Clinical Significance of Minimal Residual Disease in Childhood Acute Lymphoblastic Leukemia
Hélène Cavé Cave, Ph.D., Jutte van der Werff ten Bosch, M.D., Stefan Suciu, M.S., Christine Guidal, M.S., Christine Waterkeyn, M.S., Jacques Otten, M.D., Marleen Bakkus, Ph.D., Kris Thielemans, M.D., Bernard Grandchamp, Ph.D., M.D., Etienne Vilmer, M.D., Brigitte Nelken, Martine Fournier, Patrick Boutard, Emmanuel Lebrun, Françoise Méchinaud, Richard Garand, Alain Robert, Nicole Dastugue, Emmanuel Plouvier, Evelyne Racadot, Alice Ferster, Jan Gyselinck, Odile Fenneteau, Michel Duval, Gabriel Solbu, Anne-Marie Manel, for The European Organization for Research and Treatment of Cancer–Childhood Leukemia Cooperative Group
Background and Methods The implications of the detection ofresidual disease after treatment of acute lymphoblastic leukemia(ALL) are unclear. We conducted a prospective study at 11 centersto determine the predictive value of the presence or absenceof detectable residual disease at several points in time duringthe first six months after complete remission of childhood ALLhad been induced. Junctional sequences of T-cell–receptoror immunoglobulin gene rearrangements were used as clonal markersof leukemic cells. Residual disease was quantitated with a competitivepolymerase-chain-reaction (PCR) assay. Of 246 patients enrolledat diagnosis and treated with a uniform chemotherapy protocol,178 were monitored for residual disease with one clone-specificprobe (in 74 percent) or more than one probe (in 26 percent).The median follow-up period was 38 months.
Results The presence or absence and level of residual leukemiawere significantly correlated with the risk of early relapseat each of the times studied (P<0.001). PCR measurementsidentified patients at high risk for relapse after the completionof induction therapy (those with 10–2 residual blastsper 2x105 mononuclear bone marrow cells) or at later time points(those with 10–3 residual blasts). Multivariate analysisshowed that as compared with immunophenotype, age, risk group(standard or very high risk), and white-cell count at diagnosis,the presence or absence and level of residual disease were themost powerful independent prognostic factors.
Conclusions Residual leukemia after induction of a remissionis a powerful prognostic factor in childhood ALL. Detectionof residual disease by PCR should be used to identify patientsat risk for relapse and should be taken into account in consideringalternative treatment.
Source Information
From the Laboratoire de Biochimie Génétique and the Service d'Hémato-Immunologie, Hôpital Robert Debré, Paris (H.C., C.G., B.G., E.V.); the Department of Physiology, Vrige Universiteit Brussel, Brussels, Belgium (J.W.B., M.B., K.T.); the European Organization for Research and Treatment of Cancer Data Center, Brussels, Belgium (S.S., C.W.); and the Akademisch Ziekenhuis, Vrige Universiteit Brussel, Brussels, Belgium (J.O.). Other authors were Brigitte Nelken and Martine Fournier (Centre Hospitalier Universitaire, Lille, France), Patrick Boutard and Emmanuel Lebrun (Centre Hospitalier Universitaire, Caen, France), Françoise Méchinaud and Richard Garand (Centre Hospitalier Régional Hôtel Dieu, Nantes, France), Alain Robert and Nicole Dastugue (Centre Hospitalier Universitaire, Toulouse, France), Emmanuel Plouvier and Evelyne Racadot (Centre Hospitalier Régional, Besançon, France), Alice Ferster (Centre Hospitalier Universitaire, Reine Fabiola, Brussels, Belgium), Jan Gyselinck (Algemeen Kinderziekenhuis, Antwerp, Belgium), Odile Fenneteau and Michel Duval (Hôpital Robert Debré, Paris), Gabriel Solbu (European Organization for Research and Treatment of Cancer Data Center, Brussels, Belgium), and Anne-Marie Manel (Centre Hospitalier Régional, Lyons, France).The views expressed in this article are solely those of the authors and do not represent the official views of the National Cancer Institute.
Address reprint requests to Dr. Vilmer at the Service d'Hémato-Immunologie, Hôpital Robert Debré, 48 Blvd. Serurier, 75019 Paris, France.
Muzzafar, T., Medeiros, L. J., Wang, S. A., Brahmandam, A., Thomas, D. A., Jorgensen, J. L.
