Role of minimal residual disease monitoring in adult and pediatric acute lymphoblastic leukemia.

Assays that measure minimal residual disease (MRD) can determine the response to treatment in patients with acute lymphoblastic leukemia (ALL) much more precisely than morphologic screening of bone marrow smears. The clinical significance of MRD, detected by flow cytometry or polymerase chain reaction-based methods in childhood ALL, has been established. Hence, MRD is being used in several clinical trials to adjust treatment intensity. Similar findings have been gathered in adult patients with ALL, making MRD one of the most powerful and informative parameters to guide clinical management. This article discusses practical issues related to MRD methodologies and the evidence supporting the use of MRD for risk assignment in clinical trials.

[1]  E. Macintyre,et al.  Rapid, multifluorescent TCRG Vγ and Jγ typing: application to T cell acute lymphoblastic leukemia and to the detection of minor clonal populations , 2000, Leukemia.

[2]  D. Campana.  Determination of minimal residual disease in leukaemia patients , 2003, British journal of haematology.

[3]  T. Szczepański,et al.  Cross-lineage T cell receptor gene rearrangements occur in more than ninety percent of childhood precursor-B acute lymphoblastic leukemias: alternative PCR targets for detection of minimal residual disease , 1999, Leukemia.

[4]  F. Behm,et al.  Tandem application of flow cytometry and polymerase chain reaction for comprehensive detection of minimal residual disease in childhood acute lymphoblastic leukemia , 1999, Leukemia.

[5]  S. Smith,et al.  Diagnosis of chronic myeloid and acute lymphocytic leukemias by detection of leukemia-specific mRNA sequences amplified in vitro. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[6]  F. Behm,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. , 2002, Blood.

[7]  D. Campana,et al.  Use of peripheral blood instead of bone marrow to monitor residual disease in children with acute lymphoblastic leukemia. , 2002, Blood.

[8]  B. Schäfer,et al.  Minimal residual disease-directed risk stratification using real-time quantitative PCR analysis of immunoglobulin and T-cell receptor gene rearrangements in the international multicenter trial AIEOP-BFM ALL 2000 for childhood acute lymphoblastic leukemia , 2008, Leukemia.

[9]  T. Enver,et al.  Initiating and Cancer-Propagating Cells in TEL-AML1-Associated Childhood Leukemia , 2008, Science.

[10]  M. Schrappe,et al.  Molecular detection of minimal residual disease is a strong predictive factor of relapse in childhood B-lineage acute lymphoblastic leukemia with medium risk features. A case control study of the International BFM study group , 2000, Leukemia.

[11]  T. Klingebiel,et al.  Minimal residual disease (MRD) status prior to allogeneic stem cell transplantation is a powerful predictor for post-transplant outcome in children with ALL , 2002, Leukemia.

[12]  E. Froňková,et al.  Submicroscopic bone marrow involvement in isolated extramedullary relapses in childhood acute lymphoblastic leukemia: a more precise definition of "isolated" and its possible clinical implications, a collaborative study of the Resistant Disease Committee of the International BFM study group. , 2007, Blood.

[13]  J. Gabert,et al.  Detection of minimal residual disease in hematologic malignancies by real-time quantitative PCR: principles, approaches, and laboratory aspects , 2003, Leukemia.

[14]  J. Dongen,et al.  TCRB gene rearrangements in childhood and adult precursor-B-ALL: frequency, applicability as MRD-PCR target, and stability between diagnosis and relapse , 2004, Leukemia.

[15]  S. Armstrong,et al.  Molecular genetics of acute lymphoblastic leukemia. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[16]  S. Hunger,et al.  Clinical significance of minimal residual disease in childhood acute lymphoblastic leukemia and its relationship to other prognostic factors: a Children's Oncology Group study. , 2008, Blood.

[17]  A. Morley,et al.  Outcome prediction in childhood acute lymphoblastic leukaemia by molecular quantification of residual disease at the end of induction , 1994, The Lancet.

[18]  A. Hagemeijer,et al.  Multiple rearranged immunoglobulin genes in childhood acute lymphoblastic leukemia of precursor B-cell origin. , 1991, Leukemia.

[19]  M. Schilham,et al.  Minimal residual disease prior to stem cell transplant for childhood acute lymphoblastic leukaemia , 2003, British journal of haematology.

[20]  G. Fabbri,et al.  Minimal residual disease is an important predictive factor of outcome in children with relapsed ‘high-risk’ acute lymphoblastic leukemia , 2008, Leukemia.

