Journal Mobile Options
Table of Contents
Vol. 112, No. 1-2, 2004
Issue release date: May 2004
Acta Haematol 2004;112:8–15
(DOI:10.1159/000077554)

Minimal Residual Disease Studies by Flow Cytometry in Acute Leukemia

Campana D. · Coustan-Smith E.
To view the fulltext, log in and/or choose pay-per-view option

Individual Users: Register with Karger Login Information

Please create your User ID & Password





Contact Information











I have read the Karger Terms and Conditions and agree.

To view the fulltext, please log in

To view the pdf, please log in

Abstract

Minimal residual disease (MRD) assays are increasingly important in the clinical management of patients with acute leukemia. Among the methods available for monitoring MRD, flow cytometry holds great promise for clinical application because of its simplicity and wide availability. Several studies have demonstrated strong correlations between MRD levels by flow cytometry during clinical remission and treatment outcome, lending support to the reliability of this approach. Flow-cytometric detection of MRD is based on the identification of immunophenotypic combinations expressed on leukemic cells but not on normal hematopoietic cells. Its sensitivity depends on the specificity of the immunophenotypes used to track leukemic cells and on the number of cells available for study. Immunophenotypes that allow detection of 1 leukemic cell in 10,000 normal cells can be identified in at least 90% of patients with acute lymphoblastic leukemia; immunophenotypes that allow detection of 1 leukemic cell in 1,000–10,000 normal cells can be identified in at least 85% of patients with acute myeloid leukemia. Identification of new markers of leukemia by gene array technology should lead to the design of simple and reliable antibody panels for universal monitoring of MRD. Here we review the relative advantages and disadvantages of flow cytometry for MRD studies, as well as results obtained in correlative studies with treatment outcome.



Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

References

  1. Campana D, Pui CH: Detection of minimal residual disease in acute leukemia: Methodologic advances and clinical significance. Blood 1995;85:1416–1434.
  2. van Dongen JJ, Macintyre EA, Gabert JA, Delabesse E, Rossi V, Saglio G, Gottardi E, Rambaldi A, Dotti G, Griesinger F, Parreira A, Gameiro P, Diaz MG, Malec M, Langerak AW, San Miguel JF, Biondi A: Standardized RT-PCR analysis of fusion gene transcripts from chromosome aberrations in acute leukemia for detection of minimal residual disease. Report of the BIOMED-1 Concerted Action: Investigation of minimal residual disease in acute leukemia. Leukemia 1999;13:1901–1928.
  3. Pui CH, Campana D: New definition of remission in childhood acute lymphoblastic leukemia. Leukemia 2000;14:783–785.
  4. Foroni L, Harrison CJ, Hoffbrand AV, Potter MN: Investigation of minimal residual disease in childhood and adult acute lymphoblastic leukaemia by molecular analysis. Br J Haematol 1999;105:7–24.
  5. Szczepanski T, Orfao A, van der Velden VH, San Miguel JF, van Dongen JJ: Minimal residual disease in leukaemia patients. Lancet Oncol 2001;2:409–417.
  6. Campana D: Determination of minimal residual disease in leukemia patients. Br J Haematol 2003;121:823–838.
  7. Bradstock KF, Janossy G, Tidman N, Papageorgiou ES, Prentice HG, Willoughby M, Hoffbrand AV: Immunological monitoring of residual disease in treated thymic acute lymphoblastic leukaemia. Leuk Res 1981;5:301–309.
  8. van Dongen JJ, Breit TM, Adriaansen HJ, Beishuizen A, Hooijkaas H: Detection of minimal residual disease in acute leukemia by immunological marker analysis and polymerase chain reaction. Leukemia 1992;6(suppl 1):47–59.

