scholarly journals Detection of minimal residual disease by polymerase chain reaction in Philadelphia chromosome-positive chronic myelogenous leukemia following interferon therapy

Blood ◽  
1992 ◽  
Vol 79 (8) ◽  
pp. 1920-1923 ◽  
Author(s):  
MS Lee ◽  
H Kantarjian ◽  
M Talpaz ◽  
EJ Freireich ◽  
A Deisseroth ◽  
...  
Keyword(s):  
Polymerase Chain Reaction ◽  
Interferon Therapy ◽  
Residual Disease ◽  
Philadelphia Chromosome ◽  
Myelogenous Leukemia ◽  
Chain Reaction ◽  
Cytogenetic Remission ◽  
Polymerase Chain ◽  
Minimal Residual

The significance of the polymerase chain reaction (PCR) in the detection of minimal residual disease in Philadelphia chromosome (Ph′)- positive chronic myelogenous leukemia (CML) following interferon therapy was investigated. Forty remission blood samples obtained at various remission time points from 29 patients in complete cytogenetic remission were analyzed. All 40 samples showed minimal residual Ph′- positive cells by PCR: 22 in remission for less than 12 months, 12 in remission for 12 to 24 months, four in remission for 25 to 60 months, and two in remission for more than 60 months. Of these 29 patients, seven relapsed at 4, 6, 9, 14, 17, 19, and 50 months after their first PCR-positivity during remission. One developed extramedullary myelopoiesis at 49 months after PCR-positivity. The remaining 21 patients remained in complete hematologic and cytogenetic remission with median follow-up of 13 months (range, 4 to 36 months) after PCR analysis. These findings indicate that PCR-positivity is not associated with immediate disease recurrence. Long-term follow-up is essential to determine the relevance of PCR-positivity, since late recurrence is observed in our study.

scholarly journals Detection of minimal residual disease by polymerase chain reaction in Philadelphia chromosome-positive chronic myelogenous leukemia following interferon therapy

Blood ◽  
1992 ◽  
Vol 79 (8) ◽  
pp. 1920-1923 ◽  
Author(s):  
MS Lee ◽  
H Kantarjian ◽  
M Talpaz ◽  
EJ Freireich ◽  
A Deisseroth ◽  
...  
Keyword(s):  
Polymerase Chain Reaction ◽  
Interferon Therapy ◽  
Residual Disease ◽  
Philadelphia Chromosome ◽  
Myelogenous Leukemia ◽  
Chain Reaction ◽  
Cytogenetic Remission ◽  
Polymerase Chain ◽  
Minimal Residual

Abstract The significance of the polymerase chain reaction (PCR) in the detection of minimal residual disease in Philadelphia chromosome (Ph′)- positive chronic myelogenous leukemia (CML) following interferon therapy was investigated. Forty remission blood samples obtained at various remission time points from 29 patients in complete cytogenetic remission were analyzed. All 40 samples showed minimal residual Ph′- positive cells by PCR: 22 in remission for less than 12 months, 12 in remission for 12 to 24 months, four in remission for 25 to 60 months, and two in remission for more than 60 months. Of these 29 patients, seven relapsed at 4, 6, 9, 14, 17, 19, and 50 months after their first PCR-positivity during remission. One developed extramedullary myelopoiesis at 49 months after PCR-positivity. The remaining 21 patients remained in complete hematologic and cytogenetic remission with median follow-up of 13 months (range, 4 to 36 months) after PCR analysis. These findings indicate that PCR-positivity is not associated with immediate disease recurrence. Long-term follow-up is essential to determine the relevance of PCR-positivity, since late recurrence is observed in our study.

scholarly journals Detection of Philadelphia chromosome-positive acute lymphoblastic leukemia by polymerase chain reaction: possible eradication of minimal residual disease by marrow transplantation

Blood ◽  
1992 ◽  
Vol 79 (5) ◽  
pp. 1366-1370 ◽  
Author(s):  
K Miyamura ◽  
M Tanimoto ◽  
Y Morishima ◽  
K Horibe ◽  
K Yamamoto ◽  
...  
Keyword(s):  
Polymerase Chain Reaction ◽  
Acute Lymphoblastic Leukemia ◽  
Minimal Residual Disease ◽  
Marrow Transplantation ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Chain Reaction ◽  
Polymerase Chain ◽  
Minimal Residual

