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680 Cytogenetics Abnormalities Predict the Outcome of Allogeneic Transplantation In AML: A CIBMTR Study

Program: Oral and Poster Abstracts
Type: Oral
Session: Clinical Care - Recurrence, Secondary Neoplasia and Late Complications after Transplantation: Relapse after Transplantation
Monday, December 6, 2010: 4:45 PM
110B (Orange County Convention Center)

Philippe Armand, MD, PhD1, Waleska S. Perez, MPH2*, Mei-Jie Zhang, PhD2*, Haesook T Kim, PhD3, Thomas R. Klumpp, MD4, Paola Dal Cin, PhD5*, Edmund K Waller, MD, PhD6, Mark R. Litzow, MD7, Jane L. Liesveld, MD8, Hillard M. Lazarus, MD FACP9, Andrew Artz, MD MS10, Vikas Gupta, MD, MRCP, FRCPath11, Bipin N. Savani, MD12, Philip L. McCarthy Jr., MD13, Jean-Yves Cahn, MD14, Harry Schouten15, Jurgen Finke, MD16, Edward D. Ball, M.D.17, Mahmoud Aljurf, M.D.18, Corey Cutler, MD, MPH, FRCPC19, Jacob M. Rowe, MD20, Joseph H. Antin, MD19, Luis M Isola, MD21*, Paolo Di Bartolomeo, MD22, Bruce Camitta, MD23, Alan M Miller, MD, PhD24*, Mitchell S. Cairo, MD25, Keith E. Stockerl-Goldstein, MD26, Jorge Sierra, MD27, Mary Lynn Savoie, MD, FRCPC28, Joerg Halter, MD29*, Patrick J Stiff, MD30, Chadi Nabhan, MD, FACP31*, Ann A. Jakubowski, MD, PhD32, Donald Bunjes, MD33*, Effie W. Petersdorf, MD34*, Steven M Devine, MD35, Richard Maziarz, MD36*, Martin Bornhauser, MD37*, Victor A Lewis, MD38*, David I. Marks, MBBS, PHD39, Christopher N Bredeson, MD, MSc, FRCPC2, Robert Soiffer, MD40* and Daniel J. Weisdorf, MD41

1Dana Farber Cancer Institute, Boston, MA
2Medical College of Wisconsin, Milwaukee, WI
3Biostatistics & Computational Bio., Dana-Farber Cancer Institute, Boston, MA
4Temple University, Wynnewood, PA
5Center for Advanced Molecular Diagnostics, Brigham and Women's Hospital, Boston, MA
6Winship Cancer Institute, Atlanta, GA
7Hematology, Mayo Clinic, Rochester, MN
8Univ. of Rochester Med. Ctr., Rochester, NY
9Medicine, University Hospitals Case Medical Center, Cleveland, OH
10University of Chicago Hospital, Chicago, IL
11Princess Margaret Hospital, Toronto, ON, Canada
12Division of Hematology/ Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN
13BMT Program, Roswell Park Cancer Institute, Buffalo, NY
14Onco-Hematologie, CHU-Grenoble, Grenoble, Cedex O9, France
15HOVON, Netherlands
16Dept. of Medicine 1, Hem.-Onc., Universitatsklinikum Freiburg, Freiburg, Germany
17Moores UCSD Cancer Center, La Jolla, CA
18Oncology Center , King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
19Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, MA
20Hematology and Bone Marrow Transplantation, Rambam Medical Center, Technion, Haifa, Israel
21BMT, Mount Sinai Medical Center, New York
22Hematology, Ospedale Civile, Pescara, Italy
23Pediatric Hematology/Oncology/BMT, Medical College of Wisconsin, Wauwatosa, WI
24Baylor University Medical Center, Dallas, TX
25Div. of Pediatric Hematology and Blood and Marrow Transplantation, Columbia University Medical Center, New York, NY
26Division of Oncology, Washington University School of Medicine, Saint Louis, MO
27On behalf of CETLAM Cooperative Group, Barcelona, Spain
28Foothills Medical Centre, Calgary, AB, Canada
29University Hospital Basel, Basel, Switzerland
30Loyola University Medical Center, Maywood, IL
31Advocate Lutheran General Hospital, Park Ridge, IL
32Memorial Sloan-Kettering Cancer Center, New York, NY
33University Hospital Ulm, Ulm, Germany
34Fred Hutchinson Cancer Research Center, Seattle, WA
35The Ohio State University Medical Center
36Clinical Cancer Center, Oregon Health and Science University, Portland, WI
37University Hospital, Dresden, Germany
38Alberta Children's Hospital, Calgary, AB
39Molecular and Cellular Medicine, University Hospitals Bristol NHS Foundation Trust, Bristol, United Kingdom
40Dana-Farber Cancer Institute, Boston, MA
41Hematology, Oncology and Transplantation, University of Minnesota , Minneapolis, MN

Cytogenetics play an essential role in determining the prognosis of patients with AML.  However, there is still no validated cytogenetics grouping scheme that specifically applies to patients undergoing allogeneic stem cell transplantation, which hampers accurate prognostication and risk stratification.  We studied 821 adult patients (median age 41, range 18-74) who underwent SCT between 1999 and 2004 for AML (excluding APL) in CR1 or CR2 and who were reported to the CIBMTR from centers with >20 patients meeting study criteria.  75% of patients received a myeloablative conditioning.  496 patients had a normal karyotype.  The primary cytogenetics reports were manually reviewed for 92% of the patients with an abnormal karyotype.  We compared the ability of the 6 existing grouping schemes (MRC, CALGB, EORTC/GIMEMA, SWOG/ECOG, DFCI, and Monosomal Karyotype (MK) classifications) to stratify patients, using both the Akaike Information Criterion in multivariable models and the C-statistic.  Among all existing schemes, the DFCI system provided a marginally superior stratification for overall and leukemia-free survival.  We also built a new classification using individual cytogenetic abnormalities in a Cox model that included other significant covariates (performance status, therapy-related disease, conditioning intensity, graft source, donor match, duration of CR1, and gender match).  This CIBMTR scheme (see Table), which is similar to the DFCI scheme except for the inclusion of patients with t(8;21) in the intermediate group, could stratify patients into 3 groups with similar treatment-related mortality but significantly different overall survival, leukemia-free survival, and incidence of relapse.  This scheme appeared to apply to both patients in CR1 and in CR2 (see Figures).  This transplant-specific scheme could be adopted for prognostication purposes and to stratify patients with karyotypic abnormalities entering transplantation clinical trials.  Future studies may clarify the relative outcome of patients with t(8;21) and refine this scheme with the inclusion of molecular abnormalities.

Group

Abnormality

% of patients with

abnormal karyotype

5y OS

CR1

5y OS

CR2

Favorable

Inv(16)

12%

73%

62%

Intermediate

Normal karyotype

n/a

58%

38%

t(8;21)

11q23 abnormality

Trisomy/tetrasomy 8

Abnormal 5 or 7

Other abnormalitiesa

66%

50%

41%

Adverse

Complex (≥4 abns)

22%

18%

18%

aExcept for abn12p, abn3q, del(9q), t(1;19), and t(6;9), which are not classified in this scheme.

Disclosures: No relevant conflicts of interest to declare.

*signifies non-member of ASH