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Detection and quantification of residual disease in chronic myelogenous leukemia

Leukemia volume 14, pages 998–1005 (2000)Cite this article

Abstract

The degree of tumor load reduction after therapy is an important prognostic factor for patients with CML. Conventional metaphase analysis has been considered to be the ‘gold standard’ for evaluating patient response to treatment but this technique normally requires bone marrow aspiration and is therefore invasive. The frequency of cytogenetic analyses can be considerably reduced if patients are also monitored by molecular methods, which can be performed on peripheral blood specimens. Of the various techniques available, most attention has been paid to RT-PCR for BCR-ABL mRNA since this is by far the most sensitive. Simple, non-quantitative RT-PCR analysis gives only limited information on patients after treatment. Quantitative RT-PCR assays have been developed to monitor the kinetics of residual BCR-ABL transcripts over time. Variables in the quantitative PCR assay may be controlled for by quantification of transcripts of a normal gene (eg ABL or glucose-6-phosphate dehydrogenase, G6PD) as an internal standard. After allogeneic stem cell transplantation, most patients become RT-PCR negative, often after a period of low level positivity that may persist for several months. Those patients destined to relapse are characterized by the reappearance and/or rising levels of BCR-ABL transcripts. In contrast, for patients treated with interferon-α (IFN) residual disease is rarely, if ever, eliminated. The actual level of minimal residual disease in complete cytogenetic responders to IFN correlates with the probability of relapse. New quantitative real time procedures promise to simplify the protocols that are currently in use, but standardization and the introduction of rigorous, internationally accepted controls are required to enable RT-PCR to become a robust and routine basis for therapeutic decisions.

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References

  1. Nowell PC, Hungerford DA . A minute chromosome in human chronic granulocytic leukemia Science 1960 132: 1497–1501

    Google Scholar 

  2. Rowley JD . A new consistent chromosome abnormality in chronic myelogenous leukaemia detected by quinacrine fluorescence and Giemsa staining Nature 1973 243: 290–293

    CAS  PubMed  Google Scholar 

  3. Sawyers CL . Chronic myeloid leukemia New Engl J Med 1999 340: 1330–1340

    CAS  PubMed  Google Scholar 

  4. Groffen J, Stephenson JR, Heisterkamp N, de Klein A, Bartram CR, Grosveld G . Philadelphia chromosomal breakpoints are clustered within a limited region, bcr, on chromosome 22 Cell 1984 36: 93–99

    CAS  PubMed  Google Scholar 

  5. Stam K, Heisterkamp N, Grosveld G, de Klein A, Verma RS, Coleman M, Dosik H, Groffen J . Evidence of a new chimeric bcr/c-abl mRNA in patients with chronic myelocytic leukemia and the Philadelphia chromosome New Engl J Med 1985 313: 1429–1433

    CAS  PubMed  Google Scholar 

  6. Melo JV, Gordon DE, Cross NCP, Goldman JM . The ABL-BCR fusion gene is expressed in chronic myeloid leukemia Blood 1993 81: 158–165

    CAS  PubMed  Google Scholar 

  7. Thijsen SFT, Schuurhuis GJ, van Oostveen JW, Ossenkoppele GJ . Chronic myeloid leukemia from basics to bedside Leukemia 1999 13: 1646–1674

    CAS  PubMed  Google Scholar 

  8. Hehlmann R, Heimpel H . Current aspects of drug therapy in Philadelphia-positive CML: Correlation of tumor burden with survival Leuk Lymphoma 1996 22: (Suppl. 1) 161–167

    PubMed  Google Scholar 

  9. Hook EB . Exclusion of chromosomal mosaicism: tables of 90%, 95%, and 99% confidence limits and comments on use Am J Hum Genet 1977 29: 94–97

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Cortes J, Talpaz M, O'Brien S, Rios MB, Majlis A, Keating M, Freireich EJ, Kantarjian H . Suppression on cytogenetic clonal evolution with interferon alfa therapy in patients with Philadelphia chromosome-positive chronic myelogenous leukemia J Clin Oncol 1998 16: 3279–3285

