Haematologica (May 2020)
Impact of cytogenetic abnormalities on outcomes of adult Philadelphia-negative acute lymphoblastic leukemia after allogeneic hematopoietic stem cell transplantation: a study by the Acute Leukemia Working Committee of the Center for International Blood and Marrow Transplant Research
- Aleksandr Lazaryan,
- Michelle Dolan,
- Mei-Jie Zhang,
- Hai-Lin Wang,
- Mohamed A. Kharfan-Dabaja,
- David I. Marks,
- Nelli Bejanyan,
- Edward Copelan,
- Navneet S. Majhail,
- Edmund K. Waller,
- Nelson Chao,
- Tim Prestidge,
- Taiga Nishihori,
- Partow Kebriaei,
- Yoshihiro Inamoto,
- Betty Hamilton,
- Shahrukh K. Hashmi,
- Rammurti T. Kamble,
- Ulrike Bacher,
- Gerhard C. Hildebrandt,
- Patrick J. Stiff,
- Joseph McGuirk,
- Ibrahim Aldoss,
- Amer M. Beitinjaneh,
- Lori Muffly,
- Ravi Vij,
- Richard F. Olsson,
- Michael Byrne,
- Kirk R. Schultz,
- Mahmoud Aljurf,
- Matthew Seftel,
- Mary Lynn Savoie,
- Bipin N. Savani,
- Leo F. Verdonck,
- Mitchell S. Cairo,
- Nasheed Hossain,
- Vijaya Raj Bhatt,
- Haydar A. Frangoul,
- Hisham Abdel-Azim,
- Monzr Al Malki,
- Reinhold Munker,
- David Rizzieri,
- Nandita Khera,
- Ryotaro Nakamura,
- Olle Ringdén,
- Marjolein van der Poel,
- Hemant S. Murthy,
- Hongtao Liu,
- Shahram Mori,
- Satiro De Oliveira,
- Javier Bolaños-Meade,
- Mahmoud Elsawy,
- Pere Barba,
- Sunita Nathan,
- Biju George,
- Attaphol Pawarode,
- Michael Grunwald,
- Vaibhav Agrawal,
- Youjin Wang,
- Amer Assal,
- Paul Castillo Caro,
- Yachiyo Kuwatsuka,
- Sachiko Seo,
- Celalettin Ustun,
- Ioannis Politikos,
- Hillard M. Lazarus,
- Wael Saber,
- Brenda M. Sandmaier,
- Marcos De Lima,
- Mark Litzow,
- Veronika Bachanova,
- Daniel Weisdorf,
- Acute Leukemia Committee of the CIBMTR
Affiliations
- Aleksandr Lazaryan
- H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
- Michelle Dolan
- University of Minnesota Medical Center, Minneapolis, MN, USA
- Mei-Jie Zhang
- CIBMTR (Center for International Blood and Marrow Transplant Research), Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA;Division of Biostatistics, Institute for Health and Equity, Medical College of Wisconsin, Milwaukee, WI, USA
- Hai-Lin Wang
- CIBMTR (Center for International Blood and Marrow Transplant Research), Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA
- Mohamed A. Kharfan-Dabaja
- Division of Hematology-Oncology, Blood and Marrow Transplantation Program, Mayo Clinic, Jacksonville, FL, USA
- David I. Marks
- Adult Bone Marrow Transplant, University Hospitals Bristol NHS Trust, Bristol, UK
- Nelli Bejanyan
- Department of Blood and Marrow Transplant and Cellular Immunotherapy, Moffitt Cancer Center, Tampa, FL, USA
- Edward Copelan
- Levine Cancer Institute, Atrium Health, Carolinas HealthCare System, Charlotte, NC, USA
- Navneet S. Majhail
- Blood & Marrow Transplant Program, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH, USA
- Edmund K. Waller
- Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USA
- Nelson Chao
- Division of Cell Therapy and Hematology, Department of Medicine, Duke University Medical Center, Durham, NC, USA
- Tim Prestidge
- Blood and Cancer Centre, Starship Children’s Hospital, Auckland, New Zealand
- Taiga Nishihori
- Department of Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
- Partow Kebriaei
- Department of Stem Cell Transplantation, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, TX, USA
- Yoshihiro Inamoto
- Division of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan
- Betty Hamilton
- Blood & Marrow Transplant Program, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH, USA
- Shahrukh K. Hashmi
- Department of Internal Medicine, Mayo Clinic, MN, USA;Oncology Center, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
- Rammurti T. Kamble
- Division of Hematology and Oncology, Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX, USA
- Ulrike Bacher
- Department of Hematology, Inselspital, Bern University Hospital, Switzerland
