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Journal of Clinical Oncology, Vol 21, Issue 24 (December), 2003: 4642-4649
© 2003 American Society for Clinical Oncology


SPECIAL ARTICLE

Revised Recommendations of the International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia

Bruce D. Cheson, John M. Bennett, Kenneth J. Kopecky, Thomas Büchner, Cheryl L. Willman, Elihu H. Estey, Charles A. Schiffer, Hartmut Doehner, Martin S. Tallman, T. Andrew Lister, Francesco Lo-Coco, Roel Willemze, Andrea Biondi, Wolfgang Hiddemann, Richard A. Larson, Bob Löwenberg, Miguel A. Sanz, David R. Head, Ryuzo Ohno, Clara D. Bloomfield

From the Department of Hematology/Oncology, Georgetown University, Washington, DC; University of Rochester Medical Center, Rochester, NY; Fred Hutchinson Cancer Research Center, Seattle, WA; University of Texas M.D. Anderson Cancer Center, Houston, TX; Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI; University of Münster, Münster; University of Grosshadern, Munich; University of Ulm, Ulm, Germany; University Tor Vergata of Rome; Clinica Pediatrica Università Milano-Bicocca, Ospedale S. Gerardo, Monza, Italy; Leiden University, Leiden; Erasmus Medical Center Rotterdam; Institute of Hematology, Rotterdam, Netherlands; University of Chicago; Northwestern University, Chicago, IL; Hospital Universitario La Fe, University of Valencia, Spain; University of New Mexico Cancer Treatment and Research Center, Albuquerque, NM; Aichi Cancer Center Hospital, Nagoya, Japan; St. Bartholomew’s Hospital, London, UK; Vanderbilt University School of Medicine, Nashville, TN; and The Ohio State University Comprehensive Cancer Center, Columbus, OH.

Address reprint requests to Bruce D. Cheson, MD, Head of Hematology, Georgetown University, Lombardi Cancer Center, 3800 Reservoir Rd, NW, Washington, DC 20007; e-mail: bdc4{at}georgetown.edu.

An International Working Group met to revise the diagnostic and response criteria for acute myelogenous leukemia originally published in 1990, as well as to provide definitions of outcomes and reporting standards to improve interpretability of data and comparisons among trials. Since the original publication, there have been major advances in our understanding of the biology and molecular genetics of acute leukemia that are clinically relevant and warrant incorporation into response definitions. Differences from the 1990 recommendations included a category of leukemia-free state, new criteria for complete remission, including cytogenetic and molecular remissions and remission duration. Storage of viable blasts for correlative studies is important for future progress in the therapy of these disorders.


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  • Revised Recommendations of the International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia
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P. P. Piccaluga, M. Malagola, M. Rondoni, M. Arpinati, S. Paolini, A. Candoni, R. Fanin, E. Messa, M. T. Pirrotta, F. Lauria, et al.
Imatinib mesylate in the treatment of newly diagnosed or refractory/resistant c-KIT positive acute myeloid leukemia. Results of an italian multicentric phase II study.
Haematologica, December 1, 2007; 92(12): 1721 - 1722.
[Abstract] [Full Text] [PDF]


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BloodHome page
J. E. Karp, R. M. Ricklis, K. Balakrishnan, J. Briel, J. Greer, S. D. Gore, B. D. Smith, M. A. McDevitt, H. Carraway, M. J. Levis, et al.
A phase 1 clinical-laboratory study of clofarabine followed by cyclophosphamide for adults with refractory acute leukemias
Blood, September 15, 2007; 110(6): 1762 - 1769.
[Abstract] [Full Text] [PDF]


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JCOHome page
W. Blum, R. B. Klisovic, B. Hackanson, Z. Liu, S. Liu, H. Devine, T. Vukosavljevic, L. Huynh, G. Lozanski, C. Kefauver, et al.
Phase I Study of Decitabine Alone or in Combination With Valproic Acid in Acute Myeloid Leukemia
J. Clin. Oncol., September 1, 2007; 25(25): 3884 - 3891.
[Abstract] [Full Text] [PDF]


