Skip to main content

Advertisement

SpringerLink
Log in

Assessing minimal residual disease in chronic lymphocytic leukemia

  • Published:
Current Hematologic Malignancy Reports Aims and scope Submit manuscript

Abstract

New treatment approaches have substantially improved response rates in chronic lymphocytic leukemia. Accurate assessment of effective combination chemoimmunotherapy requires more sensitive measures of response, and a variety of techniques to measure minimal residual disease (MRD) have been developed. Because many studies demonstrate that MRD eradication is associated with prolonged treatment-free survival, detection of MRD is becoming a standard component of clinical trials. Quantitative approaches using polymerase chain reaction or multiparameter flow cytometry are preferable because they allow comparison of efficacy between different studies. In most clinical settings, the levels of chronic lymphocytic leukemia always increase from the first detection of MRD; the exception is allogeneic transplantation, in which there may be stable MRD levels or delayed MRD eradication. MRD analysis in the peripheral blood also may be used during therapy to predict eventual response and potentially to guide therapy to achieve the optimal outcome.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

  1. Rai KR, Peterson BL, Appelbaum FR, et al.: Fludarabine compared with chlorambucil as primary therapy for chronic lymphocytic leukemia. N Engl J Med 2000, 343:1750–1757.

    Article  PubMed  CAS  Google Scholar 

  2. Keating MJ, O’Brien S, Albitar M, et al.: Early results of a chemoimmunotherapy regimen of fludarabine, cyclophosphamide, and rituximab as initial therapy for chronic lymphocytic leukemia. J Clin Oncol 2005, 23:4079–4088.

    Article  PubMed  CAS  Google Scholar 

  3. Wierda W, O’Brien S, Wen S, et al.: Chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab for relapsed and refractory chronic lymphocytic leukemia. J Clin Oncol 2005, 23:4070–4078.

    Article  PubMed  CAS  Google Scholar 

  4. Robertson LE, Huh YO, Butler JJ, et al.: Response assessment in chronic lymphocytic leukemia after fludarabine plus prednisone: clinical, pathologic, immunophenotypic, and molecular analysis. Blood 1992, 80:29–36.

    PubMed  CAS  Google Scholar 

  5. Bosch F, Ferrer A, Lopez-Guillermo A, et al.: Fludarabine, cyclophosphamide and mitoxantrone in the treatment of resistant or relapsed chronic lymphocytic leukaemia. Br J Haematol 2002, 119:976–984.

    Article  PubMed  CAS  Google Scholar 

  6. Moreton P, Kennedy B, Lucas G, et al.: Eradication of minimal residual disease in B-cell chronic lymphocytic leukemia after alemtuzumab therapy is associated with prolonged survival. J Clin Oncol 2005, 23:2971–2979.

    Article  PubMed  CAS  Google Scholar 

  7. Cheson BD, Bennett JM, Grever M, et al.: National Cancer Institute-sponsored Working Group guidelines for chronic lymphocytic leukemia: revised guidelines for diagnosis and treatment. Blood 1996, 87:4990–4997.

    PubMed  CAS  Google Scholar 

  8. Robak T, Blonski JZ, Kasznicki M, et al.: Cladribine combined with cyclophosphamide is highly effective in the treatment of chronic lymphocytic leukemia. Hematol J 2002, 3:244–250.

    Article  PubMed  CAS  Google Scholar 

  9. Montillo M, Tedeschi A, Miqueleiz S, et al.: Alemtuzumab as consolidation after a response to fludarabine is effective in purging residual disease in patients with chronic lymphocytic leukemia. J Clin Oncol 2006, 24:2337–2342.

    Article  PubMed  CAS  Google Scholar 

  10. Del Poeta G, Del Principe MI, Consalvo MA, et al.: The addition of rituximab to fludarabine improves clinical outcome in untreated patients with ZAP-70-negative chronic lymphocytic leukemia. Cancer 2005, 104:2743–2752.

