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Published in: Medical Oncology 1/2009

01-03-2009 | Original Paper

Presence of t(14;18) positive cells in blood and bone marrow does not predict outcome in follicular lymphoma

Authors: E. Paszkiewicz-Kozik, J. Kulik, A. Fabisiewicz, A. Tysarowski, E. Kraszewska, J. A. Siedlecki, J. Walewski

Published in: Medical Oncology | Issue 1/2009

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Abstract

Follicular Lymphoma International Prognostic Index—FLIPI is an established clinical predictor for outcome in follicular lymphoma. The role of molecular abnormalities in blood and bone marrow of follicular lymphoma patients including t(14;18) is less clear. Seventy-five patients from a single institution diagnosed with follicular lymphoma between1999 and 2005 were included into the study. Diagnosis was based on lymph node biopsy in 62 cases (83%). Thirty-nine patients (52%) had G1 histological grade and 47 (63%) had entirely follicular growth pattern, as well as 9 patients (12%) had systemic symptoms and 33 (44%) were assigned to a good risk according to FLIPI. Median age of patients was 53 years. During a median observation time of 3 years 63 patients (84%) required initiating anti-lymphoma treatment. Seventy-five samples of peripheral blood and 65 samples of bone marrow were collected at the diagnosis. Bcl2 rearrangements including major breakpoint region and minor breakpoint cluster region were investigated using nested polymerase chain reaction technique. The primary end points of the study were time to first line lymphoma treatment and progression-free survival. Cells carrying t(14;18) were found in 31 cases (41%) including 29 samples of peripheral blood and 26 samples of bone marrow. Detection of t(14;18) in blood and bone marrow at diagnosis had no influence on clinical outcome. Age, follicular growth pattern systemic symptoms, and FLIPI score above 1 were predictive for initiation of the first lymphoma therapy. Follicular growth pattern, initial nodal involvement, serum LDH level, and FLIPI score above 1 were predictive for longer progression-free survival.
Literature
1.
go back to reference Jaffe ES, Harris NL, Stein H, Vardiman JW. Pathology and genetics of tumors of hematopoietic and lymphoid tissues. In: Kleihues P, Sobin L, editors. World Health Organization classification of tumors. vol. 3. Lyon: IARC Press; 2001. Jaffe ES, Harris NL, Stein H, Vardiman JW. Pathology and genetics of tumors of hematopoietic and lymphoid tissues. In: Kleihues P, Sobin L, editors. World Health Organization classification of tumors. vol. 3. Lyon: IARC Press; 2001.
2.
go back to reference Armitage JO, Weisenburger DD. New approach to classifying non-Hodgkin’s lymphomas: clinical features of the major histologic subtypes. Non-Hodgkin’s Lymphoma Classification Project. J Clin Oncol. 1998;16(8):2780–95.PubMed Armitage JO, Weisenburger DD. New approach to classifying non-Hodgkin’s lymphomas: clinical features of the major histologic subtypes. Non-Hodgkin’s Lymphoma Classification Project. J Clin Oncol. 1998;16(8):2780–95.PubMed
3.
go back to reference Buchonnet G, et al. Characterization of Bcl2-JH rearrangement in follicular lymphoma: PCR detection of 3’ Bcl2 breakpoints and evidence of new cluster. Leukemia 2000;14:1563–9.PubMedCrossRef Buchonnet G, et al. Characterization of Bcl2-JH rearrangement in follicular lymphoma: PCR detection of 3’ Bcl2 breakpoints and evidence of new cluster. Leukemia 2000;14:1563–9.PubMedCrossRef
4.
go back to reference Jaeger U, et al. Molecular mechanism of the t(14,18)—a model for lymphoid-specific chromosomal translocations. Leuk Lymphoma. 1994;14:197–202.PubMedCrossRef Jaeger U, et al. Molecular mechanism of the t(14,18)—a model for lymphoid-specific chromosomal translocations. Leuk Lymphoma. 1994;14:197–202.PubMedCrossRef
