lymphoma, 2 have cytopenia, and 2 still have no morphologic or clinical evidence of MDS after short follow-up (4 and 13 months). Compared with a control group matched for disease, length of follow-up, and treatment with auto-BMT, there were no statistically significant associations between the development of clonal chromosomal abnormalities and age, number of chemotherapeutic regimens, prior local radiation, BMT conditioning regimen (with or without total body irradiation), or type of lymphoma. These studies show that the risk of developing clonal cytogenetic changes after auto-BMT for malignant lymphoma is approximately 9% at 3 years, even when pre-BMT karyotypic studies are normal. The exact significance of these cytogenetic abnormalities in the absence of MDS or AML is unclear.
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PMID:Clonal karyotypic hematopoietic cell abnormalities occurring after autologous bone marrow transplantation for Hodgkin's disease and non-Hodgkin's lymphoma. 804 77

Lethally irradiated genetically resistant (C57 x AKR) mice, unlike non-resistant (C3H x AKR) mice, which display genetic resistance to transplantation of parental C57 bone marrow grafts (GR to BMT), also reject transplanted parental AKR lymphoma grafts (GR to lymphoma). Depletion of natural killer (NK) cell activity of resistant (C57 x AKR) mice by anti-asialo GM-1 serum abrogated the resistance, whereas stimulation of NK cell activity of non-resistant (C3H x AKR) mice by polyinosinic: polycytidillic acid (poly I:C) induced the resistance to parental AKR lymphoma grafts. This shows that NK cells contribute to GR of (C57 x AKR) hybrid mice to parental AKR lymphoma grafts. Further, these results indicate that NK cells which confer genetic resistance to bone marrow transplantation (GR to BMT) in lethally irradiated (C57 x AKR) hybrid mice, also mediate GR to lymphoma transplantation in these mice, thereby linking GR to BMT with GR to lymphoma-leukemia.
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PMID:Genetic resistance to lymphoma-leukemia: role of natural killer cells in the rejection of lymphoma grafts. 806 Dec 45


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