Skip to main content
Log in

Immunologic monitoring in adults with acute lymphoblastic leukemia

  • Published:
Current Oncology Reports Aims and scope Submit manuscript

Abstract

Investigation of minimal residual disease (MRD) by immunophenotyping and molecular techniques has proven to be a powerful approach for disease monitoring in patients with acute leukemia. Multiparameter flow cytometry, through the use of triple or quadruple marker combinations, identifies aberrant or uncommon phenotypic profiles in more than 90% of adult patients with acute lymphoblastic leukemia (ALL) at diagnosis. These profiles allow identification of residual leukemic cells in bone marrow or peripheral blood once morphologic complete remission is achieved. Until now, most immunophenotypic MRD studies in ALL have focused on children. In contrast, information on the value of MRD in adults with ALL is scanty and usually restricted to polymerase chain reaction studies. In this review, we focus on technical aspects of MRD detection by flow cytometry and on the clinical data concerning the value of immunologic MRD studies as a tool for relapse prediction in adult ALL. Although prospective studies are needed, we assert that immunophenotypic MRD studies are clinically useful. Such studies should be incorporated into the routine management of adult ALL patients for identification of those at high risk of relapse, who could benefit from new alternative therapeutic approaches, and to distinguish these patients from others who could be cured with more conventional approaches.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References and Recommended Reading

  1. Verma A, Stock W: Management of adult acute lymphoblastic leukemia: moving toward a risk-adapted approach. Curr Opin Oncol 2001, 13:14–20.

    Article  PubMed  CAS  Google Scholar 

  2. Hoelzer D, Gokbuget N: Recent approaches in acute lymphoblastic leukemia in adults. Crit Rev Oncol Hematol 2000, 36:49–58.

    PubMed  CAS  Google Scholar 

  3. Thomas X, Danaila C, Le QH, et al.: Long-term follow-up of patients with newly diagnosed adult acute lymphoblastic leukemia: a single institution experience of 378 consecutive patients over a 21-year period. Leukemia 2001, 15:1811–1822.

    PubMed  CAS  Google Scholar 

  4. San Miguel JF, Ciudad J, Vidriales MB, et al.: Immunophenotypical detection of minimal residual disease in acute leukemia. Crit Rev Oncol Hematol 1999, 32:175–185.

    PubMed  CAS  Google Scholar 

  5. San Miguel JF, Ciudad J, Vidriales MB, et al.: Immunophenotypical detection of minimal residual disease in acute leukemia. J Clin Oncol 1999, 32:175–185.

    CAS  Google Scholar 

  6. Sievers EL, Radich JP: Detection of minimal residual disease in acute leukemia. Curr Opin Hematol 2000, 7:212–216.

    Article  PubMed  CAS  Google Scholar 

  7. Orfao A, Schmitz G, Brando B, et al.: Clinically useful information provided by the flow cytometric immunophenotyping of hematological malignancies: current status and future directions. Clin Chem 1999, 45:1708–1717.

    PubMed  CAS  Google Scholar 

  8. Campana D, Coustan-Smith E: Advances in the immunological monitoring of childhood acute lymphoblastic leukaemia. Best Pract Res Clin Haematol 2002, 15:1–19.

    Article  PubMed  Google Scholar 

  9. Nowak R, Oelschlaegel U, Schuler U, et al.: Sensitivity of combined DNA/immunophenotype flow cytometry for the detection of low levels of aneuploid lymphoblastic leukemia cells in bone marrow. Cytometry 1997, 30:47–53.

    Article  PubMed  CAS  Google Scholar 

  10. Campana D, Pui CH: Detection of minimal residual disease in acute leukemia: methodologic advances and clinical significance. Blood 1995, 85:1416–1434.

    PubMed  CAS  Google Scholar 

  11. Campana D, Coustan-Smith E: Detection of minimal residual disease in acute leukemia by flow cytometry. Cytometry 1999, 38:139–152.

