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 Manuscript
  • Published:

Significance of the levels of bone marrow lymphoid infiltrate in chronic lymphocytic leukemia patients with nodular partial remission

Leukemia volume 16, pages 632–635 (2002)Cite this article

Abstract

Patients with chronic lymphocytic leukemia (CLL) are considered in nodular partial remission (nPR) when they are in remission but bone marrow biopsies show rare nodules. The significance of the level of residual disease in nPR is not known. We studied 91 previously untreated CLL patients who were treated with fludarabine alone, fludarabine with prednisone, or fludarabine with cyclophosphamide and achieved nPR at the end of six courses. We compared bone marrow lymphoid infiltration before therapy and at the end of three and six courses of therapy as evaluated by a pathologist in retrospective fashion with that of the routine evaluation at the time of performing bone marrow biopsy. We then compared these results with those obtained by computer-aided histomorphometry in 28 patients in nPR. There was significant correlation (P < 0.05) between pathologists as well as between pathologists and histomorphometry. Upon correlation with clinical characteristics, there was significant correlation (P 0.01) between marrow involvement before therapy and white blood cell counts (wbc), hemoglobin (hgb), absolute lymphocyte counts, and β2-microglobulin (β2-m) but none of these parameters correlated with the lymphoid infiltrate at the end of three or six courses of therapy. more importantly, lymphoid infiltration after three and six courses did not correlate with time to progression (ttp) or overall survival (os). however, patients with >70% marrow involvement before therapy had a significantly shorter TTP (P = 0.02). All 91 patients showed similar results. However, we found reverse correlation between marrow lymphoid infiltrate at the end of three courses and OS (P = 0.01).

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

Similar content being viewed by others

References

  1. Rozman C, Bosch F, Montserrat E . Chronic lymphocytic leukemia: a changing natural history? Leukemia 1997 11: 775–778

    Article  CAS  PubMed  Google Scholar 

  2. Faguet GB . Chronic lymphocytic leukemia: an updated review J Clin Oncol 1994 12: 1974–1990

    Article  CAS  PubMed  Google Scholar 

  3. Zengin N, Kars A, Sungur A, Zengin NI, Hayran M, Tekuzman G, Kansu E, Ruacan S, Firat D . The significance of bone marrow biopsy pattern in chronic lymphocytic leukemia: a prognostic dilemma Am J Hematol 1999 62: 208–211

    Article  CAS  PubMed  Google Scholar 

  4. Molica S, Levato D, Dattilo A . Natural history of early chronic lymphocytic leukemia. A single institution study with emphasis on the impact of disease-progression on overall survival Haematologica 1999 84: 1094–1099

    CAS  PubMed  Google Scholar 

  5. Keating MJ, O'Brien S, Kantarjian H, Plunkett W, Estey E, Koller C, Beran M, Freireich EJ . Long term follow-up of patients with chronic lymphocytic leukemia treated with fludarabine as a single agent Blood 1993 81: 2878–2884

    CAS  PubMed  Google Scholar 

  6. O'Brien S, Kantarjian H, Beran M, Smith T, Koller C, Estey E, Robertson LE, Lerner S, Keating M . Results of fludarabine and prednisone therapy in 264 patients with chronic lymphocytic leukemia with multivariate analysis derived prognostic model of response to treatment Blood 1993 82: 1695–1700

    CAS  PubMed  Google Scholar 

  7. Robertson LE, O'Brien S, Kantarjian H, Koller C, Beran M, Andreeff M, Lerner S, Plunkett W, Keating MJ . A 3-day schedule of Fludarabine in previously treated chronic lymphocytic leukemia Leukemia 1995 9: 1444–1449

    CAS  PubMed  Google Scholar 

  8. Hiddeman W, Rottmann R, Wormann B . Treatment of advanced chronic lymphocytic leukemia by fludarabine: results of a clinical phase II study Ann Haematol 1991 63: 1–4

