Effectiveness of Using IVD Certified Platform for Monitoring Minimal Residual Disease in Chronic Myelogenous Leukemia Patient

Abstract A substantial minority of patients with chronic myelogenous leukemia (CML) achieve a complete response (CR) to treatment with interferon- (IFN), defined as the disappearance of Philadelphia chromosome-positive metaphases. Currently it is unclear how long IFN treatment should be continued for such patients. We used a competitive reverse transcriptase-polymerase chain reaction (RT-PCR) to quantify levels of BCR-ABL transcripts in 297 peripheral blood specimens collected from 54 patients who had achieved CR with IFN. The median duration of observation was 1.9 years (range, 0.3-11.0 years). Total ABL transcripts were quantified as internal control and results were expressed as the ratio BCR-ABL/ABL. All 54 patients had molecular evidence of residual disease, although 3 patients were intermittently PCR negative. The median BCR-ABL/ABL ratio at the time of maximal response for each patient was 0.045% (range, 0%-3.6%). During the period of observation 14 patients relapsed, 11 cytogenetically to chronic phase disease and 3 directly to blastic phase. The median ratio of BCR-ABL/ABL at maximal response was significantly higher in patients who relapsed than in those who remained in CR (0.49% versus 0.021%,P < 0.0001). Our findings show that the level of residual disease falls with time in complete responders to IFN, but molecular evidence of disease is rarely if ever eliminated. The actual level of minimal residual disease correlates with the probability of relapse. We suggest that for patients who reach CR, IFN should be continued at least until relatively low levels of residual leukemia are achieved. (Blood. 2000;95:62-66)

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Detection of minimal residual disease state in chronic myelogenous leukemia patients using fluorescence in situ hybridization

Cancer Genetics and Cytogenetics ◽

10.1016/0165-4608(94)90073-6 ◽

1994 ◽

Vol 76 (1) ◽

pp. 59-64 ◽

Cited By ~ 21

Author(s):

Aliza Amiel ◽

Shai Yarkoni ◽

Shimon Slavin ◽

Reuven Or ◽

Haya Lorberboum-Galski ◽

...

Keyword(s):

In Situ Hybridization ◽

Fluorescence In Situ Hybridization ◽

Minimal Residual Disease ◽

Chronic Myelogenous Leukemia ◽

Residual Disease ◽

Disease State ◽

Myelogenous Leukemia ◽

Minimal Residual

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Minimal Residual Disease in Chronic Myelogenous Leukemia: Results of RT-PCR Detection of BCR-ABL Transcripts

Leukemia and Lymphoma ◽

10.1385/1-59259-318-6:179 ◽

2003 ◽

pp. 179-200

Author(s):

Nicholas C. P. Cross ◽

Andreas Hochhaus

Keyword(s):

Minimal Residual Disease ◽

Chronic Myelogenous Leukemia ◽

Residual Disease ◽

Pcr Detection ◽

Myelogenous Leukemia ◽

Rt Pcr ◽

Minimal Residual

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Monitoring of BCR-ABL Transcirpt Levels after Discontinuation of Imatinib Therapy in Chronic Myelogenous Leukemia Patients Achieving Complete Cytogenetic Response.

Blood ◽

10.1182/blood.v104.11.4684.4684 ◽

2004 ◽

Vol 104 (11) ◽

pp. 4684-4684 ◽

Cited By ~ 1

Author(s):

Yoo-Jin Kim ◽

Dong-Wook Kim ◽

Seok Lee ◽

Ki-Seong Eom ◽

Chang-Ki Min ◽

...

Keyword(s):

Minimal Residual Disease ◽

Chronic Myelogenous Leukemia ◽

Residual Disease ◽

Transcript Level ◽

Allogeneic Transplantation ◽

Cytogenetic Response ◽

Myelogenous Leukemia ◽

Imatinib Treatment ◽

Rt Pcr ◽

Minimal Residual

Abstract Background Imatinib induces a high complete cytogenetic response (CCR) rate in chronic myelogenous leukemia (CML). None of the studies addressed the important question of how long imatinib treatment should be continued. To answer this question, we tried to assess the minimal residual disease after cessation of imatinib in patients achieving CCR. Methods A total of 23 patients were enrolled and their disease status at the start of imatinib was chronic phase in 7, accelerated phase in 3, blast crisis in 1, and post-transplant relapse in 12 patients. All the patients were in CCR when imatinib was discontinued and BCR-ABL transcript was undetectable in 9 of them. Minimal residual disease was monitored using nested RT-PCR, real-time quantitative RT-PCR, and conventional cytogenetics. Findings Duration of imatinb treatment and CCR before cessation of imatnib was a median of 13 months (range, 6–25 months) and 10 months (range, 1–22 months), respectively. After cessation of imatinib treatment, cytogenetic relapse was observed in 12 (53%) of 23 patients and hematological relapse was followed in 8 (67%) of them. Extramedullary relapse was documented in 1 patient. Prior allogenetic transplantation, molecular remission at the time of cessation, and time to CCR were potential variables affecting probability of cytogenetic relapse. Normalized BCR-ABL transcript level progressively increased after cessation of imatinib in all but 3 patients who had been treated with allogeneic transplantation. Restart of imatinib induced down-regulation of normalized BCR-ABL transcript level in 5 patients with available data. Interpretation Imatnib should be maintained in the most of patients who achieve a short duration of CCR as in the cases with interferon treatment. However, this study suggests that it seems possible to stop imatinib treatment in the minority of CML patients who was treated with allogeneic transplantation.