    CAS  PubMed  Google Scholar 

  11. Kantarjian HM, Dixon D, Keating MJ, Talpaz M, Walters RS, McCredie KB, Freireich EJ . Characteristics of accelerated disease in chronic myelogenous leukemia Cancer 1988 61: 1441–1446

    CAS  PubMed  Google Scholar 

  12. Tkachuk DC, Westbrook CA, Andreeff M, Donlon TA, Cleary ML, Suryanarayan K, Homge M, Redner A, Gray J, Pinkel D . Detection of bcr-abl fusion in chronic myelogeneous leukemia by in situ hybridization Science 1990 250: 559–562

    CAS  PubMed  Google Scholar 

  13. Nacheva E, Holloway T, Brown K, Bloxham D, Green AR . Philadelphia-negative chronic myeloid leukaemia: detection by FISH of BCR-ABL fusion gene localized either to chromosome 9 or chromosome 22 Br J Haematol 1994 87: 409–412

    CAS  PubMed  Google Scholar 

  14. Hochhaus A, Reiter A, Skladny H, Melo JV, Sick C, Berger U, Guo JQ, Arlinghaus RB, Hehlmann R, Goldman JM, Cross NCP . A novel BCR-ABL fusion gene (e6a2) in a patient with Philadelphia chromosome negative chronic myelogenous leukemia Blood 1996 88: 2236–2240

    CAS  PubMed  Google Scholar 

  15. Melo JV . The diversity of BCR-ABL fusion proteins and their relationship to leukemia phenotype Blood 1996 88: 2375–2384

    CAS  PubMed  Google Scholar 

  16. Weber-Matthiesen K, Winkemann M, Müller-Hermelink A, Schlegelberger B, Grote W . Simultaneous fluorescence immunophenotyping and interphase cytogenetics: a contribution to characterization of tumor cells J Histochem Cytochem 1992 40: 171–175

    CAS  PubMed  Google Scholar 

  17. Haferlach T, Winkemann M, Nickenig C, Meeder M, Ramm-Petersen L, Schoch R, Nickelsen M, Weber-Matthiesen K, Schlegelberger B, Schoch C, Gassmann W, Löffler H . Which compartments are involved in Philadelphia-chromosome positive chronic myeloid leukaemia? An answer at the single cell level by combining May-Grünwald-Giemsa staining and fluorescence in situ hybridization techniques Br J Haematol 1997 97: 99–106

    CAS  PubMed  Google Scholar 

  18. Bentz M, Cabot G, Moos M, Speicher MR, Ganser A, Lichter P, Döhner H . Detection of chimeric BCR-ABL genes on bone marrow samples and blood smears in chronic myeloid and acute lymphoblastic leukemia by in situ hybridization Blood 1994 83: 1922–1928

    CAS  PubMed  Google Scholar 

  19. Garcia-Isidoro M, Tabernero MD, Garcia JL, Najera ML, Hernandez JM, Wiegant J, Raap A, San Miguel J, Orfao A . Detection of the Mbcr/abl translocation in chronic myeloid leukemia by fluorescence in situ hybridization: comparison with conventional cytogenetics and implications for minimal residual disease detection Hum Pathol 1997 28: 154–159

    CAS  PubMed  Google Scholar 

  20. Cuneo A, Bigoni R, Emmanuel B, Smit E, Rigolin GM, Roberti MG, Bardi MG, Piva N, Scapoli G, Castoldi G, Van den Berghe H, Hagemeijer A . Fluorescence in situ hybridization for the detection and monitoring of the Ph-positive clone in chronic myelogenous leukemia: comparison with metaphase banding analysis Leukemia 1998 12: 1718–1723

    CAS  PubMed  Google Scholar 

  21. Yanagi M, Shinjo K, Takeshita A, Tobita T, Yano K, Kobayashi M, Terasaki H, Naoe T, Ohnishi K, Ohno R . Simple and reliably sensitive diagnosis and monitoring of Philadelphia chromosome-positive cells in chronic myeloid leukemia by interphase fluorescence in situ hybridization of peripheral blood cells Leukemia 1999 13: 542–552

