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, and Acute Leukemia Committee of the CIBMTR
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.