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:

Chronic Lymphocytic Leukemia

Stem cell transplantation for chronic lymphocytic leukemia: different outcome after autologous and allogeneic transplantation and correlation with minimal residual disease status

Leukemia volume 15, pages 445–451 (2001)Cite this article

Abstract

The clinical outcome and its correlation with the status of minimal residual disease (MRD) was analyzed in 26 patients with chronic lymphocytic leukemia (CLL) undergoing stem cell transplantation. All patients having received autotransplant (n = 14) achieved CR which was MRD(−) in nine patients (64%) and MRD(+) in five. With a median follow-up of 26.5 months (range, 12–52), four of the five MRD(+) patients relapsed at 9, 15, 17 and 18 months after transplant, respectively. In contrast, only two patients of the nine MRD(−) patients have relapsed at 15 and 38 months (P = 0.02), and four became MRD(+) at 6, 12, 30, and 42 months after transplantation, respectively. Of the 12 patients that were allografted, three (25%) died in the early post-transplant period, one had resistant disease, and eight (67%) achieved CR. Among the latter, no evidence of MRD post-transplantation was observed in five cases, while a delayed clearance of MRD (up to 22 months after transplantation) was seen in two, and a persistent positivity of MRD after transplant was detectable in another patient until last follow-up (12 months). After a median follow-up of 43 months (range, 15–106), none of the responding patients had clinical or MRD relapse. These results show that in CLL the probability of achieving sustained MRD(−) CR is higher with allogeneic than with autologous transplants, and confirm the value of MRD assessment in the follow-up of patients transplanted for CLL.

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. Rozman C, Montserrat E . Chronic lymphocytic leukemia N Engl J Med 1995 333: 1052–1057

    Article  CAS  Google Scholar 

  2. Diehl LF, Karnell LH, Menck HR . The National Cancer data base on age, gender, treatment, and outcomes of patients with chronic lymphocytic leukemia Cancer 1999 86: 2648–2692

    Article  Google Scholar 

  3. Caligaris-Cappio F, Hamblin TJ . B-cell chronic lymphocytic leukemia: a bird of a different feather J Clin Oncol 1999 17: 791–795

    Article  Google Scholar 

  4. Gratwohl A, Passweg J, Baldomero H, Hermans J . Blood and marrow transplantation activity in Europe 1997. European Group for blood and marrow transplantation (EBMT) Bone Marrow Transplant 1999 24: 231–245

    Article  CAS  Google Scholar 

  5. Michallet M, Carreras E, Cornelissen JJ, Dreger P, Einsele H, Gratwohl A, Kimby E, Niederwieser D, Apperley J . Allotransplants and autotransplants in CLL Bone Marrow Transplant 1999 23: (Suppl. 1) S53 (Abstr.)

    Article  Google Scholar 

  6. Cheson BD, Bennet JM, Grever M, 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 

  7. Rai KR, Sawitsky A, Cronkite EP, Chanana AD, Levy RN, Pasternak BS . Clinical staging of chronic lymphocytic leukemia Blood 1975 46: 219–234

    CAS  PubMed  Google Scholar 

  8. Binet JL, Auquier A, Dighiero G, Chastang C, Piguet H, Goasguen J, Vaugier G, Potron G, Colona P, Oberling F, Thomas M, Tchernia G, Jacquillat C, Boivin P, Lesty C, Duault MT, Monconduit M, Belabbes S, Gremy F . A new prognostic classification of chronic lymphocytic leukemia derived from a multivariate survival analysis Cancer 1981 48: 198–206

    Article  CAS  Google Scholar 

  9. Rozman C, Montserrat E, Rodríguez-Fernández JM, Ayats R, Vallespí T, Parody R, Rios A, Prados D, Morey M, Gomis F, Alcalá AS, Gutiérrez M, Maldonado J, González C, Giralt M, Hernández-Nieto L, Cabrera A, Fernández-Rañada JM . Bone marrow histologic pattern – the best single prognostic parameter in chronic lymphocytic leukemia: a multivariate survival analysis of 329 cases Blood 1984 64: 642–648

    CAS  PubMed  Google Scholar 

  10. Montserrat E, Sánchez-Bisonó J, Viñolas N, Rozman C . Lymphocyte doubling time in chronic lymphocytic leukemia: analysis of its prognostic importance Br J Haematol 1986 62: 567–575

