The childhood leukemias are a study in contrasts. Acute lymphoblasticleukemia (ALL) is diagnosed in approximately 2000 children inthe United States each year, whereas acute myeloid leukemia(AML) is diagnosed in only about 500 children, and chronic myeloidleukemia (CML) in fewer than 100. Chronic lymphocytic leukemia(CLL), one of the most common leukemias in adults, seldom occursin children. Current chemotherapeutic regimens cure as manyas 70 percent of children with ALL (Figure 1)1,2,3,4 but only30 to 40 percent of those with AML,5,6,7,8,9,10 and they areineffective against CML without allogeneic bone marrow transplantation.11
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Treatment of Subclinical Leukemia in the Central Nervous System
Cell Growth and Drug-Sensitivity Testing
Detection of Minimal Residual Leukemia
Late Effects
Future Considerations
Source Information
From the Departments of HematologyOncology and Pathology and Laboratory Medicine, St. Jude Children's Research Hospital, and the University of Tennessee, Memphis, College of Medicine both in Memphis.
Address reprint requests to Dr. Pui at St. Jude Children's Research Hospital, 332 N. Lauderdale, P.O. Box 318, Memphis, TN 38101-0318.
Mody, R., Li, S., Dover, D. C., Sallan, S., Leisenring, W., Oeffinger, K. C., Yasui, Y., Robison, L. L., Neglia, J. P.
(2008). Twenty-five-year follow-up among survivors of childhood acute lymphoblastic leukemia: a report from the Childhood Cancer Survivor Study. Blood
111: 5515-5523
[Abstract][Full Text]
Winter, S. S., Jiang, Z., Khawaja, H. M., Griffin, T., Devidas, M., Asselin, B. L., Larson, R. S.
(2007). Identification of genomic classifiers that distinguish induction failure in T-lineage acute lymphoblastic leukemia: a report from the Children's Oncology Group. Blood
110: 1429-1438
[Abstract][Full Text]
Dinndorf, P. A., Gootenberg, J., Cohen, M. H., Keegan, P., Pazdur, R.
(2007). FDA Drug Approval Summary: Pegaspargase (Oncaspar(R)) for the First-Line Treatment of Children with Acute Lymphoblastic Leukemia (ALL). The Oncologist
12: 991-998
[Abstract][Full Text]
Maule, M., Scelo, G., Pastore, G., Brennan, P., Hemminki, K., Tracey, E., Sankila, R., Weiderpass, E., Olsen, J. H., McBride, M. L., Brewster, D. H., Pompe-Kirn, V., Kliewer, E. V., Chia, K. S., Tonita, J. M., Martos, C., Jonasson, J. G., Merletti, F., Boffetta, P.
(2007). Risk of Second Malignant Neoplasms After Childhood Leukemia and Lymphoma: An International Study. JNCI J Natl Cancer Inst
99: 790-800
[Abstract][Full Text]
Jeha, S., Gaynon, P. S., Razzouk, B. I., Franklin, J., Kadota, R., Shen, V., Luchtman-Jones, L., Rytting, M., Bomgaars, L. R., Rheingold, S., Ritchey, K., Albano, E., Arceci, R. J., Goldman, S., Griffin, T., Altman, A., Gordon, B., Steinherz, L., Weitman, S., Steinherz, P.
(2006). Phase II Study of Clofarabine in Pediatric Patients With Refractory or Relapsed Acute Lymphoblastic Leukemia. JCO
24: 1917-1923
[Abstract][Full Text]
Gatta, G., Capocaccia, R., Stiller, C., Kaatsch, P., Berrino, F., Terenziani, M., the EUROCARE Working Group,
(2005). Childhood Cancer Survival Trends in Europe: A EUROCARE Working Group Study. JCO
23: 3742-3751
[Abstract][Full Text]
Kikuchi, J., Shinohara, H., Nonomura, C., Ando, H., Takaku, S., Nojiri, H., Nakamura, M.
(2005). Not core 2 {beta}1,6-N-acetylglucosaminyltransferase-2 or -3 but -1 regulates sialyl-Lewis x expression in human precursor B cells. Glycobiology
15: 271-280
[Abstract][Full Text]
Hawkins, D. S., Park, J. R., Thomson, B. G., Felgenhauer, J. L., Holcenberg, J. S., Panosyan, E. H., Avramis, V. I.
(2004). Asparaginase Pharmacokinetics After Intensive Polyethylene Glycol-Conjugated L-Asparaginase Therapy for Children with Relapsed Acute Lymphoblastic Leukemia. Clin. Cancer Res.
