Levels of minimal residual disease detected by quantitative molecular monitoring herald relapse in patients with multiple myeloma

Roland Fenk, Muharrem Ak, Guido Kobbe, Ulrich G. Steidl, Carolin Arnold, Mark Korthals, Ali Hünerlitürkoglu, Ulrich Peter Rohr, Slawomir Kliszewski, Alf Bernhardt, Rainer Haas, Ralf Kronenwett

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Background and Objectives. Detection of minimal residual disease (MRD) has helped to improve the treatment of patients with leukemia. At present MRD testing in patients with multiple myeloma (MM) is not applied as a standard diagnostic or prognostic method. Design and Methods. Immunoglobulin heavy chain (IgH) polymerase chain reaction (PCR) using patient-specific TaqMan probes together with LightCycler technology was performed to quantify minimal residual disease in MM. Relative levels of clonotypic cells were assessed as IgH/2β-actin ratios with a sensitivity of 10-4 to 10 -5. Results. Following stem cell transplantation, a significant reduction of clonotypic cells was observed in bone marrow (BM) and peripheral blood (PB) samples of 11 patients, comparing pre-treatment values with those of best response (median: 13% to 0.09% and 0.03% to 0%, respectively). In 5 patients with ongoing clinical remission IgH/2β-actin ratios remained stable at a low level, while in 6 patients an increase to 2% in BM and 0.4% in PB was associated with progression of the disease. In 4 of these 6 patients the increase of clonotypic cells in PB was detectable a median of 3 months (range: 0.5-6) before relapse. Furthermore, time-to-progression of patients with pre-transplantation IgH/2β-actin ratios > 0.03% in BM was significantly shorter than that of patients with lower MRD levels. Interpretations and Conclusions. MRD in patients with MM can be quantified reliably using TaqMan chemistry adapted to the LightCycler system. Residual tumor cell levels before transplantation as well as results of sequential molecular monitoring are predictive of relapse.

Original languageEnglish (US)
Pages (from-to)557-566
Number of pages10
JournalHaematologica
Volume89
Issue number5
StatePublished - May 2004
Externally publishedYes

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Residual Neoplasm
Multiple Myeloma
Recurrence
Immunoglobulin Heavy Chains
Actins
Bone Marrow
Transplantation
Stem Cell Transplantation
Disease Progression
Leukemia
Technology
Polymerase Chain Reaction

Keywords

  • Immunoglobulin H
  • Minimal residual disease
  • Molecular monitoring
  • Multiple myeloma
  • Real-time quantitative PCR

ASJC Scopus subject areas

  • Hematology

Cite this

Levels of minimal residual disease detected by quantitative molecular monitoring herald relapse in patients with multiple myeloma. / Fenk, Roland; Ak, Muharrem; Kobbe, Guido; Steidl, Ulrich G.; Arnold, Carolin; Korthals, Mark; Hünerlitürkoglu, Ali; Rohr, Ulrich Peter; Kliszewski, Slawomir; Bernhardt, Alf; Haas, Rainer; Kronenwett, Ralf.

In: Haematologica, Vol. 89, No. 5, 05.2004, p. 557-566.

Research output: Contribution to journalArticle

Fenk, R, Ak, M, Kobbe, G, Steidl, UG, Arnold, C, Korthals, M, Hünerlitürkoglu, A, Rohr, UP, Kliszewski, S, Bernhardt, A, Haas, R & Kronenwett, R 2004, 'Levels of minimal residual disease detected by quantitative molecular monitoring herald relapse in patients with multiple myeloma', Haematologica, vol. 89, no. 5, pp. 557-566.
Fenk, Roland ; Ak, Muharrem ; Kobbe, Guido ; Steidl, Ulrich G. ; Arnold, Carolin ; Korthals, Mark ; Hünerlitürkoglu, Ali ; Rohr, Ulrich Peter ; Kliszewski, Slawomir ; Bernhardt, Alf ; Haas, Rainer ; Kronenwett, Ralf. / Levels of minimal residual disease detected by quantitative molecular monitoring herald relapse in patients with multiple myeloma. In: Haematologica. 2004 ; Vol. 89, No. 5. pp. 557-566.
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abstract = "Background and Objectives. Detection of minimal residual disease (MRD) has helped to improve the treatment of patients with leukemia. At present MRD testing in patients with multiple myeloma (MM) is not applied as a standard diagnostic or prognostic method. Design and Methods. Immunoglobulin heavy chain (IgH) polymerase chain reaction (PCR) using patient-specific TaqMan probes together with LightCycler technology was performed to quantify minimal residual disease in MM. Relative levels of clonotypic cells were assessed as IgH/2β-actin ratios with a sensitivity of 10-4 to 10 -5. Results. Following stem cell transplantation, a significant reduction of clonotypic cells was observed in bone marrow (BM) and peripheral blood (PB) samples of 11 patients, comparing pre-treatment values with those of best response (median: 13{\%} to 0.09{\%} and 0.03{\%} to 0{\%}, respectively). In 5 patients with ongoing clinical remission IgH/2β-actin ratios remained stable at a low level, while in 6 patients an increase to 2{\%} in BM and 0.4{\%} in PB was associated with progression of the disease. In 4 of these 6 patients the increase of clonotypic cells in PB was detectable a median of 3 months (range: 0.5-6) before relapse. Furthermore, time-to-progression of patients with pre-transplantation IgH/2β-actin ratios > 0.03{\%} in BM was significantly shorter than that of patients with lower MRD levels. Interpretations and Conclusions. MRD in patients with MM can be quantified reliably using TaqMan chemistry adapted to the LightCycler system. Residual tumor cell levels before transplantation as well as results of sequential molecular monitoring are predictive of relapse.",
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AU - Fenk, Roland

