FREE NEJM E-TOC    HOME   |   SUBSCRIBE   |   CURRENT ISSUE   |   PAST ISSUES   |   COLLECTIONS   |   Search Term  Advanced Search

Sign in | Get NEJM's E-Mail Table of Contents — Free | Subscribe

Previous Volume 342:998-1006 April 6, 2000 Number 14 Next

	Full Text PDF Letters Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited PubMed Citation

ABSTRACT

Background Children with Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph-positive ALL) have a poor prognosis, and there is no consensus on the optimal treatment for this variant of ALL.

Methods We reviewed the medical records of patients with Ph-positive ALL who were treated with intensive chemotherapy, with or without bone marrow transplantation, by 10 study groups or large single institutions from 1986 to 1996. Data on 326 children and young adults, who ranged in age from 0.4 to 19.9 years (median, 8.1), were analyzed to determine the rate of complete remission and the probability of event-free, disease-free, and overall survival according to standard prognostic factors and type of treatment.

Results The 267 patients who had a complete remission after induction chemotherapy (82 percent) were stratified into three subgroups according to the age and leukocyte count at the time of diagnosis: those with the best prognosis (a leukocyte count of less than 50,000 per cubic millimeter and an age of less than 10 years; 95 patients); those with an intermediate prognosis (intermediate-risk features; 92 patients); and those with the worst prognosis (a leukocyte count of more than 100,000 per cubic millimeter; 80 patients). The estimates of disease-free survival at five years (±SE) were 49±5 percent (for patients with the best prognosis), 30±5 percent (for those with an intermediate prognosis), and 20±5 percent (for those with the worst prognosis) (P<0.001 for the overall comparison). We also found that transplantation of bone marrow from an HLA-matched related donor offered significantly greater benefit than intensive chemotherapy alone in terms of protecting patients from relapse or other adverse events (relative risk, 0.3; 95 percent confidence interval, 0.2 to 0.5; P<0.001). This finding was consistent in all three subgroups.

Conclusions Unlike the usual type of ALL, Ph-positive ALL is associated with a poor prognosis. Nevertheless, in some patients with favorable prognostic features, the disease can be controlled by intensive chemotherapy. Transplantation of bone marrow from an HLA-matched related donor is superior to other types of transplantation and to intensive chemotherapy alone in prolonging initial complete remissions.

Source Information

From the Department of Pediatrics, Istituto Ricovero e Cura a Carattere Scientifico, Policlinico San Matteo, Pavia, Italy (M.A.); the Department of Public Health, University of Verona, Verona, Italy (M.G.V.); the Department of Pediatrics, Midwest Children's Cancer Center, Medical College of Wisconsin, Milwaukee (B.C.); the Department of Pediatric Hematology–Oncology, Medizinische Hochschule, Hannover, Germany (M.S.); the Leukemia Research Fund, Hematology–Oncology, Institute of Child Health, London (J.C.); Service de Pédiatrie Hématologique, Hôpital Saint Louis, Paris (A.B.); Children's Hospital of Los Angeles and University of Southern California, Los Angeles (P.G.); the Department of Pediatric Oncology, Dana–Farber Cancer Institute and Harvard Medical School, Boston (L.S.); the Department of Pediatric Hematology and Oncology, University of Hamburg, Hamburg, Germany (G.J.-S.); the Department of Pediatric Oncology, Beatrix Children's Hospital, Groningen, the Netherlands (W.K.); St. Jude Children's Research Hospital and the University of Tennessee College of Medicine, Memphis (C.-H.P.); and the Department of Pediatrics, University of Milan and Ospedale San Gerardo, Monza, Italy (G.M.). Other authors were V. Conter, M.D. (Associazione Italiana di Ematologia ed Oncologia Pediatrica); H. Riehm, M.D. (Berlin–Frankfurt–Münster Study Group); N. Heerema, Ph.D. (Children's Cancer Group); S. Sallan, M.D. (Dana–Farber Cancer Institute, Boston); M.-F. Auclerc, M.D. (French Acute Lymphoblastic Leukemia Study Group); J. Pullen, M.D., J. Shuster, Ph.D., and A. Carroll, Ph.D. (Pediatric Oncology Group); S. Raimondi, Ph.D. (St. Jude Children's Research Hospital, Memphis, Tenn.); and S. Richards, M.D. (Medical Research Council, United Kingdom Acute Lymphoblastic Leukaemia).

