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  • 1
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Sensors and Actuators B: Chemical 11 (1993), S. 273-279 
    ISSN: 0925-4005
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Chemistry and Pharmacology , Electrical Engineering, Measurement and Control Technology
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1203
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract A number of different polymorphisms have been observed in coding as well as in non-coding regions of T cell receptor (TCR) genes. We report the identification and characterization of a highly polymorphic locus in the 3′ noncoding region of the human T cell receptor α/δ (TCRAD) on chromosome 14. In 202 unrelated individuals, ten different alleles were distinguished by polymerase chain reaction (PCR) and a heterozygosity rate of 64% was calculated. Sequence analysis revealed that this polymorphic region consists of 10 bp imperfect repeat units and represents a variable number tandem repeat region (VNTR). Stable Mendelian inheritance of this novel polymorphic marker was proven in four families. The localization of this VNTR polymorphism in the TCRAD locus should make it a useful system for linkage analysis in immunological disorders with a known role of TCRAD.
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  • 3
    ISSN: 1432-0584
    Keywords: Acute myelogenous leukemia ; Allogeneic marrow transplantation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Between February 1982 and April 1995, 62 patients (37 male, 25 female) with acute myelogenous leukemia (AML) with a median age of 32 years (19–51 years) received allogeneic marrow grafts from an HLA-identical sibling (n=60) or an HLA-mismatched family member (n=2). At the time of transplant, 35 patients were in first complete remission (CR), five in second CR, eight were primary refractory, eight were in untreated relapse and six in refractory relapse. The FAB subtypes were as follows: M1 (n=17), M2 (n=13), M3 (n=6), M4 (n=19), M5 (n=6), M6 (n=1). For conditioning most patients were given total body irradiation combined with cyclophosphamide (CY,n=50) or CY and busulfan (n=9). For graft-versus-host disease prophylaxis patients received cyclosporin A (CSA) and methotrexate (MTX) (n=32), MTX alone (n=12), CSA and methylprednisone (n=5), or CSA alone (n=13). As of April 1995, probability of leukemia-free survival projected at 10 years after BMT was 60% for patients transplanted in first CR compared with 10% for patients transplanted beyond first CR. Transplant-related mortality was 11% after BMT in first CR and 39% after BMT beyond first CR. Probability of relapse projected at 10 years after BMT is 32% for patients who received transplants in first CR and 81% for patients who received transplants beyond first CR. Thus, high-dose chemo/radiotherapy followed by allogeneic marrow infusion has a high curative potential for patients with AML who receive transplants in first CR and offers the chance of long-term disease-free survival for some patients with advanced disease.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0584
    Keywords: Key words Chronic myeloid leukemia ; Graft-versus-host disease ; Transplantation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Allogeneic bone marrow transplantation is the only curative treatment for patients with Philadelphia chromosome-positive chronic myeloid leukemia (CML); however, recurrence of disease remains a major cause of treatment failure. A 26-year-old man with chronic myeloid leukemia who had a cytogenetic relapse 49 months after his first syngeneic bone marrow transplant (BMT) and hematologic relapse 23 months thereafter progressed to blast crisis despite treatment with IFN-alpha for 15 months. He underwent a second transplantation in early second blast crisis, 92 months after the first BMT with PBPC from his previous donor. Successful hematological reconstitution occurred. On day 50 after the second transplantation the patient developed a generalized rash, hepatomegaly, and cholestatic signs. Skin and liver biopsy revealed changes compatible with acute graft-versus-host disease (GVHD). Treatment with cyclosporin A (CSA) and prednisone was started, and the GVHD resolved. Fifteen months after PBPC transplantation he had a molecular relapse. Despite discontinuation of CSA, the patient progressed into blast crisis 7 months later. The occurrence of GVHD and disappearance of the BCR-ABL-positive clone suggest that a graft-versus-leukemia (GVL) effect may have been operative for 15 months in a patient given a second syngeneic BMT in blast crisis.