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Clin. Cancer Res.Home page
J. E. Karp, B. D. Smith, M. J. Levis, S. D. Gore, J. Greer, C. Hattenburg, J. Briel, R. J. Jones, J. J. Wright, and A. D. Colevas
Sequential Flavopiridol, Cytosine Arabinoside, and Mitoxantrone: A Phase II Trial in Adults with Poor-Risk Acute Myelogenous Leukemia
Clin. Cancer Res., August 1, 2007; 13(15): 4467 - 4473.
[Abstract] [Full Text] [PDF]


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BloodHome page
N. Asou, Y. Kishimoto, H. Kiyoi, M. Okada, Y. Kawai, M. Tsuzuki, K. Horikawa, M. Matsuda, K. Shinagawa, T. Kobayashi, et al.
A randomized study with or without intensified maintenance chemotherapy in patients with acute promyelocytic leukemia who have become negative for PML-RAR{alpha} transcript after consolidation therapy: The Japan Adult Leukemia Study Group (JALSG) APL97 study
Blood, July 1, 2007; 110(1): 59 - 66.
[Abstract] [Full Text] [PDF]


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BloodHome page
C. Gardin, P. Turlure, T. Fagot, X. Thomas, C. Terre, N. Contentin, E. Raffoux, S. de Botton, C. Pautas, O. Reman, et al.
Postremission treatment of elderly patients with acute myeloid leukemia in first complete remission after intensive induction chemotherapy:results of the multicenter randomized Acute Leukemia French Association (ALFA) 9803 trial
Blood, June 15, 2007; 109(12): 5129 - 5135.
[Abstract] [Full Text] [PDF]


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BloodHome page
J.-L. Harousseau, J. E. Lancet, J. Reiffers, B. Lowenberg, X. Thomas, F. Huguet, P. Fenaux, S. Zhang, W. Rackoff, P. De Porre, et al.
A phase 2 study of the oral farnesyltransferase inhibitor tipifarnib in patients with refractory or relapsed acute myeloid leukemia
Blood, June 15, 2007; 109(12): 5151 - 5156.
[Abstract] [Full Text] [PDF]


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haematolHome page
M. Schaich, R. F. Schlenk, H. K. Al-Ali, H. Dohner, A. Ganser, G. Heil, T. Illmer, R. Krahl, J. Krauter, C. Sauerland, et al.
Prognosis of acute myeloid leukemia patients up to 60 years of age exhibiting trisomy 8 within a non-complex karyotype: individual patient data-based meta-analysis of the German Acute Myeloid Leukemia Intergroup
Haematologica, June 1, 2007; 92(6): 763 - 770.
[Abstract] [Full Text] [PDF]


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BloodHome page
F. Ciceri, C. Bonini, S. Marktel, E. Zappone, P. Servida, M. Bernardi, A. Pescarollo, A. Bondanza, J. Peccatori, S. Rossini, et al.
Antitumor effects of HSV-TK engineered donor lymphocytes after allogeneic stem-cell transplantation
Blood, June 1, 2007; 109(11): 4698 - 4707.
[Abstract] [Full Text] [PDF]


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haematolHome page
L. Maurillo, F. Buccisano, A. Spagnoli, G. Del Poeta, P. Panetta, B. Neri, M. I. Del Principe, C. Mazzone, M. I. Consalvo, A. Tamburini, et al.
Monitoring of minimal residual disease in adult acute myeloid leukemia using peripheral blood as an alternative source to bone marrow
Haematologica, May 1, 2007; 92(5): 605 - 611.
[Abstract] [Full Text] [PDF]


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J. Clin. Pathol.Home page
N. Al-Shughair, G. Al-Dawsari, M. Gyger, G. Mohamed, and G. Roberts
Clinical significance of plasmacytosis in the day+14 bone marrow of patients with acute myeloid leukaemia undergoing induction chemotherapy
J. Clin. Pathol., May 1, 2007; 60(5): 520 - 523.
[Abstract] [Full Text] [PDF]