5.
go back to reference Mrózek K, Bloomfield CD. Cytogenetics of Indolent Lymphomas. Semin Oncol. 1993;20(Suppl 5):47–57.PubMed Mrózek K, Bloomfield CD. Cytogenetics of Indolent Lymphomas. Semin Oncol. 1993;20(Suppl 5):47–57.PubMed
6.
go back to reference Aster J, Longtine J. Detection of Bcl2 rearrangements in follicular lymphoma. Am J Pathol. 2002;160:759–63.PubMed Aster J, Longtine J. Detection of Bcl2 rearrangements in follicular lymphoma. Am J Pathol. 2002;160:759–63.PubMed
8.
go back to reference A predictive model for aggressive non-Hodgkin’s lymphoma. The International Non-Hodgkin’s Lymphoma Prognostic Factors Project. N Engl J Med. 1993;329:987–94.CrossRef A predictive model for aggressive non-Hodgkin’s lymphoma. The International Non-Hodgkin’s Lymphoma Prognostic Factors Project. N Engl J Med. 1993;329:987–94.CrossRef
9.
10.
go back to reference Maniatis T, et al. Molecular cloning: a laboratory manual. CSH Laboratory Press; 1982. Maniatis T, et al. Molecular cloning: a laboratory manual. CSH Laboratory Press; 1982.
11.
go back to reference Gribben JG, et al. All advanced stage non-Hodgkin’s 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. 1991;78:3275–80.PubMed Gribben JG, et al. All advanced stage non-Hodgkin’s 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. 1991;78:3275–80.PubMed
12.
go back to reference Cheson B, et al. Report of an International Workshop to Standardize Response Criteria for Non-Hodgkin’s lymphomas. J Clin Oncol. 1999;17:1244–53.PubMed Cheson B, et al. Report of an International Workshop to Standardize Response Criteria for Non-Hodgkin’s lymphomas. J Clin Oncol. 1999;17:1244–53.PubMed
13.
go back to reference Muller AM, Ihorst G, Mertelsmann R, Engelhardt M. Epidemiology of non-Hodgkin’s lymphoma (NHL): trends, geographic distribution, and etiology. Ann Hematol. 2005;84:1–12.PubMedCrossRef Muller AM, Ihorst G, Mertelsmann R, Engelhardt M. Epidemiology of non-Hodgkin’s lymphoma (NHL): trends, geographic distribution, and etiology. Ann Hematol. 2005;84:1–12.PubMedCrossRef
14.
go back to reference Biagi JJ, Seymour JF. Insights into the molecular pathogenesis of follicular lymphoma arising from analysis from geographic variation. Blood. 2002;99:4265–75.PubMedCrossRef Biagi JJ, Seymour JF. Insights into the molecular pathogenesis of follicular lymphoma arising from analysis from geographic variation. Blood. 2002;99:4265–75.PubMedCrossRef
16.
go back to reference Galazka K, Szpor J, Maryniak R, et al. Incidence of lymphomas in Poland. The National Register Data for 2006. Pol J Pathol. 2007;58:199–206.PubMed Galazka K, Szpor J, Maryniak R, et al. Incidence of lymphomas in Poland. The National Register Data for 2006. Pol J Pathol. 2007;58:199–206.PubMed
17.
go back to reference Aster JC, Longtine JA. Detection of Bcl2 rearrangements in follicular lymphoma. Am J Pathol. 2002;160:759–63.PubMed Aster JC, Longtine JA. Detection of Bcl2 rearrangements in follicular lymphoma. Am J Pathol. 2002;160:759–63.PubMed
18.
go back to reference van Dongen JJM, et al. Design of standardization of PCR primers and protocols for detection of clonal immunoglobulin and T-cell receptor gene recombinations in suspect lymphoproliferations: report of BIOMED-2 concerted action BMH4-CT98-3936. Leukemia. 2003;17:2257–317.PubMedCrossRef van Dongen JJM, et al. Design of standardization of PCR primers and protocols for detection of clonal immunoglobulin and T-cell receptor gene recombinations in suspect lymphoproliferations: report of BIOMED-2 concerted action BMH4-CT98-3936. Leukemia. 2003;17:2257–317.PubMedCrossRef
19.
go back to reference Johnson PWM, et al. Variability of polymerase chain reaction detection of bcl-2-Igh translocation in an international multicentre study. Ann Oncol. 1999;10:1349–54.PubMedCrossRef Johnson PWM, et al. Variability of polymerase chain reaction detection of bcl-2-Igh translocation in an international multicentre study. Ann Oncol. 1999;10:1349–54.PubMedCrossRef