    Article  CAS  Google Scholar 

  11. Montserrat E, Gomis F, Vallespí T, Ríos A, Romero A, Soler J, Alcalá A, Morey M, Ferrán C, Díaz-Mediavilla J, Flores A, Woessner S, Batlle J, González-Aza C, Rovira M, Reverter JC, Rozman C . Presenting features and prognosis of chronic lymphocytic leukemia in younger adults Blood 1991 78: 1545–1551

    CAS  PubMed  Google Scholar 

  12. Mauro F, Foa R, Giannarelli D, Cordone I, Crescenzi S, Pescarmona E, Sala R, Cerretti R, Mandelli F . Clinical characteristics and outcome of young chronic lymphocytic leukemia patients: a single institution study of 204 cases Blood 1999 94: 448–454

    CAS  PubMed  Google Scholar 

  13. Esteve J, Villamor N, Colomer D, Bosch F, López-Guillermo A, Rovira M, Urbano-Ispizua A, Sierra J, Carreras E, Montserrat E . Hematopoietic stem transplantation in chronic lymphocytic leukemia: a report of 12 patients from a single institution Ann Oncol 1998 9: 167–172

    Article  CAS  Google Scholar 

  14. Sambrook J, Fritsch EF, Maniatis T (eds) . Molecular Cloning, a Laboratory Manual, 2nd edn Cold Spring Harbor Laboratory Press: New York 1989

  15. Beishuizen A, Verhoeven M-A, Mol EJ, Breit TM, Wolvers-Tettero I, van Dongen J . Detection of immunoglobulin heavy-chain rearrangements by Southern blot analysis: recommendations for optimal results Leukemia 1993 7: 2045–2053

    CAS  PubMed  Google Scholar 

  16. Brisco MJ, Tan IW, Orsborn AM, Morley AA . Development of a highly sensitive assay, based on the polymerase chain reaction, for rare B-lymphocyte clones in a polyclonal population Br J Haematol 1990 75: 163–167

    Article  CAS  Google Scholar 

  17. Pollard P, Owen G, Worwood M . PCR-based immunogenotyping at the Ig heavy chain CDR3 locus: improvements in resolution Br J Haematol 1993 84: 169–171

    Article  CAS  Google Scholar 

  18. Sioutos N, Bagg A, Michaud GY, Irving SG, Hartmann DP, Siragy H, Oliveri DR, Locker J, Cossman J . Polymerase chain reaction versus Southern blot hybridization Diagn Mol Pathol 1995 4: 8–13

    Article  CAS  Google Scholar 

  19. Davis TH, Yockey CE, Balk SP . Detection of clonal immunoglobulin gene rearrangements by polymerase chain reaction amplification and single-strand conformational polymorphism analysis Am J Pathol 1993 142: 1841–1847

    CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  Google Scholar 

  21. Peto R, Pike MC, Armitage P, Breslow NE, Cox DR, Howard SV, Mantel N, McPherson K, Smith PG . Design and analysis of randomized clinical trials requiring prolonged observations of each patient. Analysis and examples Br J Cancer 1977 35: 1–39

    Article  CAS  Google Scholar 

  22. Dreger P, von Neuhoff N, Sonnen R, Kusse R, Glass B, Viehmann K, Uharek L, Kneba M, Schmitz N . Autologous stem cell transplantation for CLL. Parameters predicting feasibility and outcome Haematologica 1999 84: 258 (Abstr.)

    Google Scholar 

  23. Montserrat E, Esteve J, Schmitz N, Dreger P, Meloni G, Catovsky D, Dearden C, Scimè R, Sutton L, Kimby E, Desablens B, Pavletic S, Coiffier B, Juliusson G, Besalduch J, del Potro E, Caballero D, Michallet M . Autologous stem-cell transplantation (ASCT) for chronic lymphocytic leukemia (CLL): results in 107 patients Blood 1999 94: (Suppl. 1) 397a (Abstr.)

    Google Scholar 

  24. Provan D, Bartlett-Pandite L, Zwicky C, Neuberg D, Maddocks A, Corradini P, Soiffer R, Ritz J, Nadler LM, Gribben JG . Eradication of polymerase chain reaction-detectable chronic lymphocytic leukemia cells with improved outcome after bone marrow transplantation Blood 1996 88: 2228–2235

    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  Google Scholar 

  26. von Neuhoff N, Schmitz N, Suttorp M, Dreger P . Detection of minimal residual disease after stem-cell transplantation for chronic lymphocytic leukemia by clone-specific oligonucleotides Blood 1998 92: (Suppl. 1) 652 (Abstr.)