    External Resources

  9. Campana D, Coustan-Smith E, Janossy G: The immunologic detection of minimal residual disease in acute leukemia. Blood 1990;76/1:163–171.
  10. Coustan-Smith E, Behm FG, Sanchez J, Boyett JM, Hancock ML, Raimondi SC, Rubnitz JE, Rivera GK, Sandlund JT, Pui CH, Campana D: Immunological detection of minimal residual disease in children with acute lymphoblastic leukaemia. Lancet 1998;351:550–554.
  11. Farahat N, Morilla A, Owusu-Ankomah K, Morilla R, Pinkerton CR, Treleaven JG, Matutes E, Powles RL, Catovsky D: Detection of minimal residual disease in B-lineage acute lymphoblastic leukaemia by quantitative flow cytometry. Br J Haematol 1998;101/1:158–164.
  12. Coustan-Smith E, Sancho J, Hancock ML, Boyett JM, Behm FG, Raimondi SC, Sandlund JT, Rivera GK, Rubnitz JE, Ribeiro RC, Pui CH, Campana D: Clinical importance of minimal residual disease in childhood acute lymphoblastic leukemia. Blood 2000;96:2691–2696.
  13. San Miguel JF, Vidriales MB, Lopez-Berges C, Diaz-Mediavilla J, Gutierrez N, Canizo C, Ramos F, Calmuntia MJ, Perez JJ, Gonzalez M, Orfao A: Early immunophenotypical evaluation of minimal residual disease in acute myeloid leukemia identifies different patient risk groups and may contribute to postinduction treatment stratification. Blood 2001;98:1746–1751.
  14. Dworzak MN, Froschl G, Printz D, Mann G, Potschger U, Muhlegger N, Fritsch G, Gadner H: Prognostic significance and modalities of flow cytometric minimal residual disease detection in childhood acute lymphoblastic leukemia. Blood 2002;99:1952–1958.
  15. Coustan-Smith E, Sancho J, Behm FG, Hancock ML, Razzouk BI, Ribeiro RC, Rivera GK, Rubnitz JE, Sandlund JT, Pui CH, Campana D: Prognostic importance of measuring early clearance of leukemic cells by flow cytometry in childhood acute lymphoblastic leukemia. Blood 2002;100:52–58.
  16. Coustan-Smith E, Sancho J, Hancock ML, Razzouk BI, Ribeiro RC, Rivera GK, Rubnitz JE, Sandlund JT, Pui CH, Campana D: Use of peripheral blood instead of bone marrow to monitor residual disease in children with acute lymphoblastic leukemia. Blood 2002;100:2399–2402.
  17. Neale GA, Coustan-Smith E, Pan Q, Chen X, Gruhn B, Stow P, Behm FG, Pui CH, Campana D: Tandem application of flow cytometry and polymerase chain reaction for comprehensive detection of minimal residual disease in childhood acute lymphoblastic leukemia. Leukemia 1999;13:1221–1226.
  18. Oelschlagel U, Nowak R, Schaub A, Koppel C, Herbst R, Mohr B, Loffler C, Range U, Gunther H, Assmann M, Siegert E, Wendt E, Huhn R, Brautigam E, Ehninger G: Shift of aberrant antigen expression at relapse or at treatment failure in acute leukemia. Cytometry 2000;42/4:247–253.
  19. Baer MR, Stewart CC, Dodge RK, Leget G, Sule N, Mrozek K, Schiffer CA, Powell BL, Kolitz JE, Moore JO, Stone RM, Davey FR, Carroll AJ, Larson RA, Bloomfield CD: High frequency of immunophenotype changes in acute myeloid leukemia at relapse: Implications for residual disease detection (Cancer and Leukemia Group B Study 8361). Blood 2001;97:3574–3580.
  20. Sang BC, Shi L, Dias P, Liu L, Wei J, Wang ZX, Monell CR, Behm F, Gruenwald S: Monoclonal antibodies specific to the acute lymphoblastic leukemia t(1;19)-associated E2A/pbx1 chimeric protein: Characterization and diagnostic utility. Blood 1997;89:2909–2914.