    Article  PubMed  Google Scholar 

  11. Wendtner CM, Ritgen M, Schweighofer CD, et al.: Consolidation with alemtuzumab in patients with chronic lymphocytic leukemia (CLL) in first remission—experience on safety and efficacy within a randomized multicenter phase III trial of the German CLL Study Group (GCLLSG). Leukemia 2004, 18:1093–1101.

    Article  PubMed  CAS  Google Scholar 

  12. O’Brien SM, Kantarjian HM, Thomas DA, et al.: Alemtuzumab as treatment for residual disease after chemotherapy in patients with chronic lymphocytic leukemia. Cancer 2003, 98:2657–2663.

    Article  PubMed  CAS  Google Scholar 

  13. Elter T, Borchmann P, Schulz H, et al.: Fludarabine in combination with alemtuzumab is effective and feasible in patients with relapsed or refractory B-cell chronic lymphocytic leukemia: results of a phase II trial. J Clin Oncol 2005, 23:7024–7031.

    Article  PubMed  CAS  Google Scholar 

  14. Milligan DW, Fernandes S, Dasgupta R, et al.: Results of the MRC pilot study show autografting for younger patients with chronic lymphocytic leukemia is safe and achieves a high percentage of molecular responses. Blood 2005, 105:397–404.

    Article  PubMed  CAS  Google Scholar 

  15. Moreno C, Villamor N, Colomer D, et al.: Clinical significance of minimal residual disease, as assessed by different techniques, after stem cell transplantation for chronic lymphocytic leukemia. Blood 2006, 107:4563–4569.

    Article  PubMed  CAS  Google Scholar 

  16. Moreno C, Villamor N, Colomer D, et al.: Allogeneic stemcell transplantation may overcome the adverse prognosis of unmutated VH gene in patients with chronic lymphocytic leukemia. J Clin Oncol 2005, 23:3433–3438.

    Article  PubMed  Google Scholar 

  17. Ritgen M, Stilgenbauer S, von Neuhoff N, et al.: Graft-versus-leukemia activity may overcome therapeutic resistance of chronic lymphocytic leukemia with unmutated immunoglobulin variable heavy-chain gene status: implications of minimal residual disease measurement with quantitative PCR. Blood 2004, 104:2600–2602.

    Article  PubMed  CAS  Google Scholar 

  18. Sorror ML, Maris MB, Sandmaier BM, et al.: Hematopoietic cell transplantation after nonmyeloablative conditioning for advanced chronic lymphocytic leukemia. J Clin Oncol 2005, 23:3819–3829.

    Article  PubMed  Google Scholar 

  19. Caballero D, Garcia-Marco JA, Martino R, et al.: Allogeneic transplant with reduced intensity conditioning regimens may overcome the poor prognosis of B-cell chronic lymphocytic leukemia with unmutated immunoglobulin variable heavychain gene and chromosomal abnormalities (11q-and 17p-). Clin Cancer Res 2005, 11:7757–7763.

    Article  PubMed  CAS  Google Scholar 

  20. Cabezudo E, Matutes E, Ramrattan M, et al.: Analysis of residual disease in chronic lymphocytic leukemia by flow cytometry. Leukemia 1997, 11:1909–1914.

    Article  PubMed  CAS  Google Scholar 

  21. Bomberger C, Singh-Jairam M, Rodey G, et al.: Lymphoid reconstitution after autologous PBSC transplantation with FACS-sorted CD34+ hematopoietic progenitors. Blood 1998, 91:2588–2600.

    PubMed  CAS  Google Scholar 

  22. Vuillier F, Claisse JF, Vandenvelde C, et al.: Evaluation of residual disease in B-cell chronic lymphocytic leukemia patients in clinical and bone-marrow remission using CD5-CD19 markers and PCR study of gene rearrangements. Leuk Lymphoma 1992, 7:195–204.

    Article  PubMed  CAS  Google Scholar 

  23. Bottcher S, Ritgen M, Pott C, et al.: Comparative analysis of minimal residual disease detection using four-color flow cytometry, consensus IgH-PCR, and quantitative IgH PCR in CLL after allogeneic and autologous stem cell transplantation. Leukemia 2004, 18:1637–1645.