(2009). Aberrant Underexpression of CD81 in Precursor B-Cell Acute Lymphoblastic Leukemia: Utility in Detection of Minimal Residual Disease by Flow Cytometry. Am J Clin Pathol
132: 692-698
[Abstract][Full Text]
Basso, G., Veltroni, M., Valsecchi, M. G., Dworzak, M. N., Ratei, R., Silvestri, D., Benetello, A., Buldini, B., Maglia, O., Masera, G., Conter, V., Arico, M., Biondi, A., Gaipa, G.
(2009). Risk of Relapse of Childhood Acute Lymphoblastic Leukemia Is Predicted By Flow Cytometric Measurement of Residual Disease on Day 15 Bone Marrow. JCO
27: 5168-5174
[Abstract][Full Text]
Borrello, I. M., Levitsky, H. I., Stock, W., Sher, D., Qin, L., DeAngelo, D. J., Alyea, E. P., Stone, R. M., Damon, L. E., Linker, C. A., Maslyar, D. J., Hege, K. M.
(2009). Granulocyte-macrophage colony-stimulating factor (GM-CSF)-secreting cellular immunotherapy in combination with autologous stem cell transplantation (ASCT) as postremission therapy for acute myeloid leukemia (AML). Blood
114: 1736-1745
[Abstract][Full Text]
Stanulla, M., Schrauder, A.
(2009). Bridging the gap between the north and south of the world: the case of treatment response in childhood acute lymphoblastic leukemia. haematol
94: 748-752
[Full Text]
Scrideli, C. A., Assumpcao, J. G., Ganazza, M. A., Araujo, M., Toledo, S. R., Lee, M. L. M., Delbuono, E., Petrilli, A. S., Queiroz, R. P., Biondi, A., Viana, M. B., Yunes, J. A., Brandalise, S. R., Tone, L. G.
(2009). A simplified minimal residual disease polymerase chain reaction method at early treatment points can stratify children with acute lymphoblastic leukemia into good and poor outcome groups. haematol
94: 781-789
[Abstract][Full Text]
Irving, J., Jesson, J., Virgo, P., Case, M., Minto, L., Eyre, L., Noel, N., Johansson, U., Macey, M., Knotts, L., Helliwell, M., Davies, P., Whitby, L., Barnett, D., Hancock, J., Goulden, N., Lawson, S., on behalf of the UKALL Flow MRD group and UK MRD s,
(2009). Establishment and validation of a standard protocol for the detection of minimal residual disease in B lineage childhood acute lymphoblastic leukemia by flow cytometry in a multi-center setting;. haematol
94: 870-874
[Abstract][Full Text]
Brisco, M. J., Latham, S., Sutton, R., Hughes, E., Wilczek, V., van Zanten, K., Budgen, B., Bahar, A. Y., Malec, M., Sykes, P. J., Kuss, B. J., Waters, K., Venn, N. C., Giles, J. E., Haber, M., Norris, M. D., Marshall, G. M., Morley, A. A.
(2009). Determining the Repertoire of IGH Gene Rearrangements to Develop Molecular Markers for Minimal Residual Disease in B-Lineage Acute Lymphoblastic Leukemia. J. Mol. Diagn.
11: 194-200
[Abstract][Full Text]
Morley, A. A., Latham, S., Brisco, M. J., Sykes, P. J., Sutton, R., Hughes, E., Wilczek, V., Budgen, B., van Zanten, K., Kuss, B. J., Venn, N. C., Norris, M. D., Crock, C., Storey, C., Revesz, T., Waters, K.
(2009). Sensitive and Specific Measurement of Minimal Residual Disease in Acute Lymphoblastic Leukemia. J. Mol. Diagn.
11: 201-210
[Abstract][Full Text]
Bassan, R., Spinelli, O., Oldani, E., Intermesoli, T., Tosi, M., Peruta, B., Rossi, G., Borlenghi, E., Pogliani, E. M., Terruzzi, E., Fabris, P., Cassibba, V., Lambertenghi-Deliliers, G., Cortelezzi, A., Bosi, A., Gianfaldoni, G., Ciceri, F., Bernardi, M., Gallamini, A., Mattei, D., Di Bona, E., Romani, C., Scattolin, A. M., Barbui, T., Rambaldi, A.