10: 5335-5341
[Abstract][Full Text]
Spiegel, A., Kollet, O., Peled, A., Abel, L., Nagler, A., Bielorai, B., Rechavi, G., Vormoor, J., Lapidot, T.
(2004). Unique SDF-1-induced activation of human precursor-B ALL cells as a result of altered CXCR4 expression and signaling. Blood
103: 2900-2907
[Abstract][Full Text]
Pui, C.-H., Sandlund, J. T., Pei, D., Rivera, G. K., Howard, S. C., Ribeiro, R. C., Rubnitz, J. E., Razzouk, B. I., Hudson, M. M., Cheng, C., Raimondi, S. C., Behm, F. G., Downing, J. R., Relling, M. V., Evans, W. E.
(2003). Results of Therapy for Acute Lymphoblastic Leukemia in Black and White Children. JAMA
290: 2001-2007
[Abstract][Full Text]
Cimino, G., Elia, L., Mancini, M., Annino, L., Anaclerico, B., Fazi, P., Vitale, A., Specchia, G., Di Raimondo, F., Recchia, A., Cuneo, A., Mecucci, C., Pane, F., Saglio, G., Foa, R., Mandelli, F.
(2003). Clinico-biologic features and treatment outcome of adult pro-B-ALL patients enrolled in the GIMEMA 0496 study: absence of the ALL1/AF4 and of the BCR/ABL fusion genes correlates with a significantly better clinical outcome. Blood
102: 2014-2020
[Abstract][Full Text]
Heath, J. A., Steinherz, P. G., Altman, A., Sather, H., Jhanwar, S., Halpern, S., Pieters, R., Shah, N., Steinherz, L., Tannous, R., Terry, W., Trigg, M. E.
(2003). Human Granulocyte Colony-Stimulating Factor in Children With High-Risk Acute Lymphoblastic Leukemia: A Children's Cancer Group Study. JCO
21: 1612-1617
[Abstract][Full Text]
Moos, P. J., Raetz, E. A., Carlson, M. A., Szabo, A., Smith, F. E., Willman, C., Wei, Q., Hunger, S. P., Carroll, W. L.
(2002). Identification of Gene Expression Profiles That Segregate Patients with Childhood Leukemia. Clin. Cancer Res.
8: 3118-3130
[Abstract][Full Text]
Avramis, V. I., Sencer, S., Periclou, A. P., Sather, H., Bostrom, B. C., Cohen, L. J., Ettinger, A. G., Ettinger, L. J., Franklin, J., Gaynon, P. S., Hilden, J. M., Lange, B., Majlessipour, F., Mathew, P., Needle, M., Neglia, J., Reaman, G., Holcenberg, J. S.
(2002). A randomized comparison of native Escherichia coli asparaginase and polyethylene glycol conjugated asparaginase for treatment of children with newly diagnosed standard-risk acute lymphoblastic leukemia: a Children's Cancer Group study. Blood
99: 1986-1994
[Abstract][Full Text]
Yoshioka, M., ONeill, J. P., Vacek, P. M., Finette, B. A.
(2001). Gestational Age and Gender-specific In Utero V(D)J Recombinase-mediated Deletions. Cancer Res.
61: 3432-3438
[Abstract][Full Text]
Leung, W., Hudson, M. M., Strickland, D. K., Phipps, S., Srivastava, D. K., Ribeiro, R. C., Rubnitz, J. E., Sandlund, J. T., Kun, L. E., Bowman, L. C., Razzouk, B. I., Mathew, P., Shearer, P., Evans, W. E., Pui, C.-H.
(2000). Late Effects of Treatment in Survivors of Childhood Acute Myeloid Leukemia. JCO
18: 3273-3279
[Abstract][Full Text]
McKenna, R. W.
(2000). Multifaceted Approach to the Diagnosis and Classification of Acute Leukemias. Clin. Chem.
46: 1252-1259
[Abstract][Full Text]
Merkle, C. J., Moore, I. M., Penton, B. S., Torres, B. J., Cueny, R. K., Schaeffer, R. C. Jr., Montgomery, D. W.
(2000). Methotrexate Causes Apoptosis in Postmitotic Endothelial Cells. Biol Res Nurs
2: 5-14
[Abstract]
Pal, S., Chatterjee, M., Bhattacharya, D. K., Bandhyopadhyay, S., Mandal, C.
