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 examination of the presence of Ph chromosome and of the fused gene BCR-ABL in patients with chronic myeloid leukemia (CML) is significant for the precise diagnosis and in some cases for the prognosis of the disease. We examined peripheral blood for the presence of BCR-ABL fused gene by polymerase chain reaction (PCR) in eight patients with CML consecutively cytogenetically studied before and after the bone marrow transplantation and in two patients treated with interferon. Southern blot analysis was performed before BMT in two patients and the molecular rearrangement of Ph chromosome was found. In all cases our results have proved that cytogenetic and recombinant DNA evaluations confirm each other. Due to the high sensitivity of PCR technique the minimal residual leukemia can be detected.
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PMID:[Use of cytogenetic and molecular biology in the detection of chronic myeloid leukemia]. 128 73

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

A patient with accelerating Ph+ve chronic granulocytic leukaemia (CGL) was considered for autologous BMT using marrow 'purged' by 4 weeks long-term culture (LTC). Efficacy of purging was determined using reverse transcriptase PCR for BCR-ABL mRNA transcripts b2a2 and b3a2. Peripheral blood and bone marrow were compared. Three observations emerged: (i) the initial b2a2:b3a2 ratios for unmanipulated blood and marrow were different with values of 9:1 and 2:1 respectively; (ii) both transcripts were successfully 'purged' with LTC of blood but not marrow; and (iii) LTC of marrow caused a transient increase in relative levels of b3a2 mRNA and a corresponding reduction in the b2a2 signal. This is the first case where such differences have been demonstrated in association with LTC.
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PMID:Long-term culture and molecular biological studies highlight differences in relative BCR-ABL expression levels in the peripheral blood and bone marrow of a patient with chronic granulocytic leukaemia. 780 92

The clinical status of a homogeneous cohort of long-term survivors of allogeneic marrow transplantation was assessed and residual leukaemia was studied by reverse transcription polymerase chain reaction for leukaemia specific BCR-ABL mRNA. The group comprised 34 consecutive patients with CML in chronic phase treated by chemoradiotherapy and transplantation of bone marrow from HLA-identical sibling donors between February 1981 and December 1983 in the joint Hammersmith-Northwick Park programme. The probability of survival at 10 years was 59 +/- 17%. Eighteen of the 19 surviving (95%) patients have Karnofsky scores of 90 or 100% indicative of a good performance status. One of the survivors had evidence of relapse 6.5 years after transplant but has since been restored to complete remission by treatment with interferon-alpha followed by donor leucocyte transfusions. Surprisingly, 2 of the 19 patients who have been in remission for over 10 years have molecular evidence of persisting leukaemic cells. Quantification by competitive PCR indicated that the malignant clone persisted at low levels. The data suggest that the majority of long-term survivors after BMT for CML are in good health and may be regarded as cured. Some long-term survivors, however, may still harbour residual leukaemic cells and continued monitoring for late relapse is warranted. Late relapse is amenable to further therapy with leukocyte transfusions from the original marrow donor.
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PMID:Detection of residual leukaemia more than 10 years after allogeneic bone marrow transplantation for chronic myelogenous leukaemia. 785 36

Eight patients with chronic myeloid leukemia relapse after allogeneic BMT were treated with IFN-alpha and buffy coat transfusions (BC) of the bone marrow donor. The antileukemic effect of this treatment was directly demonstrated in 4 patients by the disappearance of Philadelphia chromosome-positive metaphases or the loss of detectable BCR-ABL transcripts by polymerase chain reaction. In 2 patients in whom cytogenetic or polymerase chain reaction analysis was not performed, a change in hemopoietic chimerism with recurrence of donor-type hemopoiesis was demonstrated. Two patients, both treated in advanced stages of hematological relapse after BMT, did not respond. However, severe side effects of the treatment were observed: graft-versus-host disease (GVHD) occurred in 5 patients. Two of these patients progressed to severe chronic GVHD and 1 patient ultimately died of this complication. GVHD occurred in 5 of the 6 responding patients; one patient responded without developing clinical symptoms of GVHD. Six patients developed bone marrow hypoplasia after IFN/BC treatment, and pancytopenia occurred in 4 patients. None of these 4 patients recovered spontaneously and 2 patients died of complications of pancytopenia (cerebral bleeding, infection). Our results demonstrate that treatment of chronic myeloid leukemia relapse with IFN and BC transfusions is highly effective in patients with relapse in chronic phase. The occurrence of GVHD and pancytopenia, however, resulted in a high treatment-associated morbidity and mortality. Whereas a response to treatment was observed in 1 patient without GVHD, indicating that GVHD and a graft-versus-leukemia effect may be clinically separable, bone marrow hypoplasia occurred in all responding patients.
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PMID:Interferon-alpha and donor buffy coat transfusions for treatment of relapsed chronic myeloid leukemia after allogeneic bone marrow transplantation. 824 10

