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)

In one case out of four, allogeneic BMT concerns a male recipient and a female donor. The monitoring of sex-matched BMT can be carried out by PCR amplification on Y-specific chromosome sequences (YCS), whatever the hematological disease. Twelve patients with sex-mismatched non-T-depleted BMT were first studied through a qualitative PCR, which gave semi-quantitative results. When the qualitative PCR revealed YCS, a competitive amplification was performed in order to estimate the YCS amount in the patient blood sample. For the purpose of the study, we classified the patients in two categories according to the results obtained 9 months after BMT. For 10 patients, we did not detect any YCS amplification after this time. These patients were in complete cytogenetic and clinical remission. For the remaining two patients, we always found male DNA in their blood samples. These patients were in cytogenetic remission but relapsed and died 21 and 25 months after BMT. Our results suggest that the persistence of male cells in peripheral blood, even at the low rate of 1% or 0.1%, 1 year after sex-mismatched BMT, is a bad prognosis.
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PMID:Monitoring and prognostic evaluation of sex-mismatched bone marrow transplantation by competitive PCR on Y chromosome sequences. 872 66

Chimerism studies after allogeneic BMT are performed to determine the donor and/or recipient origin of peripheral blood and marrow lymphoid and hematopoietic cells. These studies have been performed mostly in leukemias and aplastic anemia. We report DNA-based chimerism studies in three patients transplanted for advanced CLL from a histocompatible sibling. Following conditioning with chlorambucil, cyclophosphamide and TBI all three successfully engrafted. One has remained in continuous complete remission (CR) with a complete donor chimerism (CDC) for 110 months post-BMT. Another was in mixed chimerism (MC) with minimal residual disease (MRD) at 3 months post-BMT but was in CR and in CDC at 6 months, suggesting that the persistent CLL cells has disappeared between these two studies. The third patient has been in persistent MC since BMT (24 months follow-up), although he is in CR with no evidence of persistent CLL. We postulate that this patient's MC status is due to normal residual recipient lymphohematopoietic cells that survived the conditioning regimen. In conclusion, various patterns of chimerism can be observed in CLL patients after BMT while remaining in CR and with no evidence of residual CLL.
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PMID:Various patterns of chimerism after allogeneic bone marrow transplantation for advanced chronic lymphocytic leukemia. 875 Feb 70

A 10-year-old male with severe aplastic anemia following allogeneic BMT developed a hemolytic crisis on post-BMT day 67. The diagnosis of cold hemagglutinin disease was made based on the findings of anemia, reticulocytosis, positive direct Coombs test, and markedly elevated cold agglutinins. Anti-nuclear antibody and anti-DNA antibody were also increased. Plasmapheresis was effective as an emergency measure. Corticosteroid after plasmapheresis had a transient effect. At the second episode of hemolysis 6 months after BMT, immunosuppressive therapy with cyclophosphamide plus corticosteroid was successfully administered without negative effect on engraftment.
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PMID:Recurrent cold hemagglutinin disease following allogeneic bone marrow transplantation successfully treated with plasmapheresis, corticosteroid and cyclophosphamide. 883 28

We report a case of haploidentical T-depleted BMT that engrafted durably after a highly immunosuppressive conditioning regimen. DNA polymorphism analysis showed that granulocytes and monocytes were donor type but T and B lymphocytes were host derived. Host tolerance to donor antigens was documented. The patient suffered from serious recurrent CMV infections until split chimaerism shifted to full donor type 2 years post-BMT. Seven years after BMT the patient remains in complete remission.
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PMID:Unusual split chimaerism after mismatched T-depleted BMT. 886 66

Cytogenetic analysis is the gold standard for the follow-up of CML patients. The sensitivity of cytogenetics is fairly similar to that of Southern detection of M-BCR rearrangement (5%); this last technique has the potential advantage of being independent of cell division and yield of metaphases. IFN alpha treatment can induce lack of growth of hemopoietic precursors and poor yield of metaphases has been observed. For this reason we decided to study the grade of concordance and complementarity between analysis of karyotype and detection of M-BCR rearrangement of Southern blot. We studied 43 Ph1 positive, M-BCR positive pre-BMT CML patients (48 samples) treated with IFN alpha 2a. Karyotype was done on bone marrow cells by direct method, culture, and banding. Southern technique was performed onto DNA from peripheral blood leukocytes treated with BgIII (and Xbal if necessary) and hybridized with the universal probe (Ph1/bcr-3, Transprobe 1) labelled with dCTP32. A highly significant association between both tests was obtained. Of 48 samples analyzed, 34 were evaluable by both methods and 28 gave the same result for both tests. The concordance between the tests was good (kappa index: 0.63). Of total samples 27.1% was not evaluable by cytogenetics; this figure was 31.2% in samples from patients who were previously in complete cytogenetic response. All of the specimens not evaluable by karyotyping were evaluable by Southern. One sample was not analyzable by Southern but it was evaluable by cytogenetic analysis. The information obtained by Southern technique was clinically relevant, and decisions were made according to its results. We conclude that both tests show a significant association and a good concordance, although they are not interchangeable. Cytogenetic and molecular studies are complementary and must be employed together in CML patients treated with alpha-interferon.
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PMID:Southern technique and cytogenetics are complementary and must be used together in the evaluation of Ph1, M-BCR positive chronic myeloid leukemia (CML) patients treated with alpha interferon (IFN-alpha). 889 87

