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Annals of Hematology

, Volume 88, Issue 9, pp 829–838 | Cite as

Risk factors for poor treatment outcome and central nervous system relapse in diffuse large B-cell lymphoma with bone marrow involvement

  • Keun-Wook Lee
  • Jongyoun Yi
  • In Sil Choi
  • Jee Hyun Kim
  • Soo-Mee Bang
  • Dong-Wan Kim
  • Seock-Ah Im
  • Tae-You Kim
  • Sung-Soo Yoon
  • Jong Seok Lee
  • Yung-Jue Bang
  • Seonyang Park
  • Byoung Kook Kim
  • Han Ik Cho
  • Dae Seog HeoEmail author
Original Article

Abstract

Although several studies have described the prognostic implication of bone marrow (BM) involvement (BMI) in lymphoma, studies focused on BM-involved diffuse large B-cell lymphoma (DLBCL) are very rare and small-sized. This study was performed to examine the prognostic impact of morphologic findings of BMI by lymphoma and risk factors for central nervous system (CNS) relapse in BM-involved DLBCL. Between 1993 and 2005, 675 patients were diagnosed with DLBCL, and 88 patients who had BMI at initial diagnosis were eligible for this study. The median overall survival (OS) and failure-free survival (FFS) of 88 patients were 36.6 and 20.1 months, respectively. When three variables from BM morphologic findings (the pattern of BM infiltration, extent of BMI by lymphoma, and percentage of large cells in the infiltrate) were simultaneously included into multivariate model, the increased extent of BMI by lymphoma (≥10%) in BM area was the only negative prognostic factor, independent of the International Prognostic Index (IPI). Patients with both lower IPI scores and less extent of BMI showed an excellent prognosis with chemotherapy alone (5-year OS and FFS rates, 80% and 69%). However, morphologic BM features were not independent predictive factors for CNS recurrences. An increased lactate dehydrogenase (LDH) level at initial diagnosis was the only independent predictive factor for CNS relapse. Further efforts should be directed toward finding optimal treatment modalities based on the IPI and the extent of BMI by lymphoma. CNS prophylaxis may be considered only in patients with initial elevated LDH levels.

Keywords

Diffuse large B-cell lymphoma Bone marrow involvement Discordant histology Central nervous system Prognosis 

Notes

Acknowledgements

We are grateful to Seo-Kyung Hahn of Medical Research Collaborating Center Seoul National University Hospital for her statistical assistance in the revision of this manuscript. This study was partially supported by a grant from the Innovative Research Institute for Cell Therapy, Republic of Korea (A062260).