  21. Paolucci P, Hayward AR, Rapson NT: Pre-B and B cells in children on leukaemia remission maintenance treatment. Clin Exp Immunol 1979;37/2:259–266.
  22. Longacre TA, Foucar K, Crago S, Chen IM, Griffith B, Dressler L, McConnell TS, Duncan M, Gribble J: Hematogones: A multiparameter analysis of bone marrow precursor cells. Blood 1989;73:543–552.
  23. Caldwell CW, Poje E, Helikson MA: B-cell precursors in normal pediatric bone marrow. Am J Clin Pathol 1991;95:816–823.
  24. Lucio P, Parreira A, van den Beemd MW, van Lochem EG, Van Wering ER, Baars E, Porwit-MacDonald A, Bjorklund E, Gaipa G, Biondi A, Orfao A, Janossy G, van Dongen JJ, San Miguel JF: 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.
  25. Asma GE, van den Bergh RL, Vossen JM: Regeneration of TdT+, pre-B, and B cells in bone marrow after allogeneic bone marrow transplantation. Transplantation 1987;43:865–870.
  26. Ciudad J, San Miguel JF, Lopez-Berges MC, Garcia MM, Gonzalez M, Vazquez L, del Canizo MC, Lopez A, van Dongen JJ, Orfao A: 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.
  27. van Lochem EG, Wiegers YM, van den BR, Hahlen K, van Dongen JJ, Hooijkaas H: Regeneration pattern of precursor-B-cells in bone marrow of acute lymphoblastic leukemia patients depends on the type of preceding chemotherapy. Leukemia 2000;14:688–695.
  28. McKenna RW, Washington LT, Aquino DB, Picker LJ, Kroft SH: Immunophenotypic analysis of hematogones (B-lymphocyte precursors) in 662 consecutive bone marrow specimens by 4-color flow cytometry. Blood 2001;98:2498–2507.
  29. Porwit-MacDonald A, Bjorklund E, Lucio P, van Lochem EG, Mazur J, Parreira A, van den Beemd MW, Van Wering ER, Baars E, Gaipa G, Biondi A, Ciudad J, van Dongen JJ, San Miguel JF, Orfao A: 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.
  30. Ciudad J, San Miguel JF, Lopez-Berges MC, Vidriales B, Valverde B, Ocqueteau M, Mateos G, Caballero MD, Hernandez J, Moro MJ, Mateos MV, Orfao A: Prognostic value of immunophenotypic detection of minimal residual disease in acute lymphoblastic leukemia. J Clin Oncol 1998;16:3774–3781.
  31. Lucio P, Gaipa G, van Lochem EG, Van Wering ER, Porwit-MacDonald A, Faria T, Bjorklund E, Biondi A, van den Beemd MW, Baars E, Vidriales B, Parreira A, van Dongen JJ, San Miguel JF, Orfao A: 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.
  32. 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.
  33. Dworzak MN, Fritsch G, Fleischer C, Printz D, Froschl G, Buchinger P, Mann G, Gadner H: Comparative phenotype mapping of normal vs. malignant pediatric B-lymphopoiesis unveils leukemia-associated aberrations. Exp Hematol 1998;26:305–313.
  34. Campana D, Coustan-Smith E: Advances in the immunological monitoring of childhood acute lymphoblastic leukaemia. Best Pract Res Clin Haematol 2002;15/1:1–19.
  35. Hurwitz CA, Loken MR, Graham ML, Karp JE, Borowitz MJ, Pullen DJ, Civin CI: Asynchronous antigen expression in B lineage acute lymphoblastic leukemia. Blood 1988;72/1:299–307.
  36. Wells DA, Hall MC, Shulman HM, Loken MR: Occult B cell malignancies can be detected by three-color flow cytometry in patients with cytopenias. Leukemia 1998;12:2015–2023.
  37. Lavabre-Bertrand T, Janossy G, Ivory K, Peters R, Secker-Walker L, Porwit-MacDonald A: Leukemia-associated changes identified by quantitative flow cytometry. I. CD10 expression. Cytometry 1994;18/4:209–217.
