Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Autografting

The impact of histologic grade on the outcome of high-dose therapy and autologous stem cell transplantation for follicular lymphoma

Bone Marrow Transplantation volume 40, pages 1039–1044 (2007)Cite this article

Abstract

The impact of the follicular lymphoma (FL) histologic grade on outcomes after high-dose therapy (HDT) and autologous stem cell transplantation (ASCT) is unknown. We evaluated 219 consecutive patients with grades 1–3 FL who underwent HDT and ASCT at our center. Overall survival (OS), progression-free survival (PFS), relapse and non-relapse mortality (NRM) was estimated for each grade after controlling for other predictive factors. The number of patients with grades 1, 2 and 3 FL was 106 (48%), 75 (34%) and 38 (17%), respectively. Five-year outcome estimates for the entire cohort included 60% OS, 39% PFS and 46% relapse (median follow-up=7.8 years). PFS and relapse were nearly identical among patients with grade 3 FL versus grades 1–2 FL after adjusting for other contributing factors (hazard ratio (HR)=0.90, P=0.68; HR=1.07, P=0.80, respectively). The hazard for mortality (HR=0.70, P=0.23) and NRM (HR=0.33, P=0.07) was non-significantly lower among patients with grade 3 FL compared to patients with grades 1–2 disease. Factors associated with inferior PFS included elevated lactate dehydrogenase (HR=1.52, P=0.03), chemoresistance (HR=1.82, P=0.02), ⩾2 prior therapies (HR=1.8, P=0.03) and prior radiation (HR=1.99, P=0.003). These data suggest that the histologic grade of FL does not impact PFS or relapse following HDT and ASCT.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5

Similar content being viewed by others

References

  1. Jemal A, Murray T, Ward E, Samuels A, Tiwari RC, Ghafoor A et al. Cancer statistics, 2005. CA Cancer J Clin 2005; 55: 10–30.

    Article  Google Scholar 

  2. Fisher SG, Fisher RI . The epidemiology of non-Hodgkin's lymphoma. Oncogene 2004; 23: 6524–6534.

    Article  CAS  Google Scholar 

  3. 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: 2780–2795.

    Article  CAS  Google Scholar 

  4. Nathwani B, Harris N, Weisenburger D, Isaacson P, Piris MA, Berger F et al. Follicular lymphoma. In: Jaffe E, Harris N, Stein H, Vardiman J (eds). Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues. IARC Press: Lyons, France, 2001, pp 162–167.

    Google Scholar 

  5. National Cancer Institute sponsored study of classifications of non-Hodgkin's lymphomas: summary and description of a working formulation for clinical usage. The Non-Hodgkin's Lymphoma Pathologic Classification Project. Cancer 1982; 49: 2112–2135.

    Article  Google Scholar 

  6. Stansfeld AG, Diebold J, Noel H, Kapanci Y, Rilke F, Kelenyi G et al. Updated Kiel classification for lymphomas. Lancet 1988; 1: 292–293.

    Article  CAS  Google Scholar 

  7. Bartlett NL, Rizeq M, Dorfman RF, Halpern J, Horning SJ . Follicular large-cell lymphoma: intermediate or low grade? J Clin Oncol 1994; 12: 1349–1357.

    Article  CAS  Google Scholar 

  8. Longo DL . What's the deal with follicular lymphomas? J Clin Oncol 1993; 11: 202–208.

    Article  CAS  Google Scholar 

  9. Wendum D, Sebban C, Gaulard P, Coiffier B, Tilly H, Cazals D et al. Follicular large-cell lymphoma treated with intensive chemotherapy: an analysis of 89 cases included in the LNH87 trial and comparison with the outcome of diffuse large B-cell lymphoma. Groupe d’Etude des Lymphomes de l’Adulte. J Clin Oncol 1997; 15: 1654–1663.

    Article  CAS  Google Scholar 

  10. Rodriguez J, McLaughlin P, Hagemeister FB, Fayad L, Rodriguez MA, Santiago M et al. Follicular large cell lymphoma: an aggressive lymphoma that often presents with favorable prognostic features. Blood 1999; 93: 2202–2207.