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  • 5
    ISSN: 1432-0584
    Keywords: Key words Related and unrelated donor BMT ; CML ; Long-term follow-up
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Between January 1983 and December 1997, 88 patients (36 female, 52 male, median age 37 years, range 19–57) with chronic myelogenous leukemia (CML) underwent allogeneic bone marrow transplantation (BMT) at the University Hospital of Vienna. Sixty patients were in chronic phase, 18 in accelerated phase, and ten in blast crisis. Marrow donors were HLA-identical siblings for 64 patients (BM 58, PBSC 6), 2-antigen-mismatched related donors (RD) for two, HLA-identical unrelated donors (URD) for 17, and 1-antigen-mismatched URD for five. The median time from diagnosis to BMT was 22 months (range 2–91), and 63 patients had received prior interferon (IFN)-alpha therapy, 46 (73%) for more than 6 months. Conditioning therapy consisted of cyclophosphamide (CY) and total body irradiation (TBI) in 71 patients and CY and busulfan (BU) in 16. One patient received etoposide and TBI. For graft-versus-host disease (GVHD) prophylaxis methotrexate (MTX) was given to 12 patients, MTX and cyclosporin A (CSA) to 67, CSA alone to four, and CSA and methylprednisolone to five. Durable engraftment was documented in 80 of 82 patients (98%). As of December 31, 1997, 52 patients (59%) were alive, 38 (58%) after sibling transplantation with a median observation time of 73 months and 14 (64%) after URD transplantation with a median observation time of 12 months. Probability of overall survival is 59%, for patients undergoing transplantation in chronic phase and 44% for patients undergoing transplantation in advanced stage CML. Probability of disease-free survival (DFS) after sibling and URD BMT is 55% and 59%, respectively. Ten patients (12%) experienced relapse of CML. Transplant-related mortality was 32% both after RD and after URD transplantation. Acute GVHD occurred in 53 of 80 evaluable patients (66%), consisting of grade III or IV in 14 patients (18%). Chronic GVHD developed in 40 of 63 eligible patients (63%), including extensive disease in 26 patients (41%). Thus, sibling and URD BMT offer high cure rates with acceptable toxicity to patients with CML.
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  • 6
    ISSN: 1432-0584
    Keywords: Key words Myeloma ; Donor leukocyte infusion ; Chimerism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  A large group of patients relapsing after allogeneic bone marrow transplantation (BMT) have obtained remission after infusion of leukocytes from their original donor, suggesting a graft-versus-myeloma effect. However, side effects such as graft-versus-host disease and myelosuppression are severe, and sometimes fatal, complications of this therapeutic approach. Previously we demonstrated that patients with leukemia who lack donor hematopoiesis in relapse after BMT experience severe and lasting aplasia after infusion of donor leukocytes. In two patients – one with extramedullary and one with marrow relapse after a sex-mismatched transplantation – we analyzed hematopoietic chimerism by cell sorting and bone marrow cultures. CD34-positive cells, CD4-CD8-positive cells, committed progenitors, and LTC-IC were of donor origin, as demonstrated by two-color fluorescence in situ hybridization (FISH). Additionally, in relapse complete donor T-cell chimerism was seen. In contrast, plasma cells were of recipient origin in the patient who had a relapse in the bone marrow. Both patients were treated with infusions of donor leukocytes from their original donor. Neither patient suffered myelosuppression, and one achieved a stable complete remission.
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  • 7
    ISSN: 1432-0584
    Keywords: Mixed chimerism ; PCR ; BMT ; Molecular genetics ; von Willebrand factor gene
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Detection of host cells in peripheral blood and/or bone marrow (mixed chimerism) of patients who have undergone bone marrow transplantation (BMT) is possible using either immunological methods or cytogenetic or molecular genetic analysis. We shall report a new method for the detection of mixed chimerism, which makes use of the fact, that the von Willebrand factor (vWF) gene has a highly variable region-variable number of tandem repeats (VNTR) — within intron 40. vWF-VNTR amplification by the polymerase chain reaction (PCR) was performed as described by Peake et al. [5]. We have studied 185 peripheral blood and/or bone marrow samples of 26 patients. Median time after BMT was 14 months (range 1–83 months). Of the 11 patients who were studied sequentially during the first 100 days following BMT, mixed chimerism was detected in four, but only transiently. None of these patients has relapsed so far. Of 18 patients who were studied more than 100 days after BMT mixed chimerism was found in three; two of these patients have subsequently relapsed. The advantages of this new method are: (a) it is informative in a high percentage of patients; (b) it requires only small amounts (200μl) of peripheral blood; (c) reliable results can be obtained at leukocyte counts of even less than 50 perμl. The clinical relevance and sensitivity of the method compared with established methods for detection of mixed chimerism remain to be determined.
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  • 8
    ISSN: 1432-0584
    Keywords: Key words Acute myelogenous leukemia ; Allogeneic marrow transplantation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Between February 1982 and April 1995, 62 patients (37 male, 25 female) with acute myelogenous leukemia (AML) with a median age of 32 years (19–51 years) received allogeneic marrow grafts from an HLA-identical sibling (n=60) or an HLA-mismatched family member (n=2). At the time of transplant, 35 patients were in first complete remission (CR), five in second CR, eight were primary refractory, eight were in untreated relapse and six in refractory relapse. The FAB subtypes were as follows: M1 (n=17), M2 (n=13), M3 (n=6), M4 (n=19), M5 (n=6), M6 (n=1). For conditioning most patients were given total body irradiation combined with cyclophosphamide (CY, n=50) or CY and busulfan (n=9). For graft-versus-host disease prophylaxis patients received cyclosporin A (CSA) and methotrexate (MTX) (n=32), MTX alone (n=12), CSA and methylprednisone (n=5), or CSA alone (n=13). As of April 1995, probability of leukemia-free survival projected at 10 years after BMT was 60% for patients transplanted in first CR compared with 10% for patients transplanted beyond first CR. Transplant-related mortality was 11% after BMT in first CR and 39% after BMT beyond first CR. Probability of relapse projected at 10 years after BMT is 32% for patients who received transplants in first CR and 81% for patients who received transplants beyond first CR. Thus, high-dose chemo/radiotherapy followed by allogeneic marrow infusion has a high curative potential for patients with AML who receive transplants in first CR and offers the chance of long-term disease-free survival for some patients with advanced disease.
