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 the results of consecutive tests in nine BCR-ABL-positive ALL patients by one-step and two-step (nested primer) reverse transcriptase-polymerase chain reaction (RT-PCR). Six patients could be tested in complete haematological remission (CHR). One patient remained one-step positive; four patients became one-step negative, but remained two-step positive; only one patient became two-step negative. In five patients the haematological relapse was preceded by one-step positivity by 1.5-5 weeks. In two patients who received autologous BMT in CHR, BCR-ABL was still detectable by two-step PCR, whereas allogeneic BMT was able to transiently reduce BCR-ABL below the two-step detection level. Our results show that one-step combined with two-step RT-PCR analysis gives valuable information about the efficacy of treatment and the dynamics of the leukaemic clone.
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PMID:PCR-monitoring of minimal residual leukaemia after conventional chemotherapy and bone marrow transplantation in BCR-ABL-positive acute lymphoblastic leukaemia. 777 40

Allogeneic T cells are capable of discriminating between leukemia cells and non-malignant hematopoetic cells. This has been concluded from clinical BMT data and demonstrated by in vitro experiments. We analyzed the frequency and specificity of leukemia-reactive T cells from syngeneic and allogeneic blood donors by limiting dilution assays for interleukin-2-producing (TH1) and cytotoxic (CTLp) T cells. Target cells were leukemia blasts obtained from a patient with common ALL. Control targets were generated by EBV transformation. Effector cells were generated from the peripheral blood of the patient in remission, from his syngeneic brother and from eight healthy, HLA-mismatched volunteers. The effector cells were stimulated with leukemia cells and interleukin-2. Neither the patient nor his brother were able to generate anti-leukemic CTLp or TH1. The HLA-mismatched allogeneic donors displayed anti-leukemic CTLp frequencies with a range from 0 to 68 million. TH1 cells with anti-leukemic specificity were not detectable. We conclude that there are great inter-individual differences in the GVL potential of fully allogeneic peripheral T lymphocytes. It is possible to identify T cell lines with reactivity against leukemia blasts and non-reactivity against normal hematological cells from the same individual. These cell lines are potential effector cells for immunotherapy of human leukemia.
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PMID:Leukemia-specific allogeneic donor T cells: quantification by limiting dilution assay. 777 7

Despite reports to the contrary, only a small minority of adults with ALL are currently cured. Results have improved modestly with more intensive postremission chemotherapy and with tailoring of protocols in individuals with specific subsets of ALL. The use of growth factors may further improve treatment results. The performance of allogeneic BMT in first remission is clearly effective in some individuals, eg, those with Ph1-positive ALL, but it is unclear whether it is advantageous in most individuals. There are little data supporting the effectiveness of autotransplantation, as currently performed in ALL, despite its theoretical potential. Advances in understanding the biology of ALL have led to new approaches currently under basic and clinical investigation. These include serial studies of minimal residual disease by a variety of techniques to tailor treatment, the development of conjugated MoAbs to lymphoid cell antigens and immunologic and biochemical approaches to chimeric RNA and peptides generated by abnormal fusion genes. It seems likely that substantial improvement in the treatment of adult ALL awaits better characterization of the biology of this disease. However, some improvement will occur through empirical clinical research. It is critical that physicians recognize the poor results with current therapeutic approaches and enter patients into large well-designed clinical trials.
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PMID:The biology and treatment of acute lymphoblastic leukemia in adults. 785 47

Seven patients with relapsed acute leukemia (4 ANLL, 3 ALL) and one with juvenile chronic myelomonocytic leukemia (JCMML) received a second BMT (BMT2). Patients were conditioned with CY/TBI (n = 7) or BU/CY (n = 1) for the first BMT (BMT1), with adequate recovery in all and without the appearance of acute GVHD (n = 3) or with mild forms (grade I, n = 2; grade II, n = 3). Relapse after BMT1 occurred in < 6 months (n = 2), between 6 and 12 months (n = 5) and > 12 months (n = 1), and the interval from BMT1 to BMT2 was < 6 months (n = 1), from 6 to 12 months (n = 5) or > 12 months (n = 2). Conditioning for BMT2 was done in untreated relapse and included combinations of BU/CY (n = 2), CY/TBI (n = 1) or BU 1 mg/kg at intervals of 6 h by mouth on days -7 to -4 and melphalan 180 mg/m2 i.v. on day -2, with the addition of VP-16 in the patient with JCMML. Two patients died on day +11 with no evidence of residual leukemia at autopsy. Six patients engrafted, one of whom had an uneventful BMT2, but he relapsed 6 months later. The other five developed severe acute GVHD (grades III-IV), with a fatal outcome in three cases, while two responded to treatment and are currently alive in continuous CR at 12 and 36 months. All patients had received conventional prophylaxis against acute GVHD.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Second bone marrow transplantation for leukemia in untreated relapse. 785 33