    CAS  PubMed  Google Scholar 

  11. Anderson JR, Vose JM, Bierman PJ, Weisenberger DD, Sanger WG, Pierson J et al. Clinical features and prognosis of follicular large-cell lymphoma: a report from the Nebraska Lymphoma Study Group. J Clin Oncol 1993; 11: 218–224.

    Article  CAS  Google Scholar 

  12. Horning SJ, Weiss LM, Nevitt JB, Warnke RA . Clinical and pathologic features of follicular large cell (nodular histiocytic) lymphoma. Cancer 1987; 59: 1470–1474.

    Article  CAS  Google Scholar 

  13. Miller TP, LeBlanc M, Grogan TM, Fisher RI . Follicular lymphomas: do histologic subtypes predict outcome? Hematol Oncol Clin North Am 1997; 11: 893–900.

    Article  CAS  Google Scholar 

  14. Schouten HC, Qian W, Kvaloy S, Porcellini A, Hagberg H, Johnson HE et al. High-dose therapy improves progression-free survival and survival in relapsed follicular non-Hodgkin's lymphoma: results from the randomized European CUP trial. J Clin Oncol 2003; 21: 3918–3927.

    Article  CAS  Google Scholar 

  15. Apostolidis J, Gupta RK, Grenzelias D, Johnson PW, Pappa VI, Summers KE et al. High-dose therapy with autologous bone marrow support as consolidation of remission in follicular lymphoma: long-term clinical and molecular follow-up. J Clin Oncol 2000; 18: 527.

    Article  CAS  Google Scholar 

  16. Freedman AS, Neuberg D, Mauch P, Soiffer RJ, Anderson KC, Fisher DC et al. Long-term follow-up of autologous bone marrow transplantation in patients with relapsed follicular lymphoma. Blood 1999; 94: 3325–3333.

    CAS  PubMed  Google Scholar 

  17. Gopal AK, Gooley TA, Maloney DG, Petersdorf SH, Eary JF, Rajendran JG et al. High-dose radioimmunotherapy versus conventional high-dose therapy and autologous hematopoietic stem cell transplantation for relapsed follicular non-Hodgkin lymphoma: a multivariable cohort analysis. Blood 2003; 102: 2351–2357.

    Article  CAS  Google Scholar 

  18. Vose JM, Zhang MJ, Rowlings PA, Lazarus HM, Bolwell BJ, Freytes CO et al. Autologous transplantation for diffuse aggressive non-Hodgkin's lymphoma in patients never achieving remission: a report from the Autologous Blood and Marrow Transplant Registry. J Clin Oncol 2001; 19: 406–413.

    Article  CAS  Google Scholar 

  19. Stiff PJ, Dahlberg S, Forman SJ, McCall AR, Horning SJ, Nademanee AP et al. Autologous bone marrow transplantation for patients with relapsed or refractory diffuse aggressive non-Hodgkin's lymphoma: value of augmented preparative regimens—a Southwest Oncology Group trial. J Clin Oncol 1998; 16: 48–55.

    Article  CAS  Google Scholar 

  20. Philip T, Guglielmi C, Hagenbeek A, Somers R, Van der Lelie H, Bron D et al. Autologous bone marrow transplantation as compared with salvage chemotherapy in relapses of chemotherapy-sensitive non-Hodgkin's lymphoma [see comments]. N Engl J Med 1995; 333: 1540–1545.

    Article  CAS  Google Scholar 

  21. Cheson BD, Horning SJ, Coiffier B, Shipp MA, Fisher RI, Connors JM et al. Report of an international workshop to standardize response criteria for Non-Hodgkin's Lymphomas. J Clin Oncol 1999; 17: 1244–1253.

    Article  CAS  Google Scholar 

  22. Kaplan EL, Meier P . Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958; 53: 457–481.

    Article  Google Scholar 

  23. Press OW, Eary JF, Appelbaum FR, Martin PJ, Badger CC, Nelp WB et al. Radiolabeled-antibody therapy of B-cell lymphoma with autologous bone marrow support. N Engl J Med 1993; 329: 1219–1224.

