Detection of residual BCR/ABL transcripts in chronic myeloid leukaemia patients in complete remission using the polymerase chain reaction and nested primers

Martiat, Philippe; Maisin, Diane; Philippe, Marianne; Ferrant, Augustin; Michaux, Jean‐Louis; Cassiman, Jean‐Jacques; Berghe, Herman Van den; Sokal, G.

doi:10.1111/j.1365-2141.1990.tb04348.x

Cited by 67 publications

(20 citation statements)

References 17 publications

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“…In fact, our results confirm those of Lee et al 7 and Hochhaus et al 12 who reported that all complete cytogenetic responders on IFN-␣ have detectable residual disease by two-step RT-PCR independent of the duration of CCR. Although at least 23 cases have been reported 12,13,[16][17][18][19][20][21][22][23] with intermittent or persistent PCR negativity on IFN-␣ using different PCR techniques, these observations may be due to the considerable variability in the sensitivity of PCR techniques performed in different laboratories. Consequently, the PCR negativity reported in CCR patients could be due more to technical discrepancies among different laboratories than to a real cure of the patients.…”

Section: Discussionmentioning

confidence: 77%

Quantification of BCR-ABL transcripts in CML patients in cytogenetic remission after interferon-α-based therapy

Martinelli

Testoni

Amabile

et al. 2000

Bone Marrow Transplant

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Summary:We measured using a competitive quantitative polymerase chain reaction-capillary electrophoresis (PCR-CE)-based assay, the levels of bcr-abl transcripts in 44 patients with chronic myeloid leukemia (CML) after interferon-␣ (IFN-␣) therapy, who achieved a major (10 patients, MCR group) or complete (34 patients, CCR group) cytogenetic response. All 34 CCR patients had molecular evidence of residual disease detected in bone marrow samples at the time of best karyotypic response. The median number of bcr-abl transcripts of 34 evaluable patients in the CCR group at the time of complete cytogenetic remission was 4/ g RNA (range 3-4600), while the median number of bcr-abl transcripts of 10 patients in the MCR group at the time of best cytogenetic response was 4490/ g RNA (range 600-23 900) (P = 0.000024). In nine CCR and five MCR patients we were able to quantify the amount of bcr-abl transcript both at diagnosis and after interferon therapy: no statistical difference (P = 0.18) was found between the two groups at diagnosis (median bcr-abl transcripts/ g RNA was 30 000 vs 39 650, respectively). During IFN-␣ therapy, the two groups were evaluable at the time of major karyotypic conversion: at this point, there was a statistical difference of expression of bcr-abl transcript between the CCR group (17 patients) (median 2700; range 76-40 000) and the MCR group (10 patients) (median 4490; range 600-23 900), respectively (P = 0.046). No differences of bcr-abl amount of transcript were found in patients with CCR obtained either by IFN-␣ therapy alone (20 patients) vs IFN-␣ plus ABMT (13 patients) (P = 0.47). We firstly demonstrated that although the CCR and MCR groups were clinically, cytogenetically and molecularly indistinguishable at diagnosis, the two groups could be recognized successfully during interferon therapy based on the level of bcr-abl transcript. Bone Marrow Transplantation (2000) 25, 729-736.

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Section: Discussionmentioning

confidence: 77%

Quantification of BCR-ABL transcripts in CML patients in cytogenetic remission after interferon-α-based therapy

Martinelli

Testoni

Amabile

et al. 2000

Bone Marrow Transplant

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“…The following rearrangements or fusion transcripts were investigated on diagnostic material using Southern blot for the detection of MLL rearrangements (Poirel et al, 1996) or reverse transcriptase PCR for t(12;21), t(9;22), t(1;19) and t(4;11) according to previously described methods (Biondi et al, 1993;Hunger et al, 1991;Martiat et al, 1990;Maurer et al, 1991;Shurtleff et al, 1995).…”

Section: Methodsmentioning

confidence: 99%

A prospective study of minimal residual disease in childhood B‐lineage acute lymphoblastic leukaemia: MRD level at the end of induction is a strong predictive factor of relapse