Address reprint requests to Dr. Aricò at the Clinica Pediatrica, IRCCS Policlinico San Matteo, 27100 Pavia, Italy, or at aricom{at}unipv.it.

Full Text of this Article

Related Letters:

Philadelphia Chromosome–Positive Acute Lymphoblastic Leukemia in Children
Oki Y., Kishi Y., Kami M., Fruchter O., Valsecchi M. G., Schrappe M., Pui C.-H.
Extract | Full Text  
N Engl J Med 2000; 343:1043-1044, Oct 5, 2000. Correspondence

This article has been cited by other articles:

• Williams, R.T., Sherr, C.J. (2008). The INK4-ARF (CDKN2A/B) Locus in Hematopoiesis and BCR-ABL-induced Leukemias. Cold Spring Harb Symp Quant Biol 0: sqb.2008.73.039v2-sqb.2008.73.039 [Abstract]  
• Schrappe, M. (2008). RISK-ADAPTED STRATIFICATION AND TREATMENT OF CHILDHOOD ACUTE LYMPHOBLASTIC LEUKAEMIA. Radiat Prot Dosimetry 0: ncn289v1-4 [Abstract] [Full Text]  
• Tucci, F., Arico, M. (2008). Treatment of pediatric acute lymphoblastic leukemia. haematol 93: 1124-1128 [Full Text]  
• Mullighan, C. G., Williams, R. T., Downing, J. R., Sherr, C. J. (2008). Failure of CDKN2A/B (INK4A/B-ARF)-mediated tumor suppression and resistance to targeted therapy in acute lymphoblastic leukemia induced by BCR-ABL. Genes Dev. 22: 1411-1415 [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]  
• Fuster, J. L., Bermudez, M., Galera, A., Llinares, M. E., Calle, D., Ortuno, F. J. (2007). Imatinib mesylate in combination with chemotherapy in four children with de novo and advanced stage Philadelphia chromosome-positive acute lymphoblastic leukemia. haematol 92: 1723-1724 [Abstract] [Full Text]  
• Iori, A. P., Arcese, W., Milano, F., Calabrese, E., Torelli, G. F., Barberi, W., Mascolo, M. G., De Felice, L., Screnci, M., Lucarelli, B., Malandruccolo, L., Perrone, M. P., Salvatori, S., Laurenti, L., Iannella, E., Ricci, R., Moleti, M. L., Foa, R. (2007). Unrelated cord blood transplant in children with high-risk acute lymphoblastic leukemia: a long-term follow-up. haematol 92: 1051-1058 [Abstract] [Full Text]  
• Ribera, J.-M., Ortega, J.-J., Oriol, A. (2007). In Reply. JCO 25: 2627-2628 [Full Text]  
• Feldhahn, N., Henke, N., Melchior, K., Duy, C., Soh, B. N., Klein, F., von Levetzow, G., Giebel, B., Li, A., Hofmann, W.-K., Jumaa, H., Muschen, M. (2007). Activation-induced cytidine deaminase acts as a mutator in BCR-ABL1-transformed acute lymphoblastic leukemia cells. JEM 204: 1157-1166 [Abstract] [Full Text]  
• Fujii, H., Trudeau, J. D., Teachey, D. T., Fish, J. D., Grupp, S. A., Schultz, K. R., Reid, G. S. D. (2007). In vivo control of acute lymphoblastic leukemia by immunostimulatory CpG oligonucleotides. Blood 109: 2008-2013 [Abstract] [Full Text]  
• Schultz, K. R., Pullen, D. J., Sather, H. N., Shuster, J. J., Devidas, M., Borowitz, M. J., Carroll, A. J., Heerema, N. A., Rubnitz, J. E., Loh, M. L., Raetz, E. A., Winick, N. J., Hunger, S. P., Carroll, W. L., Gaynon, P. S., Camitta, B. M. (2007). Risk- and response-based classification of childhood B-precursor acute lymphoblastic leukemia: a combined analysis of prognostic markers from the Pediatric Oncology Group (POG) and Children's Cancer Group (CCG). Blood 109: 926-935 [Abstract] [Full Text]  
