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

Acute Leukemia Committee of the CIBMTR

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6 Scopus citations

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/nonmyeloablative 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.

Original languageEnglish (US)
Pages (from-to)1329-1338
Number of pages10
JournalHaematologica
Volume105
Issue number5
DOIs
StatePublished - May 1 2020

Bibliographical note

Funding Information:
The CIBMTR is supported primarily by a public health service grant/cooperative agreement U24CA076518 from the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Diseases (NIAID); grant/cooperative agreement U24HL138660 from the NHLBI and NCI; grant U24CA233032 from the NCI; grants OT3HL147741, R21HL140314 and U01HL128568 from the NHLBI; a contract HHSH250201700006C with Health Resources and Services Administration (HRSA/DHHS); grants N00014-18-1-2888 and N00014-17-1-2850 from the Office of Naval Research; and grants from *Actinium Pharmaceuticals, Inc.; Adaptive Biotechnologies; *Amgen, Inc.; Anonymous donation to the Medical College of Wisconsin; *Anthem, Inc.; Astellas Pharma US; Atara Biotherapeutics, Inc.; Be the Match Foundation; *bluebird bio, Inc.; Boston Children’s Hospital; *Bristol Myers Squibb Co.; *Celgene Corp.; Children’s Hospital of Los Angeles; *Chimerix, Inc.; *CSL Behring; *CytoSen Therapeutics, Inc.; Dana Farber Cancer Institute; *Daiichi Sankyo Co., Ltd.; Fred Hutchinson Cancer Research Center; *Gamida-Cell, Ltd.; Gilead Sciences, Inc.; *GlaxoSmithKline (GSK); HistoGenetics, Inc.; Immucor; Incyte Corporation; Janssen Biotech, Inc.; *Janssen Pharmaceuticals, Inc.; Janssen Scientific Affairs, LLC; *Jazz Pharmaceuticals, Inc.; Karius, Inc.; Karyopharm Therapeutics, Inc.; *Kite, a Gilead Company; *Magenta Therapeutics; Medac GmbH; The Medical College of Wisconsin; Mediware; Merck & Company, Inc.; *Mesoblast; MesoScale Diagnostics, Inc.; Millennium, the Takeda Oncology Co.; *Miltenyi Biotec, Inc.; Mundipharma EDO; National Marrow Donor Program; Novartis Oncology; Novartis Pharmaceuticals Corporation; *Omeros Corporation; *Oncoimmune, Inc.; PCORI; *Pfizer, Inc.; *Phamacyclics, LLC; PIRCHE AG; *Regeneron Pharmaceuticals, Inc.; REGiMMUNE Corp.; *Sanofi Genzyme; *Seattle Genetics; *Shire; Sobi, Inc.; Spectrum Pharmaceuticals, Inc.; St. Baldrick's Foundation; Swedish Orphan Biovitrum, Inc.; *Takeda Oncology; University of Minnesota; University of Pittsburgh; University of Texas-MD Anderson; University of Wisconsin – Madison and Viracor Eurofins. The views expressed in this article do not reflect the official policy or position of the National Institute of Health, the Department of the Navy, the Department of Defense, Health Resources and Services Administration (HRSA) or any other agency of the U.S. Government. *Corporate Members.

Funding Information:
The CIBMTR is supported primarily by a public health service grant/cooperative agreement U24CA076518 from the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Diseases (NIAID); grant/cooperative agreement U24HL138660 from the NHLBI and NCI; grant U24CA233032 from the NCI; grants OT3HL147741, R21HL140314 and U01HL128568 from the NHLBI; a contract HHSH250201700006C with Health Resources and Services Administration (HRSA/DHHS); grants N00014-18- 1-2888 and N00014-17-1-2850 from the Office of Naval Research; and grants from Actinium Pharmaceuticals, Inc.; Adaptive Biotechnologies; Amgen, Inc.; Anonymous donation to the Medical College of Wisconsin; Anthem, Inc.; Astellas Pharma US; Atara Biotherapeutics, Inc.; Be the Match Foundation; bluebird bio, Inc.; Boston Children's Hospital; Bristol Myers Squibb Co.; Celgene Corp.; Children's Hospital of Los Angeles; Chimerix, Inc.; CSL Behring; CytoSen Therapeutics, Inc.; Dana Farber Cancer Institute; Daiichi Sankyo Co., Ltd.; Fred Hutchinson Cancer Research Center; Gamida-Cell, Ltd.; Gilead Sciences, Inc.; GlaxoSmithKline (GSK); HistoGenetics, Inc.; Immucor; Incyte Corporation; Janssen Biotech, Inc.; Janssen Pharmaceuticals, Inc.; Janssen Scientific Affairs, LLC; Jazz Pharmaceuticals, Inc.; Karius, Inc.; Karyopharm Therapeutics, Inc.; Kite, a Gilead Company; Magenta Therapeutics; Medac GmbH; The Medical College of Wisconsin; Mediware; Merck & Company, Inc.; Mesoblast; MesoScale Diagnostics, Inc.; Millennium, the Takeda Oncology Co.; Miltenyi Biotec, Inc.; Mundipharma EDO; National Marrow Donor Program; Novartis Oncology; Novartis Pharmaceuticals Corporation; Omeros Corporation; Oncoimmune, Inc.; PCORI; Pfizer, Inc.; Phamacyclics, LLC; PIRCHE AG; Regeneron Pharmaceuticals, Inc.; REGiMMUNE Corp.; Sanofi Genzyme; Seattle Genetics; Shire; Sobi, Inc.; Spectrum Pharmaceuticals, Inc.; St. Baldrick's Foundation; Swedish Orphan Biovitrum, Inc.; Takeda Oncology; University of Minnesota; University of Pittsburgh; University of Texas-MD Anderson; University of Wisconsin - Madison and Viracor Eurofins. The views expressed in this article do not reflect the official policy or position of the National Institute of Health, the Department of the Navy, the Department of Defense, Health Resources and Services Administration (HRSA) or any other agency of the U.S. Government. Corporate Members.

Publisher Copyright:
© 2020 Ferrata Storti Foundation.

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

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