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BloodHome page
I. Gojo, A. Jiemjit, J. B. Trepel, A. Sparreboom, W. D. Figg, S. Rollins, M. L. Tidwell, J. Greer, E. J. Chung, M.-J. Lee, et al.
Phase 1 and pharmacologic study of MS-275, a histone deacetylase inhibitor, in adults with refractory and relapsed acute leukemias
Blood, April 1, 2007; 109(7): 2781 - 2790.
[Abstract] [Full Text] [PDF]


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haematolHome page
F. Lo-Coco, E. Ammatuna, and M. A. Sanz
Current treatment of acute promyelocytic leukemia
Haematologica, March 1, 2007; 92(3): 289 - 291.
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BloodHome page
F. R. Appelbaum, D. Rosenblum, R. J. Arceci, W. L. Carroll, P. P. Breitfeld, S. J. Forman, R. A. Larson, S. J. Lee, S. B. Murphy, S. O'Brien, et al.
End points to establish the efficacy of new agents in the treatment of acute leukemia
Blood, March 1, 2007; 109(5): 1810 - 1816.
[Abstract] [Full Text] [PDF]


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JCOHome page
D. A. Rizzieri, L. P. Koh, G. D. Long, C. Gasparetto, K. M. Sullivan, M. Horwitz, J. Chute, C. Smith, J. Z. Gong, A. Lagoo, et al.
Partially Matched, Nonmyeloablative Allogeneic Transplantation: Clinical Outcomes and Immune Reconstitution
J. Clin. Oncol., February 20, 2007; 25(6): 690 - 697.
[Abstract] [Full Text] [PDF]


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haematolHome page
B. Xicoy, J.-M. Ribera, P. Miralles, J. Berenguer, R. Rubio, B. Mahillo, M.-E. Valencia, E. Abella, A. Lopez-Guillermo, A. Sureda, et al.
Results of treatment with doxorubicin, bleomycin, vinblastine and dacarbazine and highly active antiretroviral therapy in advanced stage, human immunodeficiency virus-related Hodgkin's lymphoma
Haematologica, February 1, 2007; 92(2): 191 - 198.
[Abstract] [Full Text] [PDF]


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BloodHome page
H. Kantarjian, Y. Oki, G. Garcia-Manero, X. Huang, S. O'Brien, J. Cortes, S. Faderl, C. Bueso-Ramos, F. Ravandi, Z. Estrov, et al.
Results of a randomized study of 3 schedules of low-dose decitabine in higher-risk myelodysplastic syndrome and chronic myelomonocytic leukemia
Blood, January 1, 2007; 109(1): 52 - 57.
[Abstract] [Full Text] [PDF]


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BloodHome page
D. J. DeAngelo, R. M. Stone, M. L. Heaney, S. D. Nimer, R. L. Paquette, R. B. Klisovic, M. A. Caligiuri, M. R. Cooper, J.-M. Lecerf, M. D. Karol, et al.
Phase 1 clinical results with tandutinib (MLN518), a novel FLT3 antagonist, in patients with acute myelogenous leukemia or high-risk myelodysplastic syndrome: safety, pharmacokinetics, and pharmacodynamics
Blood, December 1, 2006; 108(12): 3674 - 3681.
[Abstract] [Full Text] [PDF]


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BloodHome page
M. Heuser, G. Beutel, J. Krauter, K. Dohner, N. von Neuhoff, B. Schlegelberger, and A. Ganser
High meningioma 1 (MN1) expression as a predictor for poor outcome in acute myeloid leukemia with normal cytogenetics
Blood, December 1, 2006; 108(12): 3898 - 3905.
[Abstract] [Full Text] [PDF]


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ASH ANNUAL MEETING ABSTRACTSHome page
E. Jabbour, H. M. Kantarjian, J. Cortes, W. G. Wierda, A. Ferrajoli, S. Faderl, S. O'Brien, F. Ravandi-Kashani, S. Verstovsek, G. Garcia-Manero, et al.
Survival Benefit with Decitabine Compared to Historical Experience with Intensive Chemotherapy in Patients with Higher Risk Myelodysplastic Syndrome (MDS).
Blood (ASH Annual Meeting Abstracts), November 16, 2006; 108(11): 2652 - 2652.
[Abstract] [PDF]