Abstract Minimal residual disease (MRD) in patients with Philadelphia chromosome- positive acute lymphoblastic leukemia (Ph1 ALL) who received allogeneic (n = 9) or autologous (n = 6) bone marrow transplantation (BMT) was evaluated by the polymerase chain reaction (PCR) for the bcr-abl transcript. Twelve patients received BMT at the time of hematologic and cytogenetic remission. However, MRD was detected in 8 of 10 patients evaluated. Seven patients, including three who had MRD before BMT, continue to have a disease-free survival 5 to 64 months after BMT. Twenty-one specimens obtained from these patients at various times after BMT did not show MRD. In three patients, MRD detected just before BMT seems to be eradicated by BMT protocol. The other eight patients developed cytogenetic or hematologic relapses 2 to 8 months after BMT. Seven of 14 samples from these patients demonstrated MRD, which preceded clinical relapse by 3 to 9 weeks. Thus, this technique for the detection of MRD appears to be useful for the more precise assessment of various antileukemia therapies and for early detection of leukemia recurrence.

scholarly journals Detection of two alternative bcr/abl mRNA junctions and minimal residual disease in Philadelphia chromosome positive chronic myelogenous leukemia by polymerase chain reaction

Blood ◽  
1989 ◽  
Vol 73 (8) ◽  
pp. 2165-2170
Author(s):  
MS Lee ◽  
A LeMaistre ◽  
HM Kantarjian ◽  
M Talpaz ◽  
EJ Freireich ◽  
...  
Keyword(s):  
Polymerase Chain Reaction ◽  
Chronic Myelogenous Leukemia ◽  
Philadelphia Chromosome ◽  
Rare Event ◽  
Chronic Phase ◽  
Myelogenous Leukemia ◽  
Rt Pcr ◽  
Chain Reaction ◽  
Polymerase Chain ◽  
Minimal Residual

The Philadelphia (Ph′) chromosome in chronic myelogenous leukemia (CML) results in fusion of the bcr gene and c-abl oncogene, which transcribes into two types of chimeric bcr/abl mRNAs: the L-6 junction and the K-28 junction. By means of a highly sensitive assay, combination of reverse transcription and polymerase chain reaction (RT/PCR), we analyzed 38 blood samples obtained from 31 patients with Ph′-positive CML and two patients with Ph′-negative bcr rearranged CML. Among the 21 samples obtained in chronic phase, eight patients had the L-6 mRNA, 11 had the K-28 mRNA, and two had both the L-6 and K-28 mRNAs. Among the nine samples obtained in blast crisis, four contained the L-6 mRNA, two contained the K-28 mRNA, and three contained both the K-28 and L-6 mRNAs. This finding supports the concept of alternative splicing of bcr/abl mRNAs transcribed in Ph′-positive CML. However, it appears to be a rare event. Of the eight samples obtained from eight patients who had achieved complete cytogenetic remission and negativity for bcr region rearrangement for 6 months to 3 years after recombinant alpha interferon (r alpha-IFN) therapy, all of them showed evidence of minimal residual Ph′-positive clones as detected by the RT/PCR assay. This finding suggests that interferon therapy suppresses the proliferation of the Ph′-positive clones, but it does not completely eradicate the Ph′-positive stem cells.

Conversion of interferon-induced, long-term cytogenetic remissions in chronic myelogenous leukemia to polymerase chain reaction negativity.

1998 ◽  
Vol 16 (4) ◽  
pp. 1526-1531 ◽  
Author(s):  
R Kurzrock ◽  
Z Estrov ◽  
H Kantarjian ◽  
M Talpaz
Keyword(s):  
Polymerase Chain Reaction ◽  
Chronic Myelogenous Leukemia ◽  
Myelogenous Leukemia ◽  
Rt Pcr ◽  
Chain Reaction ◽  
Ifn Alpha ◽  
Cytogenetic Remission ◽  
Polymerase Chain

PURPOSE Interferon alfa (IFN-alpha) induces complete cytogenetic remission in a significant minority of patients with chronic myelogenous leukemia (CML). To date, use of the polymerase chain reaction (PCR) has suggested that residual disease is present in virtually all these individuals at median follow-up intervals of approximately 1 year after initial achievement of cytogenetic remission. We sought to determine the PCR status of CML patients with very long continuous complete cytogenetic remissions on IFN-alpha. PATIENTS AND METHODS Blood and/or bone marrow samples from 18 CML patients maintained in continuous cytogenetic remission by IFN-alpha for at least 1 year were studied for residual BCR-ABL mRNA by single-step reverse-transcriptase (RT)-PCR methodology, followed by detection of the amplification product by the hybridization protection assay (HPA). RESULTS Ten of 18 patients showed RT-PCR negativity for BCR-ABL. The median duration of continuous complete cytogenetic remission at the time of sample collection for the negative patients was 42 months versus 21 months for the patients whose tests remained positive (P = .05). CONCLUSION Very long-term follow-up of IFN-alpha-treated CML patients in continuous complete cytogenetic remission is associated with a decrease in the number of BCR-ABL transcripts to a level below that detectable by the RT-PCR assay used in this study.

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