Jacquy¹,

Délépaut²,

daele³

et al. 1997

Br J Haematol

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Summary. We prospectively investigated minimal residual disease (MRD) in 51 children with B-lineage acute lymphoblastic leukaemia (ALL) treated according to the Fralle 93 protocol. PCR follow-up was performed in children in morphological and cytogenetic complete remission, provided an immunoglobulin (IgH) gene rearrangement could be detected using FR3/J H amplimers. MRD was studied according to our previously described methodology, with a few modifications including the use of a consensus J H probe to control for PCR efficiency variations.Out of the initial 51 patients, 34 were assessable for MRD at the end of induction at the time of analysis. MRD levels were as follows: >1/10 3 in 26%, 1/10 3 to 1/10 4 in 50% and <1/10 4 or not detectable in 24%. With a median follow-up of 20 months there were five relapses, all of which occurred in the group of patients with MRD >1/10 3 . To date, none of the patients with MRD р1/10 3 (good molecular responder) has relapsed. Classification according to molecular response at the end of induction did not correlate with the conventional risks groups: there were no statistically significant differences between good and bad molecular responders. Of particular interest is the absence of correlation between WBC at diagnosis and MRD level at the end of induction. We conclude that classification of patients into good and bad molecular responders using PCR seems to be a better prognostic indicator than conventional risk factors in childhood B-lineage ALL. Patients with MRD level >1/10 3 have a particularly poor outcome and should always be considered for alternative therapeutic strategies in the future, whereas in good molecular responders belonging to poor or intermediate risk categories, treatment de-escalation might be contemplated.

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“…cDNA synthesis and RT PCR was carried out using the 'Geneamp' kit (Applied Biosystems, U.K.) using 1 mg of RNA. PCR primers for the BCR gene were as described by Martiat et al (1990) and for all the ABL exon a3 as described by Cross et al (1993). Primers were purchased from Oswell (Edinburgh, Scotland) and thermal cycling was carried out on a Perkin Elmer 9600 thermal cycler.…”

Section: Patientsmentioning

confidence: 99%

Treatment of chronic myeloid leukaemia in first chronic phase with idarubicin and cytarabine: mobilization of Philadelphia‐negative peripheral blood stem cells

Franklin

Kelsey

et al. 1997

Br J Haematol

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Summary. Peripheral blood stem cell (PBSC) mobilization using idarubicin and cytarabine was investigated in 40 patients with chronic myeloid leukaemia in first chronic phase (CML CP1). Disease contamination was evaluated in harvests from 41/44 (93%) mobilization episodes. Using cytogenetics, 22/37 (59%) showed a complete or major response; Southern blot analysis demonstrated a complete or major response in 9/17 (53%). No harvests were RT-PCR negative. In the 41 evaluable episodes, more complete or major responses were seen when PBSC mobilization occurred within 24 months [17/23 (74%) versus 6/18 (33%); P ¼ 0 : 02] and within 12 months of diagnosis [10/11 (91%) versus 13/30 (43%); P ¼ 0 : 018]. 20 patients underwent PBSC transplantation and 18/20 successfully engrafted. Post-transplant cytogenetic analysis was available on 15 cases, of whom five achieved a major cytogenetic response at 1-3 months, with five partial cytogenetic remissions. Two of 40 patients died during mobilization therapy (5%) and three of 20 after the transplant (15%). Overall mortality was high at five of 40 patients, and the procedural mortality was 20%. This study demonstrates that Ph-negative PBSCs can be mobilized in a significant proportion of patients with CML CP1, with the best results observed within a year of diagnosis. These cells can subsequently be used for autologous transplantation, however, the impact on long-term survival requires longer follow-up, and potential benefits may be compromised by the high mortality.

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Detection of residual BCR/ABL transcripts in chronic myeloid leukaemia patients in complete remission using the polymerase chain reaction and nested primers

Cited by 67 publications

References 17 publications

Quantification of BCR-ABL transcripts in CML patients in cytogenetic remission after interferon-α-based therapy

Quantification of BCR-ABL transcripts in CML patients in cytogenetic remission after interferon-α-based therapy

A prospective study of minimal residual disease in childhood B‐lineage acute lymphoblastic leukaemia: MRD level at the end of induction is a strong predictive factor of relapse

Treatment of chronic myeloid leukaemia in first chronic phase with idarubicin and cytarabine: mobilization of Philadelphia‐negative peripheral blood stem cells

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