[21]  A Orfao,et al.  Prognostic value of immunophenotypic detection of minimal residual disease in acute lymphoblastic leukemia. , 1998, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[22]  D. Campana,et al.  Concurrent detection of minimal residual disease (MRD) in childhood acute lymphoblastic leukaemia by flow cytometry and real‐time PCR , 2005, British journal of haematology.

[23]  J. Hancock,et al.  Minimal Residual Disease Status Before Allogeneic Bone Marrow Transplantation Is an Important Determinant of Successful Outcome for Children and Adolescents With Acute Lymphoblastic Leukemia , 1998 .

[24]  H. Cavé,et al.  Clinical Significance of Minimal Residual Disease in Childhood Acute Lymphoblastic Leukemia , 1998 .

[25]  J. V. van Dongen,et al.  Unusual immunoglobulin and T-cell receptor gene rearrangement patterns in acute lymphoblastic leukemias. , 1999, Current topics in microbiology and immunology.

[26]  Cheng Cheng,et al.  Genes contributing to minimal residual disease in childhood acute lymphoblastic leukemia: prognostic significance of CASP8AP2. , 2006, Blood.

[27]  E. Macintyre,et al.  Standardized RT-PCR analysis of fusion gene transcripts from chromosome aberrations in acute leukemia for detection of minimal residual disease , 1999, Leukemia.

[28]  L. Foroni,et al.  Minimal residual disease tests provide an independent predictor of clinical outcome in adult acute lymphoblastic leukemia. , 2002, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[29]  J. Cayuela,et al.  Analysis of minimal residual disease by Ig/TCR gene rearrangements: guidelines for interpretation of real-time quantitative PCR data , 2007, Leukemia.

[30]  Michael N Dworzak,et al.  Prognostic significance and modalities of flow cytometric minimal residual disease detection in childhood acute lymphoblastic leukemia. , 2002, Blood.

[31]  D. Campana,et al.  Comparative analysis of flow cytometry and polymerase chain reaction for the detection of minimal residual disease in childhood acute lymphoblastic leukemia , 2004, Leukemia.

[32]  J. V. van Dongen,et al.  Analysis of immunoglobulin and T cell receptor genes. Part II: Possibilities and limitations in the diagnosis and management of lymphoproliferative diseases and related disorders. , 1991, Clinica chimica acta; international journal of clinical chemistry.

[33]  Cheng Cheng,et al.  Genome-wide interrogation of germline genetic variation associated with treatment response in childhood acute lymphoblastic leukemia. , 2009, JAMA.

[34]  D. Campana,et al.  Clinical significance of minimal residual disease in childhood acute lymphoblastic leukemia after first relapse , 2004, Leukemia.

[35]  Prognostic value of minimal residual disease in acute lymphoblastic leukaemia in childhood , 1998 .

[36]  J J Shuster,et al.  Minimal residual disease detection in childhood precursor–B-cell acute lymphoblastic leukemia: relation to other risk factors. A Children's Oncology Group study , 2003, Leukemia.

[37]  G. Basso,et al.  Drug-induced immunophenotypic modulation in childhood ALL: implications for minimal residual disease detection , 2005, Leukemia.

[38]  D. Campana,et al.  Detection of minimal residual disease in acute leukemia by flow cytometry. , 1999, Cytometry.

[39]  Elaine Coustan-Smith,et al.  A simplified flow cytometric assay identifies children with acute lymphoblastic leukemia who have a superior clinical outcome. , 2006, Blood.

[40]  M. Remberger,et al.  The significance of graft-versus-host disease and pretransplantation minimal residual disease status to outcome after allogeneic stem cell transplantation in patients with acute lymphoblastic leukemia. , 2001, Blood.

[41]  Christopher B. Miller,et al.  Deletion of IKZF1 and prognosis in acute lymphoblastic leukemia. , 2009, The New England journal of medicine.

[42]  T. Barbui,et al.  Improved risk classification for risk-specific therapy based on the molecular study of minimal residual disease (MRD) in adult acute lymphoblastic leukemia (ALL). , 2009, Blood.

[43]  A. Órfão,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 , 1999, Leukemia.

[44]  J. Downing,et al.  A set of genes that regulate cell proliferation predicts treatment outcome in childhood acute lymphoblastic leukemia. , 2007, Blood.

[45]  G. Janossy,et al.  Immunological monitoring of residual disease in treated thymic acute lymphoblastic leukaemia. , 1981, Leukemia research.

[46]  H. Cavé,et al.  Standardization and quality control studies of ‘real-time’ quantitative reverse transcriptase polymerase chain reaction of fusion gene transcripts for residual disease detection in leukemia – A Europe Against Cancer Program , 2003, Leukemia.