  38. Terstappen LW, Loken MR: Myeloid cell differentiation in normal bone marrow and acute myeloid leukemia assessed by multi-dimensional flow cytometry. Anal Cell Pathol 1990;2/4:229–240.
  39. Coustan-Smith E, Ribeiro RC, Rubnitz JE, Razzouk BI, Pui CH, Pounds S, Andreansky M, Behm FG, Raimondi SC, Shurtleff SA, Downing JR, Campana D: Clinical significance of residual disease during treatment in childhood acute myeloid leukemia. Br J Haematol 2003;123:243–252.
  40. Venditti A, Buccisano F, Del Poeta G, Maurillo L, Tamburini A, Cox C, Battaglia A, Catalano G, Del Moro B, Cudillo L, Postorino M, Masi M, Amadori S: Level of minimal residual disease after consolidation therapy predicts outcome in acute myeloid leukemia. Blood 2000;96:3948–3952.
  41. Sievers EL, Lange BJ, Alonzo TA, Gerbing RB, Bernstein ID, Smith FO, Arceci RJ, Woods WG, Loken MR: Immunophenotypic evidence of leukemia after induction therapy predicts relapse: Results from a prospective Children’s Cancer Group study of 252 patients with acute myeloid leukemia. Blood 2003;101:3398–3408.
  42. Yeoh EJ, Ross ME, Shurtleff SA, Williams WK, Patel D, Behm FG, Raimondi SC, Relling MV, Patel A, Cheng C, Campana D, Wilkins D, Zhou X, Li J, Pui CH, Evans WE, Wong L, Downing JR: Classification, subtype discovery, and prediction of outcome in pediatric acute lymphoblastic leukemia by gene expression profiling. Cancer Cell 2002;1:133–143.
  43. Chen JS, Coustan-Smith E, Suzuki T, Neale GA, Mihara K, Pui CH, Campana D: Identification of novel markers for monitoring minimal residual disease in acute lymphoblastic leukemia. Blood 2001;97:2115–2120.
  44. De Waele M, Renmans W, Jochmans K, Schots R, Lacor P, Trullemans F, Otten J, Balduck N, Vander GK, Van Camp B, van Schie RC, Van Riet I: Different expression of adhesion molecules on CD34+ cells in AML and B-lineage ALL and their normal bone marrow counterparts. Eur J Haematol 1999;63/3:192–201.
  45. Gross HJ, Verwer B, Houck D, Recktenwald D: Detection of rare cells at a frequency of one per million by flow cytometry. Cytometry 1993;14:519–526.
  46. Sanchez J, Serrano J, Gomez P, Martinez F, Martin C, Madero L, Herrera C, Garcia JM, Casano J, Torres A: Clinical value of immunological monitoring of minimal residual disease in acute lymphoblastic leukaemia after allogeneic transplantation. Br J Haematol 2002;116:686–694.
  47. van der Velden V, Jacobs DC, Wijkhuijs AJ, Comans-Bitter WM, Willemse MJ, Hahlen K, Kamps WA, Van Wering ER, van Dongen JJ: Minimal residual disease levels in bone marrow and peripheral blood are comparable in children with T cell acute lymphoblastic leukemia (ALL), but not in precursor-B-ALL. Leukemia 2002;16:1432–1436.
  48. Reichle A, Rothe G, Krause S, Zaiss M, Ullrich H, Schmitz G, Andreesen R: Transplant characteristics: Minimal residual disease and impaired megakaryocytic colony growth as sensitive parameters for predicting relapse in acute myeloid leukemia. Leukemia 1999;13:1227–1234.
  49. Lorenzana R, Coustan-Smith E, Antillon F, Ribeiro RC, Campana D: Simple methods for the rapid exchange of flow cytometric data between remote centers. Leukemia 1999;14:336–337.


Pay-per-View Options
Direct payment This item at the regular price: USD 38.00
Payment from account With a Karger Pay-per-View account (down payment USD 150) you profit from a special rate for this and other single items.
This item at the discounted price: USD 26.50