(2009). Improved risk classification for risk-specific therapy based on the molecular study of minimal residual disease (MRD) in adult acute lymphoblastic leukemia (ALL). Blood
113: 4153-4162
[Abstract][Full Text]
Yang, J. J., Cheng, C., Yang, W., Pei, D., Cao, X., Fan, Y., Pounds, S. B., Neale, G., Trevino, L. R., French, D., Campana, D., Downing, J. R., Evans, W. E., Pui, C.-H., Devidas, M., Bowman, W. P., Camitta, B. M., Willman, C. L., Davies, S. M., Borowitz, M. J., Carroll, W. L., Hunger, S. P., Relling, M. V.
(2009). Genome-wide Interrogation of Germline Genetic Variation Associated With Treatment Response in Childhood Acute Lymphoblastic Leukemia. JAMA
301: 393-403
[Abstract][Full Text]
Borowitz, M. J., Devidas, M., Hunger, S. P., Bowman, W. P., Carroll, A. J., Carroll, W. L., Linda, S., Martin, P. L., Pullen, D. J., Viswanatha, D., Willman, C. L., Winick, N., Camitta, B. M., for the Children's Oncology Group,
(2008). Clinical significance of minimal residual disease in childhood acute lymphoblastic leukemia and its relationship to other prognostic factors: a Children's Oncology Group study. Blood
111: 5477-5485
[Abstract][Full Text]
Oudot, C., Auclerc, M.-F., Levy, V., Porcher, R., Piguet, C., Perel, Y., Gandemer, V., Debre, M., Vermylen, C., Pautard, B., Berger, C., Schmitt, C., Leblanc, T., Cayuela, J.-M., Socie, G., Michel, G., Leverger, G., Baruchel, A.
(2008). Prognostic Factors for Leukemic Induction Failure in Children With Acute Lymphoblastic Leukemia and Outcome After Salvage Therapy: The FRALLE 93 Study. JCO
26: 1496-1503
[Abstract][Full Text]
Campana, D.
(2008). Molecular Determinants of Treatment Response in Acute Lymphoblastic Leukemia. ASH Education Book
2008: 366-373
[Abstract][Full Text]
Mussolin, L., Pillon, M., Conter, V., Piglione, M., Lo Nigro, L., Pierani, P., Micalizzi, C., Buffardi, S., Basso, G., Zanesco, L., Rosolen, A.
(2007). Prognostic Role of Minimal Residual Disease in Mature B-Cell Acute Lymphoblastic Leukemia of Childhood. JCO
25: 5254-5261
[Abstract][Full Text]
Furuichi, Y., Goi, K., Inukai, T., Sato, H., Nemoto, A., Takahashi, K., Akahane, K., Hirose, K., Honna, H., Kuroda, I., Zhang, X., Kagami, K., Hayashi, Y., Harigaya, K., Nakazawa, S., Sugita, K.
(2007). Fms-like Tyrosine Kinase 3 Ligand Stimulation Induces MLL-Rearranged Leukemia Cells into Quiescence Resistant to Antileukemic Agents. Cancer Res.
67: 9852-9861
[Abstract][Full Text]
Zhou, J., Goldwasser, M. A, Li, A., Dahlberg, S. E., Neuberg, D., Wang, H., Dalton, V., McBride, K. D, Sallan, S. E., Silverman, L. B, Gribben, J. G., for the Dana-Farber Cancer Institute ALL Consortiu,
(2007). Quantitative analysis of minimal residual disease predicts relapse in children with B-lineage acute lymphoblastic leukemia in DFCI ALL Consortium Protocol 95-01. Blood
110: 1607-1611
[Abstract][Full Text]
Choi, S., Henderson, M. J., Kwan, E., Beesley, A. H., Sutton, R., Bahar, A. Y., Giles, J., Venn, N. C., Pozza, L. D., Baker, D. L., Marshall, G. M., Kees, U. R., Haber, M., Norris, M. D.
(2007). Relapse in children with acute lymphoblastic leukemia involving selection of a preexisting drug-resistant subclone. Blood
110: 632-639
[Abstract][Full Text]
Sposto, R., London, W. B., Alonzo, T. A.
(2007). Criteria for Optimizing Prognostic Risk Groups in Pediatric Cancer: Analysis of Data From the Children's Oncology Group. JCO
25: 2070-2077
[Abstract][Full Text]
Moghrabi, A., Levy, D. E., Asselin, B., Barr, R., Clavell, L., Hurwitz, C., Samson, Y., Schorin, M., Dalton, V. K., Lipshultz, S. E., Neuberg, D. S., Gelber, R. D., Cohen, H. J., Sallan, S. E., Silverman, L. B.