    Article  PubMed  CAS  Google Scholar 

  12. Ciudad J, San Miguel JF, Lopez-Berges MC, et al.: Detection of abnormalities in B-cell differentiation pattern is a useful tool to predict relapse in precursor-B-ALL. Br J Haematol 1999, 104:695–705.

    Article  PubMed  CAS  Google Scholar 

  13. Weir EG, Cowan K, LeBeau P, Borowitz MJ: A limited antibody panel can distinguish B-precursor acute lymphoblastic leukemia from normal B precursors with four color flow cytometry: implications for residual disease detection. Leukemia 1999, 13:558–567.

    Article  PubMed  CAS  Google Scholar 

  14. Lucio P, Parreira A, van den Beemd MW, et al.: Flow cytometric analysis of normal B cell differentiation: a frame of reference for the detection of minimal residual disease in precursor-B-ALL. Leukemia 1999, 13:419–427. The precise definition of normal B-cell differentiation could help in the identification of blast cells in patients in mCR.

    Article  PubMed  CAS  Google Scholar 

  15. Porwit-MacDonald A, Bjorklund E, Lucio P, et al.: BIOMED-1 concerted action report: flow cytometric characterization of CD7+ cell subsets in normal bone marrow as a basis for the diagnosis and follow-up of T cell acute lymphoblastic leukemia (T-ALL). Leukemia 2000, 14:816–825. Knowledge of T-cell populations in normal bone marrow allows identification of blast T cells and is a valuable tool for MRD follow-up.

    Article  PubMed  CAS  Google Scholar 

  16. Ciudad J, Orfao A, Vidriales B, et al.: Immunophenotypic analysis of CD19+ precursors in normal human adult bone marrow: implications for minimal residual disease detection. Haematologica 1998, 83:1069–1075. The existence of an altered B-cell differentiation pathway in bone marrow is associated with a high relapse rate and shorter disease-free survival.

    PubMed  CAS  Google Scholar 

  17. Lamkin T, Brooks J, Annett G, et al.: Immunophenotypic differences between putative hematopoietic stem cells and childhood B-cell precursor acute lymphoblastic leukemia cells. Leukemia 1994, 8:1871–1878.

    PubMed  CAS  Google Scholar 

  18. Dworzak MN, Froschl G, Printz D, et al.: Prognostic significance and modalities of flow cytometric minimal residual disease detection in childhood acute lymphoblastic leukemia. Blood 2002, 99:1952–1958.

    Article  PubMed  CAS  Google Scholar 

  19. Dworzak MN, Fritsch G, Panzer-Grumayer ER, et al.: Detection of residual disease in pediatric B-cell precursor acute lymphoblastic leukemia by comparative phenotype mapping: method and significance. Leukemia Lymphoma 2000, 38:295–308. Comparative phenotype mapping enables us to detect MRD efficiently.

    PubMed  CAS  Google Scholar 

  20. Szczepanski T, Orfao A, van der Velden VH, et al.: Minimal residual disease in leukaemia patients. Lancet Oncol 2001, 2:409–417.

    Article  PubMed  CAS  Google Scholar 

  21. Muñoz L, Lopez O, Martino R, et al.: Combined use of reverse transcriptase polymerase chain reaction and flow cytometry to study minimal residual disease in Philadelphia positive acute lymphoblastic leukemia. Haematologica 2000, 85:704–710.

    PubMed  Google Scholar 

  22. Ciudad J, San Miguel JF, López-Berges MC, et al.: Prognostic value of immunophenotypic detection of minimal residual disease in acute lymphoblastic leukemia. J Clin Oncol 1998, 16:3774–3781.

    PubMed  CAS  Google Scholar 

  23. Sánchez J, Serrano J, Gomez P, et al.: Clinical value of immunological monitoring of minimal residual disease in acute lymphoblastic leukaemia after allogeneic transplantation. Br J Haematol 2002, 116:686–694. Immunologic evaluation of MRD in ALL is a valuable tool in allogeneic transplantation settings.