    Article  Google Scholar 

  9. Montserrat E, Lopez-Lorenzo JL, Manso F, Martin A, Prieto E, Arias-Sampedro J, Fernandez MN, Oyarzabal FJ, Odrizaba J, Alcala A, Garcia-Conde J, Guardia R, Bosch F . Fludarabine in resistant or relapsing B-cell chronic lymphocytic leukemia. The Spanish Group experience Leuk Lymphoma 1996 21: 467–472

    Article  CAS  PubMed  Google Scholar 

  10. Pott-Hoeck C, Hiddemann W . Purine analogs in the treatment of low-grade lymphomas and chronic lymphocytic leukemia Ann Oncol 1995 5: 421–433

    Article  Google Scholar 

  11. Johnson SA, Catovsky D, Child JA, Newland AC, Milligan DW, Janmohamed R . Phase I/II evaluation of pentostatin (2′-deoxyco formycin) in a five-day schedule for the treatment of relapsed/refractory B-cell chronic lymphocytic leukemia Invest New Drugs 1998 16: 155–160

    Article  CAS  PubMed  Google Scholar 

  12. Keating MJ, O'Beran S, Lerner S, Koller C, Beran M, Robertson LE, Freireich EJ, Estey E, Kantarjian H . Long-term follow-up of patients with chronic lymphocytic leukemia (CLL) receiving Fludarabine regimens as initial therapy Blood 1998 92: 1165–1171

    CAS  PubMed  Google Scholar 

  13. Keating MJ, Kantarjian H, O'Brien S, Koller C, Talpaz M, Schachner J, Childs CC, Freireich EJ, McCredie KB . Fludarabine: a new agent with marked cyto-reductive activities in untreated chronic lymphocytic leukemia J Clin Oncol 1991 9: 44–49

    Article  CAS  PubMed  Google Scholar 

  14. Johnson S, Smith AG, Loffler H, Osby E, Juliusson G, Emmerich B, Wyld PJ, Hiddemann W . Multicentre prospective randomised trial of fludarabine versus cyclophosphamide, doxorubicin, and prednisone (CAP) for treatment of advanced-stage chronic lymphocytic leukemia. The French Cooperative Group on CLL Lancet 1996 347: 1432–1438

    Article  CAS  PubMed  Google Scholar 

  15. Robak T, Blonski JZ, Kasznicki M, Blasinska-Morawiec M, Krykowski E, Dmoszynska A, Mrugala-Spiewak H, Skotnicki AB, Nowak W, Konopka L, Ceglarek B, Maj S, Dwilewicz-Trojaczek J, Hellmann A, Urasinski I, Zdziarska B, Kotlarek-Haus S, Potoczek S, Grieb P . Cladribine with prednisone versus chlorambucil with prednisone as first-line therapy in chronic lymphocytic leukemia: report of a prospective, randomized, multicenter trial Blood 2000 96: 2723–2729

    CAS  PubMed  Google Scholar 

  16. Rai KR, Peterson BL, Appelbaum FR, Kolitz J, Elias L, Shepherd L, Hines J, Threatte GA, Larson RA, Cheson BD, Schiffer CA . Fludarabine compared with chlorambucil as primary therapy for chronic lymphocytic leukemia N Engl J Med 2000 343: 1750–1757

    Article  CAS  PubMed  Google Scholar 

  17. Robertson LE, Huh YO, Butler JJ, Pugh WC, Hirsch-Ginsberg C, Stass S, Kantarjian H, Keating MJ . Response assessment in chronic lymphocytic leukemia treated with fludarabine plus prednisone: clinical, pathologic, immunophenotypic, and molecular analysis Blood 1992 80: 29–36

    CAS  PubMed  Google Scholar 

  18. Keating MJ, O'Brien S, Robertson L, Huh Y, Kantarjian H, Plunkett W . Chronic lymphocytic leukemia – correlation of response and survival Leuk Lymphoma 1993 11: 167–175