• Choi, J., Hwang, Y. K., Sung, K. W., Lee, S. H., Yoo, K. H., Jung, H. L., Koo, H. H., Kim, H.-J., Kang, H. J., Shin, H. Y., Ahn, H. S. (2007). Expression of Livin, an antiapoptotic protein, is an independent favorable prognostic factor in childhood acute lymphoblastic leukemia. Blood 109: 471-477 [Abstract] [Full Text]  
• Ribera, J.-M., Ortega, J.-J., Oriol, A., Bastida, P., Calvo, C., Perez-Hurtado, J.-M., Gonzalez-Valentin, M.-E., Martin-Reina, V., Molines, A., Ortega-Rivas, F., Moreno, M.-J., Rivas, C., Egurbide, I., Heras, I., Poderos, C., Martinez-Revuelta, E., Guinea, J.-M., del Potro, E., Deben, G. (2007). Comparison of Intensive Chemotherapy, Allogeneic, or Autologous Stem-Cell Transplantation As Postremission Treatment for Children With Very High Risk Acute Lymphoblastic Leukemia: PETHEMA ALL-93 Trial. JCO 25: 16-24 [Abstract] [Full Text]  
• Schrauder, A., Reiter, A., Gadner, H., Niethammer, D., Klingebiel, T., Kremens, B., Peters, C., Ebell, W., Zimmermann, M., Niggli, F., Ludwig, W.-D., Riehm, H., Welte, K., Schrappe, M. (2006). Superiority of Allogeneic Hematopoietic Stem-Cell Transplantation Compared With Chemotherapy Alone in High-Risk Childhood T-Cell Acute Lymphoblastic Leukemia: Results From ALL-BFM 90 and 95. JCO 24: 5742-5749 [Abstract] [Full Text]  
• Meshinchi, S., Arceci, R. J., Sanders, J. E., Smith, F. O., Woods, W. B., Radich, J. P., Alonzo, T. A., Gale, R. E., Hills, R., Wheatley, K., Burnett, A. K., Linch, D. C. (2006). Role of allogeneic stem cell transplantation in FLT3/ITD-positive AML.. Blood 108: 400-401 [Full Text]  
• Coustan-Smith, E., Ribeiro, R. C., Stow, P., Zhou, Y., Pui, C.-H., Rivera, G. K., Pedrosa, F., Campana, D. (2006). A simplified flow cytometric assay identifies children with acute lymphoblastic leukemia who have a superior clinical outcome. Blood 108: 97-102 [Abstract] [Full Text]  
• Loh, M. L., Goldwasser, M. A., Silverman, L. B., Poon, W.-M., Vattikuti, S., Cardoso, A., Neuberg, D. S., Shannon, K. M., Sallan, S. E., Gilliland, D. G. (2006). Prospective analysis of TEL/AML1-positive patients treated on Dana-Farber Cancer Institute Consortium Protocol 95-01. Blood 107: 4508-4513 [Abstract] [Full Text]  
• Pui, C.-H., Evans, W. E. (2006). Treatment of Acute Lymphoblastic Leukemia. NEJM 354: 166-178 [Full Text]  
• Armstrong, S. A., Look, A. T. (2005). Molecular Genetics of Acute Lymphoblastic Leukemia. JCO 23: 6306-6315 [Abstract] [Full Text]  
• Zhang, B., Groffen, J., Heisterkamp, N. (2005). Resistance to farnesyltransferase inhibitors in Bcr/Abl-positive lymphoblastic leukemia by increased expression of a novel ABC transporter homolog ATP11a. Blood 106: 1355-1361 [Abstract] [Full Text]  
• Hotfilder, M., Rottgers, S., Rosemann, A., Schrauder, A., Schrappe, M., Pieters, R., Jurgens, H., Harbott, J., Vormoor, J. (2005). Leukemic Stem Cells in Childhood High-Risk ALL/t(9;22) and t(4;11) Are Present in Primitive Lymphoid-Restricted CD34+CD19- Cells. Cancer Res. 65: 1442-1449 [Abstract] [Full Text]  