(2000). Identification and purification of cytolytic antibodies directed against O-acetylated sialic acid in childhood acute lymphoblastic leukemia. Glycobiology
10: 539-549
[Abstract][Full Text]
Locatelli, F., Zecca, M., Rondelli, R., Bonetti, F., Dini, G., Prete, A., Messina, C., Uderzo, C., Ripaldi, M., Porta, F., Giorgiani, G., Giraldi, E., Pession, A.
(2000). Graft versus host disease prophylaxis with low-dose cyclosporine-A reduces the risk of relapse in children with acute leukemia given HLA-identical sibling bone marrow transplantation: results of a randomized trial. Blood
95: 1572-1579
[Abstract][Full Text]
Stanulla, M., Schrappe, M., Brechlin, A. M., Zimmermann, M., Welte, K.
(2000). Polymorphisms within glutathione S-transferase genes (GSTM1, GSTT1, GSTP1) and risk of relapse in childhood B-cell precursor acute lymphoblastic leukemia: a case-control study. Blood
95: 1222-1228
[Abstract][Full Text]
Tao, J., Valderrama, E., Kahn, L.
(2000). Congenital acute T lymphoblastic leukaemia: report of a case with immunohistochemical and molecular characterisation. J. Clin. Pathol.
53: 150-152
[Abstract][Full Text]
(1999). Degree of Fatness after Treatment for Acute Lymphoblastic Leukemia in Childhood. J. Clin. Endocrinol. Metab.
84: 4591-4596
[Abstract][Full Text]
Cardoso, A. A., Veiga, J. P., Ghia, P., Afonso, H. M., Haining, W. N., Sallan, S. E., Nadler, L. M.
(1999). Adoptive T-Cell Therapy for B-Cell Acute Lymphoblastic Leukemia: Preclinical Studies. Blood
94: 3531-3540
[Abstract][Full Text]
Fulgoni, P., Zoia, M. C., Corsico, A., Beccaria, M., Georgiani, G., Bossi, G., Cerveri, I.
(1999). Lung Function in Survivors of Childhood Acute Lymphoblastic Leukemia. Chest
116: 1163-1167
[Abstract][Full Text]
Rots, M. G., Pieters, R., Peters, G. J., van Zantwijk, C. H., Mauritz, R., Noordhuis, P., Willey, J. C., Hahlen, K., Creutzig, U., Janka-Schaub, G., Kaspers, G. J.L., Veerman, A. J.P., Jansen, G.
(1999). Circumvention of Methotrexate Resistance in Childhood Leukemia Subtypes by Rationally Designed Antifolates. Blood
94: 3121-3128
[Abstract][Full Text]
Shu, X. O., Linet, M. S., Steinbuch, M., Wen, W. Q., Buckley, J. D., Neglia, J. P., Potter, J. D., Reaman, G. H., Robison, L. L.
(1999). Breast-Feeding and Risk of Childhood Acute Leukemia. JNCI J Natl Cancer Inst
91: 1765-1772
[Abstract][Full Text]
Zecca, M., Pession, A., Messina, C., Bonetti, F., Favre, C., Prete, A., Cesaro, S., Porta, F., Mazzarino, I., Giorgiani, G., Rondelli, R., Locatelli, F.
(1999). Total Body Irradiation, Thiotepa, and Cyclophosphamide as a Conditioning Regimen for Children With Acute Lymphoblastic Leukemia in First or Second Remission Undergoing Bone Marrow Transplantation With HLA-Identical Siblings. JCO
17: 1838-1838
[Abstract][Full Text]
Keengwe, I. N, Stansfield, F., Eden, O. B, Nelhans, N. D, Dearlove, O. R, Sharples, A.
(1999). Paediatric oncology and intensive care treatments: changing trends. Arch. Dis. Child.
80: 553-555
[Abstract][Full Text]
Hosler, G. A., Bash, R. O., Bai, X., Jain, V., Scheuermann, R. H.
(1999). Development and Validation of a Quantitative Polymerase Chain Reaction Assay to Evaluate Minimal Residual Disease for T-Cell Acute Lymphoblastic Leukemia and Follicular Lymphoma. Am. J. Pathol.
154: 1023-1035
[Abstract][Full Text]
Rots, M. G., Pieters, R., Peters, G. J., Noordhuis, P., van Zantwijk, C. H., Kaspers, G. J.L., Hahlen, K., Creutzig, U., Veerman, A. J.P., Jansen, G.