[47]  L. Terstappen,et al.  Myeloid cell differentiation in normal bone marrow and acute myeloid leukemia assessed by multi-dimensional flow cytometry. , 1990, Analytical cellular pathology : the journal of the European Society for Analytical Cellular Pathology.

[48]  Thomas Flohr,et al.  Distinct gene expression profiles determine molecular treatment response in childhood acute lymphoblastic leukemia. , 2005, Blood.

[49]  W. Jędrzejczak,et al.  Status of minimal residual disease after induction predicts outcome in both standard and high‐risk Ph‐negative adult acute lymphoblastic leukaemia. The Polish Adult Leukemia Group ALL 4‐2002 MRD Study , 2008, British journal of haematology.

[50]  C. Eckert,et al.  Prognostic value of minimal residual disease in relapsed childhood acute lymphoblastic leukaemia , 2001, The Lancet.

[51]  A. Morley,et al.  Monitoring minimal residual disease in peripheral blood in B‐lineage acute lymphoblastic leukaemia , 1997, British journal of haematology.

[52]  G. Specchia,et al.  Significant reduction of the hybrid BCR/ABL transcripts after induction and consolidation therapy is a powerful predictor of treatment response in adult Philadelphia-positive acute lymphoblastic leukemia , 2005, Leukemia.

[53]  G. Ledderose,et al.  Ph Philadelphia-positive acute lymphoblastic leukemia + outcome in MRD Early molecular response to posttransplantation imatinib determines , 2005 .

[54]  J. V. Dongen,et al.  Real-time quantitative PCR for detection of minimal residual disease before allogeneic stem cell transplantation predicts outcome in children with acute lymphoblastic leukemia , 2001, Leukemia.

[55]  J. V. van Dongen,et al.  Detection of immunoglobulin heavy-chain gene rearrangements by Southern blot analysis: recommendations for optimal results. , 1993, Leukemia.

[56]  N. Goulden,et al.  Practical application of minimal residual disease assessment in childhood acute lymphoblastic leukaemia , 2001, British journal of haematology.

[57]  J. V. van Dongen,et al.  Southern blot patterns, frequencies, and junctional diversity of T-cell receptor-delta gene rearrangements in acute lymphoblastic leukemia. , 1993, Blood.

[58]  D. Campana,et al.  Childhood acute lymphoblastic leukaemia--current status and future perspectives. , 2001, The Lancet. Oncology.

[59]  Cheng Cheng,et al.  Early T-cell precursor leukaemia: a subtype of very high-risk acute lymphoblastic leukaemia. , 2009, The Lancet. Oncology.

[60]  T. Szczepański,et al.  T cell receptor gamma (TCRG) gene rearrangements in T cell acute lymphoblastic leukemia reflect ‘end-stage’ recombinations: implications for minimal residual disease monitoring , 2000, Leukemia.

[61]  M. van der Burg,et al.  Comparative analysis of Ig and TCR gene rearrangements at diagnosis and at relapse of childhood precursor-B-ALL provides improved strategies for selection of stable PCR targets for monitoring of minimal residual disease. , 2002, Blood.

[62]  D. Campana.  Molecular determinants of treatment response in acute lymphoblastic leukemia. , 2008, Hematology. American Society of Hematology. Education Program.

[63]  A. Órfão,et al.  Minimal residual disease in leukaemia patients. , 2001, The Lancet. Oncology.

[64]  F. Galibert,et al.  In vitro amplification of T cell gamma gene rearrangements: a new tool for the assessment of minimal residual disease in acute lymphoblastic leukemias. , 1989, Leukemia.

[65]  T. Barbui,et al.  Clearance of minimal residual disease after allogeneic stem cell transplantation and the prediction of the clinical outcome of adult patients with high-risk acute lymphoblastic leukemia. , 2007, Haematologica.

[66]  H. Gadner,et al.  Rapid molecular response during early induction chemotherapy predicts a good outcome in childhood acute lymphoblastic leukemia. , 2000, Blood.

[67]  J. Radich,et al.  Detection of bcr-abl transcripts in Philadelphia chromosome-positive acute lymphoblastic leukemia after marrow transplantation. , 1997, Blood.

[68]  D. Campana,et al.  The immunologic detection of minimal residual disease in acute leukemia. , 1990, Blood.

[69]  F. Behm,et al.  Prognostic importance of measuring early clearance of leukemic cells by flow cytometry in childhood acute lymphoblastic leukemia. , 2002, Blood.