AU - Ak, Muharrem

AU - Kobbe, Guido

AU - Steidl, Ulrich G.

AU - Arnold, Carolin

AU - Korthals, Mark

AU - Hünerlitürkoglu, Ali

AU - Rohr, Ulrich Peter

AU - Kliszewski, Slawomir

AU - Bernhardt, Alf

AU - Haas, Rainer

AU - Kronenwett, Ralf

PY - 2004/5

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N2 - Background and Objectives. Detection of minimal residual disease (MRD) has helped to improve the treatment of patients with leukemia. At present MRD testing in patients with multiple myeloma (MM) is not applied as a standard diagnostic or prognostic method. Design and Methods. Immunoglobulin heavy chain (IgH) polymerase chain reaction (PCR) using patient-specific TaqMan probes together with LightCycler technology was performed to quantify minimal residual disease in MM. Relative levels of clonotypic cells were assessed as IgH/2β-actin ratios with a sensitivity of 10-4 to 10 -5. Results. Following stem cell transplantation, a significant reduction of clonotypic cells was observed in bone marrow (BM) and peripheral blood (PB) samples of 11 patients, comparing pre-treatment values with those of best response (median: 13% to 0.09% and 0.03% to 0%, respectively). In 5 patients with ongoing clinical remission IgH/2β-actin ratios remained stable at a low level, while in 6 patients an increase to 2% in BM and 0.4% in PB was associated with progression of the disease. In 4 of these 6 patients the increase of clonotypic cells in PB was detectable a median of 3 months (range: 0.5-6) before relapse. Furthermore, time-to-progression of patients with pre-transplantation IgH/2β-actin ratios > 0.03% in BM was significantly shorter than that of patients with lower MRD levels. Interpretations and Conclusions. MRD in patients with MM can be quantified reliably using TaqMan chemistry adapted to the LightCycler system. Residual tumor cell levels before transplantation as well as results of sequential molecular monitoring are predictive of relapse.

AB - Background and Objectives. Detection of minimal residual disease (MRD) has helped to improve the treatment of patients with leukemia. At present MRD testing in patients with multiple myeloma (MM) is not applied as a standard diagnostic or prognostic method. Design and Methods. Immunoglobulin heavy chain (IgH) polymerase chain reaction (PCR) using patient-specific TaqMan probes together with LightCycler technology was performed to quantify minimal residual disease in MM. Relative levels of clonotypic cells were assessed as IgH/2β-actin ratios with a sensitivity of 10-4 to 10 -5. Results. Following stem cell transplantation, a significant reduction of clonotypic cells was observed in bone marrow (BM) and peripheral blood (PB) samples of 11 patients, comparing pre-treatment values with those of best response (median: 13% to 0.09% and 0.03% to 0%, respectively). In 5 patients with ongoing clinical remission IgH/2β-actin ratios remained stable at a low level, while in 6 patients an increase to 2% in BM and 0.4% in PB was associated with progression of the disease. In 4 of these 6 patients the increase of clonotypic cells in PB was detectable a median of 3 months (range: 0.5-6) before relapse. Furthermore, time-to-progression of patients with pre-transplantation IgH/2β-actin ratios > 0.03% in BM was significantly shorter than that of patients with lower MRD levels. Interpretations and Conclusions. MRD in patients with MM can be quantified reliably using TaqMan chemistry adapted to the LightCycler system. Residual tumor cell levels before transplantation as well as results of sequential molecular monitoring are predictive of relapse.

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KW - Minimal residual disease

KW - Molecular monitoring

KW - Multiple myeloma

KW - Real-time quantitative PCR

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