Skip to main content
Erschienen 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

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

Erschienen in: Medical Oncology | Ausgabe 1/2009

Einloggen, um Zugang zu erhalten

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.
Literatur
1.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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
7.
8.
Zurück zum Zitat 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.
Zurück zum Zitat Solal-Celigny P, et al. Follicular lymphoma international index. Blood 2004;104:1258–65.PubMedCrossRef Solal-Celigny P, et al. Follicular lymphoma international index. Blood 2004;104:1258–65.PubMedCrossRef
10.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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
Metadaten
Titel
Presence of t(14;18) positive cells in blood and bone marrow does not predict outcome in follicular lymphoma
verfasst von
E. Paszkiewicz-Kozik
J. Kulik
A. Fabisiewicz
A. Tysarowski
E. Kraszewska
J. A. Siedlecki
J. Walewski
Publikationsdatum
01.03.2009
Verlag
Humana Press Inc
Erschienen in
Medical Oncology / Ausgabe 1/2009
Print ISSN: 1357-0560
Elektronische ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-008-9071-1

Weitere Artikel der Ausgabe 1/2009

Medical Oncology 1/2009 Zur Ausgabe

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.