    CAS  PubMed  Google Scholar 

  22. Chase A, Grand F, Zhang JG, Blackett N, Goldman J, Gordon M . Factors influencing the false positive and negative rates of BCR-ABL fluorescence in-situ hybridization Genes Chromosom Cancer 1997 18: 246–253

    CAS  PubMed  Google Scholar 

  23. Cox Froncillo MC, Cantonetti M, Masi M, Lentini R, Giudiceandrea P, Maffei L, Tribalto M, Amadori S, Papa G . Cytogenetic analysis is non-informative for assessing the remission rate in chronic myeloid leukemia (CML) patients on interferon-alpha (IFN-alpha) therapy Cancer Genet Cytogenet 1995 84: 15–18

    CAS  PubMed  Google Scholar 

  24. Mühlmann J, Thaler J, Hilbe W, Bechter O, Erdel M, Utermann G, Duba HC . Fluorescence in situ hybridization (FISH) on peripheral blood smears for monitoring Philadelphia chromosome-positive chronic myeloid leukemia (CML) during interferon treatment: a new strategy for remission asssessment Genes Chromosom Cancer 1998 21: 90–100

    PubMed  Google Scholar 

  25. Cox Froncillo MC, Maffei L, Cantonetti M, Del Poeta G, Lentini R, Bruno A, Masi M, Tribalto M, Amadori S . FISH analysis for CML monitoring? Ann Hematol 1996 73: 113–119

    CAS  Google Scholar 

  26. Tchirkov A, Giollant M, Tavernier F, Briancon G, Tournilhac O, Kwiatkowski F, Philippe P, Choufi B, Demeocq F, Travade P, Malet P . Interphase cytogenetics and competitive RT-PCR for residual disease monitoring in patients with chronic myeloid leukaemia during interferon-α therapy Br J Haematol 1998 101: 552–557

    CAS  PubMed  Google Scholar 

  27. Verfaillie C, Bhatia R, Miller W, Mortari F, Roy V, Burger S, McCullough J, Stieglbauer K, Dewald G, Heimfeld S, Miller JS, McGlave P . BCR/ABL-negative primitive progenitors suitable for transplantation can be selected from the marrow of most early-chronic phase but not accelerated-phase chronic myelogenous leukemia patients Blood 1996 87: 4770–4779

    CAS  PubMed  Google Scholar 

  28. Kirk JA, Reems JA, Roecklein BA, Van Devanter DR, Bryant EM, Radich J, Edmands S, Lee A, Torok Storb B . Benign marrow progenitors are enriched in the CD34+/HLA-DRlo population but not in the CD34+/CD38lo population in chronic myeloid leukemia: an analysis using interphase fluorescence in situ hybridization Blood 1995 86: 737–743

    CAS  PubMed  Google Scholar 

  29. Sinclair PB, Green AR, Grace C, Nacheva EP . Improved sensitivity of BCR-ABL detection: a triple-probe three-color fluorescence in situ hybridization system Blood 1997 90: 1395–1402

    CAS  PubMed  Google Scholar 

  30. Buno I, Wyatt WA, Zinsmeister AR, Dietz-Band J, Silver RT, Dewald GW . A special fluorescent in situ hybridization technique to study peripheral blood and assess the effectiveness of interferon therapy in chronic myeloid leukemia Blood 1998 92: 2315–2321

    CAS  PubMed  Google Scholar 

  31. Dewald GW, Wyatt WA, Juneau AL, Carlson RO, Zinsmeister AR, Jalal SM, Spurbeck JL, Silver RT . Highly sensitive fluorescence in situ hybridization method to detect double BCR/ABL fusion and monitor response to therapy in chronic myeloid leukemia Blood 1998 91: 3357–3365