20.
go back to reference Bagg A, Braziel RM, Arber DA, Bijwaard KE, Chu AY. Immunoglobulin heavy chain gene analisis in lymphomas. A multi-center study demonstrating the heterogenity of performance of polymerase chain reaction assays. J Mol Diagn. 2002;4:81–9.PubMed Bagg A, Braziel RM, Arber DA, Bijwaard KE, Chu AY. Immunoglobulin heavy chain gene analisis in lymphomas. A multi-center study demonstrating the heterogenity of performance of polymerase chain reaction assays. J Mol Diagn. 2002;4:81–9.PubMed
21.
go back to reference Liu J, Johson RM, Traweek ST. Rearrangement of BCL-2 gene in follicular lymphoma. Detection by PCR in both fresh and fixed tissue samples. Diagn Mol Pathol. 1993;2:241–7.PubMed Liu J, Johson RM, Traweek ST. Rearrangement of BCL-2 gene in follicular lymphoma. Detection by PCR in both fresh and fixed tissue samples. Diagn Mol Pathol. 1993;2:241–7.PubMed
22.
go back to reference Albinger-Hegyi A, et al. High frequency of t(14;18)-translocation breakpoints outside of major breakpoint and minor cluster regions in follicular lymphomas. Improved polymerase chain reaction protocols for their detection. Am J Pathol. 2002;160:823–32.PubMed Albinger-Hegyi A, et al. High frequency of t(14;18)-translocation breakpoints outside of major breakpoint and minor cluster regions in follicular lymphomas. Improved polymerase chain reaction protocols for their detection. Am J Pathol. 2002;160:823–32.PubMed
23.
go back to reference James A, et al. Follicular lymphoma with novel t(14;18) breakpoint involving the immunoglobulin heavy chain switch mu region indicates an origin from germinal center B cells. Blood. 2002;15:716–8. James A, et al. Follicular lymphoma with novel t(14;18) breakpoint involving the immunoglobulin heavy chain switch mu region indicates an origin from germinal center B cells. Blood. 2002;15:716–8.
24.
go back to reference Lubinski J, et al. Environmental factors may regulate BCL2 associated lymphomagenesis: a very low incidence of BCL2-MBR translocation in Poland. Pol J Pathol. 1995;46:219–24.PubMed Lubinski J, et al. Environmental factors may regulate BCL2 associated lymphomagenesis: a very low incidence of BCL2-MBR translocation in Poland. Pol J Pathol. 1995;46:219–24.PubMed
25.
go back to reference Dölken G, Illerhaus G, Hirt C, Mertelsmann R. BCL-2/JH rearrangement in circulating B cells of healthy blood donors and patients with non-malignant diseases. J Clin Oncol. 1996;14:1333–44.PubMed Dölken G, Illerhaus G, Hirt C, Mertelsmann R. BCL-2/JH rearrangement in circulating B cells of healthy blood donors and patients with non-malignant diseases. J Clin Oncol. 1996;14:1333–44.PubMed
26.
go back to reference Summers K, et al. Frequency of the BCL-2/JH rearrangement in normal individuals: implication for the monitoring of disease in patients with follicular lymphoma. J Clin Oncol. 2001;19:420–4.PubMed Summers K, et al. Frequency of the BCL-2/JH rearrangement in normal individuals: implication for the monitoring of disease in patients with follicular lymphoma. J Clin Oncol. 2001;19:420–4.PubMed
27.
go back to reference McGregor D, et al. The implication of follicular lymphoma patients receiving allogeneic stem cell transplantation from donors carrying t(14;18)-positive cells. Bone Marrow Transplant. 2005;35:1049–54.PubMedCrossRef McGregor D, et al. The implication of follicular lymphoma patients receiving allogeneic stem cell transplantation from donors carrying t(14;18)-positive cells. Bone Marrow Transplant. 2005;35:1049–54.PubMedCrossRef
28.
go back to reference Sehn LH, Gascoyne RD, Connors JM, Klasa RJ, Horsman DE. Comparison of t(14;18) positive and t(14;18) negative follicular lymphoma (FL): clinical characteristics, outcomes and cytogenetics. Blood. 2000;96:574. Sehn LH, Gascoyne RD, Connors JM, Klasa RJ, Horsman DE. Comparison of t(14;18) positive and t(14;18) negative follicular lymphoma (FL): clinical characteristics, outcomes and cytogenetics. Blood. 2000;96:574.
