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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.

Publication ,  Journal Article
Lazaryan, A; Dolan, M; Zhang, M-J; Wang, H-L; Kharfan-Dabaja, MA; Marks, DI; Bejanyan, N; Copelan, E; Majhail, NS; Waller, EK; Chao, N; Vij, R ...
Published in: Haematologica
May 2020

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.

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Published In

Haematologica

DOI

EISSN

1592-8721

Publication Date

May 2020

Volume

105

Issue

5

Start / End Page

1329 / 1338

Location

Italy

Related Subject Headings

  • Transplantation, Homologous
  • Transplantation Conditioning
  • Retrospective Studies
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Leukemia, Myeloid, Acute
  • Immunology
  • Humans
  • Hematopoietic Stem Cell Transplantation
  • Chromosome Aberrations
  • Adult
 

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Lazaryan, A., Dolan, M., Zhang, M.-J., Wang, H.-L., Kharfan-Dabaja, M. A., Marks, D. I., … Acute Leukemia Committee of the CIBMTR. (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. Haematologica, 105(5), 1329–1338. https://doi.org/10.3324/haematol.2019.220756
Lazaryan, Aleksandr, Michelle Dolan, Mei-Jie Zhang, Hai-Lin Wang, Mohamed A. Kharfan-Dabaja, David I. Marks, Nelli Bejanyan, et al. “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.Haematologica 105, no. 5 (May 2020): 1329–38. https://doi.org/10.3324/haematol.2019.220756.
Lazaryan A, Dolan M, Zhang M-J, Wang H-L, Kharfan-Dabaja MA, Marks DI, Bejanyan N, Copelan E, Majhail NS, Waller EK, Chao N, Prestidge T, Nishihori T, Kebriaei P, Inamoto Y, Hamilton B, Hashmi SK, Kamble RT, Bacher U, Hildebrandt GC, Stiff PJ, McGuirk J, Aldoss I, Beitinjaneh AM, Muffly L, Vij R, Olsson RF, Byrne M, Schultz KR, Aljurf M, Seftel M, Savoie ML, Savani BN, Verdonck LF, Cairo MS, Hossain N, Bhatt VR, Frangoul HA, Abdel-Azim H, Malki MA, Munker R, Rizzieri D, Khera N, Nakamura R, Ringdén O, van der Poel M, Murthy HS, Liu H, Mori S, De Oliveira S, Bolaños-Meade J, Elsawy M, Barba P, Nathan S, George B, Pawarode A, Grunwald M, Agrawal V, Wang Y, Assal A, Caro PC, Kuwatsuka Y, Seo S, Ustun C, Politikos I, Lazarus HM, Saber W, Sandmaier BM, De Lima M, Litzow M, Bachanova V, Weisdorf D, Acute Leukemia Committee of the CIBMTR. 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. Haematologica. 2020 May;105(5):1329–1338.

Published In

Haematologica

DOI

EISSN

1592-8721

Publication Date

May 2020

Volume

105

Issue

5

Start / End Page

1329 / 1338

Location

Italy

Related Subject Headings

  • Transplantation, Homologous
  • Transplantation Conditioning
  • Retrospective Studies
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Leukemia, Myeloid, Acute
  • Immunology
  • Humans
  • Hematopoietic Stem Cell Transplantation
  • Chromosome Aberrations
  • Adult