    CAS  PubMed  Google Scholar 

  32. Grand F, Kulkarni S, Chase A, Goldman JM, Gordon MY, Cross NCP . Frequent deletion of hSNF5/INI1, a component of the SWI/SNF complex, during progression of chronic myeloid leukemia Cancer Res 1999 59: 3870–3874

    CAS  PubMed  Google Scholar 

  33. El Rifai W, Ruutu T, Vettentanta K, Temtamy S, Knuutila S . Minimal residual disease after allogeneic bone marrow transplantation for chronic myeloid leukaemia: a metaphase-FISH study Br J Haematol 1996 92: 365–369

    CAS  PubMed  Google Scholar 

  34. Seong DC, Kantarjian HM, Ro JY, Talpaz M, Xu J, Robinson JR, Deisseroth AB, Champlin RE, Siciliano MJ . Hypermetaphase fluorescence in situ hybridization for quantitative monitoring of Philadelphia chromosome-positive cells in patients with chronic myelogenous leukemia during treatment Blood 1995 86: 2343–2349

    CAS  PubMed  Google Scholar 

  35. Seong D, Giralt S, Fischer H, Hayes K, Glassman A, Arlinghaus R, Xu J, Kantarjian H, Siciliano M, Champlin R . Usefulness of detection of minimal residual disease by ‘hypermetaphase’ fluorescent in situ hybridization after allogeneic BMT for chronic myelogenous leukemia Bone Marrow Transplant 1997 19: 565–570

    CAS  PubMed  Google Scholar 

  36. Reiter A, Skladny H, Hochhaus A, Seifarth W, Heimpel H, Bartram CR, Cross NCP, Hehlmann R . Molecular response of CML patients treated with interferon-α monitored by quantitative Southern blot analysis Br J Haematol 1997 97: 86–93

    CAS  PubMed  Google Scholar 

  37. Fishleder AJ, Shadrach B, Tuttle C . bcr rearrangement: potential false positive secondary to an EcoRI restriction fragment length polymorphism Leukemia 1989 3: 746–748

    CAS  PubMed  Google Scholar 

  38. Grossman A, Mathew A, O'Connell MP, Tiso P, Distenfeld A, Benn P . Multiple restriction enzyme digests are required to rule out polymorphism in the molecular diagnosis of chronic myeloid leukemia Leukemia 1990 4: 63–64

    CAS  PubMed  Google Scholar 

  39. Popenoe DW, Schaefer Rego K, Mears JG, Bank A, Leibowitz D . Frequent and extensive deletion during the 9,22 translocation in CML Blood 1986 68: 1123–1128

    CAS  PubMed  Google Scholar 

  40. Bartram CR, Bross Bach U, Schmidt H, Waller HD . Philadelphia-positive chronic myelogenous leukemia with breakpoint 5′ of the breakpoint cluster region but within the bcr gene Blut 1987 55: 505–511

    CAS  PubMed  Google Scholar 

  41. Saglio G, Guerrasio A, Rosso C, Zaccaria A, Tassinari A, Serra A, Rege Cambrin G, Mazza U, Gavosto F . New type of Bcr/Abl junction in Philadelphia chromosome-positive chronic myelogenous leukemia Blood 1990 76: 1819–1824

    CAS  PubMed  Google Scholar 

  42. Stock W, Westbrook CA, Peterson B, Arthur DC, Szatrowski TP, Silver RT, Sher DA, Wu D, LeBeau MM, Schiffer CA, Bloomfield CD . Value of molecular monitoring during treatment of chronic myeloid leukemia: a Cancer and Leukemia Group B Study J Clin Oncol 1997 15: 26–36

    CAS  PubMed  Google Scholar 

  43. Verschraegen CF, Talpaz M, Hirsch Ginsberg CF, Pherwani R, Rios MB, Stass SA, Kantarjian HM . Quantification of the breakpoint cluster region rearrangement for clinical monitoring in Philadelphia chromosome-positive chronic myeloid leukemia Blood 1995 85: 2705–2710