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  • 9
    ISSN: 1432-0584
    Keywords: CDR3-PCR ; Clone-specific PCR ; TCRγ-PCR ; Adult B-lineage ALL
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We have compared the kinetics of minimal residual disease (MRD) by simultaneous polymerase chain reaction (PCR) monitoring with oligonucleotides for the immunoglobulin heavy chain (IgH) complementarity-determining region 3 (CDR3) and the T-cell receptorγ chain gene (TCRγ), as well as clone-specific CDR3 sequences in adult patients (aged 17–51 years) with acute lymphoblastic leukemia (ALL) who entered a complete hematological remission (CR) after chemotherapy with the German multicenter ALL (GMALL) protocol. The sensitivities were one in 102–3 for the CDR3- and TCRγ-PCR and one in 105–6 for a two-step, seminested CDR3/clone-specific PCR. At diagnosis, 7/7 patients were CDR3 positive and four were TCRγ positive in their bone marrow (BM). At the end of induction therapy (after 2 months) 4/6 tested positive for CDR3, 2/6 for TCRγ, and 5/6 for clone-specific rearrangements. At the end of consolidation treatment (after 7 months) only 1/7 remained positive for CDR3, 2/7 for TCRγ, and 5/7 for clone-specific rearrangements. After an observation period of 18–36 months, 4/7 patients were still in CR and all were PCR negative by the clone-specific method during or after maintenance therapy. Two patients died in leukemic relapse; one patient relapsed but is still alive. All three of these patients remained PCR positive throughout the course of their disease. Clonal evolution in the IgH locus was found in one of these patients. We conclude that the molecular response to chemotherapy in adult B-lineage ALL is slow, even in patients without risk factors other than age. As in childhood ALL, most patients with long-term CR convert to PCR negativity approximately 18 months after the start of chemotherapy. The data also suggest the existence of early clone-specific PCR negativity in a small proportion of long-term survivors. The predictive value of this observation will now have to be confirmed in a larger study.
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  • 10
    ISSN: 1432-0584
    Keywords: Key words CDR3-PCR ; Clone-specific PCR ; TCRγ-PCR ; Adult B-lineage ALL
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  We have compared the kinetics of minimal residual disease (MRD) by simultaneous polymerase chain reaction (PCR) monitoring with oligonucleotides for the immunoglobulin heavy chain (IgH) complementarity-determining region 3 (CDR3) and the T-cell receptor γ chain gene (TCRγ), as well as clone-specific CDR3 sequences in adult patients (aged 17–51 years) with acute lymphoblastic leukemia (ALL) who entered a complete hematological remission (CR) after chemotherapy with the German multicenter ALL (GMALL) protocol. The sensitivities were one in 102–3 for the CDR3- and TCRγ-PCR and one in 105–6 for a two-step, seminested CDR3/clone-specific PCR. At diagnosis, 7/7 patients were CDR3 positive and four were TCRγ positive in their bone marrow (BM). At the end of induction therapy (after 2 months) 4/6 tested positive for CDR3, 2/6 for TCRγ, and 5/6 for clone-specific rearrangements. At the end of consolidation treatment (after 7 months) only 1/7 remained positive for CDR3, 2/7 for TCRγ, and 5/7 for clone-specific rearrangements. After an observation period of 18–36 months, 4/7 patients were still in CR and all were PCR negative by the clone-specific method during or after maintenance therapy. Two patients died in leukemic relapse; one patient relapsed but is still alive. All three of these patients remained PCR positive throughout the course of their disease. Clonal evolution in the IgH locus was found in one of these patients. We conclude that the molecular response to chemotherapy in adult B-lineage ALL is slow, even in patients without risk factors other than age. As in childhood ALL, most patients with long-term CR convert to PCR negativity approximately 18 months after the start of chemotherapy. The data also suggest the existence of early clone-specific PCR negativity in a small proportion of long-term survivors. The predictive value of this observation will now have to be confirmed in a larger study.
    Type of Medium: Electronic Resource
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