Abstract
Intensified treatments aimed at maximal tumor reduction are an important therapeutic option for patients affected by B-cell malignancies. The possibility of obtaining a relevant number of clinical complete remissions after these treatments prompted the application of molecular techniques for the detection of extremely low numbers of residual malignant cells. These cells can be present either in the stem cell graft or, during the follow-up, in the bone marrow of patients attaining a clinical complete remission. The most sensitive and widely used techniques for minimal residual disease (MRD) assessment are those based on the PCR method. These methods allow the detection of autologous graft contamination and the identification of patients at high risk of disease recurrence by means of post-transplant MRD monitoring. In this setting, quantitative PCR assays can evaluate the kinetics of tumor clone growth in complete remission (CR) patients showing a persistence of PCR detectable tumor cells with standard qualitative methods.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Corradini, P., Ladetto, M., Zallio, F. et al. (2004) Long-term follow-up of indolent lymphoma patients treated with high-dose sequential chemotherapy and autografting: evidence that durable molecular and clinical remission frequently can be attained only in follicular subtypes. J. Clin. Oncol. 22, 1460–1468.
Hunault-Berger, M., Ifrah, N., Solal-Celigny, P., Groupe Ouest-Est des Leucemies Aiguee et des Maladies du Sang (2002) Intensive therapies in follicular non-Hodgkin lymphomas. Blood 100, 1141–1152.
Gribben, J. G., Freedman, A., Woo, S. D., et al. (1991) All advanced stage non-Hodgkins lymphomas with a polymerase chain reaction amplifiable breakpoint of bcl-2 have residual cells containing the bcl-2 rearrangement at evaluation and after treatment. Blood 78, 3275–3280.
Gribben, J. G., Freedman, A. S., Neuberg, D., et al. (1991) Immunologie purging of marrow assessed by PCR before autologous bone marrow transplantation for B-cell lymphoma. N. Eng. J. Med. 325, 1525–1533.
Gribben, J. G., Neuberg, D., Freedman, A. S., et al. (1993) Detection by polymerase chain reaction of residual cells with the bcl-2 traslocation is associated with increased risk for relapse after autologous bone marrow transplantation for B-cell lymphoma. Blood 81, 3449–3457.
Freedman, A. S., Neuberg, D., Mauch, P., et al. (1999) Long-term follow up of autologous bone marrow transplantation in patients with relapsed follicular lymphoma. Blood 94, 3325–3333.
Moos, M., Schulz, R., Martin, S., et al (1998) The remission status before and the PCR status after high-dose therapy with peripheral blood stem cell support are prognostic factors for relapse-free survival in patients with follicular non-Hodgkin’s lymphoma. Leukemia 12, 1971–1976.
Gianni, A. M., Magni, M., Martelli, M., et al. (2003) Long-term remission in mantle cell lymphoma following high-dose sequential chemotherapy and in vivo rituximab-purged stem cell autografting (R-HDS regimen). Blood 102, 749–755.
van Besien, K., Keralavarma, B., Devine, S., and Stock, W. (2001) Allogeneic and autologous transplantation for chronic lymphocytic leukemia. Leukemia 15, 1317–1325.
Dreger, P. and Montserrat, E. (2002) Autologous and allogeneic stem cell transplantation for chronic lymphocytic leukemia. Leukemia 16, 985–992.
Milligan, D. W., Fernandes, S., Dasgupta, R., et al (2005) 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 105, 397–404.
Pavletic, Z. S., Bierman, P. J., Vose, J. M., et al. (1998) High incidence of relapse after autologous stem-cell transplantation for B-cell chronic lymphocytic leukemia or small lymphocytic lymphoma. Ann. Oncol. 9, 1023–1026.
Esteve, J., Villamor, N., Colomer, D., et al. (2001) Stem cell transplantation for chronic lymphocytic leukemia: different outcome after autologous and allogeneic transplantation and correlation with minimal residual disease status. Leukemia 15, 445–451.
Provan, D., Bartlett-Pandite, L., Zwicky, C., et al. (1996) Eradication of polymerase chain reaction-detectable chronic lymphocytic leukemia cells is associated with improved outcome after bone marrow transplantation. Blood 88, 2228–2235.
Szczepanski, T., Willemse, M. J., Brinkhof, B., et al. (2002) Comparative analysis of Ig and TCR gene rearrangements at diagnosis and at relapse of childhood precursor-B-ALL provides improved strategies for selection of stable PCR targets for monitoring of minimal residual disease. Blood 99, 2315–2323.
van Dongen, J. J., Seriu, T., Panzer-Grumayer, E. R., et al. (1998) Prognostic value of minimal residual disease in acute lymphoblastic leukaemia in childhood. Lancet 352, 1731–1738.