[70]  B. Lange,et al.  Detection of minimal disease in hematopoietic malignancies of the B-cell lineage by using third-complementarity-determining region (CDR-III)-specific probes. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[71]  M. Borowitz,et al.  Asynchronous Antigen Expression in B Lineage Acute Lymphoblastic Leukemia , 1988 .

[72]  W. Hiddemann,et al.  Analysis of rearranged T-cell receptor beta-chain genes by polymerase chain reaction (PCR) DNA sequencing and automated high resolution PCR fragment analysis. , 1995, Blood.

[73]  G. Mathé,et al.  Extensive Histological and Cytological Survey of Patients with Acute Leukaemia in “Complete Remission”* , 1966, British medical journal.

[74]  L. Madero,et al.  Clinical value of immunological monitoring of minimal residual disease in acute lymphoblastic leukaemia after allogeneic transplantation , 2002, British journal of haematology.

[75]  C. Murre,et al.  Pbx1 is converted into a transcriptional activator upon acquiring the N-terminal region of E2A in pre-B-cell acute lymphoblastoid leukemia. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[76]  A. Hagenbeek,et al.  Nonhomogeneous distribution of leukemia in the bone marrow during minimal residual disease. , 1987, Blood.

[77]  E. Thiel,et al.  Clinical significance of minimal residual disease quantification in adult patients with standard-risk acute lymphoblastic leukemia. , 2006, Blood.

[78]  J. V. Dongen,et al.  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 , 2002, Leukemia.

[79]  Clinical importance of minimal residual disease in childhood acute lymphoblastic leukemia. , 2000 .

[80]  A. Hagemeijer,et al.  bcr-abl oncogene activation in Philadelphia chromosome-positive acute lymphoblastic leukemia. , 1988, Leukemia.

[81]  I. Bernstein,et al.  The human homologue of rat NG2, a chondroitin sulfate proteoglycan, is not expressed on the cell surface of normal hematopoietic cells but is expressed by acute myeloid leukemia blasts from poor-prognosis patients with abnormalities of chromosome band 11q23. , 1996, Blood.

[82]  M. Schilham,et al.  Level of minimal residual disease prior to haematopoietic stem cell transplantation predicts prognosis in paediatric patients with acute lymphoblastic leukaemia: a report of the Pre-BMT MRD Study Group , 2003, Bone Marrow Transplantation.

[83]  Elaine Coustan-Smith,et al.  Immunological detection of minimal residual disease in children with acute lymphoblastic leukaemia , 1998, The Lancet.

[84]  M. Kneba,et al.  Molecular relapse in adult standard-risk ALL patients detected by prospective MRD monitoring during and after maintenance treatment: data from the GMALL 06/99 and 07/03 trials. , 2007, Blood.

[85]  M. König,et al.  Minimal residual disease values discriminate between low and high relapse risk in children with B-cell precursor acute lymphoblastic leukemia and an intrachromosomal amplification of chromosome 21: the Austrian and German acute lymphoblastic leukemia Berlin-Frankfurt-Munster (ALL-BFM) trials. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[86]  D. Campana.  Minimal residual disease in acute lymphoblastic leukemia. , 2010, Hematology. American Society of Hematology. Education Program.

[87]  C. Bartram,et al.  Detection of minimal residual disease in acute lymphoblastic leukemia by in vitro amplification of rearranged T-cell receptor delta chain sequences. , 1989, Blood.

[88]  E. Cook,et al.  Pharmacogenetics of outcome in children with acute lymphoblastic leukemia. , 2004, Blood.

[89]  D. Campana,et al.  Minimal disseminated disease in childhood T-cell lymphoblastic lymphoma: a report from the children's oncology group. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[90]  G. Janossy,et al.  Cellular phenotypes of normal and leukemic hemopoietic cells determined by analysis with selected antibody combinations. , 1980, Blood.

[91]  I. Bernstein,et al.  Human homologue of the rat chondroitin sulfate proteoglycan, NG2, detected by monoclonal antibody 7.1, identifies childhood acute lymphoblastic leukemias with t(4;11)(q21;q23) or t(11;19)(q23;p13) and MLL gene rearrangements. , 1996, Blood.

[92]  Christopher B. Miller,et al.  Genome-wide analysis of genetic alterations in acute lymphoblastic leukaemia , 2007, Nature.

[93]  J. Gribben,et al.  Quantitative analysis of minimal residual disease predicts relapse in children with B-lineage acute lymphoblastic leukemia in DFCI ALL Consortium Protocol 95-01. , 2007, Blood.