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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bone marrow samples of 16 patients (two adults and 14 children) with a B lineage acute lymphoblastic leukaemia (ALL), and in whom Ig heavy chain gene rearrangements were detectable at diagnosis using polymerase chain reaction (PCR), were studied during evolution using PCR. The VDJ junctional fragment of the Ig heavy chain rearranged gene was amplified at diagnosis. After length reduction by restriction digestion, the amplified fragment was recovered by chromatography, labelled using a specific hexamer as a primer and directly used as a clonospecific probe. The sensitivity of the PCR ranged from 1:10(4) to 1:10(5) cells, depending on the patient's rearrangement. Residual disease (MRD) was detected in most of the patients achieving a complete remission after induction therapy, regardless of the long-term outcome of treatment. However, in patients remaining in complete remission, the level of MRD showed a tendency to decrease and ultimately become undetectable for variable periods of time, while in patients eventually relapsing there was a trend for MRD to persist at stable levels and even to increase before relapse was clinically evident. We conclude that the use of a simplified methodology for obtaining a clonospecific probe from the Ig heavy chain gene, though less sensitive than the sequencing methodology, is a valuable and readily available tool to monitor MRD in a high proportion of B lineage ALL.
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PMID:Follow-up of residual disease (MRD) in B lineage acute leukaemias using a simplified PCR strategy: evolution of MRD rather than its detection is correlated with clinical outcome. 195 77

The media has recently been featuring organ transplantation from various viewpoints. Furthermore, Novel Prizes 1990 for Medical & Physiological fields were awarded to Drs. JE Murray and ED Thomas, both pioneers of clinical transplantation. Our topic has been timely indeed. This symposium mainly dealt with laboratory tests vs. various types of organ transplantation. In reality though, only kidney and bone marrow transplantations have been practiced in Japan; thus, Dr. I Yokoyama, University of Pittsburgh, discussed liver transplantation. First, Dr. K Uchida lectured on the recent advancement of immunosuppressive drugs and improvement in the clinical outcome of kidney transplantation. Serum creatinine determination is the only parameter for rejection besides renal biopsy. Drs. K Miyamura & Y Morishima discussed about PCR method to detect MRD (minimal residual diseases). There are positive relationships between the remaining leukemic cells and the relapse of leukemia even though the patients are in clinical remission. Dr. H Funada dealt with the importance of "sterile room treatment" for bone marrow transplantation. It protects patients from infection, minimizes GVHD and prolongs survival time after transplantation. Dr. Yokoyama stressed the importance of back-up system, i.e. drug-monitoring, coagulation tests, pathological examination, biochemical tests, blood transfusion services for successful liver transplantations. Dr. T Fukunishi discussed the importance of developing the organ donor and coordinator system to promote kidney transplantation from cadaver. He also dealt with virus antibody tests for selecting donors. All discusssions stressed on the importance of the 24-hour laboratory back-up system performing emergency tests but no specific laboratory test for organ transplantation was necessary.
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PMID:[Organ transplantation and laboratory tests]. 207 64

The present study is a retrospective analysis of the outcome in 210 patients diagnosed and treated as having acute lymphoblastic leukaemia (ALL) in Sweden during 1977-84. 131 patients were morphologically rediagnosed as ALL. For the ALL-patients, nine different remission induction regimens were used. Remission frequency was 69%, without statistical difference according to induction treatment. However, the reasons for remission failure differed among therapy groups. The number of responders was significantly higher among patients who received a remission induction therapy with an anthracycline and/or L-asparaginase. Maintenance therapy consisted in most cases of 6-mercaptopurine and methotrexate with reinduction courses for 2-3 years. Median survival time was 13 months and median duration of first remission (MRD) 11 months. For a subgroup of patients (n = 29) treated with the most intense remission induction regimens, including at least 4 cytostatic drugs with both an anthracyclilne and L-asparaginase, the MRD is not yet reached, the shortest follow up time is 43 + months, and the probability of remaining in complete remission is 66%. We conclude that aggressive cytostatic therapy, with induction regimens including both an anthracycline and L-asparaginase, may cure a considerable number of adult ALL-patients.
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PMID:Acute lymphoblastic leukaemia in adults in Sweden 1977-84: a retrospective analysis. Swedish ALL-Group. 279 24

The monitoring of MRD by FISH and PCR is now clinically evaluated for a prediction of the relapse of leukemia. However, these methods include several technical limitations. In FISH, an appropriate cut off value should be settled for each probe or procedure in estimating chromosomal gain, loss, or translocation and the sensitivity depends on the cut off values but it may reach to 10(-3). In PCR, the sensitivity is higher than that of FISH especially using genomic DNA as a template. However, the detection of chromosomal translocation-specific DNA or RNA constructs is currently applicable to limited cases and the amplification of Ig or TCR gene rearrangement has a major pitfall caused by the clonal evolution. Clinically, MRD can be an indicator for a prediction of the relapse. For example, a greater MRD on entering CR tends to be related with an early relapse, a return to MRD-positive after disappearance of MRD will be a sign of impending relapse, and MRD negativity at the termination of therapy may be correlated with a long-term disease free status. More precise evaluation of MRD is necessary with regard to therapeutic strategy.
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PMID:[Detection of minimal residual disease by means of FISH and PCR methods and its clinical evaluation]. 778 32