29.
go back to reference Lopez-Guillermo A, et al. Correlation of BCL-2 rearrangement with clinical characteristics and outcome in indolent follicular lymphomas. Blood. 1999;91:2955–60. Lopez-Guillermo A, et al. Correlation of BCL-2 rearrangement with clinical characteristics and outcome in indolent follicular lymphomas. Blood. 1999;91:2955–60.
30.
go back to reference Iqubal S, et al. Reliable detection of clonal IgH/BCL2 MBR rearrangements in follicular lymphoma: methodology and clinical significance. Br J Haematol. 2004;124:325–8.CrossRef Iqubal S, et al. Reliable detection of clonal IgH/BCL2 MBR rearrangements in follicular lymphoma: methodology and clinical significance. Br J Haematol. 2004;124:325–8.CrossRef
31.
go back to reference Montoto S, et al. Incidence and clinical significance of BCL-2/IgH rearrangements in follicular lymphoma. Leuk Lymphoma. 2003:44:71–6.PubMedCrossRef Montoto S, et al. Incidence and clinical significance of BCL-2/IgH rearrangements in follicular lymphoma. Leuk Lymphoma. 2003:44:71–6.PubMedCrossRef
32.
go back to reference Gascoyne RD, et al. Prognostic significance of BCL 2 protein expression and BCL 2 gene rearrangements in diffuse aggressive non-Hodgkin’s lymphoma. Blood. 1997;90:244–51.PubMed Gascoyne RD, et al. Prognostic significance of BCL 2 protein expression and BCL 2 gene rearrangements in diffuse aggressive non-Hodgkin’s lymphoma. Blood. 1997;90:244–51.PubMed
33.
go back to reference Barrans SL, et al. The t(14;18) is associated with germinal center-derived diffuse large B-cell lymphoma and is a strong predictor of outcome. Clin Cancer Res. 2003;9:2133–39.PubMed Barrans SL, et al. The t(14;18) is associated with germinal center-derived diffuse large B-cell lymphoma and is a strong predictor of outcome. Clin Cancer Res. 2003;9:2133–39.PubMed
34.
go back to reference Goodlad JR, et al. BCL2 gene abnormalities define distinct clinical subsets of follicular lymphoma. Histopathology 2006;49:229–41.PubMedCrossRef Goodlad JR, et al. BCL2 gene abnormalities define distinct clinical subsets of follicular lymphoma. Histopathology 2006;49:229–41.PubMedCrossRef
35.
go back to reference Franco R, et al. Cutaneous follicular B-cell lymphoma: description of a series of 18 cases. Am J Surg Pathol. 2001;25:875–83.PubMedCrossRef Franco R, et al. Cutaneous follicular B-cell lymphoma: description of a series of 18 cases. Am J Surg Pathol. 2001;25:875–83.PubMedCrossRef
36.
go back to reference Lopez-Guillermo A, et al. The significance of molecular response in indolent follicular lymphomas. Blood. 1998;91:2955–60.PubMed Lopez-Guillermo A, et al. The significance of molecular response in indolent follicular lymphomas. Blood. 1998;91:2955–60.PubMed
37.
go back to reference Finke J, Slanina J, Lange W, Dölken G. Persistence of circulating t(14;18)-positive cells in long term remission after radiation therapy for localized-stage follicular lymphoma. J Clin Oncol. 1993;11:1668–73.PubMed Finke J, Slanina J, Lange W, Dölken G. Persistence of circulating t(14;18)-positive cells in long term remission after radiation therapy for localized-stage follicular lymphoma. J Clin Oncol. 1993;11:1668–73.PubMed
Metadata
Title
Presence of t(14;18) positive cells in blood and bone marrow does not predict outcome in follicular lymphoma
Authors
E. Paszkiewicz-Kozik
J. Kulik
A. Fabisiewicz
A. Tysarowski
E. Kraszewska
J. A. Siedlecki
J. Walewski
Publication date
01-03-2009
Publisher
Humana Press Inc
Published in
Medical Oncology / Issue 1/2009
Print ISSN: 1357-0560
Electronic ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-008-9071-1

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