    Article  CAS  Google Scholar 

  24. Krishnan A, Nademanee A, Fung H, Angelopoulou M, Molina A, Gaal K et al. Does follicularity in large cell lymphoma predict outcome after autologous stem cell transplantation? Biol Blood Marrow Transplant 2006; 12: 641–647.

    Article  Google Scholar 

  25. Vose JM, Bierman PJ, Lynch JC, Weisenburger DD, Kessinger A, Chan WC et al. Effect of follicularity on autologous transplantation for large-cell non-Hodgkin's lymphoma. J Clin Oncol 1998; 16: 844–849.

    Article  CAS  Google Scholar 

  26. Ott G, Katzenberger T, Lohr A, Kindelberger S, Rudiger T, Wilhelm M et al. Cytomorphologic, immunohistochemical, and cytogenetic profiles of follicular lymphoma: 2 types of follicular lymphoma grade 3. Blood 2002; 99: 3806–3812.

    Article  CAS  Google Scholar 

  27. Hans CP, Weisenburger DD, Vose JM, Hock LM, Lynch JC, Aoun P et al. A significant diffuse component predicts for inferior survival in grade 3 follicular lymphoma, but cytologic subtypes do not predict survival. Blood 2003; 101: 2363–2367.

    Article  CAS  Google Scholar 

  28. Wang SA, Wang L, Hochberg EP, Muzikansky A, Harris NL, Hasserjian RP . Low histologic grade follicular lymphoma with high proliferation index: morphologic and clinical features. Am J Surg Pathol 2005; 29: 1490–1496.

    Article  Google Scholar 

  29. Husson H, Carideo EG, Neuberg D, Schultze J, Munoz O, Marks PW et al. Gene expression profiling of follicular lymphoma and normal germinal center B cells using cDNA arrays. Blood 2002; 99: 282–289.

    Article  CAS  Google Scholar 

  30. Dave SS, Wright G, Tan B, Rosenwald A, Gascoyne RD, Chan WC et al. Prediction of survival in follicular lymphoma based on molecular features of tumor-infiltrating immune cells. N Engl J Med 2004; 351: 2159–2169.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank Martha Bien, Mark Brockman, Jennifer Davies, Britt Kammerer and Nancy Knudsen, RN for their assistance in data collection.

Presented in abstract at the 47th American Society of Hematology Meeting, Atlanta, GA, 2005.

This study was supported by P01CA44991, K23CA85479, K08CA095448, SCOR Grant 7040 from the Leukemia and Lymphoma Society, the Medical Student Research Training Program of the University of Washington (RNP, GEK), the American Society of Hematology Trainee Award (RNP), a Career Development Award from the Lymphoma Research Foundation (JMP) and a Damon Runyon Career Development Award (JMP), The Westlund Foundation and a gift from Frank and Betty Vandermeer.

Author information

Authors and Affiliations

  1. Division of Medical Oncology, Department of Medicine, University of Washington, Seattle, WA, USA

    R N Pham, G E Keeney, O W Press, J M Pagel, W I Bensinger, L A Holmberg, S H Petersdorf, D G Maloney & A K Gopal

  2. Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    T A Gooley, O W Press, J M Pagel, W I Bensinger, L A Holmberg, S H Petersdorf, D G Maloney & A K Gopal

  3. Department of Laboratory Medicine, University of Washington, Seattle, WA, USA

    H A Greisman

Authors
  1. R N Pham
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. T A Gooley
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. G E Keeney
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. O W Press
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. J M Pagel
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. H A Greisman
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. W I Bensinger
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. L A Holmberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. S H Petersdorf
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. D G Maloney
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. A K Gopal
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to A K Gopal.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Pham, R., Gooley, T., Keeney, G. et al. The impact of histologic grade on the outcome of high-dose therapy and autologous stem cell transplantation for follicular lymphoma. Bone Marrow Transplant 40, 1039–1044 (2007). https://doi.org/10.1038/sj.bmt.1705864

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.bmt.1705864

Keywords

This article is cited by

Search

Advanced search

Quick links