    CAS  PubMed  Google Scholar 

  44. Steegmann JL, Requena MJ, Casado LF, Pico M, Panarrubia MJ, Ferro MT, Resino M, Fernandez-Ranada JM . Southern technique and cytogenetics are complementary and must be used together in the evaluation of Ph1, M-BCR positive chronic myeloid leukemia (CML) patients treated with alpha interferon (IFN-ALPHA) Am J Hematol 1996 53: 169–174

    CAS  PubMed  Google Scholar 

  45. Yoffe G, Blick M, Kantarjian H, Spitzer G, Gutterman J, Talpaz M . Molecular analysis of interferon-induced suppression of Philadelphia chromosome in patients with chronic myeloid leukemia Blood 1987 69: 961–963

    CAS  PubMed  Google Scholar 

  46. Guo JQ, Lian JY, Xian YM, Lee MS, Deisseroth AB, Stass SA, Champlin RE, Talpaz M, Wang JY, Arlinghaus RB . BCR-ABL protein expression in peripheral blood cells of chronic myelogenous leukemia patients undergoing therapy Blood 1994 83: 3629–3637

    CAS  PubMed  Google Scholar 

  47. Guo JQ, Lian J, Glassman A, Talpaz M, Kantarjian H, Deisseroth AB, Arlinghaus RB . Comparison of bcr-abl protein expression and Philadelphia chromosome analyses in chronic myelogenous leukemia patients Am J Clin Pathol 1996 106: 442–448

    CAS  PubMed  Google Scholar 

  48. Morgan GJ, Hughes T, Janssen JW, Gow J, Guo AP, Goldman JM, Wiedemann LM, Bartram CR . Polymerase chain reaction for detection of residual leukaemia Lancet 1989 1: 928–929

    CAS  PubMed  Google Scholar 

  49. Hughes T, Martiat P, Morgan G, Sawyers C, Witte ON, Goldman JM . Significance of residual leukaemia transcripts after bone marrow transplant for CML Lancet 1990 335: 50

    CAS  PubMed  Google Scholar 

  50. Hughes T, Janssen JWG, Morgan G, Martiat P, Saglio G, Pignon JM, Pignatti FP, Mills K, Keating A, Gluckman E, Bartram CR, Goldman JM . False-positive results with PCR to detect leukaemia-specific transcript Lancet 1990 335: 1037–1038

    CAS  PubMed  Google Scholar 

  51. Hughes T, Goldman JM . Improved results with PCR for chronic myeloid leukaemia Lancet 1990 336: 812

    CAS  PubMed  Google Scholar 

  52. Cross NCP, Feng L, Chase A, Bungey J, Hughes TP, Goldman JM . Competitive polymerase chain reaction to estimate the number of BCR-ABL transcripts in chronic myeloid leukemia patients after bone marrow transplantation Blood 1993 82: 1929–1936

    CAS  PubMed  Google Scholar 

  53. Lion T, Henn T, Gaiger A, Kalhs P, Gadner H . Early detection of relapse after bone marrow transplantation in patients with chronic myelogenous leukaemia Lancet 1993 341: 275–276

    CAS  PubMed  Google Scholar 

  54. Malinge MC, Mahon FX, Delfau MH, Daheron L, Kitzis A, Guilhot F, Tanzer J, Grandchamp B . Quantitative determination of the hybrid Bcr-Abl RNA in patients with chronic myelogenous leukaemia under interferon therapy Br J Haematol 1992 82: 701–707

    CAS  PubMed  Google Scholar 

  55. Hochhaus A, Lin F, Reiter A, Skladny H, Mason PJ, van Rhee F, Shepherd PCA, Allan NC, Hehlmann R, Goldman JM, Cross NCP . Quantification of residual disease in chronic myelogenous leukemia patients on interferon-α therapy by competitive polymerase chain reaction Blood 1996 87: 1549–1555

    CAS  PubMed  Google Scholar 

  56. Cross NCP, Melo JV, Feng L, Goldman JM . An optimized multiplex polymerase chain reaction (PCR) for detection of BCR-ABL fusion mRNAs in haematological disorders Leukemia 1994 8: 186–189