A male patient with CML received a BMT from his sister and developed chronic GVHD. The host-origin normal karyotype (46,XY) was identified for the first time in the 60th month after BMT. Detection of Y-chromosome-specific DNA in BM and peripheral blood (PB) showed that all BM samples obtained 6 months from BMT were positive for Y-specific DNA, while PB became positive in the 60th month after BMT. The BCR-ABL mRNA derived from leukemic cells was detected in the 36th month post-BMT, but not in the 60th month or thereafter. Fluorescence in situ hybridization revealed that 1.5% and 0.6% in BM and PB cells were Y-positive in the 70th month post-BMT, respectively. DNA analysis of hematopoietic progenitor colonies revealed 1 of 42 erythroid colonies to be host derived. These results indicate that host-origin hematopoietic cells survive chronic GVHD, while the Ph1 clone was eliminated.
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PMID:Hematopoietic recovery from host progenitors with normal karyotype devoid of Philadelphia chromosome in a patient with CML after allogeneic BMT. 837 40

Results for adult ALL have improved, with CR rates of 68% to 91% and a cure rate of 25% to 41%. The outcome for patients with T-ALL has especially improved, and the major drugs responsible are C and ara-C. Outcome for B-ALL has improved by using short intensive cycles including, among other drugs, C and high-dose MTX. The inferior outcome of adult ALL compared with childhood ALL seems related to the high proportion of Ph1/BCR-ABL positive ALL patients, which constitute about 30% in adults versus less than 5% in children. The major prognostic factors for survival in adult ALL are age, time to achieve CR, cytogenetic abnormalities, immunologic subtype, and WBC; these may serve as a guide for BMT in first CR. New approaches in the treatment of adult ALL include the use of HGFs, the use of biologic response modifiers, and the detection of MRD to tailor treatment decisions.
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PMID:Therapy of the newly diagnosed adult with acute lymphoblastic leukemia. 844 56

An allogeneic sex-mismatched BMT which was performed in a male patient with BCR-ABL-positive ALL in second hematological and central nervous system relapse resulted in a CR for 12 months. After BMT, the patient was closely monitored with reverse transcription (RT)-PCR. One month before a third relapse RT-PCR became positive. During relapse G-CSF was administered. It specifically stimulated the donor-derived myelopoiesis and led to the stabilization of the disease for 8 months. Fluorescence in situ hybridization analyses of individual cell populations revealed that during the whole course of G-CSF administration granulocytes, CD4+, CD8+ and CD34+/CD10- cells were of female (donor) origin and only the CD34+/CD10+ cells which represented the leukemic blasts, were of male (host) origin.
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PMID:G-CSF stimulation of donor myelopoiesis prolongs survival of relapsed BCR-ABL-positive acute lymphoblastic leukemia after allogeneic marrow transplantation. 887 36

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

Serial quantification of residual disease in CML patients after allogeneic BMT is useful for early detection of relapse. However, the fact that some cytogenetic relapses appear to be transient may complicate protocols for early therapeutic intervention based on molecular analysis and could result in the unnecessary treatment of some patients. To determine the frequency and significance of transient cytogenetic relapse, we have studied serial samples from 98 CML patients after allogeneic BMT by conventional cytogenetics and competitive RT-PCR for BCR-ABL mRNA. During the period of study, 26 patients had cytogenetic or haematologic evidence or relapse. In four cases (15% of those who relapsed; 4% of all patients) relapse appeared to be transient; i.e., subsequent marrow samples were completely Ph chromosome-negative despite the fact that there had been no change in treatment, including the level of immunosuppression. BCR-ABL mRNA levels broadly paralleled the cytogenetic findings. Of these four patients, two subsequently progressed to frank haematologic relapse and two remained strongly positive for BCR-ABL transcripts and are therefore presumably still at risk of relapse. Analysis of B cell-enriched, T cell-enriched and lymphoid-depleted fractions for three patients demonstrated that transient relapse was not due to the proliferations of BCR-ABL-positive lymphoid cells. In contrast, BCR-ABL-positive myeloid precursor cells were detected in two of three patients tested. We conclude that transient cytogenetic relapse followed by sustained remission is a relatively infrequent occurrence after current allogeneic transplant regimens.
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PMID:Molecular analysis of transient cytogenetic relapse after allogeneic bone marrow transplantation for chronic myeloid leukaemia. 897 86


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