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ASH ANNUAL MEETING ABSTRACTSHome page
R. A. Mesa, A. Tefferi, and D. P. Steensma
Hematologic and Cytogenetic Response to Lenalidomide Therapy in an 82 Year Old Female with Acute Myeloid Leukemia (AML) Arising from JAK2V617F Positive, del(5)(q13q33) Myelodysplastic Syndrome (MDS).
Blood (ASH Annual Meeting Abstracts), November 16, 2006; 108(11): 4827 - 4827.
[Abstract] [PDF]


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BloodHome page
S. Frohling, R. F. Schlenk, S. Kayser, M. Morhardt, A. Benner, K. Dohner, H. Dohner, and for the German-Austrian AML Study Group
Cytogenetics and age are major determinants of outcome in intensively treated acute myeloid leukemia patients older than 60 years: results from AMLSG trial AML HD98-B
Blood, November 15, 2006; 108(10): 3280 - 3288.
[Abstract] [Full Text] [PDF]


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BloodHome page
S. Knapper, A. K. Burnett, T. Littlewood, W. J. Kell, S. Agrawal, R. Chopra, R. Clark, M. J. Levis, and D. Small
A phase 2 trial of the FLT3 inhibitor lestaurtinib (CEP701) as first-line treatment for older patients with acute myeloid leukemia not considered fit for intensive chemotherapy
Blood, November 15, 2006; 108(10): 3262 - 3270.
[Abstract] [Full Text] [PDF]


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Cancer Res.Home page
G. Cimino, F. Lo-Coco, S. Fenu, L. Travaglini, E. Finolezzi, M. Mancini, M. Nanni, A. Careddu, F. Fazi, F. Padula, et al.
Sequential Valproic Acid/All-trans Retinoic Acid Treatment Reprograms Differentiation in Refractory and High-Risk Acute Myeloid Leukemia.
Cancer Res., September 1, 2006; 66(17): 8903 - 8911.
[Abstract] [Full Text] [PDF]


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BloodHome page
A. Tefferi, G. Barosi, R. A. Mesa, F. Cervantes, H. J. Deeg, J. T. Reilly, S. Verstovsek, B. Dupriez, R. T. Silver, O. Odenike, et al.
International Working Group (IWG) consensus criteria for treatment response in myelofibrosis with myeloid metaplasia, for the IWG for Myelofibrosis Research and Treatment (IWG-MRT)
Blood, September 1, 2006; 108(5): 1497 - 1503.
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BloodHome page
B. D. Cheson, P. L. Greenberg, J. M. Bennett, B. Lowenberg, P. W. Wijermans, S. D. Nimer, A. Pinto, M. Beran, T. M. de Witte, R. M. Stone, et al.
Clinical application and proposal for modification of the International Working Group (IWG) response criteria in myelodysplasia
Blood, July 15, 2006; 108(2): 419 - 425.
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Ann OncolHome page
S. Palmieri, A. M. D'Arco, M. Celentano, G. Mele, C. Califano, F. Pollio, M. R. D'Amico, and F. Ferrara
An antecedent diagnosis of refractory anemia with excess blasts has no prognostic relevance in acute myeloid leukemia of older adult patients
Ann. Onc., July 1, 2006; 17(7): 1146 - 1151.
[Abstract] [Full Text] [PDF]