References

  1. 1.
    Bennett JM, Cain KC, Glick JH, Johnson GJ, Ezdinli E, O’Connell MJ (1986) The significance of bone marrow involvement in non-Hodgkin’s lymphoma: the Eastern Cooperative Oncology Group experience. J Clin Oncol 4:1462–1469PubMedGoogle Scholar
  2. 2.
    Fisher DE, Jacobson JO, Ault KA, Harris NL (1989) Diffuse large cell lymphoma with discordant bone marrow histology. Clinical features and biological implications. Cancer 64:1879–1887 doi: 10.1002/1097-0142(19891101)64:9<1879::AID-CNCR2820640921>3.0.CO;2-D PubMedCrossRefGoogle Scholar
  3. 3.
    Conlan MG, Bast M, Armitage JO, Weisenburger DD (1990) Bone marrow involvement by non-Hodgkin’s lymphoma: the clinical significance of morphologic discordance between the lymph node and bone marrow. Nebraska Lymphoma Study Group. J Clin Oncol 8:1163–1172PubMedGoogle Scholar
  4. 4.
    Robertson LE, Redman JR, Butler JJ, Osborne BM, Velasquez WS, McLaughlin P, Swan F, Rodriguez MA, Hagemeister FB, Fuller LM et al (1991) Discordant bone marrow involvement in diffuse large-cell lymphoma: a distinct clinical-pathologic entity associated with a continuous risk of relapse. J Clin Oncol 9:236–242PubMedGoogle Scholar
  5. 5.
    Hodges GF, Lenhardt TM, Cotelingam JD (1994) Bone marrow involvement in large-cell lymphoma. Prognostic implications of discordant disease. Am J Clin Pathol 101:305–311PubMedGoogle Scholar
  6. 6.
    Lee WI, Lee JH, Kim IS, Lee KN, Kim SH (1994) Bone marrow involvement by non-Hodgkin’s lymphom. J Korean Med Sci 9:402–408PubMedGoogle Scholar
  7. 7.
    Campbell J, Seymour JF, Matthews J, Wolf M, Stone J, Juneja S (2006) The prognostic impact of bone marrow involvement in patients with diffuse large cell lymphoma varies according to the degree of infiltration and presence of discordant marrow involvement. Eur J Haematol 76:473–480 doi: 10.1111/j.1600-0609.2006.00644.x PubMedCrossRefGoogle Scholar
  8. 8.
    No authors listed (1982) 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 49:2112–2135. doi: 10.1002/1097-0142(19820515)49:10<2112::AID-CNCR2820491024>3.0.CO;2-2
  9. 9.
    Yan Y, Chan WC, Weisenburger DD, Anderson JR, Bast MA, Vose JM, Bierman PJ, Armitage JO (1995) Clinical and prognostic significance of bone marrow involvement in patients with diffuse aggressive B-cell lymphoma. J Clin Oncol 13:1336–1342PubMedGoogle Scholar
  10. 10.
    Harris NL, Jaffe ES, Stein H, Banks PM, Chan JK, Cleary ML, Delsol G, De Wolf-Peeters C, Falini B, Gatter KC et al (1994) A revised European–American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group. Blood 84:1361–1392PubMedGoogle Scholar
  11. 11.
    Jaffe ES, Harris NL, Stein H, Vardiman JW (2001) World Health Organization classification of tumours, pathology and genetics: tumours of hematopoietic and lymphoid tissues. Lyon: IARCGoogle Scholar
  12. 12.
    No authors listed (1993) A predictive model for aggressive non-Hodgkin’s lymphoma. The International Non-Hodgkin’s Lymphoma Prognostic Factors Project. N Engl J Med 329:987–994Google Scholar
  13. 13.
    Chung R, Lai R, Wei P, Lee J, Hanson J, Belch AR, Turner AR, Reiman T (2007) Concordant but not discordant bone marrow involvement in diffuse large B-cell lymphoma predicts a poor clinical outcome independent of the International Prognostic Index. Blood 110:1278–1282 doi: 10.1182/blood-2007-01-070300 PubMedCrossRefGoogle Scholar
  14. 14.
    Cheung CW, Burton C, Smith P, Linch DC, Hoskin PJ, Ardeshna KM (2005) Central nervous system chemoprophylaxis in non-Hodgkin lymphoma: current practice in the UK. Br J Haematol 131:193–200 doi: 10.1111/j.1365-2141.2005.05756.x PubMedCrossRefGoogle Scholar
  15. 15.
    Hill QA, Owen RG (2006) CNS prophylaxis in lymphoma: who to target and what therapy to use. Blood Rev 20:319–332 doi: 10.1016/j.blre.2006.02.001 PubMedCrossRefGoogle Scholar
  16. 16.
    Lee KW, Kim DY, Yun T, Kim DW, Kim TY, Yoon SS, Heo DS, Bang YJ, Park S, Kim BK, Kim NK (2003) Doxorubicin-based chemotherapy for diffuse large B-cell lymphoma in elderly patients: comparison of treatment outcomes between young and elderly patients and the significance of doxorubicin dosage. Cancer 98:2651–2656 doi: 10.1002/cncr.11846 PubMedCrossRefGoogle Scholar
  17. 17.
