Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have sought to determine whether peripheral blood or bone marrow is more sensitive for assessment of minimal residual disease in chronic myeloid leukaemia (CML). Contemporaneous blood and marrow specimens were taken from 21 patients at various times after allogeneic bone marrow transplant (BMT) and from one patient in complete cytogenetic remission on alpha-interferon. Samples were analysed for evidence of BCR-ABL mRNA by RT-PCR: four were PCR negative and 19 PCR positive. Results with blood and marrow were concordant in all cases. BCR-ABL transcripts were quantified in PCR-positive samples using a competitive PCR titration assay. Results ranged from < 10 to 2 x 10(6) BCR-ABL transcripts/micrograms RNA. In all 19 cases a high degree of concordance in BCR-ABL levels with blood and marrow (r = 0.99) was found. We conclude that either tissue may be used for residual disease studies after BMT for CML.
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PMID:A comparison of the sensitivity of blood and bone marrow for the detection of minimal residual disease in chronic myeloid leukaemia. 773 83

Detection of minimal residual disease is one of the major goals in bone marrow transplantation. We used a fluorescence in-situ hybridization technique to detect residual Philadelphia-chromosome positive cells in chronic myelogenous leukemia (CML) patients after sex-mismatch BMT. We analyzed the level of detection using probes for the BCR/ABL fusion product by comparison with results obtained with probes for the Y and X sex chromosomes. Detection of sex-mismatch chromosomes was significantly higher than that of the BCR/ABL translocation. In contrast, a higher specificity of residual tumor cell detection by the BCR/ABL probe was demonstrated because most of the sex-mismatch cells detected by FISH had a normal karyotype. Tumor-specific markers probes are thus superior and more accurate than sex-mismatch probes for detection of MRD in CML patients after BMT.
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PMID:Detection of minimal residual disease after sex-mismatch bone marrow transplantation in chronic myelogenous leukemia by fluorescence in situ hybridization. 817 87

We have studied 61 patients who underwent allogeneic bone marrow transplantation (BMT) for chronic myeloid leukaemia (CML) in first chronic phase. Minimal residual disease was detected by the amplification of the leukaemia-specific BCR-ABL fusion mRNA with the polymerase chain reaction (PCR) using a highly sensitive nested primer strategy. As a general pattern, patients often had detectable BCR-ABL (PCR positive) for up to 6 or 9 months post BMT after which time BCR-ABL became undetectable (PCR negative). The conversion from PCR positive to PCR negative was not associated with the time at which cyclosporin A treatment was stopped. Six patients (10%) have relapsed during the period of this study, two within 1 year and four more than 1 year after transplant. The relationship between PCR positivity more than 1 year post transplant and relapse was significant (P = 0.036) but 15 patients who were PCR positive beyond 1 year remain in complete clinical and cytogenetic remission. Thus late positivity identifies a group of patients at increased risk of relapse but is of little predictive value for individual patients. Of the four late relapses, two had been persistently PCR positive and two were initially PCR positive, converted to negative and subsequently to positive again. Although all relapses were preceded by PCR positivity, relapse may occur only 12 months after a PCR negative result. The proportion of patients PCR negative at 3/4 months after BMT was found to increase significantly with the severity of acute GVHD (P = 0.002) but no relationship was found between acute GVHD and subsequent PCR results. There was no clear association between severity of chronic GVHD and PCR result.
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PMID:Minimal residual disease after allogeneic bone marrow transplantation for chronic myeloid leukaemia in first chronic phase: correlations with acute graft-versus-host disease and relapse. 833 80