The use of peripheral blood stem cells (PBSC) for allogeneic transplantation (PBSCT) is increasing steadily so that it cannot be considered an experimental practice any longer. Collection of PBSC requires the treatment of donors with G-CSF. With this drug, 10 to 16 mg/kg/day, side-effects are acceptable, but thrombocytopenia may follow the PBSC harvest. After transplant, allogenic PBSC engraft quickly in comparison with marrow. This has been shown for platelets, and to a lesser extent for granulocytes. Stability of graft has been documented by DNA analysis. With PBSC a high number of T- and NK-cells is infused, with a possible increase of GVL effect. However, we only have experimental evidence in the mouse that this may be the case. Incidence of acute GVHD equals that after BMT, but data on chronic GVHD are controversial, with an increased incidence reported in some studies. There is currently no indication for T-cell depletion of PBSC in HLA-identical sibling pair transplants. Experiments with CD34+ cell selection have sometimes produced a paradoxical increase of acute GVHD. The challenge of allogeneic PBSCT is improvement in survival, but available data only show that results are no worse than BMT. Prospective studies of allogeneic PBSCT versus bone marrow transplantation are in progress in Europe and USA.
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PMID:Peripheral blood stem cells for allogeneic transplantation. 893 24

Langerhans' cell histiocytosis (LCH) is an uncommon disorder of childhood, formerly referred to histiocytosis X. A significant proportion of children with disseminated disease may undergo progression to a fatal outcome despite chemotherapy with single or multiple agents. Only six cases of LCH treated with BMT have been reported in the literature, including two cases of autologous BMT. Of them, only one was less than 14 years of age. We describe a 4-year-old child whose disseminated, refractory Langerhans' cell histiocytosis was not controlled by front-line monotherapy with etoposide, nor by rescue treatment with combined chemotherapy (vinblastine and etoposide) and immunotherapy (steroids and cyclosporine). Due to the high risk of fatal progressive disease, he underwent bone marrow transplantation from his HLA-identical sister who was heterozigous for beta-thalassemia. On day 24 after transplantation marrow reconstitution was evident, with WBC count 2.3 x 10(9)/L, neutrophil count > 0.5 x 10(9)/L, and platelet count 72 x 10(9)/L. Engraftment was demonstrated by PCR DNA analysis. The patient was discharged on day 25. After transplantation he experienced fever for 11 days and developed signs of grade I cutaneous and intestinal graft-versus-host disease, that was treated with methylprednisolone from days 11 to day 68 (1 mg/kg/day for 18 days, then tapered). He became transfusion independent on day 24; the hemoglobin value was 7.5 g/dL on day 54 and has remained > 10 g/dL since day 200. Features of heterozygous beta-thalassemia have been evident since then. Bone marrow aspirate was normal on days 25 and 94. At the time of this writing he remains in excellent condition, disease and treatment free, 25 months after transplantation. Although limited, current experience suggests that bone marrow transplantation has the potential to cure refractory Langerhans' cell histiocytosis.
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PMID:Bone marrow transplantation for refractory Langerhans' cell histiocytosis. 895 63

