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Blood, 1 June 2007, Vol. 109, No. 11, pp. 4641-4647.
Prepublished online as a Blood First Edition Paper on February 13, 2007; DOI 10.1182/blood-2006-10-051342.


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CLINICAL TRIALS AND OBSERVATIONS

Monosomy 7 and deletion 7q in children and adolescents with acute myeloid leukemia: an international retrospective study

Henrik Hasle1, Todd A. Alonzo2, Anne Auvrignon3, Catherine Behar4, Myron Chang5, Ursula Creutzig6, Alexandra Fischer7, Erik Forestier8, Alcira Fynn9, Oskar A. Haas10,11, Jochen Harbott12, Christine J. Harrison13, Nyla A. Heerema14, Marry M. van den Heuvel-Eibrink15,16, Gertjan J. L. Kaspers17, Franco Locatelli18, Peter Noellke7, Sophia Polychronopoulou19, Yaddanapudi Ravindranath20, Bassem Razzouk21, Dirk Reinhardt22, Natalia N. Savva23, Batia Stark24, Stefan Suciu25, Ichiro Tsukimoto26, David K. Webb27, Dorora Wojcik28, William G. Woods29, Martin Zimmermann22, Charlotte M. Niemeyer7, and Susana C. Raimondi30

1 Department of Pediatrics, Aarhus University Hospital Skejby, Aarhus, Denmark; 2 Children's Oncology Group, University of Southern California, Los Angeles; 3 French Leucémie Aique Myeloide Enfant (LAME), Hôpital Trousseau, Paris, France; 4 Hôpital Americain, Reims, France; 5 Pediatric Oncology Group Statistical Office, Gainesville, FL; 6 AML-BFM Trials, Pediatric Hematology/Oncology, University Hospital Münster, Germany; 7 Department of Pediatrics and Adolescent Medicine, University of Freiburg, Germany; 8 Department of Clinical Science, Pediatrics, Umeå University Hospital, Sweden; 9 Servicio de Hematologia, Hospital de Ninos S. M. Ludovica, La Plata, Argentina; 10 Children's Cancer Research Institute (CCRI), Vienna, Austria; 11 St Anna Children's Hospital, Vienna, Austria; 12 Department of Pediatric Hematology and Oncology, University of Giessen, Germany; 13 Leukaemia Research Fund Group, University of Southampton, United Kingdom; 14 Department of Pathology, The Ohio State University, Columbus; 15 Dutch Childhood Oncology Group (DCOG), Rotterdam, The Netherlands; 16 Department of Pediatric Oncology/Hematology, Sophia Children's Hospital, Erasmus University Medical Center, Rotterdam, The Netherlands; 17 AML Committee I-BFM-SG, Department of Pediatric Hematology/Oncology, Vrije Universiteit (VU) University Medical Center, Amsterdam, The Netherlands; 18 Oncoematologia Pediatrica, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico San Matteo, University of Pavia, Italy; 19 Department of Pediatric Hematology/Oncology, Aghia Sophia Children's Hospital, Athens, Greece; 20 Wayne State University, Department of Pediatrics, Children's Hospital of Michigan, Detroit; 21 St Jude Children's Research Hospital, Memphis, TN; 22 AML-BFM Trials, Pediatric Hematology/Oncology, Medical School, Hannover, Germany; 23 Department of Hematology, National Research Center for Pediatric Oncology and Hematology, Minsk, Belarus; 24 Pediatric Hematology Oncology, Schneider Children's Medical Center of Israel, Petah-Tikva, Israel; 25 European Organization for Research and Treatment of Cancer (EORTC), Brussels, Belgium; 26 Department of Pediatrics, Toho University School of Medicine, Otaku, Tokyo, Japan; 27 Great Ormond Street Hospital for Children, London, United Kingdom; 28 Department of Pediatric Bone Marrow Transplantation, Oncology and Hematology, Wroclaw Medical University, Poland; 29 Children's Healthcare of Atlanta, Emory University, Atlanta, GA; 30 Department of Pathology, St Jude Children's Research Hospital, Memphis, TN

Monosomy 7 (–7) and deletion 7q \del(7q)] are rare in childhood acute myeloid leukemia (AML). We retrospectively collected data on 258 children with AML or refractory anemia with excess blasts in transformation (RAEB-T) and –7 or del(7q) with or without other cytogenetic aberrations \± other]. Karyotypes included –7 (n = 90), –7 other (n = 82), del(7q) (n = 21), and del(7q) other (n = 65). Complete remission (CR) was achieved in fewer patients with –7 ± other compared with del(7q) ± other (61% versus 89%, P < .001). Overall, the 5-year survival rate was 39% (SE, 3%). Survival was superior in del(7q) ± other compared with –7 ± other (51% versus 30%, P < .01). Cytogenetic aberrations considered favorable in AML \t(8;21)(q22;q22), inv(16)(p13q22), t(15;17)(q22;q21), t(9;11)(p22;q23)] (n = 24) were strongly associated with del(7q) and a higher 5-year survival rate compared with del(7q) without favorable cytogenetics (75% versus 46%, P = .03). Patients with –7 and inv(3),–5/del(5q), or + 21 had a 5-year survival rate of 5%. Stem cell transplantation analyzed as a time-dependent variable had no impact on overall survival. However, patients not achieving CR had a 31% survival rate after stem cell transplantation. Childhood AML with chromosome 7 aberrations represents a heterogeneous group of disorders with additional cytogenetic aberrations having a major prognostic impact which should be reflected in future risk-group stratification.


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G. J.L. Kaspers and C. M. Zwaan
Pediatric acute myeloid leukemia: towards high-quality cure of all patients
Haematologica, November 1, 2007; 92(11): 1519 - 1532.
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