    Coller BS, Chabner BA, Gralnick HR (1977) Frequencies and patterns of bone marrow involvement in non-Hodgkin lymphomas: observations on the value of bilateral biopsies. Am J Hematol 3:105–119PubMedGoogle Scholar
  18. 18.
    Thiele J, Zirbes TK, Kvasnicka HM, Fischer R (1999) Focal lymphoid aggregates (nodules) in bone marrow biopsies: differentiation between benign hyperplasia and malignant lymphoma—a practical guideline. J Clin Pathol 52:294–300PubMedCrossRefGoogle Scholar
  19. 19.
    Foucar K (2001) Non-Hodgkin lymphoma and Hodgkin lymphoma (disease) in bone marrow. In: Foucar K (ed) Bone marrow pathology. 2nd edn. ASCP Press, Chicago, pp 438–483Google Scholar
  20. 20.
    Bartl R, Frisch B, Burkhardt R, Jager K, Pappenberger R, Hoffmann-Fezer G (1984) Lymphoproliferations in the bone marrow: identification and evolution, classification and staging. J Clin Pathol 37:233–254 doi: 10.1136/jcp.37.3.233 PubMedCrossRefGoogle Scholar
  21. 21.
    Schmid C, Isaacson PG (1992) Bone marrow trephine biopsy in lymphoproliferative disease. J Clin Pathol 45:745–750 doi: 10.1136/jcp.45.9.745 PubMedCrossRefGoogle Scholar
  22. 22.
    Arber DA, George TI (2005) Bone marrow biopsy involvement by non-Hodgkin’s lymphoma: frequency of lymphoma types, patterns, blood involvement, and discordance with other sites in 450 specimens. Am J Surg Pathol 29:1549–1557 doi: 10.1097/01.pas.0000182405.65041.8b PubMedCrossRefGoogle Scholar
  23. 23.
    Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, Carbone PP (1982) Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol 5:649–655 doi: 10.1097/00000421-198212000-00014 PubMedCrossRefGoogle Scholar
  24. 24.
    Cox DR (1972) Regression models and life-tables. J R Stat Soc B 34:187–220Google Scholar
  25. 25.
    van Besien K, Ha CS, Murphy S, McLaughlin P, Rodriguez A, Amin K, Forman A, Romaguera J, Hagemeister F, Younes A, Bachier C, Sarris A, Sobocinski KS, Cox JD, Cabanillas F (1998) Risk factors, treatment, and outcome of central nervous system recurrence in adults with intermediate-grade and immunoblastic lymphoma. Blood 91:1178–1184PubMedGoogle Scholar
  26. 26.
    Feugier P, Virion JM, Tilly H, Haioun C, Marit G, Macro M, Bordessoule D, Recher C, Blanc M, Molina T, Lederlin P, Coiffier B (2004) Incidence and risk factors for central nervous system occurrence in elderly patients with diffuse large-B-cell lymphoma: influence of rituximab. Ann Oncol 15:129–133 doi: 10.1093/annonc/mdh013 PubMedCrossRefGoogle Scholar
  27. 27.
    Coiffier B, Lepage E, Briere J, Herbrecht R, Tilly H, Bouabdallah R, Morel P, Van Den Neste E, Salles G, Gaulard P, Reyes F, Lederlin P, Gisselbrecht C (2002) CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med 346:235–242 doi: 10.1056/NEJMoa011795 PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Keun-Wook Lee
    • 1
    • 4
  • Jongyoun Yi
    • 6
    • 8
  • In Sil Choi
    • 1
    • 7
  • Jee Hyun Kim
    • 1
    • 4
  • Soo-Mee Bang
    • 1
    • 4
  • Dong-Wan Kim
    • 1
    • 3
    • 5
  • Seock-Ah Im
    • 1
    • 3
    • 5
  • Tae-You Kim
    • 1
    • 3
    • 5
  • Sung-Soo Yoon
    • 1
    • 3
    • 5
  • Jong Seok Lee
    • 1
    • 4
  • Yung-Jue Bang
    • 1
    • 3
    • 5
  • Seonyang Park
    • 1
    • 3
    • 5
  • Byoung Kook Kim
    • 1
    • 3
    • 5
  • Han Ik Cho
    • 2
    • 6
  • Dae Seog Heo
    • 1
    • 3
    • 5
    • 9
    Email author
  1. 1.Department of Internal MedicineSeoul National University College of MedicineSeoulSouth Korea
  2. 2.Department of Laboratory MedicineSeoul National University College of MedicineSeoulSouth Korea
  3. 3.Cancer Research InstituteSeoul National University College of MedicineSeoulSouth Korea
  4. 4.Department of Internal MedicineSeoul National University Bundang HospitalSeongnamKorea
  5. 5.Department of Internal MedicineSeoul National University HospitalSeoulSouth Korea
  6. 6.Department of Laboratory MedicineSeoul National University HospitalSeoulSouth Korea
  7. 7.Department of Internal MedicineSeoul Municipal Boramae HospitalSeoulSouth Korea
  8. 8.Aerospace Medical Center, ROKAFCheongwonSouth Korea
  9. 9.Department of Internal Medicine, Cancer Research InstituteSeoul National University College of MedicineSeoulSouth Korea

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