    Google Scholar 

  27. Rabinowe SN, Soiffer RJ, Gribben JG, Daley H, Freedman AS, Daley J, Pesek K, Neuberg D, Pinkus G, Leavitt PR, Spector NA, Grossbard ML, Anderson K, Robertson MJ, Mauch P, Chayt-Marcus K, Ritz J, Nadler LM . Autologous and allogeneic bone marrow transplantation for poor prognosis patients with B-cell chronic lymphocytic leukemia Blood 1993 82: 1366–1376

    CAS  PubMed  Google Scholar 

  28. Khouri IF, Keating MJ, Vriesendorp HM, Reading CL, Przepiorka D, Huh YO, Andersson BS, van Besien KW, Mehra RC, Giralt SA, Ippoliti C, Marshall M, Thomas MW, O'Brien S, Robertson LE, Deisseroth AB, Champlin RE . Autologous and allogeneic bone marrow transplantation for chronic lymphocytic leukemia: preliminary results J Clin Oncol 1994 12: 748–758

    Article  CAS  Google Scholar 

  29. Khouri I, Przepiorka K, van Besien K, O'Brien S, Palmer JL, Lerner S, Mehra RC, Vriesendorp HM, Andersson BS, Giralt S, Korbling M, Keating MJ, Champlin RE . Allogeneic blood or bone marrow transplantation for chronic lymphocytic leukemia: timing of transplantation and potential effect of fludarabine on acute graft-versus-host disease Br J Haematol 1997 97: 466–473

    Article  CAS  Google Scholar 

  30. Pavletic ZS, Bierman PJ, Vose JM, Bishop MR, Wu CD, Pierson JL, Kollath JP, Weisenburger DD, Kessinger A, Armitage JO . High incidence of relapse after autologous stem-cell transplantation for B-cell chronic lymphocytic leukemia or small lymphocytic leukemia Ann Oncol 1998 9: 1023–1026

    Article  CAS  Google Scholar 

  31. Pavletic ZS, Bierman PJ, Vose JM, Bishop M, Wu D, Pierson J, Kollath J, Kessinger A, Armitage J . Long term outcome of autologous stem cell transplantation for chronic lymphocytic leukemia or small lymphocytic leukemia (B-CLL) Blood 1997 97: (Suppl. 1) 234a

    Google Scholar 

  32. Meloni G, Mauro F, DeFabritis P, Guglielmi C, Pescarmona E, Proia A, Vignetti M, Foà R, Mnadelli F . Unmanipulated peripheral blood stem cell transplantation in chronic lymphocytic leukemia patients in remission after fludarabine therapy Blood 1997 90: 331b (Abstr.)

    Google Scholar 

  33. Dyer MJ, Kelsey SM, Mackay HJ, Emmett E, Thornton P, Hale G, Waldmann H, Newland AC, Catovsky D . In vivo ‘purging’ of residual disease in CLL with Campath-1H Br J Haematol 1997 97: 669–672

    Article  CAS  Google Scholar 

  34. Michallet M, Archimbaud E, Bandini G, Rowlings PA, Deeg HJ, Gahrton G, Montserrat E, Rozman C, Gratwohl A, Gale RP . HLA-identical sibling bone marrow transplanation in younger patients with chronic lymphocytic leukemia Ann Intern Med 1996 124: 311–315

    Article  CAS  Google Scholar 

  35. Pavletic ZS, Arrowsmith ER, Bierman PJ, Goodman SA, Vose JM, Tarantolo SR, Stein RS, Bocieck G, Greer JP, Wu CD, Kollath JP, Weisenburger DD, Kessinger A, Wolff SN, Armitage JO, Bishop MR . Outcome of allogeneic stem cell transplantation for B cell chronic lymphocytic leukemia Bone Marrow Transplant 2000 25: 712–722

    Article  Google Scholar 

  36. Gribben JG, Neuberg D, Soiffer RJ, Fisher DC, Schlossman R, Alyea EP, Kuhlman C, Ritz J, Nadler LM . Autologous versus allogeneic bone marrow transplantation for patients with poor prognosis CLL Blood 1998 92: 322a (Abstr.)