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 have developed a competitive polymerase chain reaction (PCR) titration assay that estimates the number of BCR-ABL transcripts in chronic myeloid leukemia patients to monitor minimal residual disease after bone marrow transplantation (BMT). The assay gave reproducible results and allowed differences in BCR-ABL message levels of half an order of magnitude to be distinguished. Of 91 patients studied by nonquantitative PCR, 28 who had a positive PCR result on at least one occasion posttransplant were analyzed by competitive PCR. Seventeen patients had no evidence in their marrow of cytogenetic relapse during the period of observation; BCR-ABL transcript numbers in these cases ranged from approximately 10 to 800/micrograms RNA. Ten of the 11 patients who relapsed cytogenetically were studied when Philadelphia-positive metaphases were first detected in their marrow; transcript numbers ranged from 1,600 to 7 x 10(5)/micrograms RNA. Patients in hematologic relapse had between 9 x 10(4) and 10(6) BCR-ABL transcripts/micrograms RNA. Patients who progressed from cytogenetic remission to cytogenetic relapse and then to hematologic relapse had increasing numbers of BCR-ABL transcripts in their blood. Three patients had clear evidence of rising numbers of BCR-ABL transcripts before routine detection of cytogenetic relapse. Conversely patients without cytogenetic relapse generally had low or falling numbers of transcripts. We conclude that serial monitoring of residual disease post-BMT by estimating the number of BCR-ABL transcripts provides more information than conventional cytogenetics or nonquantitative PCR and may identify patients in need of therapeutic intervention before the onset of overt relapse.
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PMID:Competitive polymerase chain reaction to estimate the number of BCR-ABL transcripts in chronic myeloid leukemia patients after bone marrow transplantation. 840 Feb 43

This article reviews both the role of signal transduction in human cancer and the recently uncovered molecular mechanisms involved in a large number of human hematologic malignancies. Chronic myelogenous leukemia, follicular lymphoma, and colorectal carcinoma are used as models to illustrate the different, as well as partly convergent, molecular pathways involved in the multistep process of human neoplasias. Examples are also provided as to how unique molecular markers can be used as fast, sensitive, and precise tools for cancer prevention, early diagnosis, and the management of residual disease.
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PMID:Molecular mechanisms of hematologic malignancies. 842 May 72

The polymerase chain reaction (PCR) was used to amplify the bcr/abl transcript as a marker of minimal residual disease (MRD) in 76 patients with chronic myeloid leukemia (CML) subjected to allogeneic BMT and in complete hematological remission. We examined 56 patients transplanted in chronic phase (CP) and 20 in advanced phase (AD), including 16 in accelerated phase and four in blastic transformation. A total of 135 samples collected between 4 and 105 months from BMT were analyzed and the PCR analysis was positive in 33 (24%) samples from 20 patients. The bcr/abl chimeric transcript was detected in 7/13 (54%) patients analyzed within 1 year and in 21/88 (23%) beyond 1 year from BMT. Fluctuation of the residual disease at the molecular level in individual patients was recorded. The results have been correlated with a number of clinical parameters obtained before and after BMT; among the tested variables only the phase of the disease at BMT was associated with higher frequency of PCR positivity after BMT. The probability of finding persisting disease 1 year beyond BMT was significantly higher (P = 0.00005) in patients allografted in AD (14/26, 54%) as compared to patients grafted in CP (7/62, 11%). At any interval from BMT the difference between the two groups remained statistically significant: the bcr/abl transcript was present in 5/31 patients transplanted in CP compared to 9/15 patients transplanted in AD (P = 0.003) between 12 and 36 months from BMT, and in 2/31 CP vs 5/11 AD patients (P = 0.008) beyond 36 months from BMT.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:bcr/abl chimeric transcript in patients in remission after marrow transplantation for chronic myeloid leukemia: higher frequency of detection and slower clearance in patients grafted in advanced disease as compared to patients grafted in chronic phase. 852 78

