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 HildebrandtPatrick 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, Acute Leukemia Committee of the CIBMTR

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

13 Citations (Web of Science)

Abstract

Cytogenetic risk stratification at diagnosis has long been one of the most useful tools to assess prognosis in acute lymphoblastic leukemia. To examine the prognostic impact of cytogenetic abnormalities on outcomes after allogeneic hematopoietic cell transplantation, we studied 1731 adults with Philadelphia-negative acute lymphoblastic leukemia in complete remission who underwent myeloablative or reduced intensity/non-myeloablative conditioning transplant from unrelated or matched sibling donors reported to Center for International Blood and Marrow Transplant Research. A total of 632 patients had abnormal conventional metaphase cytogenetics. Patients with abnormal cytogenetics had 40% leukemia-free survival and 42% overall survival at 5-years post-transplant, which was similar to those with 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=2.11; 95% confidence interval, 1.04-4.27) and treatment failure (hazard ratio=1.97; 1.20-3.24). Complex karyotype was prognostic for relapse (hazard ratio=1.69; 1.06-2.69), whereas t(8;14) predicted treatment failure (hazard ratio=2.85; 1.35-6.02) and overall mortality (hazard ratio=3.03; 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 of acute lymphoblastic leukemia can be overcome by transplant, monosomy 7, complex karyotype, and t(8;14) continue to pose significant risks and yield inferior outcomes.

Original languageEnglish
Pages (from-to)1329-1338
Number of pages10
JournalHaematologica-the Hematology Journal
Volume105
Issue number5
Early online date26 Sep 2019
DOIs
Publication statusPublished - 1 May 2020

Keywords

  • MINIMAL RESIDUAL DISEASE
  • ACUTE MYELOID-LEUKEMIA
  • MONOSOMAL KARYOTYPE
  • TRANSLOCATIONS
  • PROGNOSIS
  • THERAPY
  • IKZF1

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