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Minimal residual disease is more common in patients who have mixed T- cell chimerism after bone marrow transplantation for chronic myelogenous leukemia

Blood ◽

10.1182/blood.v83.11.3409.3409 ◽

1994 ◽

Vol 83 (11) ◽

pp. 3409-3416 ◽

Cited By ~ 133

Author(s):

S Mackinnon ◽

L Barnett ◽

G Heller ◽

RJ O'Reilly

Keyword(s):

Bone Marrow ◽

T Cells ◽

Bone Marrow Transplantation ◽

T Cell ◽

Minimal Residual Disease ◽

Chronic Myelogenous Leukemia ◽

Marrow Transplantation ◽

Residual Disease ◽

Myelogenous Leukemia ◽

Minimal Residual

Abstract Determining both lymphoid chimerism and the presence of minimal residual disease after allogeneic bone marrow transplantation (BMT) for chronic myelogenous leukemia (CML) could be helpful to the understanding of the biology of leukemic relapse in this disease. We prospectively investigated 32 patients with CML post-BMT by assessing T- cell chimerism and minimal residual disease using sensitive polymerase chain reaction (PCR) methodologies. Patients were studied between 1 and 24 months post-BMT. Thirty patients received a T-cell-depleted marrow grafts and 2 received unmanipulated marrow. All but 1 patient were conditioned with total body irradiation (TBI)+thiotepa+cyclophosphamide (Cy). The other patient received TBI+Cy as conditioning. The T cells were exclusively of donor origin in 12 of 16 patients who were tested at 1 month post-BMT, but were mixed chimeric in 11 of these patients by e or = 3 months. Once mixed T-cell chimerism was documented, no patient returned to having all donor T-cells. At a median follow-up of 12 months, minimal residual disease was present in 18 of 22 patients with mixed T-cell chimerism and in 3 of 10 patients with full donor chimerism. The actuarial molecular relapse rate at 24 months for the two groups is 91% and 33%, respectively (P < .02). The finding of BCR- ABL mRNA within the first 6 months of transplant or on two consecutive assays was highly predictive of subsequent cytogenetic or hematologic relapse (P = .032 and P < .02, respectively). Ten patients, 9 with mixed T-cell chimerism, have relapsed (4 clinical, 6 cytogenetic) at a median of 12 months post-BMT. These data suggest that mixed T-cell chimerism may be a marker for abrogation of graft-versus-leukemia activity that is thought to be pivotal in eradicating minimal residual disease after BMT for CML.

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Standardization of Preanalytical Factors for Minimal Residual Disease Analysis in Chronic Myelogenous Leukemia

Acta Haematologica ◽

10.1159/000077557 ◽

2004 ◽

Vol 112 (1-2) ◽

pp. 30-33 ◽

Cited By ~ 20

Author(s):

Martin C. Müller ◽

Tanja Hördt ◽

Peter Paschka ◽

Kirsten Merx ◽

Paul La Rosée ◽

...

Keyword(s):

Minimal Residual Disease ◽

Chronic Myelogenous Leukemia ◽

Residual Disease ◽

Myelogenous Leukemia ◽

Disease Analysis ◽

Minimal Residual

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Molecular heterogeneity in complete cytogenetic responders after interferon-α therapy for chronic myelogenous leukemia: low levels of minimal residual disease are associated with continuing remission

Blood ◽

10.1182/blood.v95.1.62.001k41_62_66 ◽

2000 ◽

Vol 95 (1) ◽

pp. 62-66 ◽

Cited By ~ 2

Author(s):

Andreas Hochhaus ◽

Andreas Reiter ◽

Susanne Saußele, Anja Reichert ◽

Michael Emig ◽

Jaspal Kaeda ◽

...

Keyword(s):

Minimal Residual Disease ◽

Chronic Myelogenous Leukemia ◽

Residual Disease ◽

Philadelphia Chromosome ◽

Myelogenous Leukemia ◽

Maximal Response ◽

Molecular Evidence ◽

Molecular Heterogeneity ◽

Low Levels ◽

Minimal Residual

A substantial minority of patients with chronic myelogenous leukemia (CML) achieve a complete response (CR) to treatment with interferon- (IFN), defined as the disappearance of Philadelphia chromosome-positive metaphases. Currently it is unclear how long IFN treatment should be continued for such patients. We used a competitive reverse transcriptase-polymerase chain reaction (RT-PCR) to quantify levels of BCR-ABL transcripts in 297 peripheral blood specimens collected from 54 patients who had achieved CR with IFN. The median duration of observation was 1.9 years (range, 0.3-11.0 years). Total ABL transcripts were quantified as internal control and results were expressed as the ratio BCR-ABL/ABL. All 54 patients had molecular evidence of residual disease, although 3 patients were intermittently PCR negative. The median BCR-ABL/ABL ratio at the time of maximal response for each patient was 0.045% (range, 0%-3.6%). During the period of observation 14 patients relapsed, 11 cytogenetically to chronic phase disease and 3 directly to blastic phase. The median ratio of BCR-ABL/ABL at maximal response was significantly higher in patients who relapsed than in those who remained in CR (0.49% versus 0.021%,P < 0.0001). Our findings show that the level of residual disease falls with time in complete responders to IFN, but molecular evidence of disease is rarely if ever eliminated. The actual level of minimal residual disease correlates with the probability of relapse. We suggest that for patients who reach CR, IFN should be continued at least until relatively low levels of residual leukemia are achieved. (Blood. 2000;95:62-66)

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