Cure can now be achieved in a proportion of patients with ALL. However, relapse and eventual treatment failure occur in many cases receiving identical treatment, presumably as a result of failure to eradicate MRD. While for many years marrow morphology has been the standard by which leukaemic remission has been assessed, more sensitive techniques have been developed for detection of MRD including immunophenotypic analysis, and as discussed in this chapter, methods which detect leukemia-associated clonal genetic changes at the karyotypic and genomic levels. Table 10 lists the applicability and sensitivity of various markers used in MRD analysis in ALL. It is apparent that of the karyotypic and molecular approaches described, only PCR-based strategies for detection of either leukaemia-specific translocations or clonal Ag receptor rearrangements are reliably applicable to a high proportion of both B- and T-ALL at sufficiently high sensitivity. Initial clinical studies of patients undergoing therapy for ALL using a variety of PCR-based methods suggest that in some cases a persistent or increasing level of residual disease may be predictive for clinical relapse, although a number of technical factors and the phenomena of oligo-clonality and clonal evolution may limit the usefulness of this analysis in a few instances. From current available data it appears that in order to define the potential predictive value of PCR detection of MRD a large number of patients will need to be prospectively assessed over several years at multiple time points during and after therapy, preferably using more than one semi-quantitative PCR approach. In addition to reliable prediction of clinical relapse allowing appropriate individual treatment modification, progress in the molecular detection of MRD in ALL is also likely to be of benefit in the assessment of the efficacy of autograft purging and the evaluation of new therapeutic strategies such as the use of biological response modifiers to eliminate a low tumour burden.
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PMID:Genetic changes: relevance for diagnosis and detection of minimal residual disease in acute lymphoblastic leukaemia. 780 99

Approximately one-third of first relapses of childhood ALL occur at an extramedullary site without morphological evidence of bone marrow disease. However, the high incidence of subsequent medullary relapse in these cases strongly suggests that leukaemia is present at submicroscopic levels at the time of 'isolated' relapse. PCR analysis of immunoglobulin heavy chain (IgH) and T-cell receptor (TCR) gene rearrangements now allows detection of leukaemia at levels as low as 0.001%. We have therefore used this technique to reassess bone marrow status at morphologically isolated relapse in 13 children with B-lineage ALL (11 with off-treatment relapses, two on treatment). In 12 of these 13 patients marrow disease was detectable by PCR at the time of this relapse--in all cases at levels below the threshold of light microscopy. Where relapse occurred off-therapy this indicated re-emergence of disease. since MRD has never been detected by PCR at this stage in patients remaining in long-term remission. In both patients who relapsed on-therapy the level of MRD at the time of relapse represented an increase on that seen in their previous marrow sample. We conclude that re-emerging bone marrow disease can be detected in most cases of 'isolated' relapse when investigated by this highly sensitive technique. Our findings at a molecular level confirm a long-held clinical suspicion and indicate that full systemic re-induction as well as local therapy is obligatory for these children.
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PMID:PCR assessment of bone marrow status in 'isolated' extramedullary relapse of childhood B-precursor acute lymphoblastic leukaemia. 794 68

In acute lymphoblastic leukaemia (ALL), investigation of minimal residual disease by conventional morphology and immunology fails to detect levels of residual disease of < 1 leukaemic in 10-100 normal cells. The use of polymerase chain reaction (PCR) to exploit the diversity of the complementarity determining region (CDR) and immunoglobulin variable heavy chain (VH) family specific usage has greatly improved the sensitivity up to one leukaemic cell in 10(5)-10(6) normal bone marrow cells. Here we report on a prospective study of 14 patients with ALL of B-cell lineage by using a combined PCR approach which estimates levels of disease between 1:10(3) and 1:10(5). The sequential use of allele-specific oligoprimer (ASO) independent tests (using framework 1. FR1 and 3, FR3 primers with a JH consensus primer, sensitivity up to 1:5 x 10(3)) and ASO-dependent PCR (sensitivity up to 1:10(5)) assays were applied to 64 bone marrow (BM) follow-up samples in a sequential array of tests. Results presented in this study indicate high concordance of MRD among different tests for samples with level of residual disease > 1:5 x 10(3). Consequently, samples positive by the FR1 and FR3 fingerprinting tests were confirmed by the more sensitive ASO-dependent tests, as expected. However, the ASO-dependent assays revealed levels of disease undetected by the FR1 and FR3 test. Although a higher level of sensitivity is provided by the ASO-dependent tests, the FR1 and FR3 fingerprinting tests allow MRD investigation in patients with oligoclonal B cell proliferations, CDR3 region of size < 15 bp or with ASO primers unsuitable for PCR investigation on technical grounds (i.e. background signal). If a sequential order of investigation from less (e.g. FR1 and FR3 fingerprinting) to more sensitive tests (ASO-dependent) is applied, an indirect estimate of MRD is obtained for patients with level of disease < 1:10(3).
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PMID:The use of IgH fingerprinting and ASO-dependent PCR for the investigation of residual disease (MRD) in ALL. 856 80