(2007). Results of the Dana-Farber Cancer Institute ALL Consortium Protocol 95-01 for children with acute lymphoblastic leukemia. Blood
109: 896-904
[Abstract][Full Text]
Raff, T., Gokbuget, N., Luschen, S., Reutzel, R., Ritgen, M., Irmer, S., Bottcher, S., Horst, H.-A., Kneba, M., Hoelzer, D., Bruggemann, M., for the GMALL Study Group,
(2007). 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. Blood
109: 910-915
[Abstract][Full Text]
Mims, M. P., Prchal, J. T.
(2007). Molecular basis of hematology. ASH-SAP
2007: 1-22
[Full Text]
Flotho, C., Coustan-Smith, E., Pei, D., Iwamoto, S., Song, G., Cheng, C., Pui, C.-H., Downing, J. R., Campana, D.
(2006). Genes contributing to minimal residual disease in childhood acute lymphoblastic leukemia: prognostic significance of CASP8AP2. Blood
108: 1050-1057
[Abstract][Full Text]
Steinbach, D., Schramm, A., Eggert, A., Onda, M., Dawczynski, K., Rump, A., Pastan, I., Wittig, S., Pfaffendorf, N., Voigt, A., Zintl, F., Gruhn, B.
(2006). Identification of a Set of Seven Genes for the Monitoring of Minimal Residual Disease in Pediatric Acute Myeloid Leukemia. Clin. Cancer Res.
12: 2434-2441
[Abstract][Full Text]
Zehentner, B. K., Fritschle, W., Stelzer, T., Ghirardelli, K. M., Hunter, K., Wentzel, C., Bennington, R., Hansen, C. L., Myerson, D., Kalnoski, M., Wells, D. A., Loken, M. R.
(2006). Minimal Disease Detection and Confirmation in Hematologic Malignancies: Combining Cell Sorting with Clonality Profiling. Clin. Chem.
52: 430-437
[Abstract][Full Text]
Bruggemann, M., Raff, T., Flohr, T., Gokbuget, N., Nakao, M., Droese, J., Luschen, S., Pott, C., Ritgen, M., Scheuring, U., Horst, H.-A., Thiel, E., Hoelzer, D., Bartram, C. R., Kneba, M., for the German Multicenter Study Group for Adult A,
(2006). Clinical significance of minimal residual disease quantification in adult patients with standard-risk acute lymphoblastic leukemia. Blood
107: 1116-1123
[Abstract][Full Text]
Mandrell, B. N., Pritchard, M.
(2006). Understanding the Clinical Implications of Minimal Residual Disease in Childhood Leukemia. Journal of Pediatric Oncology Nursing
23: 38-44
[Abstract]
Jabbour, E. J., Faderl, S., Kantarjian, H. M.
(2005). Adult Acute Lymphoblastic Leukemia. Mayo Clin Proc.
80: 1517-1527
[Abstract]
Holleman, A., Boer, M. L. d., Kazemier, K. M., Beverloo, H. B., von Bergh, A. R. M., Janka-Schaub, G. E., Pieters, R.
(2005). Decreased PARP and procaspase-2 protein levels are associated with cellular drug resistance in childhood acute lymphoblastic leukemia. Blood
106: 1817-1823
[Abstract][Full Text]
Laughton, S. J., Ashton, L. J., Kwan, E., Norris, M. D., Haber, M., Marshall, G. M.
(2005). Early Responses to Chemotherapy of Normal and Malignant Hematologic Cells Are Prognostic in Children With Acute Lymphoblastic Leukemia. JCO
23: 2264-2271
[Abstract][Full Text]
Stanulla, M., Schaeffeler, E., Flohr, T., Cario, G., Schrauder, A., Zimmermann, M., Welte, K., Ludwig, W.-D., Bartram, C. R., Zanger, U. M., Eichelbaum, M., Schrappe, M., Schwab, M.
(2005). Thiopurine Methyltransferase (TPMT) Genotype and Early Treatment Response to Mercaptopurine in Childhood Acute Lymphoblastic Leukemia. JAMA
293: 1485-1489
[Abstract][Full Text]
Jeng, K.-S., Sheen, I-S., Tsai, Y.-C.