It still remains unclear whether patients with mixed hematopoietic chimerism (MC) after allogeneic bone marrow transplantation (allo-BMT) have an increased risk of developing relapse or graft failure. To address this question, we monitored the individual dynamics of chimerism after allo-BMT in pediatric patients within a prospective case control study. The individual ratio of donor to recipient peripheral white cells was determined by quantification of genomic variable number of tandem repeats (VNTRs) with a polymerase chain reaction (PCR) approach. Within the study period from 1 January 1994 until 1 July 1996 we investigated 50 sequences of 46 pediatric patients after allo-BMT (32 with malignant, 18 with nonmalignant diseases). We found complete chimerism (CC) in 34/50 cases, MC in 12/50 follow-ups and 4/50 patients revealed autologous recovery (AC). Eight of 12 patients with MC showed increasing autologous patterns and subsequently relapsed or rejected their graft, 3/12 decreasing amounts of recipient DNA and turned to CC upon further follow-up. One patient of 12 who had severe combined immunodeficiency (SCID), attained engraftment with a stable MC pattern. Three patients of 34 with CC relapsed lacking a transitional MC interval. However, the time span between last CC confirmation and relapse in each of these three patients was 6 months or longer. We suggest that these patients also developed a stage of transitional MC but that the critical timepoint of molecular confirmation by PCR was missed as time intervals in the individual follow-up of these three patients were too long (> or = 6 months). In summary, the results demonstrate that the individual risk of developing relapse or graft failure is significantly enhanced in the MC situation (P < 0.0005). Therefore the quantitative analysis of MC at short time intervals might be of great value to identify high risk patients which will have a significantly/enhanced risk for relapse or graft rejection.
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PMID:Mixed hematopoietic chimerism after allogeneic bone marrow transplantation: the impact of quantitative PCR analysis for prediction of relapse and graft rejection in children. 915 47

A 33-year-old man with an atypical course of hypereosinophilic syndrome including malignant hypercalcemia, osteolytic lesions and evolution into severe myelofibrosis was treated by allogeneic bone marrow transplantation after conditioning with cytoxan and total body irradiation. As the transplant was sex-mismatched, chimerism was studied by means of cytogenetic analysis and Y chromosomal DNA amplification by PCR assay. Long-term complete remission has been assessed by normalization of blood cell counts, magnetic resonance imaging and karyotypic analysis. A relapse was observed 40 months after transplantation. The patient remains alive 44 months post-BMT. This case report is compared with those reported in the literature.
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PMID:Allogeneic bone marrow transplantation for hypereosinophilic syndrome with advanced myelofibrosis. 915 53

We have retrospectively analyzed the impact of prognostic factors on the outcome of serologically HLA-matched unrelated donor (UD) BMT for CML. For this purpose, we have studied a cohort of 366 patients transplanted in Europe between January 1985 and December 1994. The median age of the 211 males and 155 females was 34 years; 238 patients were transplanted in first chronic phase and 116 in advanced phases. The median interval from diagnosis to BMT was 827 days. GVHD prophylaxis consisted of CsA and MTX in 202 patients or of ex vivo or in vivo T cell depletion (TCD) in 129. Recently, DNA-based methods of HLA-class II typing have been used to improve donor selection. We obtained complete data on 300 donor/recipient (D/R) pairs. Among them, we have identified three groups of patients, according to specific HLA-DRB1 D/R compatibility. Two hundred and ten patients received marrow from donors identical for HLA-DRB1 (group 1). Thirty-one patients received BMT from a donor who was HLA-DRB1 mismatched (group 2) and 59 from a donor in whom specific HLA-DRB1 typing was not performed (group 3). The overall survival was 37 +/- 3% at 2 years and leukemia-free survival (LFS) was 31 +/- 3%. In univariate analysis, five variables had a favorable effect on LFS: transplant in first chronic phase (P = 0.0001), time interval from diagnosis to BMT shorter than the median (P = 0.01), prophylaxis of GVHD without TCD (P + 0.001), acute GVHD < grade III (P = 0.0009) and HLA-DRB1 D/R matching (P = 0.0001). Transplant-related mortality (TRM) was 49 +/- 4% in group 1, 79 +/- 8% in group 2 and 80 +/- 6% in group 3 (P = 0.0001). Multivariate analysis confirmed that HLA-DRB1 matching was the most significant factor influencing survival (P = 0.04), LFS (P = 0.013) and TRM (P = 0.0049). From these results, we have defined a 'good risk' group, ie patients transplanted in first chronic phase, from an HLA-DRB1 matched donor, without TCD as prophylaxis against GVHD. The 2 year LFS, TRM and relapse incidence for this group were 51 +/- 5%, 47 +/- 5% and 2 +/- 2%, respectively. This suggests that the long-term outcome of patients with favorable prognostic features can approach that of patients transplanted from geno-identical siblings. In contrast, the TRM for patients transplanted for advanced disease from non HLA-DRB1-identical donors was 94%. Such a high TRM clearly indicates that UD BMT is not justifiable for these individuals.
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PMID:European results of matched unrelated donor bone marrow transplantation for chronic myeloid leukemia. Impact of HLA class II matching. Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation. 923 50


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