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JCOHome page
T. Buchner, W. E. Berdel, C. Schoch, T. Haferlach, H. L. Serve, J. Kienast, S. Schnittger, W. Kern, J. Tchinda, A. Reichle, et al.
Double Induction Containing Either Two Courses or One Course of High-Dose Cytarabine Plus Mitoxantrone and Postremission Therapy by Either Autologous Stem-Cell Transplantation or by Prolonged Maintenance for Acute Myeloid Leukemia
J. Clin. Oncol., June 1, 2006; 24(16): 2480 - 2489.
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Clin. Cancer Res.Home page
C. D. Bloomfield, K. Mrozek, and M. A. Caligiuri
Cancer and Leukemia Group B Leukemia Correlative Science Committee: Major Accomplishments and Future Directions.
Clin. Cancer Res., June 1, 2006; 12(11): 3564s - 3571s.
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J. Immunol.Home page
M.-T. Krauth, S. Florian, A. Bohm, K. Sonneck, H. Agis, P. Samorapoompichit, A. W. Hauswirth, W. R. Sperr, and P. Valent
Immunological Characterization and Antibacterial Function of Persisting Granulocytes in Leukemic Patients Receiving Pulse Cytosine Arabinoside-Consolidation Chemotherapy on Days 1, 3, and 5
J. Immunol., February 1, 2006; 176(3): 1759 - 1768.
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Mayo Clin Proc.Home page
E. J. Jabbour, E. Estey, and H. M. Kantarjian
Adult Acute Myeloid Leukemia
Mayo Clin. Proc., February 1, 2006; 81(2): 247 - 260.
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ASH Education BookHome page
M. A. Sanz
Treatment of Acute Promyelocytic Leukemia
Hematology, January 1, 2006; 2006(1): 147 - 155.
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ASH Education BookHome page
F. Lo-Coco and E. Ammatuna
The Biology of Acute Promyelocytic Leukemia and Its Impact on Diagnosis and Treatment
Hematology, January 1, 2006; 2006(1): 156 - 161.
[Abstract] [Full Text] [PDF]


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ASH Education BookHome page
K. Mrozek and C. D. Bloomfield
Chromosome Aberrations, Gene Mutations and Expression Changes, and Prognosis in Adult Acute Myeloid Leukemia
Hematology, January 1, 2006; 2006(1): 169 - 177.
[Abstract] [Full Text] [PDF]


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JCOHome page
S. Tauro, C. Craddock, K. Peggs, G. Begum, P. Mahendra, G. Cook, J. Marsh, D. Milligan, A. Goldstone, A. Hunter, et al.
Allogeneic Stem-Cell Transplantation Using a Reduced-Intensity Conditioning Regimen Has the Capacity to Produce Durable Remissions and Long-Term Disease-Free Survival in Patients With High-Risk Acute Myeloid Leukemia and Myelodysplasia
J. Clin. Oncol., December 20, 2005; 23(36): 9387 - 9393.
[Abstract] [Full Text] [PDF]


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Clin. Cancer Res.Home page
J. E. Karp, A. Passaniti, I. Gojo, S. Kaufmann, K. Bible, T. S. Garimella, J. Greer, J. Briel, B. D. Smith, S. D. Gore, et al.
Phase I and Pharmacokinetic Study of Flavopiridol followed by 1-{beta}-D-Arabinofuranosylcytosine and Mitoxantrone in Relapsed and Refractory Adult Acute Leukemias
Clin. Cancer Res., December 1, 2005; 11(23): 8403 - 8412.
[Abstract] [Full Text] [PDF]


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BloodHome page
K. Dohner, R. F. Schlenk, M. Habdank, C. Scholl, F. G. Rucker, A. Corbacioglu, L. Bullinger, S. Frohling, H. Dohner, and for the AML Study Group (AMLSG)
Mutant nucleophosmin (NPM1) predicts favorable prognosis in younger adults with acute myeloid leukemia and normal cytogenetics: interaction with other gene mutations
Blood, December 1, 2005; 106(12): 3740 - 3746.
[Abstract] [Full Text] [PDF]


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JCOHome page
J. J. Ortega, L. Madero, G. Martin, A. Verdeguer, P. Garcia, R. Parody, J. Fuster, A. Molines, A. Novo, G. Deben, et al.
Treatment With All-Trans Retinoic Acid and Anthracycline Monochemotherapy for Children With Acute Promyelocytic Leukemia: A Multicenter Study by the PETHEMA Group
J. Clin. Oncol., October 20, 2005; 23(30): 7632 - 7640.
[Abstract] [Full Text] [PDF]