• Gutierrez, M. I., Timson, G., Siraj, A. K., Bu, R., Barbhaya, S., Banavali, S., Bhatia, K. (2005). Single Monochrome Real-Time RT-PCR Assay for Identification, Quantification, and Breakpoint Cluster Region Determination of t(9;22) Transcripts. J. Mol. Diagn. 7: 40-47 [Abstract] [Full Text]  
• Hunault, M., Harousseau, J.-L., Delain, M., Truchan-Graczyk, M., Cahn, J.-Y., Witz, F., Lamy, T., Pignon, B., Jouet, J.-P., Garidi, R., Caillot, D., Berthou, C., Guyotat, D., Sadoun, A., Sotto, J.-J., Lioure, B., Casassus, P., Solal-Celigny, P., Stalnikiewicz, L., Audhuy, B., Blanchet, O., Baranger, L., Bene, M.-C., Ifrah, N., for the GOELAMS (Groupe Ouest-Est des Leucemies Ai, (2004). Better outcome of adult acute lymphoblastic leukemia after early genoidentical allogeneic bone marrow transplantation (BMT) than after late high-dose therapy and autologous BMT: a GOELAMS trial. Blood 104: 3028-3037 [Abstract] [Full Text]  
• Champagne, M. A., Capdeville, R., Krailo, M., Qu, W., Peng, B., Rosamilia, M., Therrien, M., Zoellner, U., Blaney, S. M., Bernstein, M. (2004). Imatinib mesylate (STI571) for treatment of children with Philadelphia chromosome-positive leukemia: results from a Children's Oncology Group phase 1 study. Blood 104: 2655-2660 [Abstract] [Full Text]  
• Lee, J., Sait, S. N., Wetzler, M. (2004). Characterization of dendritic-like cells derived from t(9;22) acute lymphoblastic leukemia blasts. Int Immunol 16: 1377-1389 [Abstract] [Full Text]  
• Harata, M., Soda, Y., Tani, K., Ooi, J., Takizawa, T., Chen, M., Bai, Y., Izawa, K., Kobayashi, S., Tomonari, A., Nagamura, F., Takahashi, S., Uchimaru, K., Iseki, T., Tsuji, T., Takahashi, T. A., Sugita, K., Nakazawa, S., Tojo, A., Maruyama, K., Asano, S. (2004). CD19-targeting liposomes containing imatinib efficiently kill Philadelphia chromosome-positive acute lymphoblastic leukemia cells. Blood 104: 1442-1449 [Abstract] [Full Text]  
• Soda, Y., Tani, K., Bai, Y., Saiki, M., Chen, M., Izawa, K., Kobayashi, S., Takahashi, S., Uchimaru, K., Kuwabara, T., Warashina, M., Tanabe, T., Miyoshi, H., Sugita, K., Nakazawa, S., Tojo, A., Taira, K., Asano, S. (2004). A novel maxizyme vector targeting a bcr-abl fusion gene induced specific cell death in Philadelphia chromosome-positive acute lymphoblastic leukemia. Blood 104: 356-363 [Abstract] [Full Text]  
• Thomas, D. A., Faderl, S., Cortes, J., O'Brien, S., Giles, F. J., Kornblau, S. M., Garcia-Manero, G., Keating, M. J., Andreeff, M., Jeha, S., Beran, M., Verstovsek, S., Pierce, S., Letvak, L., Salvado, A., Champlin, R., Talpaz, M., Kantarjian, H. (2004). Treatment of Philadelphia chromosome-positive acute lymphocytic leukemia with hyper-CVAD and imatinib mesylate. Blood 103: 4396-4407 [Abstract] [Full Text]  
• Pui, C.-H., Relling, M. V., Downing, J. R. (2004). Acute Lymphoblastic Leukemia. NEJM 350: 1535-1548 [Full Text]  
• Fine, B. M., Stanulla, M., Schrappe, M., Ho, M., Viehmann, S., Harbott, J., Boxer, L. M. (2004). Gene expression patterns associated with recurrent chromosomal translocations in acute lymphoblastic leukemia. Blood 103: 1043-1049 [Abstract] [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]  
• Carroll, W. L. (2003). Race and Outcome in Childhood Acute Lymphoblastic Leukemia. JAMA 290: 2061-2063 [Full Text]  