(2004). Circulating Messenger RNA of {alpha}-Fetoprotein: A Possible Risk Factor of Recurrence After Resection of Hepatocellular Carcinoma. Arch Surg
139: 1055-1060
[Abstract][Full Text]
Eisenberger, M., Partin, A.
(2004). Progress toward Identifying Aggressive Prostate Cancer. NEJM
351: 180-181
[Full Text]
Pui, C.-H., Schrappe, M., Ribeiro, R. C., Niemeyer, C. M.
(2004). Childhood and Adolescent Lymphoid and Myeloid Leukemia. ASH Education Book
2004: 118-145
[Abstract][Full Text]
Li, A., Zhou, J., Zuckerman, D., Rue, M., Dalton, V., Lyons, C., Silverman, L. B., Sallan, S. E., Gribben, J. G.
(2003). Sequence analysis of clonal immunoglobulin and T-cell receptor gene rearrangements in children with acute lymphoblastic leukemia at diagnosis and at relapse: implications for pathogenesis and for the clinical utility of PCR-based methods of minimal residual disease detection. Blood
102: 4520-4526
[Abstract][Full Text]
Krauter, J., Gorlich, K., Ottmann, O., Lubbert, M., Dohner, H., Heit, W., Kanz, L., Ganser, A., Heil, G.
(2003). Prognostic Value of Minimal Residual Disease Quantification by Real-Time Reverse Transcriptase Polymerase Chain Reaction in Patients With Core Binding Factor Leukemias. JCO
21: 4413-4422
[Abstract][Full Text]
Marshall, G., Norris, M., Haber, M.
(2003). In Reply:. JCO
21: 4464-4465
[Full Text]
Goldberg, J. M., Silverman, L. B., Levy, D. E., Dalton, V. K., Gelber, R. D., Lehmann, L., Cohen, H. J., Sallan, S. E., Asselin, B. L.
(2003). Childhood T-Cell Acute Lymphoblastic Leukemia: The Dana-Farber Cancer Institute Acute Lymphoblastic Leukemia Consortium Experience. JCO
21: 3616-3622
[Abstract][Full Text]
Vidriales, M.-B., Perez, J. J., Lopez-Berges, M. C., Gutierrez, N., Ciudad, J., Lucio, P., Vazquez, L., Garcia-Sanz, R., del Canizo, M. C., Fernandez-Calvo, J., Ramos, F., Rodriguez, M. J., Calmuntia, M. J., Porwith, A., Orfao, A., San-Miguel, J. F.
(2003). Minimal residual disease in adolescent (older than 14 years) and adult acute lymphoblastic leukemias: early immunophenotypic evaluation has high clinical value. Blood
101: 4695-4700
[Abstract][Full Text]
Moppett, J, Burke, G A A, Steward, C G, Oakhill, A, Goulden, N J
(2003). The clinical relevance of detection of minimal residual disease in childhood acute lymphoblastic leukaemia. J. Clin. Pathol.
56: 249-253
[Abstract][Full Text]
Marshall, G. M., Haber, M., Kwan, E., Zhu, L., Ferrara, D., Xue, C., Brisco, M. J., Sykes, P. J., Morley, A., Webster, B., Dalla Pozza, L., Waters, K., Norris, M. D.
(2003). Importance of Minimal Residual Disease Testing During the Second Year of Therapy for Children With Acute Lymphoblastic Leukemia. JCO
21: 704-709
[Abstract][Full Text]
Carroll, W. L., Bhojwani, D., Min, D.-J., Raetz, E., Relling, M., Davies, S., Downing, J. R., Willman, C. L., Reed, J. C.
(2003). Pediatric Acute Lymphoblastic Leukemia. ASH Education Book
2003: 102-131
[Abstract][Full Text]
Scheuring, U. J., Pfeifer, H., Wassmann, B., Bruck, P., Atta, J., Petershofen, E. K., Gehrke, B., Gschaidmeier, H., Hoelzer, D., Ottmann, O. G.
(2003). Early minimal residual disease (MRD) analysis during treatment of Philadelphia chromosome/Bcr-Abl-positive acute lymphoblastic leukemia with the Abl-tyrosine kinase inhibitor imatinib (STI571). Blood
101: 85-90
[Abstract][Full Text]
Dombret, H., Gabert, J., Boiron, J.-M., Rigal-Huguet, F., Blaise, D., Thomas, X., Delannoy, A., Buzyn, A., Bilhou-Nabera, C., Cayuela, J.-M., Fenaux, P., Bourhis, J.-H., Fegueux, N., Charrin, C., Boucheix, C., Lheritier, V., Esperou, H., MacIntyre, E., Vernant, J.-P., Fiere, D.