Cave, H., van der Werff ten Bosch, J., Suciu, S., et al. (1998) Clinical significance of minimal residual disease in childhood acute lymphoblastic leukemia. European Organization for Research and Treatment of Cancer—Childhood Leukemia Cooperative Group. N. Eng. J. Med. 339, 591–598.
Mortuza, F. Y., Papaioannou, M., Moreira, I. M., et al. (2002) Minimal residual disease tests provide an independent predictor of clinical outcome in adult acute lymphoblastic leukemia. J. Clin. Oncol. 20, 1094–1104.
Holland, P. M., Abramson, R. D., Watson, R., and Gelfand, D. H. (1991) Detection of specific polymerase chain reaction product by utilizing the 5′→3′ exonuclease activity of Thermus aquaticus DNA polymerase. Proc Natl Acad Sci USA 88, 7276–7280.
Ladetto, M., Sametti, S., Donovan, J. W., et al. (2001) A validated real-time quantitative PCR approach shows a correlation berween tumor burden and successful ex vivo purging in follicular lymphoma patients. J. Exp. Hematol. 29, 183–193.
Tsujimoto, Y., Finger, L. R., Yunis, J., et al. (1984) Cloning of the chromosome breakpoint of neoplastic B cells with the t(14;18) chromosome translocation. Science 226, 1097–1099.
Cleary, M. L. and Sklar, J. (1985) Nucleotide sequence of a t(14;18) chromosomal breakpoint in follicular lymphoma and demonstration of a breakpoint-cluster region near a transcriptionally active locus on chromosome 18. Proc Natl Acad Sci USA 82, 7439–7443.
Cleary, M. L., Galili, N., and Sklar, J. (1986) Detection of a sond t(14;18) breakpoint cluster region in human follicular lymphomas. J. Exp. Med. 164, 315–320.
Tsujimoto, Y., Yunis, J., Onorato-Showe, L., et al. (1984) Molecular cloning of the chromosomal breakpoint of B-cell lymphomas and leukemias with the t(11; 14) chromosome traslocation. Science 224, 1403–1406.
Early, P., Huang, H., Davis, M., et al. (1980) An immunoglobulin heavy chain variable region gene is generated from three segments of DNA. Cell 19, 281.
Tonegawa, S. (1983) Somatic generation of antibody diversity. Nature 302, 575–581.
Deane, M., McCarthy, K. P., Wiedemann, L. M., and Norton, J. D. (1991) An improved method for detection of B-lymphoid clonality by polymerase chain reaction. Leukemia 5, 726–730.
Voena, C., Ladetto, M., Astolfi, M., et al. (1997) A novel nested-PCR strategy for detection of rearranged immunoglobulin heavy chain genes in B-cell tumours. Leukemia 11, 1793–1798.
Corradini, P., Ladetto, M., Voena, C., et al. (1993) Mutational activation of N-and K-ras oncogenes in plasma cell dyscrasias. Blood 81, 2708–2713.
Van der Velden, V. H. J., Hochhaus, A., Cazzaniga, G., Szczepanski, T., Gabert, J., and van Dongen, J. J. M. (2003) Detection of minimal residual disease in hematologic malignancies by real-time quantitative PCR: principles, approaches, and laboratory aspects. Leukemia 17, 1013–1034
Luthra, R., McBride, J. A., Cabanillas, F., and Sards, A. (1998) Novel 5′ exonuclease-based real-time PCR assay for the detection of t(14; 18)(q32;q21)in patients with follicular lymphoma. Am. J. Pathol. 153, 63–68.
Donovan, J. W., Ladetto, M., Zou, G., et al. (2000) Immunoglobulin heavy-chain consensus probes for real-time PCR quantification of residual disease in acute lymphoblastic leukemia. Blood 95, 2651–2658.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2007 Humana Press Inc.
About this protocol
Cite this protocol
Corradini, P., Carrabba, M.G., Farina, L. (2007). Molecular Methods Used for The Detection of Autologous Graft Contamination in Lymphoid Disorders. In: Beksac, M. (eds) Bone Marrow and Stem Cell Transplantation. Methods in Molecular Medicine, vol 134. Humana Press. https://doi.org/10.1007/978-1-59745-223-6_13
Download citation
DOI: https://doi.org/10.1007/978-1-59745-223-6_13
Publisher Name: Humana Press
Print ISBN: 978-1-58829-595-8
Online ISBN: 978-1-59745-223-6
eBook Packages: Springer Protocols