    Article  PubMed  Google Scholar 

  24. Vidriales MB, Perez JJ, Lopez-Berges C, et al.: Minimal residual disease (MRD) in adolescent (> 14 years) and adult acute lymphoblastic leukaemias (ALL): early immunophenotypical evaluation has high clinical value. Blood 2003, 101:4695–4700. Immunologic evaluation of MRD early during induction therapy in adult ALL discriminates patients at different risks of relapse.

    Article  PubMed  CAS  Google Scholar 

  25. Krampera M, Vitale A, Vincenzi C, et al.: Outcome prediction by immunophenotypic minimal residual disease detection in adult T-cell acute lymphoblastic leukaemia. Br J Haematol 2003, 120:74–79. Immunologic detection of MRD in T-cell ALL adult patients at different follow-up points during the first year of treatment is significantly associated with a high risk of relapse.

    Article  PubMed  Google Scholar 

  26. Mortuza FY, Papaioannou M, Moreira IM, et al.: Minimal residual disease tests provide an independent predictor of clinical outcome in adult acute lymphoblastic leukemia. J Clin Oncol 2002, 20:1094–1104.

    Article  PubMed  Google Scholar 

  27. Radich J, Gehly G, Lee A, et al.: Detection of bcr-abl transcripts in Philadelphia chromosome-positive acute lymphoblastic leukemia after marrow transplantation. Blood 1997, 89:2602–2609.

    PubMed  CAS  Google Scholar 

  28. Brisco J, Hughes E, Neoh SH, et al.: Relationship between minimal residual disease and outcome in adult acute lymphoblastic leukemia. Blood 1996, 87:5251–5256.

    PubMed  CAS  Google Scholar 

  29. Mitterbauer G, Nemeth P, Wacha S, et al.: Quantification of minimal residual disease in patients with BCR-ABL-positive acute lymphoblastic leukaemia using quantitative competitive polymerase chain reaction. Br J Haematol 1999 106:634–643.

    Article  PubMed  CAS  Google Scholar 

  30. Foroni L, Coyle LA, Papaioannou M, et al.: Molecular detection of minimal residual disease in adult and childhood acute lymphoblastic leukaemia reveals differences in treatment response. Leukemia 1997, 11:1732–1741.

    Article  PubMed  CAS  Google Scholar 

  31. Chami I, Perot C, Portnoi MF, et al.: Molecular analysis of an unusual rearrangement between chromosomes 4 and 11 in adult pre-B-cell acute lymphoblastic leukemia. Cancer Genet Cytogenet 2002, 133:129–133.

    Article  PubMed  CAS  Google Scholar 

  32. Chucrallah AE, Stass SA, Huh YO, et al.: Adult acute lymphoblastic leukemia at relapse: cytogenetic, immunophenotypic, and molecular changes. Cancer 1995, 76:985–991.

    Article  PubMed  CAS  Google Scholar 

  33. Guglielmi C, Cordone I, Boecklin F, et al.: Immunophenotype of adult and childhood acute lymphoblastic leukemia: changes at first relapse and clinico-prognostic implications. Leukemia 1997, 11:1501–1507.

    Article  PubMed  CAS  Google Scholar 

  34. Tomova A, Babusikova O: Shifts in expression of immunological cell markers in relapsed acute leukemia. Neoplasma 2001, 48:164–168.

    PubMed  CAS  Google Scholar 

  35. Oelschlagel U, Nowak R, Schaub A, et al.: Shift of aberrant antigen expression at relapse or at treatment failure in acute leukemia. Cytometry 2000, 42:247–253.

    Article  PubMed  CAS  Google Scholar 

  36. Coustan-Smith E, Behm FG, Sanchez J, et al.: Immunological detection of minimal residual disease in children with acute lymphoblastic leukaemia. Lancet 1998, 351:550–554.

    Article  PubMed  CAS  Google Scholar 

  37. Drexler HG, Thield E, Ludwig WD: Review of the incidence and clinical relevance of myeloid antigen-positive acute lymphoblastic leukemia. Leukemia 1991, 5:637–645.