    Article  PubMed  CAS  Google Scholar 

  24. Rawstron AC, Kennedy B, Evans PA, et al.: Quantitation of minimal disease levels in chronic lymphocytic leukemia using a sensitive flow cytometric assay improves the prediction of outcome and can be used to optimize therapy. Blood 2001, 98:29–35.

    Article  PubMed  CAS  Google Scholar 

  25. Davies FE, Forsyth PD, Rawstron AC, et al.: The impact of attaining a minimal disease state after high-dose melphalan and autologous transplantation for multiple myeloma. Br J Haematol 2001, 112:814–819.

    Article  PubMed  CAS  Google Scholar 

  26. Garcia VJ, Delgado I, Benito L, et al.: CD79b expression in B cell chronic lymphocytic leukemia: its implication for minimal residual disease detection. Leukemia 1999, 13:1501–1505.

    Article  Google Scholar 

  27. Esteve J, Villamor N, Colomer D, et al.: Stem cell transplantation for chronic lymphocytic leukemia: different outcome after autologous and allogeneic transplantation and correlation with minimal residual disease status. Leukemia 2001, 15:445–451.

    Article  PubMed  CAS  Google Scholar 

  28. Maloum K, Sutton L, Baudet S, et al.: Novel flow-cytometric analysis based on BCD5+ subpopulations for the evaluation of minimal residual disease in chronic lymphocytic leukaemia. Br J Haematol 2002, 119:970–975.

    Article  PubMed  Google Scholar 

  29. Rawstron AC, Villamor N, Ritgen M, et al.: International standardized approach for flow cytometric residual disease monitoring in chronic lymphocytic leukaemia. Leukemia 2007, 21:956–964.

    PubMed  CAS  Google Scholar 

  30. van der Velden VH, Panzer-Grümayer ER, Cazzaniga G, et al.: Optimization of PCR-based minimal residual disease diagnostics for childhood acute lymphoblastic leukemia in a multi-center setting. Leukemia 2007, 21:706–713.

    PubMed  Google Scholar 

  31. van der Velden VH, Cazzaniga G, Schrauder A, et al.: Analysis of minimal residual disease by Ig/TCR gene rearrangements: guidelines for interpretation of real-time quantitative PCR data. Leukemia 2007, 21:604–611.

    PubMed  Google Scholar 

  32. Gribben JG, Zahrieh D, Stephans K, et al.: Autologous and allogeneic stem cell transplantations for poor-risk chronic lymphocytic leukemia. Blood 2005, 106:4389–4396.

    Article  PubMed  CAS  Google Scholar 

  33. Rawstron AC, Kennedy B, Moreton P, et al.: Early prediction of outcome and response to alemtuzumab therapy in chronic lymphocytic leukemia. Blood 2004, 103:2027–2031.

    Article  PubMed  CAS  Google Scholar 

  34. de Tute RM, Jack AS, Child JA, et al.: A single-tube six-colour flow cytometry screening assay for the detection of minimal residual disease in myeloma. Leukemia 2007, 21:2046–2049.

    Article  PubMed  Google Scholar 

  35. Pekova S, Markova J, Pajer P, et al.: Touch-down reverse transcriptase-PCR detection of IgV(H) rearrangement and Sybr-Green-based real-time RT-PCR quantitation of minimal residual disease in patients with chronic lymphocytic leukemia. Mol Diagn 2005, 9:23–34.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Haematological Malignancy Diagnostic Service, Leeds Teaching Hospitals, Leeds, LS1 3EX, UK

    Andy C. Rawstron

Authors
  1. Andy C. Rawstron
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Peter Hillmen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Andy C. Rawstron.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rawstron, A.C., Hillmen, P. Assessing minimal residual disease in chronic lymphocytic leukemia. Curr Hematol Malig Rep 3, 47–53 (2008). https://doi.org/10.1007/s11899-008-0008-8

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11899-008-0008-8

Keywords

Search

Navigation