(2002). Outcome of treatment in adults with Philadelphia chromosome-positive acute lymphoblastic leukemia---results of the prospective multicenter LALA-94 trial. Blood
100: 2357-2366
[Abstract][Full Text]
Kottaridis, P. D., Gale, R. E., Langabeer, S. E., Frew, M. E., Bowen, D. T., Linch, D. C.
(2002). Studies of FLT3 mutations in paired presentation and relapse samples from patients with acute myeloid leukemia: implications for the role of FLT3 mutations in leukemogenesis, minimal residual disease detection, and possible therapy with FLT3 inhibitors. Blood
100: 2393-2398
[Abstract][Full Text]
Coustan-Smith, E., Sancho, J., Hancock, M. L., Razzouk, B. I., Ribeiro, R. C., Rivera, G. K., Rubnitz, J. E., Sandlund, J. T., Pui, C.-H., Campana, D.
(2002). Use of peripheral blood instead of bone marrow to monitor residual disease in children with acute lymphoblastic leukemia. Blood
100: 2399-2402
[Abstract][Full Text]
Willemse, M. J., Seriu, T., Hettinger, K., d'Aniello, E., Hop, W. C. J., Panzer-Grumayer, E. R., Biondi, A., Schrappe, M., Kamps, W. A., Masera, G., Gadner, H., Riehm, H., Bartram, C. R., van Dongen, J. J. M.
(2002). Detection of minimal residual disease identifies differences in treatment response between T-ALL and precursor B-ALL. Blood
99: 4386-4393
[Abstract][Full Text]
Duval, M., Suciu, S., Ferster, A., Rialland, X., Nelken, B., Lutz, P., Benoit, Y., Robert, A., Manel, A.-M., Vilmer, E., Otten, J., Philippe, N.
(2002). Comparison of Escherichia coli-asparaginase with Erwinia-asparaginase in the treatment of childhood lymphoid malignancies: results of a randomized European Organisation for Research and Treatment of Cancer---Children's Leukemia Group phase 3 trial. Blood
99: 2734-2739
[Abstract][Full Text]
Szczepanski, T., Willemse, M. J., Brinkhof, B., van Wering, E. R., van der Burg, M., van Dongen, J. J. M.
(2002). 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. Blood
99: 2315-2323
[Abstract][Full Text]
Dworzak, M. N., Froschl, G., Printz, D., Mann, G., Potschger, U., Muhlegger, N., Fritsch, G., Gadner, H.
(2002). Prognostic significance and modalities of flow cytometric minimal residual disease detection in childhood acute lymphoblastic leukemia. Blood
99: 1952-1958
[Abstract][Full Text]
Nyvold, C., Madsen, H. O., Ryder, L. P., Seyfarth, J., Svejgaard, A., Clausen, N., Wesenberg, F., Jonsson, O. G., Forestier, E., Schmiegelow, K.
(2002). Precise quantification of minimal residual disease at day 29 allows identification of children with acute lymphoblastic leukemia and an excellent outcome. Blood
99: 1253-1258
[Abstract][Full Text]
Hoelzer, D., Gokbuget, N., Ottmann, O., Pui, C.-H., Relling, M. V., Appelbaum, F. R., van Dongen, J. J.M., Szczepanski, T.
(2002). Acute Lymphoblastic Leukemia. ASH Education Book
2002: 162-192
[Abstract][Full Text]
zur Stadt, U., Rischewski, J., Schneppenheim, R., Kabisch, H.
(2001). Denaturing HPLC for Identification of Clonal T-Cell Receptor {gamma} Rearrangements in Newly Diagnosed Acute Lymphoblastic Leukemia. Clin. Chem.
47: 2003-2011
[Abstract][Full Text]
San Miguel, J. F., Vidriales, M. B., Lopez-Berges, C., Diaz-Mediavilla, J., Gutierrez, N., Canizo, C., Ramos, F., Calmuntia, M. J., Perez, J. J., Gonzalez, M., Orfao, A.