(1999). Role of Folylpolyglutamate Synthetase and Folylpolyglutamate Hydrolase in Methotrexate Accumulation and Polyglutamylation in Childhood Leukemia. Blood
93: 1677-1683
[Abstract][Full Text]
Rots, M. G., Pieters, R., Kaspers, G.-J. L., van Zantwijk, C. H., Noordhuis, P., Mauritz, R., Veerman, A. J.P., Jansen, G., Peters, G. J.
(1999). Differential Methotrexate Resistance in Childhood T- Versus Common/PreB-Acute Lymphoblastic Leukemia Can Be Measured by an In Situ Thymidylate Synthase Inhibition Assay, But Not by the MTT Assay. Blood
93: 1067-1074
[Abstract][Full Text]
Ito, C., Kumagai, M.-a., Manabe, A., Coustan-Smith, E., Raimondi, S. C., Behm, F. G., Murti, K. G., Rubnitz, J. E., Pui, C.-H., Campana, D.
(1999). Hyperdiploid Acute Lymphoblastic Leukemia With 51 to 65 Chromosomes: A Distinct Biological Entity With a Marked Propensity to Undergo Apoptosis. Blood
93: 315-320
[Abstract][Full Text]
Tsuganezawa, K., Kiyokawa, N., Matsuo, Y., Kitamura, F., Toyama-Sorimachi, N., Kuida, K., Fujimoto, J., Karasuyama, H.
(1998). Flow Cytometric Diagnosis of the Cell Lineage and Developmental Stage of Acute Lymphoblastic Leukemia by Novel Monoclonal Antibodies Specific to Human Pre-B-Cell Receptor. Blood
92: 4317-4324
[Abstract][Full Text]
Ludwig, W.-D., Rieder, H., Bartram, C. R., Heinze, B., Schwartz, S., Gassmann, W., Loffler, H., Hossfeld, D., Heil, G., Handt, S., Heyll, A., Diedrich, H., Fischer, K., Weiss, A., Volkers, B., Aydemir, U., Fonatsch, C., Gokbuget, N., Thiel, E., Hoelzer, D.
(1998). Immunophenotypic and Genotypic Features, Clinical Characteristics, and Treatment Outcome of Adult Pro-B Acute Lymphoblastic Leukemia: Results of the German Multicenter Trials GMALL 03/87 and 04/89. Blood
92: 1898-1909
[Abstract][Full Text]
Pui, C.-H., Evans, W. E.
(1998). Acute Lymphoblastic Leukemia. NEJM
339: 605-615
[Full Text]
Altura, R. A., Inukai, T., Ashmun, R. A., Zambetti, G. P., Roussel, M. F., Look, A. T.
(1998). The Chimeric E2A-HLF Transcription Factor Abrogates p53-Induced Apoptosis in Myeloid Leukemia Cells. Blood
92: 1397-1405
[Abstract][Full Text]
Birkebæk, N H, Clausen, N
(1998). Height and weight pattern up to 20 years after treatment for acute lymphoblastic leukaemia. Arch. Dis. Child.
79: 161-164
[Abstract][Full Text]
Pui, C.-H., Mahmoud, H. H., Rivera, G. K., Hancock, M. L., Sandlund, J. T., Behm, F. G., Head, D. R., Relling, M. V., Ribeiro, R. C., Rubnitz, J. E., Kun, L. E., Evans, W. E.
(1998). Early Intensification of Intrathecal Chemotherapy Virtually Eliminates Central Nervous System Relapse in Children With Acute Lymphoblastic Leukemia. Blood
92: 411-415
[Abstract][Full Text]
Faderl, S., Kantarjian, H. M., Talpaz, M., Estrov, Z.
(1998). Clinical Significance of Cytogenetic Abnormalities in Adult Acute Lymphoblastic Leukemia. Blood
91: 3995-4019
[Full Text]
Evans, W. E., Relling, M. V., Rodman, J. H., Crom, W. R., Boyett, J. M., Pui, C.-H.
(1998). Conventional Compared with Individualized Chemotherapy for Childhood Acute Lymphoblastic Leukemia. NEJM
338: 499-505
[Abstract][Full Text]
Ito, C., Ribeiro, R. C., Behm, F. G., Raimondi, S. C., Pui, C.-H., Campana, D.
(1998). Cyclosporin A Induces Apoptosis in Childhood Acute Lymphoblastic Leukemia Cells. Blood
91: 1001-1007
[Abstract][Full Text]
Rubnitz, J. E., Pui, C.-H.
(1997). Childhood Acute Lymphoblastic Leukemia. The Oncologist
2: 374-380
[Abstract][Full Text]
Kersey, J. H.