We prospectively performed repeated cytogenetic and PCR monitoring of residual disease in all cases Ph positive of chronic myeloid leukemia (CML) allografted with non T cell depleted marrow at our institution over a period of 8 years. Thirty eight patients who survived the immediate post transplant period could be analyzed (median of 3 cytogenetic analyses/patient, examining 100 mitoses, and 4 PCR analyses/patient). Seven of the 38 patients had a hematological relapse (which was extramedullary in one case) and one a purely cytogenetic relapse, possibly stabilised by interferon treatment. Within 6 months of transplant, Ph positive mitoses were seen in 2 patients, and positive PCR in most cases, without implying subsequent relapse. Six of the 32 patients analyzed cytogenetically more than 6 months post transplant had Ph positive mitoses on at least one occasion: 5 had a hematological relapse within 7 months of positive cytogenetic analysis, and the remaining patient, treated by interferon remained in purely cytogenetic relapse. (The extramedullary relapse was not preceded by a positive marrow karyotype). Eight of the 38 patients had positive PCR findings on at least one occasion more than 6 months post transplant. Seven relapsed (6 hematological relapses including the extramedullary relapse, and 1 cytogenetic relapse) after 3 to 20 months, but the remaining patient remained in CR 36 months later, with negative PCR. The 30 patients who never had positive PCR findings remained in CR. In this relatively large series of patients, we found a good correlation between PCR findings more than 6 months post transplant and remission or relapse status.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Good predictive value of combined cytogenetic and molecular follow up in chronic myelogenous leukemia after non T-cell depleted allogeneic bone marrow transplantation: a report on 38 consecutive cases. 853 92

Complete hematologic and cytogenetic responses can be obtained with interferon-alpha (IFN-alpha) in 15-25% of the patients with chronic myelogenous leukemia (CML). In these patients, reverse-transcription polymerase chain reaction (RT-PCR) can be used to evaluate minimal residual disease. We studied 12 patients who remained Philadelphia-negative for a median period of 21 months on IFN-alpha therapy. Using RT-PCR, the specific transcript was found in all bone marrow (BM) samples. Ten patients still exhibiting a persistent residual clone remained in cytogenetic remission for a median period of 14 months. As we observed a dissociation between bcr-abl expression in BM and peripheral blood (PB) cells, and given the known fluctuations of the bcr-abl PCR results, we suggest that PB negative results should be confirmed on BM specimens. Alternatively, it remains to be demonstrated whether longitudinal monitoring of residual disease would benefit from quantitative PCR or double fluorescence in situ hybridization.
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PMID:Persistence of BCR/ABL mRNA-expressing bone-marrow cells in patients with chronic myelogenous leukemia in complete cytogenetic remission induced by interferon-alpha therapy. 858 Aug 18

We report minimal residual disease evaluation in 18 chronic myelocytic leukemia patients who achieved a durable complete cytogenetic conversion (CCC) under interferon alpha (IFN) therapy. Monitoring was performed every 3-6 months using bone marrow (BM) karyotypes and/or two-step reverse transcription polymerase chain reaction (RT-PCR) on peripheral blood samples. Median follow-up after first CCC was 47 months (range 15-69). All patients maintained complete hematological remission during follow-up. A median of five BM karyotypes were performed per patient (range: 3-11). The estimated chances of maintaining a major cytogenetic response (either CCC or less than 35% Ph positive metaphases were 93 +/- 13% (95% CI) at 36 months. One patient lost his cytogenetic response. A median of seven RT-PCR reactions were performed per patient (range: 1-11). A residual disease was detectable even in cases with long periods of CCC. However, in two patients, RT-PCRs were often negative; one, who had four successive negative RT-PCR was taken off IFN therapy and did not receive any other treatment; later in this case, RT-PCRs were again positive, but CCC was maintained for 39 months. Of the three who were taken off IFN and no longer treated, two maintained CCC (39+ and 33+ months); the third had a recurrence of 7% Ph-positive metaphases, and later returned to CCC. These results confirm that in most well-responding patients, the disease is not eradicated. However, it seems that the clonogenic potential of the residual leukemic clone is low. In patients taken off IFN therapy, IFN may have a particular remnant effect.
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PMID:Chronic myelocytic leukemia patients achieving complete cytogenetic conversion under interferon alpha therapy: minimal residual disease follow-up. 860 18


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