(2001). Early immunophenotypical evaluation of minimal residual disease in acute myeloid leukemia identifies different patient risk groups and may contribute to postinduction treatment stratification. Blood
98: 1746-1751
[Abstract][Full Text]
Seeger, K., Stackelberg, A. V., Taube, T., Buchwald, D., Korner, G., Suttorp, M., Dorffel, W., Tausch, W., Henze, G.
(2001). Relapse of TEL-AML1-Positive Acute Lymphoblastic Leukemia in Childhood: A Matched-Pair Analysis. JCO
19: 3188-3193
[Abstract][Full Text]
Chen, J.-S., Coustan-Smith, E., Suzuki, T., Neale, G. A., Mihara, K., Pui, C.-H., Campana, D.
(2001). Identification of novel markers for monitoring minimal residual disease in acute lymphoblastic leukemia. Blood
97: 2115-2120
[Abstract][Full Text]
Olavarria, E., Kanfer, E., Szydlo, R., Kaeda, J., Rezvani, K., Cwynarski, K., Pocock, C., Dazzi, F., Craddock, C., Apperley, J. F., Cross, N. C. P., Goldman, J. M.
(2001). Early detection of BCR-ABL transcripts by quantitative reverse transcriptase-polymerase chain reaction predicts outcome after allogeneic stem cell transplantation for chronic myeloid leukemia. Blood
97: 1560-1565
[Abstract][Full Text]
Seeger, K., Kreuzer, K.-A., Lass, U., Taube, T., Buchwald, D., Eckert, C., Körner, G., Schmidt, C.-A, Henze, G.
(2001). Molecular Quantification of Response to Therapy and Remission Status in TEL-AML1-Positive Childhood ALL by Real-Time Reverse Transcription Polymerase Chain Reaction. Cancer Res.
61: 2517-2522
[Abstract][Full Text]
Silverman, L. B., Gelber, R. D., Dalton, V. K., Asselin, B. L., Barr, R. D., Clavell, L. A., Hurwitz, C. A., Moghrabi, A., Samson, Y., Schorin, M. A., Arkin, S., Declerck, L., Cohen, H. J., Sallan, S. E.
(2001). Improved outcome for children with acute lymphoblastic leukemia: results of Dana-Farber Consortium Protocol 91-01. Blood
97: 1211-1218
[Abstract][Full Text]
Arber, D. A.
(2000). Molecular Diagnostic Approach to Non-Hodgkin's Lymphoma. J. Mol. Diagn.
2: 178-190
[Full Text]
Coustan-Smith, E., Sancho, J., Hancock, M. L., Boyett, J. M., Behm, F. G., Raimondi, S. C., Sandlund, J. T., Rivera, G. K., Rubnitz, J. E., Ribeiro, R. C., Pui, C.-H., Campana, D.
(2000). Clinical importance of minimal residual disease in childhood acute lymphoblastic leukemia. Blood
96: 2691-2696
[Abstract][Full Text]
Brumpt, C., Delabesse, E., Beldjord, K., Davi, F., Cayuela, J.-M., Millien, C., Villarese, P., Quartier, P., Buzyn, A., Valensi, F., Macintyre, E.
(2000). The incidence of clonal T-cell receptor rearrangements in B-cell precursor acute lymphoblastic leukemia varies with age and genotype. Blood
96: 2254-2261
[Abstract][Full Text]
Brisco, M. J., Sykes, P. J., Dolman, G., Hughes, E., Neoh, S.-H., Peng, L., Snell, L. E., Toogood, I. R. G., Rice, M. S., Morley, A. A.
(2000). Early Resistance to Therapy during Induction in Childhood Acute Lymphoblastic Leukemia. Cancer Res.
60: 5092-5096
[Abstract][Full Text]
Uckun, F. M., Stork, L., Seibel, N., Sarquis, M., Bedros, C., Sather, H., Sensel, M., Reaman, G. H., Gaynon, P. S.
(2000). Residual Bone Marrow Leukemic Progenitor Cell Burden after Induction Chemotherapy in Pediatric Patients with Acute Lymphoblastic Leukemia. Clin. Cancer Res.
6: 3123-3130
[Abstract][Full Text]
Friedmann, A. M., Weinstein, H. J.
(2000). The Role of Prognostic Features in the Treatment of Childhood Acute Lymphoblastic Leukemia. The Oncologist
5: 321-328
[Abstract][Full Text]
Nakao, M., Janssen, J. W. G., Flohr, T., Bartram, C. R.