• Kochling, J., Konig-Merediz, S. A., Stripecke, R., Buchwald, D., Korte, A., von Einsiedel, H. G., Sack, F., Henze, G., Seeger, K., Wittig, B., Schmidt, M. (2003). Protection of Mice against Philadelphia Chromosome-positive Acute Lymphoblastic Leukemia by Cell-based Vaccination Using Nonviral, Minimalistic Expression Vectors and Immunomodulatory Oligonucleotides. Clin. Cancer Res. 9: 3142-3149 [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]  
• 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]  
• Hotfilder, M., Rottgers, S., Rosemann, A., Jurgens, H., Harbott, J., Vormoor, J. (2002). Immature CD34+CD19- progenitor/stem cells in TEL/AML1-positive acute lymphoblastic leukemia are genetically and functionally normal. Blood 100: 640-646 [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]  
• Woolfrey, A. E., Anasetti, C., Storer, B., Doney, K., Milner, L. A., Sievers, E. L., Carpenter, P., Martin, P., Petersdorf, E., Appelbaum, F. R., Hansen, J. A., Sanders, J. E. (2002). Factors associated with outcome after unrelated marrow transplantation for treatment of acute lymphoblastic leukemia in children. Blood 99: 2002-2008 [Abstract] [Full Text]  
• Savage, D. G., Antman, K. H. (2002). Imatinib Mesylate -- A New Oral Targeted Therapy. NEJM 346: 683-693 [Full Text]  
• Annino, L., Vegna, M. L., Camera, A., Specchia, G., Visani, G., Fioritoni, G., Ferrara, F., Peta, A., Ciolli, S., Deplano, W., Fabbiano, F., Sica, S., Di Raimondo, F., Cascavilla, N., Tabilio, A., Leoni, P., Invernizzi, R., Baccarani, M., Rotoli, B., Amadori, S., Mandelli, F. (2002). Treatment of adult acute lymphoblastic leukemia (ALL): long-term follow-up of the GIMEMA ALL 0288 randomized study. Blood 99: 863-871 [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]  
• Kudoh, T., Suzuki, N., Hatakeyama, N., Mizue, N., Hori, T., Oda, T., Watanabe, J., Imamura, M., Chiba, S. (2001). Successful Unrelated Cord Blood Transplantation in Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia During Pulmonary Aspergillosis Treated by Anti-fungal Therapy, Granulocyte Colony-stimulating Factor-mobilized Granulocytes and Surgical Resection: Case Report. Jpn J Clin Oncol 31: 290-293 [Abstract] [Full Text]  
• Druker, B. J., Sawyers, C. L., Kantarjian, H., Resta, D. J., Reese, S. F., Ford, J. M., Capdeville, R., Talpaz, M. (2001). Activity of a Specific Inhibitor of the BCR-ABL Tyrosine Kinase in the Blast Crisis of Chronic Myeloid Leukemia and Acute Lymphoblastic Leukemia with the Philadelphia Chromosome. NEJM 344: 1038-1042 [Abstract] [Full Text]  
• Cornelissen, J. J., Carston, M., Kollman, C., King, R., Dekker, A. W., Lowenberg, B., Anasetti, C. (2001). Unrelated marrow transplantation for adult patients with poor-risk acute lymphoblastic leukemia: strong graft-versus-leukemia effect and risk factors determining outcome. Blood 97: 1572-1577 [Abstract] [Full Text]  
• Oki, Y., Kishi, Y., Kami, M., Fruchter, O., Valsecchi, M. G., Schrappe, M., Pui, C.-H. (2000). Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia in Children. NEJM 343: 1043-1044 [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]