    CAS  PubMed  Google Scholar 

  57. Melo JV, Myint H, Galton DA, Goldman JM . P190BCR-ABL chronic myeloid leukaemia: the missing link with chronic myelomonocytic leukaemia? Leukemia 1994 8: 208–211

    CAS  PubMed  Google Scholar 

  58. Rubinstein R, Purves LR . A novel BCR-ABL rearrangement in a Philadelphia chromosome-positive chronic myelogenous leukaemia variant with thrombocythaemia Leukemia 1998 12: 230–232

    CAS  PubMed  Google Scholar 

  59. Clarkson B, Strife A . Linkage of proliferative and maturational abnormalities in chronic myelogenous leukemia and relevance to treatment Leukemia 1993 7: 1683–1721

    CAS  PubMed  Google Scholar 

  60. Morley A . Quantifying leukemia New Engl J Med 1998 339: 627–629

    CAS  PubMed  Google Scholar 

  61. van Dongen JJM, MacIntyre EA, Gabert JA, Delabesse E ., Rossi V, Saglio G, Gotardi E, Rambaldi A, Dotti G, Giesinger F, Parreira A, Gameiro P, Gonzalez Diaz M, 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 Leukemia 1999 12: 1901–1928

    Google Scholar 

  62. Cross NCP . Assessing residual leukaemia Baillières Clin Haematol 1997 10: 389–403

    CAS  PubMed  Google Scholar 

  63. Cross NCP, Feng L, Zhang JG, Goldman JM . Competitive PCR to monitor residual disease after bone marrow transplantation for chronic myeloid leukaemia. In: Borden EC, Goldman JM, Grignani F (eds) Molecular Diagnosis and Monitoring of Leukaemia and Lymphoma Ares-Serono Symposia Publications: Rome 1994 119–126

    Google Scholar 

  64. Potter MN, Cross NCP, van Dongen JJ, Saglio G, Oakhill A, Bartram CR, Goldman JM . Molecular evidence of minimal residual disease after treatment for leukaemia and lymphoma: an updated meeting report and review Leukemia 1993 7: 1302–1314

    CAS  PubMed  Google Scholar 

  65. Reiter E, Greinix HT, Keil F, Brugger S, Rabitsch W, Schulenburg A, Mannhalter C, Schwarzinger I, Worel N, Volc-Platzer B, Fischer G, Dieckmann K, Hinterberger W, Schneider B, Haas OA, Geissler K, Kalhs P . Long-term follow-up of patients after related- and unrelated-donor bone marrow transplantation for chronic myelogenous leukemia Ann Hematol 1999 78: 507–513

    CAS  PubMed  Google Scholar 

  66. Zhang JG, Lin F, Chase A, Goldman JM, Cross NCP . Comparison of genomic DNA and cDNA for detection of residual disease after treatment of chronic myeloid leukemia with allogeneic bone marrow transplantation Blood 1996 87: 2588–2593

    CAS  PubMed  Google Scholar 

  67. Hochhaus A, Lin F, Reiter A, Skladny H, van Rhee F, Shepherd PCA, Allan NC, Hehlmann R, Goldman JM, Cross NCP . Variable numbers of BCR-ABL transcripts persist in CML patients whoachieve complete cytogenetic remission with interferon-α Br J Haematol 1995 91: 126–131

    CAS  PubMed  Google Scholar 

  68. Biernaux C, Loos M, Sels A, Huez G, Stryckmans P . Detection of major bcr-abl gene expression at a very low level in blood cells of some healthy individuals Blood 1995 88: 3118–3122

    Google Scholar 

  69. Bose S, Deininger M, Gora-Tybor J, Goldman JM, Melo JV . The presence of typical and atypical BCR-ABL fusion genes in leukocytes of normal individuals: biological significance and implications for the assessment of minimal residual disease Blood 1998 92: 3362–3367