- Gerhard C. Hildebrandt
- Markey Cancer Center, University of Kentucky, Lexington, KY, USA
- Patrick J. Stiff
- Loyola University Medical Center, Maywood, IL, USA
- Joseph McGuirk
- University of Kansas Medical Center, Westwood, KS, USA
- Ibrahim Aldoss
- City of Hope Comprehensive Cancer Center, Duarte, CA, USA
- Amer M. Beitinjaneh
- University of Miami, Miami, FL, USA
- Lori Muffly
- Division of Blood and Marrow Transplantation, Stanford University, Stanford, CA, USA
- Ravi Vij
- Division of Hematology and Oncology, Washington University School of Medicine, St. Louis, MO, USA
- Richard F. Olsson
- Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden;Centre for Clinical Research Sormland, Uppsala University, Uppsala, Sweden
- Michael Byrne
- Vanderbilt University Medical Center, Nashville, TN, USA
- Kirk R. Schultz
- Department of Pediatric Hematology, Oncology and Bone Marrow Transplant, British Columbia’s Children’s Hospital, The University of British Columbia, Vancouver, British Columbia, Canada
- Mahmoud Aljurf
- Oncology Center, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
- Matthew Seftel
- Department of Medical Oncology and Hematology, CancerCare Manitoba, Winnipeg, Manitoba, Canada
- Mary Lynn Savoie
- Tom Baker Cancer Centre, Calgary, Alberta, Canada
- Bipin N. Savani
- Division of Hematology/Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
- Leo F. Verdonck
- Department of Hematology/Oncology, Isala Clinic, Zwolle, the Netherlands
- Mitchell S. Cairo
- Division of Pediatric Hematology, Oncology and Stem Cell Transplantation, Department of Pediatrics, New York Medical College, Valhalla, NY, USA
- Nasheed Hossain
- Loyola University Chicago Stritch School of Medicine, Maywood, IL, USA
- Vijaya Raj Bhatt
- The Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA
- Haydar A. Frangoul
- The Children’s Hospital at TriStar Centennial and Sarah Cannon Research Institute, Nashville, TN, USA
- Hisham Abdel-Azim
- Division of Hematology, Oncology and Blood & Marrow Transplantation, Children’s Hospital Los Angeles, University of Southern California Keck School of Medicine, Los Angeles, CA, USA
- Monzr Al Malki
- City of Hope Comprehensive Cancer Center, Duarte, CA, USA
- Reinhold Munker
- Section of Hematology/Oncology, Department of Internal Medicine, Louisiana State University Health Shreveport, Shreveport, LA, USA
- David Rizzieri
- Division of Hematologic Malignancies and Cellular Therapy, Duke University, Durham, NC, USA
- Nandita Khera
- Department of Hematology/Oncology, Mayo Clinic, Phoenix, AZ, USA
- Ryotaro Nakamura
- Department of Hematology & Hematopoietic Cell Transplantation, City of Hope, Duarte, CA, USA
- Olle Ringdén
- Translational Cell Therapy Group, CLINTEC (Clinical Science, Intervention and Technology), Karolinska Institutet, Stockholm Sweden
- Marjolein van der Poel
- Academische Ziekenhuis Maastricht, Maastricht, the Netherlands
- Hemant S. Murthy
- Mayo Clinic Florida, Jacksonville, FL, USA
- Hongtao Liu
- University of Chicago Medicine, Chicago, IL, USA
- Shahram Mori
- Blood & Marrow Transplant Center, Florida Hospital Medical Group, Orlando, FL, USA
- Satiro De Oliveira
- UCLA Medical Center, Los Angeles, CA, USA
- Javier Bolaños-Meade
- The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA
- Mahmoud Elsawy
- QE II Health Sciences Centre, Dalhousie University, Halifax, Nova Scotia, Canada
- Pere Barba
- Hospital Vall d’Hebron, Barcelona, Spain
- Sunita Nathan
- Rush University Medical Center, Chicago, IL, USA
- Biju George
- Christian Medical College, Vellore, India
- Attaphol Pawarode
- Blood and Marrow Transplantation Program, Division of Hematology/Oncology, Department of Internal Medicine, The University of Michigan Medical School, Ann Arbor, MI, USA
- Michael Grunwald
- Department of Hematologic Oncology and Blood Disorders, Levine Cancer Institute, Atrium Health, Charlotte, NC, USA