Immunophenotyping improves both accuracy and reproducibility of the FAB classification and is considered particularly useful for identifying poorly differentiated FAB subtypes of AML, such as AML with minimal differentiation (M0), microgranular promyelocytic leukaemia (M3V), and megakaryoblastic leukaemia (M7). Immunological studies of myeloid leukaemic blasts has become critical also in identifying biphenotypic leukaemias and AML expressing lymphoid-associated markers (Ly+ AML). At present, while the prognostic value of individual antigen expressions is still controversial, due to technical questions, the immunological detection of MRD seems to be important in monitoring AML patients in remission and, perhaps, in detecting leukaemic cell contamination into bone marrow or peripheral blood progenitor cells collected for autologous transplantation. In addition, the relationship established between genetic abnormalities and certain phenotypes within different FAB subtypes suggests that, in the future, immunophenotypical studies could be used for the screening of AML cases carrying specific genetic aberrations. Compared to acute leukaemias, little information is available concerning immunological patterns in MDS, and the role of the immunophenotype in diagnosis, subclassification, and prognosis of MDS is currently not well established.
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PMID:Immunophenotyping of AML and MDS and detection of residual disease. 873 May 50

The clinical and biological significance of additional chromosome aberrations was investigated in a large series of 66 adult patients with Philadelphia (Ph) chromosome positive acute lymphoblastic leukaemia (ALL). Additional chromosome changes were observed in 71% of the cases. 9p abnormalities were identified in 26%, and monosomy 7 as well as hyperdiploid karyotypes 50 were both found in 17% of cases. 9p anomalies were characterized by a low complete remission (CR) rate (58%) and an extremely short median remission duration (MRD: 100 d). In patients with monosomy 7, the poor treatment outcome was confirmed (CR rate 55%: MRD 113 d). In contrast, all patients with hyperdiploid karyotypes 50 achieved CR, and the overall survival was superior to all other Ph-positive ALL patients except those without additional chromosome aberrations. Exclusive rearrangement of the minor breakpoint cluster region of the BCR gene and lack of coexpression of myeloid-associated antigens in cases with 9p anomalies as well as a high frequency of rearrangements of the major breakpoint cluster region of the BCR gene in patients with monosomy 7 (89%) further substantiated that additional chromosome aberrations may characterize distinct subgroups of Ph-positive ALL. Moreover, the necessity of the complementing use of chromosome banding analyses, polymerase chain reaction (PCR) assays, and fluorescence in situ hybridizations in the accurate identification of Ph-positive patients has become evident due to variant Ph translocations in 3%, and negative PCR assays in 4% of the cases.
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PMID:Prognostic significance of additional chromosome abnormalities in adult patients with Philadelphia chromosome positive acute lymphoblastic leukaemia. 898 45

We sequentially performed cytogenetic analysis and RT-PCR analysis of BCR-ABL transcripts in 17 cases of Ph1-positive ALL who had achieved hematological complete remission (CR) with intensive chemotherapy (CT). Sixteen cases were studied prospectively. All but one of the patients had reached cytogenetic CR, but cytogenetic has low sensitivity in predicting relapse. Twelve patients relapsed, three died in first CR and two were alive in first CR. Two of five, two of four, and five of nine patients who were allografted (in first or second CR), autografted and received consolidation CT, respectively, achieved negative two-round PCR in the bone marrow (BM): three died in CR, three remained in CR with negative two-step PCR in the BM and three relapsed after 22 to 28 months. In all cases, relapse was preceded by switch to PCR positivity in the BM by 4 to 6 months. The remaining nine patients remained PCR-positive in the BM and relapsed after 2 to 16 months. In the four autografted cases, PCR was positive at the time of bone marrow harvest. The two patients who received a purged transplant achieved negative PCR and prolonged CR, whereas the two patients who received an unpurged transplant remained PCR positive and relapsed. In 34% of the samples where analysis was concomitant, sensitivity of PCR proved lower in the blood than in the BM. These findings show that RT-PCR is a useful tool in the monitoring of MRD in Ph1 positive ALL.
Leukemia 1997 Feb
PMID:Good correlation between RT-PCR analysis and relapse in Philadelphia (Ph1)-positive acute lymphoblastic leukemia (ALL). 900 95


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