    CAS  PubMed  Google Scholar 

  70. Melo JV . The molecular biology of chronic myeloid leukaemia Leukemia 1996 10: 751–756

    CAS  PubMed  Google Scholar 

  71. Lion T, Izraeli S, Henn T, Gaiger A, Mor W, Gadner H . Monitoring of residual disease in chronic myelogenous leukemia by quantitative polymerase chain reaction Leukemia 1992 6: 495–499

    CAS  PubMed  Google Scholar 

  72. Thompson JD, Brodsky I, Yunis JJ . Molecular quantification of residual disease in chronic myelogenous leukemia after bone marrow transplantation Blood 1992 79: 1629–1635

    CAS  PubMed  Google Scholar 

  73. Nagel S, Schmidt M, Thiede C, Huhn D, Neubauer A . Quantification of Bcr-Abl transcripts in chronic myelogenous leukemia (CML) using standardized, internally controlled, competitive differential PCR (CD-PCR) Nucleic Acids Res 1996 24: 4102–4103

    CAS  PubMed  PubMed Central  Google Scholar 

  74. Delage R, Soiffer RJ, Dear K, Ritz J . Clinical significance of bcr-abl gene rearrangement detected by polymerase chain reaction after allogeneic bone marrow transplantation in chronic myelogenous leukemia Blood 1991 78: 2759–2767

    CAS  PubMed  Google Scholar 

  75. Lin F, van Rhee F, Goldman JM, Cross NCP . Kinetics of increasing BCR-ABL transcript numbers in chronic myeloid leukemia patients who relapse after bone marrow transplantation Blood 1996 87: 4473–4478

    CAS  PubMed  Google Scholar 

  76. Lin F, Kirkland MA, van Rhee F, Chase A, Coulthard S, Bungey J, Goldman JM, Cross NCP . Molecular analysis of transient cytogenetic relapse after allogeneic bone marrow transplantation for chronic myeloid leukaemia Bone Marrow Transplant 1996 18: 1147–1152

    CAS  PubMed  Google Scholar 

  77. van Rhee F, Lin F, Cullis JO, Spencer A, Cross NCP, Chase A, Garicochea B, Bungey J, Barrett J, Goldman JM . Relapse of chronic myeloid leukemia after allogeneic bone marrow transplant: the case for giving donor leukocyte transfusions before the onset of hematologic relapse Blood 1994 83: 3377–3383

    CAS  PubMed  Google Scholar 

  78. Raanani P, Dazzi F, Sohal J, Szydlo R, van Rhee F, Reiter A, Lin F, Goldman JM, Cross NCP . The rate and kinetics of molecular response to donor leucocyte transfusions in chronic myeloid leukaemia patients treated for relapse after allogeneic bone marrow transplantation Br J Haematol 1997 99: 945–950

    CAS  PubMed  Google Scholar 

  79. Corsetti MT, Lerma E, Dejana A, Basta P, Ferrara R, Benvenuto F, Vassallo F, Abate M, Piaggio G, Parodi C, Sessarego M, Pira GL, Manca F, Carella AM . Quantitative competitive reverse transcriptase-polymerase chain reaction for BCR-ABL on Philadelphia-negative leukaphereses allows the selection of low-contaminated peripheral blood progenitor cells for autografting in chronic myelogenous leukemia Leukemia 1999 13: 999–1008

    CAS  PubMed  Google Scholar 

  80. Hochhaus A, Reiter A, Saußele S, Reichert A, Emig M, Kaeda J, Schultheis B, Berger U, Shepherd PCA, Allan N, Hehlmann R, Goldman JM, Cross NCP, for the German CML Study Group and the UK MRC CML Study Group . Molecular heterogeneity in complete cytogenetic responders after interferon-α therapy for chronic myeloid leukaemia: low levels of minimal residual disease are associated with continuing remission Blood 2000 95: 62–66

    CAS  PubMed  Google Scholar 

  81. Kurzrock R, Estrov Z, Kantarjian H, Talpaz M . Conversion of interferon-induced, long-term cytogenetic remissions in chronic myelogenous leukemia to polymerase chain reaction negativity J Clin Oncol 1998 16: 1526–1531