- Vaibhav Agrawal
- Division of Hematology-Oncology, Indiana University School of Medicine, Indianapolis, IN, USA
- Youjin Wang
- National Cancer Institute (NCI), Rockville, MD, USA
- Amer Assal
- New York Presbyterian Hospital/Columbia University Medical Center, New York, NY, USA
- Paul Castillo Caro
- UF Health Shands Children’s Hospital, Gainesville, FL, USA
- Yachiyo Kuwatsuka
- Department of Advanced Medicine, Nagoya University Hospital, Nagoya, Japan
- Sachiko Seo
- Department of Hematology and Oncology, Dokkyo Medical University, Tochigi, Japan
- Celalettin Ustun
- Division of Hematology/Oncology/Cell Therapy, Rush University, Chicago, IL, USA
- Ioannis Politikos
- Memorial Sloan Kettering Cancer Center, New York, NY, USA
- Hillard M. Lazarus
- Case Western Reserve University, Cleveland, OH, USA
- Wael Saber
- CIBMTR (Center for International Blood and Marrow Transplant Research), Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA
- Brenda M. Sandmaier
- Division of Medical Oncology, University of Washington and Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
- Marcos De Lima
- Department of Medicine, Seidman Cancer Center, University Hospitals Case Medical Center, Cleveland, OH, USA
- Mark Litzow
- Division of Hematology and Transplant Center, Mayo Clinic Rochester, Rochester, MN, USA
- Veronika Bachanova
- Blood and Marrow Transplant Program, University of Minnesota Medical Center, Minneapolis, MN, USA
- Daniel Weisdorf
- Division of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota Medical Center, Minneapolis, MN, USA
- Acute Leukemia Committee of the CIBMTR
- CIBMTR (Center for International Blood and Marrow Transplant Research), Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA
- DOI
- https://doi.org/10.3324/haematol.2019.220756
- Journal volume & issue
-
Vol. 105,
no. 5
Abstract
Cytogenetic risk stratification at diagnosis has long been one of the most useful tools to assess prognosis in acute lymphoblastic leukemia (ALL). To examine the prognostic impact of cytogenetic abnormalities on outcomes after allogeneic hematopoietic cell transplantation, we studied 1731 adults with Philadelphia-negative ALL in complete remission who underwent myeloablative or reduced intensity/non-myeloablative conditioning transplant from unrelated or matched sibling donors reported to the Center for International Blood and Marrow Transplant Research. A total of 632 patients had abnormal conventional metaphase cytogenetics. The leukemia-free survival and overall survival rates at 5 years after transplantation in patients with abnormal cytogenetics were 40% and 42%, respectively, which were similar to those in patients with a normal karyotype. Of the previously established cytogenetic risk classifications, modified Medical Research Council-Eastern Cooperative Oncology Group score was the only independent prognosticator of leukemia-free survival (P=0.03). In the multivariable analysis, monosomy 7 predicted post-transplant relapse [hazard ratio (HR)=2.11; 95% confidence interval (95% CI): 1.04-4.27] and treatment failure (HR=1.97; 95% CI: 1.20-3.24). Complex karyotype was prognostic for relapse (HR=1.69; 95% CI: 1.06-2.69), whereas t(8;14) predicted treatment failure (HR=2.85; 95% CI: 1.35-6.02) and overall mortality (HR=3.03; 95% CI: 1.44-6.41). This large study suggested a novel transplant-specific cytogenetic scheme with adverse [monosomy 7, complex karyotype, del(7q), t(8;14), t(11;19), del(11q), tetraploidy/near triploidy], intermediate (normal karyotype and all other abnormalities), and favorable (high hyperdiploidy) risks to prognosticate leukemia-free survival (P=0.02). Although some previously established high-risk Philadelphia-negative cytogenetic abnormalities in ALL can be overcome by transplantation, monosomy 7, complex karyotype, and t(8;14) continue to pose significant risks and yield inferior outcomes.
