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 very rapid development in the last few years of techniques based on use of the polymerase chain reaction (PCR) for characterizing molecular lesions in leukaemia and lymphoma now offers the opportunity for monitoring residual disease at a sensitivity of one malignant cell in 10(5) or 10(6) normal cells. Maximal specificity is presumably achieved when the DNA sequences amplified are truly leukaemia-specific, such as BCR/ABL in chronic myelogenous leukemia, RARA PML/RARA in t(15;17) acute myelogenous leukemia, DEK/CAN in t(6;9) AML, PBX1/E2A in t(1;19) acute lymphoblastic leukemia (ALL), or TAL-1 deletions in other T-ALLs. Comparable sensitivity may be achieved by using immunoglobulin heavy chain (IGH) and T-cell receptor (TCR) gene rearrangements if a clonospecific probe can be generated. However, the presence of similar sequences in IgH genes from normal B lymphocytes may decrease the specificity. For clinical purposes the crucial issues are the following. Can PCR techniques be used for confirmation of diagnosis and evaluation of extent of disease? Can PCR data obtained in remission provide information about the probability of cure or of relapse? Can techniques be developed to quantitate the PCR product and thereby increase its predictive value? These and other issues were addressed at the 4th Workshop of the Molecular Biology/BMT Study Group that took place in Bristol UK on 9-10 May 1992.
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PMID:Molecular evidence of minimal residual disease after treatment for leukaemia and lymphoma: an updated meeting report and review. 835 Jun 33

We studied 20 patients who had received allogeneic bone marrow transplants for acute lymphoblastic leukemia. Using the polymerase chain reaction (PCR), we examined them for the presence of immunoglobulin heavy chain variable-diversity-junctional (IgH V-D-J) gene rearrangements as a marker of minimal residual disease (MRD). Seventeen of the patients were transplanted in relapse or for primary refractory disease, and three were transplanted in "high risk" remission. Thirteen patients had at least one positive PCR assay for MRD in the first 100 days after transplant; two died of nonleukemic causes, while all the remaining 11 relapsed. Seven patients had all negative PCR assays; two died of nonleukemic causes, four remain alive and well, and one patient with consistently negative PCR assays relapsed 47 days after his last negative test. Considering PCR status as a time-dependent covariate, the relative risk of relapse for PCR-positive patients compared to PCR-negative patients is 6.4 (p = 0.0067; 95% CI, 1.6-24.4), and the relative risk of relapse or death is 4.8 (p = 0.0052; 95% CI, 1.6-14.2). The Kaplan-Meier estimate of relapse at 1 year for PCR-positive patients is 100% compared to 33% for PCR-negative patients. The estimate for disease-free survival at 1 year for PCR-positive patients is 0% compared to 44% at 3 years for the PCR-negative group. The PCR assay for MRD appears to be a sensitive and specific test, identifying patients at high risk of relapse following allogeneic BMT who might benefit from further therapeutic interventions.
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PMID:Polymerase chain reaction-based detection of minimal residual disease in acute lymphoblastic leukemia predicts relapse after allogeneic BMT. 911 86

The use of allogeneic BMT in patients with relapsed non-Hodgkin lymphoma (NHL) offers the advantage of tumor-free bone marrow and possibly a 'graft-versus-lymphoma effect' which may decrease the risk of recurrence. However, allogeneic BMT also poses an increased risk of death due to graft-versus-host disease (GVHD) which can be ameliorated by T cell depletion. We performed a retrospective review of 37 patients who underwent T cell-depleted allogeneic BMT for aggressive and indolent NHL between 1988 and 1996. Polymerase chain reaction (PCR) was used to identify indolent NHL patients with the BCL2/IgH translocation which served as a marker of residual disease. Sixteen of 37 patients (44%) are alive and progression-free with a median follow-up of 4.4 years (range 1-10.3). The incidence of grade 2-4 acute GVHD was 36% and extensive chronic GVHD developed in 12%. Patients with aggressive NHL have an overall PFS of 33% (12-54%); those with chemotherapy-resistant and sensitive disease have PFS of 17% (0-47%), and 40% (15-65%) respectively at 5 years. Patients with indolent histologies have overall PFS of 62% (37-86%); those with chemotherapy-resistant and sensitive disease have PFS of 55% (25-85%) and 80% (45-100%) respectively at 5 years. Eight patients with indolent disease had a BCL2/IgH translocation detectable by PCR. Five of these eight patients remain alive and progression free at a median of 6.5 years after BMT (range 2.1-7.4 years), four of whom remain PCR positive from 1.7 to 2.9 years after transplantation. We conclude that T cell-depleted allogeneic BMT poses a low risk for death due to GVHD, and should be considered for patients with relapsed and refractory indolent NHL.
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PMID:T cell-depleted allogeneic bone marrow transplantation for high-risk non-Hodgkin's lymphoma: clinical and molecular follow-up. 961 81