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

Between May 1984 and May 1992, 75 children 3-19 (median 9) years of age underwent autologous marrow transplant. Clinical data were obtained from the BMT Registry of the AIEOP (Italian Association of Pediatric Hemato/Oncology). Fifty-six children were transplanted after marrow +/- other site(s) relapse and 19 after an isolated extramedullary relapse. The transplant preparative regimens varied according to the center performing the transplant. Seven patients (9%) died of transplant-related complications. Forty-four (58.6%) of 75 patients relapsed again following autologous BMT. The 5-year DFS was 27.8%. An isolated extramedullary relapse was the only variable that statistically influenced DFS. In this retrospective study, autologous BMT for patients with ALL in second CR following marrow relapse did not offer an encouraging result (13% probability of DFS at 5 years), whereas autologous BMT following an (early) isolated extramedullary relapse resulted in nearly 70% DFS. Autologous BMT may be appropriate for this latter group of patients.
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PMID:Autologous bone marrow transplantation for childhood acute lymphoblastic leukemia in remission: first choice for isolated extramedullary relapse? 788 16

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

The outcome of 171 children with ALL who relapsed for the first time after elective cessation of therapy (1-86 mo) and followed over 10 years (median 60 mo; range 1-232 mo) has been evaluated. One hundred and three patients relapsed in the bone marrow (BM), 29 in the testis (T), 21 in the central nervous system (CNS), 14 in the BM plus another site and 4 in other sites. Second remission was achieved in 97% of patients (97% BM, 100% T, 90% CNS, respectively) with reinduction schedules including three or more drugs. All but 4 out of 100 patients who relapsed in the BM received cranial reprophylaxis with intrathecal CT alone or CT plus radiotherapy. Seven patients in second CR underwent allogeneic bone marrow transplantation from an HLA matched sibling. The overall survival was 34% and disease-free survival (DFS) probability at 100 years was 22%. A second relapse was observed in 73% of patients. Forty children are alive in second continuous remission and 24 are alive after a second or subsequent relapse. Patients with isolated T relapse showed a significant better outcome than those with BM or CNS involvement. Most patients (62%) with isolated BM relapse showed a further disease recurrence in BM, and DFS was shorter when relapse occurred within 12 months from off-therapy. Eighty-two patients in second CR stopped the treatment a second time and showed a survival and DFS probabilities, respectively, of 69% and 43%. Thus, children with ALL who relapse after cessation of therapy still have a high risk of further late relapses and should be treated with intensive chemotherapy and CNS reprophylaxis. BMT must be considered for all patients relapsing in the BM within 12 months from off-therapy.
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PMID:Relapse after first cessation of therapy in childhood acute lymphoblastic leukemia: a 10-year follow-up study. Italian Association of Pediatric Hematology-Oncology (AIEOP). 799 Jul 66

A 7-month-old boy with a high risk ALL harbouring the translocation (4;11) was grafted with an haploidentical bone marrow from paternal origin. At time of relapse, 11 months after BMT, he received donor leukocyte infusions (DLI) which put him in second CR. GVHD and pancytopenia occurred 2 weeks after DLI and were fully reversed with CsA + prednisolone. Six months later, the child continues to be in second CR, off steroid therapy, without any signs of GVHD. Our limited experience indicates that a second CR can be obtained with acceptable toxicity by DLI in very high risk ALL children who have been previously grafted with haploidentical bone marrow cells.
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PMID:Complete remission following donor leukocyte infusion in ALL relapsing after haploidentical bone marrow transplantation. 799 52

We report 12 years' experience with histocompatible, related donor marrow transplantation for 123 patients with acute lymphoblastic leukaemia; 104 > or = second remission. Four regimens were studied: cyclophosphamide (Cy)-+total body irradiation (TBI) (n = 35); Cy+fractionated TBI (n = 45); TBI+high-dose cytarabine (n = 15); and hyperfractionated TBI+Cy (n = 28). 45 patients survive (34 +/- 9%; 95% confidence interval) between 1 and 12.7 years (median 7.8 years) following BMT and 29 +/- 8% survive leukaemia-free. Significantly improved disease-free survival was observed in patients with an initial WBC < 50 x 10(9)/l (P = 0.02). Conditioning regimens tested yielded similar outcomes, though TBI/cytarabine led to greater treatment-associated mortality. Leukaemia relapse was the most frequent cause of failure in 56 +/- 11%; median time of relapse 8 months following BMT, none beyond 2.2 years. Relapse was more frequent with higher WBC, shorter initial remission and previous CNS leukaemia. Acute and/or chronic GVHD was associated with a strong trend (P = 0.06) towards less relapse. Allogeneic BMT may be curative for a substantial fraction of patients with ALL, but additional anti-leukaemic measures beyond these conditioning modifications tested will be required to prevent post-transplant leukaemia recurrence.
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PMID:Allogeneic bone marrow transplantation for acute lymphoblastic leukaemia: risk factors and clinical outcome. 801 50


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