(1997). Fifty Years of Studies of the Biology and Therapy of Childhood Leukemia. Blood
90: 4243-4251
[Full Text]
Look, A. T.
(1997). Oncogenic Transcription Factors in the Human Acute Leukemias. Science
278: 1059-1064
[Abstract][Full Text]
Jennings, C. D., Foon, K. A.
(1997). Recent Advances in Flow Cytometry: Application to the Diagnosis of Hematologic Malignancy. Blood
90: 2863-2892
[Full Text]
Mayer, R. J., Schnipper, L. E., Broder, S., Hughes-Davies, T.H., Rand, T. S., Cole, P., Rodu, B., Corey, S., Suit, H., Isselbacher, K., Chabner, B., Feldman, A., Atkins, R. N., Arlen, P. A., Noxon, C. L., Wilcken, N., Bailar, J. C., Gornik, H. L.
(1997). Winning the War on Cancer. NEJM
337: 935-938
[Full Text]
Borkhardt, A., Cazzaniga, G., Viehmann, S., Valsecchi, M. G., Ludwig, W. D., Burci, L., Mangioni, S., Schrappe, M., Riehm, H., Lampert, F., Basso, G., Masera, G., Harbott, J., Biondi, A.
(1997). Incidence and Clinical Relevance of TEL/AML1 Fusion Genes in Children With Acute Lymphoblastic Leukemia Enrolled in the German and Italian Multicenter Therapy Trials. Blood
90: 571-577
[Abstract][Full Text]
Campion, E. W.
(1997). Power Lines, Cancer, and Fear. NEJM
337: 44-46
[Full Text]
Rubnitz, J. E., Crist, W. M.
(1997). Molecular Genetics of Childhood Cancer: Implications for Pathogenesis, Diagnosis, and Treatment. Pediatrics
100: 101-108
[Full Text]
Pui, C.-H., Boyett, J. M., Hughes, W. T., Rivera, G. K., Hancock, M. L., Sandlund, J. T., Synold, T., Relling, M. V., Ribeiro, R. C., Crist, W. M., Evans, W. E.
(1997). Human Granulocyte Colony-Stimulating Factor after Induction Chemotherapy in Children with Acute Lymphoblastic Leukemia. NEJM
336: 1781-1787
[Abstract][Full Text]
Kees, U. R., Burton, P. R., Lu, C., Baker, D. L.
(1997). Homozygous Deletion of the p16/MTS1 Gene in Pediatric Acute Lymphoblastic Leukemia Is Associated With Unfavorable Clinical Outcome. Blood
89: 4161-4166
[Abstract][Full Text]
Nishigaki, H., Ito, C., Manabe, A., Kumagai, M.-a., Coustan-Smith, E., Yanishevski, Y., Behm, F. G., Raimondi, S. C., Pui, C.-H., Campana, D.
(1997). Prevalence and Growth Characteristics of Malignant Stem Cells in B-Lineage Acute Lymphoblastic Leukemia. Blood
89: 3735-3744
[Abstract][Full Text]
Uckun, F. M., Yang, Z., Sather, H., Steinherz, P., Nachman, J., Bostrom, B., Crotty, L., Sarquis, M., Ek, O., Zeren, T., Tubergen, D., Reaman, G., Gaynon, P.
(1997). Cellular Expression of Antiapoptotic BCL-2 Oncoprotein in Newly Diagnosed Childhood Acute Lymphoblastic Leukemia: A Children's Cancer Group Study. Blood
89: 3769-3777
[Abstract][Full Text]
Hongo, T., Yajima, S., Sakurai, M., Horikoshi, Y., Hanada, R.
(1997). In Vitro Drug Sensitivity Testing Can Predict Induction Failure and Early Relapse of Childhood Acute Lymphoblastic Leukemia. Blood
89: 2959-2965
[Abstract][Full Text]
Rubnitz, J. E., Shuster, J. J., Land, V. J., Link, M. P., Pullen, D. J., Camitta, B. M., Pui, C.-H., Downing, J. R., Behm, F. G.
(1997). Case-Control Study Suggests a Favorable Impact of TEL Rearrangement in Patients With B-Lineage Acute Lymphoblastic Leukemia Treated With Antimetabolite-Based Therapy: A Pediatric Oncology Group Study. Blood
89: 1143-1146
[Abstract][Full Text]
Gorlick, R., Goker, E., Trippett, T., Waltham, M., Banerjee, D., Bertino, J. R.
(1996). Intrinsic and Acquired Resistance to Methotrexate in Acute Leukemia. NEJM
335: 1041-1048
[Full Text]