We have analysed the behaviour of minimal residual disease (MRD) after allogeneic bone marrow transplantation (allo-BMT) in 71 children with acute lymphoblastic leukaemia (ALL). The method relied on PCR of IgH, TCRdelta and/or TCRgamma gene rearrangements followed by electrophoretic size resolution and allele-specific oligoprobing. Patients were similarly conditioned; 55 received marrow from unrelated donors and 16 from related donors. MRD was assessed at various time-points up to 24 months after BMT. Three children were not evaluable due to transplant-related mortality. MRD was detected in 28/32 patients (88%) who relapsed post-BMT; 16 were positive at all times and 12 were initially negative but became positive at a median of 3 months (range 1.5-11) prior to relapse. In contrast, only eight of 36 (22%) patients who remained in continuing complete remission (CCR) (median follow-up 43 months, range 20-94) showed MRD at any time after BMT (P<0.0001). In these eight patients MRD was found up to 9 months after transplant and at low levels (0.01-0.001%). All eight (median follow-up 39 months, range 24-87) had at least two MRD-negative samples tested subsequently and five of the eight had evidence of grade I-II acute graft-versus-host disease (GvHD), raising the possibility of a graft-versus-leukaemia effect. In general, any evidence of MRD after allo-BMT is a poor prognostic sign. However, if immunotherapy were to be targeted towards patients with evidence of persisting MRD after BMT, the method described would expose only a small proportion of patients to unnecessary additional toxicity.
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PMID:Minimal residual disease status as a predictor of relapse after allogeneic bone marrow transplantation for children with acute lymphoblastic leukaemia. 972 17

A 14-year-old male and a maternally related cousin were diagnosed with X-linked lymphoproliferative disease (XLP) after developing recurrent B-NHL, characterized by long disease-free intervals and absence of an increased chemoresistance of the recurrent lymphomas. The demonstration of different clonal IgH gene rearrangements in two of the lymphomas from one of the patients further supports that the lymphomas were clonally unrelated. The cousin underwent matched related BMT, whereas the proband received a deliberately delayed MUD BMT in third CR. Both are in CR 68 months and 21 months, respectively, post-BMT. Delaying BMT probably contributes to reducing treatment-related morbidity. We suggest MUD BMT as a feasible curative strategy for XLP patients with B-NHL lacking matched related donors.
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PMID:Matched unrelated allogeneic bone marrow transplantation for recurrent malignant lymphoma in a patient with X-linked lymphoproliferative disease (XLP). 975 53

Lineage switch from AML to ALL is an extremely rare phenomenon, and we report the case of an adult diagnosed with AML at 46 years of age who relapsed with ALL. At initial diagnosis, blast cell morphology and immunophenotyping were consistent with the diagnosis of M4-AML. Complete remission was achieved, and the patient underwent autologous BMT. At relapse, six months after ABMT, blast cells were different from those seen at initial diagnosis, for morphology (L2-ALL), cytochemistry, and immunophenotyping. The karyotype was normal at both diagnosis and relapse. No evidence of bcr-abl fusion genes was found by RT-PCR. Monoclonal IgH and TCR gamma gene rearrangement were evidenced by PCR analysis at relapse but not on blast cells at AML diagnosis.
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PMID:Lineage switch from acute myeloid leukemia to acute lymphoblastic leukemia: report of an adult case and review of the literature. 1107 63