    Google Scholar 

  37. Rondon G, Giralt S, Huh Y, Khouri I, Andersson B, Andreef M, Champlin R . Graft-versus-leukemia effect after allogeneic bone marrow transplantation for chronic lymphocytic leukemia Bone Marrow Transplant 1996 18: 669–672

    CAS  PubMed  Google Scholar 

  38. Mehta J, Powles R, Singhal S, Iveson T, Treleaven J, Catovsky D . Clinical and hematological response of chronic lymphocytic leukemia and prolymphocytic leukemia persisting after allogeneic bone marrow transplantation with the onset of acute-versus-host disease: possible role of graft-versus-leukemia Bone Marrow Transplant 1996 17: 371–375

    CAS  PubMed  Google Scholar 

  39. Jarque I, Palau J, Sanz GF, Guinot M, Gomis F, Martín G, Martínez J, Sanz MA . Delayed complete response after allogeneic bone marrow transplantation in chronic lymphocytic leukemia (letter) Blood 1993 82: 1036–1037

    CAS  PubMed  Google Scholar 

  40. Brugiatelli M, Claisse JF, Lenormand B, Morabito F, Callea V, Malloum K, Chevret S, Binet JL, Dighiero G, Travade Ph . Long-term clinical outcome of B-cell chronic lymphocytic leukemia in clinical remission phase evaluated at phenotypic level Br J Haematol 1997 97: 113–118

    Article  CAS  Google Scholar 

  41. Magnac C, Sutton L, Cazin B, Laurent C, Binet JL, Merle-Béral H, Dighiero G, Maloum K . Detection of minimal residual disease in B chronic lymphocytic leukemia (CLL) Hematol Cell Ther 1999 41: 13–18

    Article  CAS  Google Scholar 

  42. Vuillier F, Claisse JF, Vandenvelde C, Travade Ph, Magnac C, Chevret S, Desablens B, Binet JL, Dighiero G . Evaluation of residual disease in B-cell chronic lymphocytic leukemia patients in clinical and bone marrow remission using CD5-CD19 markers and PCR study of gene rearrangements Leuk Lymphoma 1992 7: 195–204

    Article  CAS  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  44. Rawstron AC, Richards SJ, Davis FE, Evans P, Jack AS, Morgan GJ, Hillmen P . Development of a highly sensitive flow cytometry technique to monitor residual disease in CLL patients treated with Campath-1H Br J Haematol 1999 105: (1S) 32 (Abstr.)

    Google Scholar 

  45. Kipps TJ . The CD5 B cell Adv Immunol 1989 47: 117–185

    Article  CAS  Google Scholar 

  46. Bomberger C, Singh-Jairam M, Rodey G, Guerriero A, Yeager AM, Fleming WH, Holland HK, Waller E . Lymphoid reconstitution after autologous PBSC transplantation with FACS-sorted CD34+ hematopoietic progenitors Blood 1998 91: 2588–2600

    CAS  PubMed  Google Scholar 

  47. Pfitzner T, Engert A, Wittor H, Schinköthe T, Oberhäuser 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  Google Scholar 

  48. Brüggemann M, Droese J, Bolz I, Lüth P, Pott C, von Neuhoff N, Scheuering U, Kneba M . Improved assessment of minimal residual disease in B cell malignancies using fluorogenic consensus probes for real-time quantitative PCR Leukemia 2000 14: 1419–1425

    Article  Google Scholar 

Download references

Acknowledgements

This work was supported in part by grants 97/626 from the Fondo de Investigaciones Sanitarias of the Spanish Ministry of Health, JS/1996 from Fundación Ramón Areces, 00/P-EM and 00/P-CR from the José Carreras International Foundation Against Leukemia, and Generalitat de Catalunya 1999 SGR 225.

Author information

Authors and Affiliations

  1. Department of Hematology, Institute of Hematology and Oncology, Postgraduate School of Hematology ‘Farreras-Valenti’, Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, University of Barcelona, Spain

    J Esteve, F Cervantes, E Carreras & E Montserrat

  2. Institute of Hematology and Oncology, Hematopathology Unit, Postgraduate School of Hematology ‘Farreras-Valenti’, Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, University of Barcelona, Spain

    N Villamor, D Colomer & E Campo

Authors
  1. J Esteve
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. N Villamor
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. D Colomer
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. F Cervantes
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. E Campo
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. E Carreras
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. E Montserrat
    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

Esteve, J., Villamor, N., Colomer, D. et al. Stem cell transplantation for chronic lymphocytic leukemia: different outcome after autologous and allogeneic transplantation and correlation with minimal residual disease status. Leukemia 15, 445–451 (2001). https://doi.org/10.1038/sj.leu.2402036

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.leu.2402036

Keywords

This article is cited by

Search

Advanced search

Quick links