    PubMed  CAS  Google Scholar 

  38. Lauria F, Raspadori D, Martinelli G, et al.: Increased expression of myeloid antigen markers in adult acute lymphoblastic leukaemia patients: diagnostic and prognostic implications. Br J Haematol 1994, 87:286–292.

    PubMed  CAS  Google Scholar 

  39. Boldt DH, Kopecky KJ, Head D, et al.: Expression of myeloid antigens by blast cells in acute lymphoblastic leukemia of adults. The Southwest Oncology Group experience. Leukemia 1994, 8:2118–2126.

    PubMed  CAS  Google Scholar 

  40. Preti HA, Huh YO, O’Brien SM, et al.: Myeloid markers in adult acute lymphocytic leukemia: correlations with patient and disease characteristics and with prognosis. Cancer 1995, 76:1564–1570.

    Article  PubMed  CAS  Google Scholar 

  41. Borowitz MJ, Shuster J, Carroll AJ, et al.: Prognostic significance of fluorescence intensity of surface marker expression in childhood B-precursor acute lymphoblastic leukemia: a Pediatric Oncology Group Study. Blood 1997, 89:3960–3966.

    PubMed  CAS  Google Scholar 

  42. Casasnovas RO, Campos L, Mugneret F, et al.: Immunophenotypic patterns and cytogenetic anomalies in acute nonlymphoblastic leukemia subtypes: a prespective study of 432 patients. Leukemia 1998, 12:34–43.

    Article  PubMed  CAS  Google Scholar 

  43. Lucio P, Gaipa G, van Lochem EG, et al.: BIOMED-I concerted action report: flow cytometric immunophenotyping of precursor B-ALL with standardized triple-stainings. BIOMED-1 Concerted Action Investigation of Minimal Residual Disease in Acute Leukemia: International Standardization and Clinical Evaluation. Leukemia 2001, 15:1185–1192.

    Article  PubMed  CAS  Google Scholar 

  44. Cavé H, Van der Werff J, Bosch T, et al.: Clinical significance of minimal residual disease in childhood acute lymphoblastic leukemia. N Engl J Med 1998, 339:591–598.

    Article  PubMed  Google Scholar 

  45. Malec M, Bjorklund E, Soderhall S, et al.: Flow cytometry and allele-specific oligonucleotide PCR are equally effective in detection of minimal residual disease in ALL. Leukemia 2001, 15:716–727.

    Article  PubMed  CAS  Google Scholar 

  46. Gajjar A, Ribeiro R, Hancock ML, et al.: Persistance of circulating blasts after one week of multiagent chemotherapy confers a poor prognosis in childhood acute lymphoblastic leukemia. Blood 1995, 86:1292–1295.

    PubMed  CAS  Google Scholar 

  47. Sandlund JT, Harrison PL, Rivera G, et al.: Persistence of lymphoblasts in bone marrow on day 15 and days 22 to 25 of remission induction predicts a dismal treatment outcome in children with acute lymphoblastic leukemia. Blood 2002, 100:43–47.

    Article  PubMed  CAS  Google Scholar 

  48. Griffin TC, Shuster JJ, Buchanan GR, et al.: Slow disappearance of peripheral blood blasts is an adverse prognostic factor in childhood T cell acute lymphoblastic leukemia: a Pediatric Oncology Group study. Leukemia 2000, 14:792–795.

    Article  PubMed  CAS  Google Scholar 

  49. Donadieu J, Hill C: Early response to chemotherapy as a prognostic factor in childhood acute lymphoblastic leukaemia: a methodological review. Br J Haematol 2001, 115:34–45.

    Article  PubMed  CAS  Google Scholar 

  50. Panzer-Grümayer ER, Schneider M, Panzer S, et al.: Rapid molecular response during early induction chemotherapy predicts a good outcome in childhood acute lymphoblastic leukemia. Blood 2000, 95:790–794.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Vidriales, MB., Orfao, A. & San-Miguel, J.F. Immunologic monitoring in adults with acute lymphoblastic leukemia. Curr Oncol Rep 5, 413–418 (2003). https://doi.org/10.1007/s11912-003-0028-4

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11912-003-0028-4

Keywords

Navigation