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Clin. Cancer Res.Home page
S. H. Kaufmann, J. E. Karp, L. Letendre, T. J. Kottke, S. Safgren, J. Greer, I. Gojo, P. Atherton, P. A. Svingen, D. A. Loegering, et al.
Phase I and Pharmacologic Study of Infusional Topotecan and Carboplatin in Relapsed and Refractory Acute Leukemia
Clin. Cancer Res., September 15, 2005; 11(18): 6641 - 6649.
[Abstract] [Full Text] [PDF]


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JCOHome page
S. Frohling, C. Scholl, D. G. Gilliland, and R. L. Levine
Genetics of Myeloid Malignancies: Pathogenetic and Clinical Implications
J. Clin. Oncol., September 10, 2005; 23(26): 6285 - 6295.
[Abstract] [Full Text] [PDF]


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JCOHome page
J. Cortes, S. Faderl, E. Estey, R. Kurzrock, D. Thomas, M. Beran, G. Garcia-Manero, A. Ferrajoli, F. Giles, C. Koller, et al.
Phase I Study of BMS-214662, a Farnesyl Transferase Inhibitor in Patients With Acute Leukemias and High-Risk Myelodysplastic Syndromes
J. Clin. Oncol., April 20, 2005; 23(12): 2805 - 2812.
[Abstract] [Full Text] [PDF]


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BloodHome page
M. A. Sanz, M. S. Tallman, and F. Lo-Coco
Tricks of the trade for the appropriate management of newly diagnosed acute promyelocytic leukemia
Blood, April 15, 2005; 105(8): 3019 - 3025.
[Abstract] [Full Text] [PDF]


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BloodHome page
M. Dreyling, G. Lenz, E. Hoster, A. Van Hoof, C. Gisselbrecht, R. Schmits, B. Metzner, L. Truemper, M. Reiser, H. Steinhauer, et al.
Early consolidation by myeloablative radiochemotherapy followed by autologous stem cell transplantation in first remission significantly prolongs progression-free survival in mantle-cell lymphoma: results of a prospective randomized trial of the European MCL Network
Blood, April 1, 2005; 105(7): 2677 - 2684.
[Abstract] [Full Text] [PDF]


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JCOHome page
G. Lenz, M. Dreyling, E. Hoster, B. Wormann, U. Duhrsen, B. Metzner, H. Eimermacher, A. Neubauer, H. Wandt, H. Steinhauer, et al.
Immunochemotherapy With Rituximab and Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone Significantly Improves Response and Time to Treatment Failure, But Not Long-Term Outcome in Patients With Previously Untreated Mantle Cell Lymphoma: Results of a Prospective Randomized Trial of the German Low Grade Lymphoma Study Group (GLSG)
J. Clin. Oncol., March 20, 2005; 23(9): 1984 - 1992.
[Abstract] [Full Text] [PDF]


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BloodHome page
K. F. Bradstock, J. P. Matthews, R. M. Lowenthal, H. Baxter, J. Catalano, T. Brighton, D. Gill, P. Eliadis, D. Joshua, P. Cannell, et al.
A randomized trial of high-versus conventional-dose cytarabine in consolidation chemotherapy for adult de novo acute myeloid leukemia in first remission after induction therapy containing high-dose cytarabine
Blood, January 15, 2005; 105(2): 481 - 488.
[Abstract] [Full Text] [PDF]


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BloodHome page
R. M. Stone, D. J. DeAngelo, V. Klimek, I. Galinsky, E. Estey, S. D. Nimer, W. Grandin, D. Lebwohl, Y. Wang, P. Cohen, et al.
Patients with acute myeloid leukemia and an activating mutation in FLT3 respond to a small-molecule FLT3 tyrosine kinase inhibitor, PKC412
Blood, January 1, 2005; 105(1): 54 - 60.
[Abstract] [Full Text] [PDF]


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BloodHome page
M. A. Sanz, E. Vellenga, C. Rayon, J. Diaz-Mediavilla, C. Rivas, E. Amutio, J. Arias, G. Deben, A. Novo, J. Bergua, et al.
All-trans retinoic acid and anthracycline monochemotherapy for the treatment of elderly patients with acute promyelocytic leukemia
Blood, December 1, 2004; 104(12): 3490 - 3493.
[Abstract] [Full Text] [PDF]



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