(2000). Rapid and Reliable Quantification of Minimal Residual Disease in Acute Lymphoblastic Leukemia Using Rearranged Immunoglobulin and T-Cell Receptor Loci by LightCycler Technology. Cancer Res.
60: 3281-3289
[Abstract][Full Text]
Donovan, J. W., Ladetto, M., Zou, G., Neuberg, D., Poor, C., Bowers, D., Gribben, J. G.
(2000). Immunoglobulin heavy-chain consensus probes for real-time PCR quantification of residual disease in acute lymphoblastic leukemia. Blood
95: 2651-2658
[Abstract][Full Text]
Kröber, S M, Greschniok, A, Kaiserling, E, Horny, H-P
(2000). Acute lymphoblastic leukaemia: correlation between morphological/immunohistochemical and molecular biological findings in bone marrow biopsy specimens. Mol. Pathol.
53: 83-87
[Abstract][Full Text]
Mahoney, D. H. Jr, Shuster, J. J., Nitschke, R., Lauer, S., Steuber, C. P., Camitta, B.
(2000). Intensification With Intermediate-Dose Intravenous Methotrexate Is Effective Therapy for Children With Lower-Risk B-Precursor Acute Lymphoblastic Leukemia: A Pediatric Oncology Group Study. JCO
18: 1285-1294
[Abstract][Full Text]
Panzer-Grumayer, E. R., Schneider, M., Panzer, S., Fasching, K., Gadner, H.
(2000). Rapid molecular response during early induction chemotherapy predicts a good outcome in childhood acute lymphoblastic leukemia. Blood
95: 790-794
[Abstract][Full Text]
Macintyre, E., Willerford, D., Morris, S. W.
(2000). Non-Hodgkin's Lymphoma: Molecular Features of B Cell Lymphoma. ASH Education Book
2000: 180-204
[Abstract][Full Text]
Felix, C. A., Lange, B. J., Chessells, J. M.
(2000). Pediatric Acute Lymphoblastic Leukemia: Challenges and Controversies in 2000. ASH Education Book
2000: 285-302
[Abstract][Full Text]
Moravcova, J., Nadvornikova, S., Lukasova, M., Klamova;, H., Faderl, S., Talpaz, M., Kantarjian, H. M., Estrov, Z.
(1999). Polymerase Chain Reaction Analyses Should Be Used as a Basis for Clinical Decision Making in Patients With Chronic Myelogenous Leukemia. Blood
94: 3609-3611
[Full Text]
Sweeney, T. J., Mailander, V., Tucker, A. A., Olomu, A. B., Zhang, W., Cao, Y.-a., Negrin, R. S., Contag, C. H.
(1999). Visualizing the kinetics of tumor-cell clearance in living animals. Proc. Natl. Acad. Sci. USA
96: 12044-12049
[Abstract][Full Text]
Uckun, F. M., Gaynon, P. S., Stram, D. O., Sensel, M. G., Sarquis, M. B., Lazarus, K. H., Willoughby, M.
(1999). Paucity of Leukemic Progenitor Cells in the Bone Marrow of Pediatric B-Lineage Acute Lymphoblastic Leukemia Patients with an Isolated Extramedullary First Relapse. Clin. Cancer Res.
5: 2415-2420
[Abstract][Full Text]
Cortes, J., Fayad, L., O'Brien, S., Keating, M., Kantarjian, H.
(1999). Persistence of Peripheral Blood and Bone Marrow Blasts during Remission Induction in Adult Acute Lymphoblastic Leukemia Confers a Poor Prognosis Depending on Treatment Intensity. Clin. Cancer Res.
5: 2491-2497
[Abstract][Full Text]
Faderl, S., Estrov, Z., Machida, U., Kami, M., Hirai, H., Cave, H., Suciu, S., Vilmer, E.
(1999). Detection of Residual Disease in Childhood Acute Lymphoblastic Leukemia. NEJM
340: 152-154
[Full Text]
Pui, C.-H., Evans, W. E.
(1998). Acute Lymphoblastic Leukemia. NEJM
339: 605-615
[Full Text]
Morley, A.
(1998). Quantifying Leukemia. NEJM
339: 627-629
[Full Text]
10–2 residual blasts per 2x105 mononuclear bone marrow cells) or at later time points (those with 
Previous