    Article  PubMed  Google Scholar 

  19. Keating MJ . Chronic lymphocytic leukemia Semin Oncol 1999 26: 107–114

    CAS  PubMed  Google Scholar 

  20. Cheson BD, Bennett JM, Grever M, Kay N, Keating MJ, O'Brien S, Rai KR . National Cancer Institute-sponsored Working Group guidelines for chronic lymphocytic leukemia: revised guidelines for diagnosis and treatment Blood 1996 87: 4990–4997

    CAS  PubMed  Google Scholar 

  21. O'Brien SM, Kantarjian HM, Cortes J, Beran M, Koller CA, Giles FJ, Lerner S, Keating M . Results of the fludarabine and cyclophosphamide combination regimen in chronic lymphocytic leukemia J Clin Oncol 2001 19: 1414–1420

    Article  CAS  PubMed  Google Scholar 

  22. Rywlin AM . Histopathology of the Bone Marrow Boston: Little Brown 1976

    Google Scholar 

  23. Noy A, Verma R, Glenn M, Maslak P, Rahman ZU, Keenan JR, Weiss M, Filippa D, Zelenetz AD . Clonotypic polymerase chain reaction confirms minimal residual disease in CLL nodular PR: results from a sequential treatment CLL protocol Blood 2001 97: 1929–1936

    Article  CAS  PubMed  Google Scholar 

  24. Pfitzner T, Engert A, Wittor H, Schinkothe T, Oberhauser F, Schulz H, Diehl V, Barth S . A real-time PCR assay for the quantification of residual malignant cells in B cell chronic lymphatic leukemia Leukemia 2000 14: 754–766

    Article  CAS  PubMed  Google Scholar 

  25. Mattsson J, Uzunel M, Remberger M, Ljungman P, Kimby E, Ringden O, Zetterquist H . Minimal residual disease is common after allogeneic stem cell transplantation in patients with B cell chronic lymphocytic leukemia and may be controlled by graft-versus-host disease Leukemia 2000 14: 247–254

    Article  CAS  PubMed  Google Scholar 

  26. Geisler CH, Hou-Jensen K, Jensen OM, Tinggaard-Pedersen N, Hansen MM, Hansen NE, Holm M, Christensen BE, Drivsholm A, Nielsen JB, Thorling K, Andersen E, Larsen JK, Anderson PK . The bone marrow infiltration pattern in B-cell chronic lymphocytic leukemia is not an important prognostic factor Eur J Haematol 1996 57: 292–300

    Article  CAS  PubMed  Google Scholar 

  27. Keating MJ, Smith TL, Lerner S, O'Brien S, Robertson LE, Kantarjian H, Freireich EJ . Prediction of prognosis following fludarabine used as secondary therapy for chronic lymphocytic leukemia Leuk Lymphoma 2000 37: 71–85

    Article  CAS  PubMed  Google Scholar 

  28. Keating MJ, Lerner S, Kantarjian H, O'Brien S, Estey E, Freireich E . The serum B2-microglobulin (B2M) level is more powerful than stage in predicting response and survival in chronic lymphocytic leukemia (CLL) Blood 1995 86 (Suppl. 1): 606a

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Hematopathology, University of Texas MD Anderson Cancer Center, Houston, Tx, USA

    R Oudat & M Albitar

  2. Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, USA

    MJ Keating, S Lerner & S O'Brien

Authors
  1. R Oudat
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. MJ Keating
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S Lerner
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. S O'Brien
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M Albitar
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Oudat, R., Keating, M., Lerner, S. et al. Significance of the levels of bone marrow lymphoid infiltrate in chronic lymphocytic leukemia patients with nodular partial remission. Leukemia 16, 632–635 (2002). https://doi.org/10.1038/sj.leu.2402439

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.leu.2402439

Keywords

This article is cited by

Search

Advanced search

Quick links