    CAS  PubMed  Google Scholar 

  82. Reiter A, Marley SB, Hochhaus A, Sohal J, Raanani P, Hehlmann R, Gordon MY, Goldman JM, Cross NCP . BCR-ABL positive progenitors in chronic myeloid leukaemia patients in complete cytogenetic remission after treatment with interferon-α Br J Haematol 1998 102: 1271–1278.y

    CAS  PubMed  Google Scholar 

  83. Mensink E, van de Locht A, Schattenberg A, Linders E, Schaap N, Guerts van Kessel A, de Witte T . Quantitation of minimal residual disease in Philadelphia chromosome positive chronic myeloid leukaemia patients using real-time quantitative RT-PCR Br J Haematol 1998 102: 768–774

    CAS  PubMed  Google Scholar 

  84. Preudhomme C, Révillion F, Merlat A, Hornez L, Roumier C, Duflos-Grardel N, Jouet JP, Cosson A, Peyrat JP, Fenaux P . Detection of BCR-ABL transcripts in chronic myeloid leukemia (CML) using a ‘real time’ quantitative RT-PCR assay Leukemia 1999 13: 957–964

    CAS  PubMed  Google Scholar 

  85. Eder M, Battner K, Kafert S, Stucki A, Ganser A, Hertenstein B . Monitoring of BCR-ABL expression using real-time RT-PCR in CML after bone marrow or peripheral blood stem cell transplantation Leukemia 1999 13: 1383–1389

    CAS  PubMed  Google Scholar 

  86. Branford S, Hughes TP, Rudzki Z . Monitoring chronic myeloid leukaemia therapy by real-time quantitative PCR in blood is a reliable alternative to bone marrow cytogenetics Br J Haematol 1999 107: 587–599

    CAS  PubMed  Google Scholar 

  87. Heid CA, Stevens J, Livak KJ, Williams PM . Real time quantitative PCR Genome Res 1996 6: 986–994

    CAS  Google Scholar 

  88. Wittwer CT, Herrmann MG, Moss AA, Rasmussen RP . Continuous fluorescence monitoring of rapid cycle DNA amplification Biotechniques 1997 22: 130–138

    CAS  PubMed  Google Scholar 

  89. Wittwer CT, Ririe KM, Andrew RV, David DA, Gundry RA, Balis UJ . The LightCycler: a microvolume multisample fluorimeter with rapid temperature control Biotechniques 1997 22: 176–181

    CAS  Google Scholar 

  90. Emig M, Saussele S, Wittor H, Weisser A, Reiter A, Willer A, Berger U, Hehlmann R, Cross NCP, Hochhaus A . Accurate and rapid analysis of residual disease in patients with CML using specific fluorescent hybridization probes for real time quantitative RT-PCR Leukemia 1999 13: 1825–1832

    CAS  PubMed  Google Scholar 

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Acknowledgements

The authors thank the Deutsche José-Carreras-Stiftung eV, the Leukaemia Research Fund (UK), the Tumorzentrum Heidelberg/Mannheim, and the Forschungsfonds der Fakultät für Klinische Medizin, Mannheim, Germany for financial support. The paper is based on a presentation at the ‘Workshop on Minimal residual disease’ at Reisensburg Castle/Ulm, Germany, funded by the Kind-Philipp-Foundation, October 24–26, 1999.

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  1. III. Medizinische Universitätsklinik, Klinikum Mannheim der Universität Heidelberg, Mannheim, Germany

    A Hochhaus, A Weisser, P La Rosée, M Emig, MC Müller, S Saußele, A Reiter, C Kuhn, U Berger & R Hehlmann

  2. Department of Haematology, Imperial College School of Medicine, Hammersmith Hospital, London, UK

    NCP Cross

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Hochhaus, A., Weisser, A., Rosée, P. et al. Detection and quantification of residual disease in chronic myelogenous leukemia. Leukemia 14, 998–1005 (2000). https://doi.org/10.1038/sj.leu.2401811

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  • DOI: https://doi.org/10.1038/sj.leu.2401811

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