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

doi:10.3324/HAEMATOL.2019.220756

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

Research output: Contribution to journal › Article › peer-review

15 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 language	English
Pages (from-to)	1329-1338
Number of pages	10
Journal	Haematologica
Volume	105
Issue number	5
DOIs	https://doi.org/10.3324/HAEMATOL.2019.220756
State	Published - 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.

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Hematology

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(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

@article{019d14f7dc8b434bb17d02e6cb8161e0,

title = "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",

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.",

author = "Aleksandr Lazaryan and Michelle Dolan and Zhang, {Mei Jie} and Wang, {Hai Lin} and Kharfan-Dabaja, {Mohamed A.} and Marks, {David I.} and Nelli Bejanyan and Edward Copelan and Majhail, {Navneet S.} and Waller, {Edmund K.} and Nelson Chao and Tim Prestidge and Taiga Nishihori and Partow Kebriaei and Yoshihiro Inamoto and Betty Hamilton and Hashmi, {Shahrukh K.} and Kamble, {Rammurti T.} and Ulrike Bacher and Hildebrandt, {Gerhard C.} and Stiff, {Patrick J.} and Joseph McGuirk and Ibrahim Aldoss and Beitinjaneh, {Amer M.} and Lori Muffly and Ravi Vij and Olsson, {Richard F.} and Michael Byrne and Schultz, {Kirk R.} and Mahmoud Aljurf and Matthew Seftel and Savoie, {Mary Lynn} and Savani, {Bipin N.} and Verdonck, {Leo F.} and Cairo, {Mitchell S.} and Nasheed Hossain and Bhatt, {Vijaya Raj} and Frangoul, {Haydar A.} and Hisham Abdel-Azim and {Al Malki}, Monzr and Reinhold Munker and David Rizzieri and Nandita Khera and Ryotaro Nakamura and Olle Ringd{\'e}n and {Van Der Poel}, Marjolein and Murthy, {Hemant S.} and Hongtao Liu and Shahram Mori and {De Oliveira}, Satiro",

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{\textquoteright}s Hospital; *Bristol Myers Squibb Co.; *Celgene Corp.; Children{\textquoteright}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: {\textcopyright} 2020 Ferrata Storti Foundation.",

year = "2020",

month = may,

day = "1",

doi = "10.3324/HAEMATOL.2019.220756",

language = "English",

volume = "105",

pages = "1329--1338",

number = "5",

}

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, vol. 105, no. 5, pp. 1329-1338. https://doi.org/10.3324/HAEMATOL.2019.220756

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. /.

In: Haematologica, Vol. 105, No. 5, 01.05.2020, p. 1329-1338.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Impact of cytogenetic abnormalities on outcomes of adult Philadelphia-negative acute lymphoblastic leukemia after allogeneic hematopoietic stem cell transplantation

T2 - A study by the Acute Leukemia Working Committee of the Center for International Blood and Marrow Transplant Research

AU - Lazaryan, Aleksandr

AU - Dolan, Michelle

AU - Zhang, Mei Jie

AU - Wang, Hai Lin

AU - Kharfan-Dabaja, Mohamed A.

AU - Marks, David I.

AU - Bejanyan, Nelli

AU - Copelan, Edward

AU - Majhail, Navneet S.

AU - Waller, Edmund K.

AU - Chao, Nelson

AU - Prestidge, Tim

AU - Nishihori, Taiga

AU - Kebriaei, Partow

AU - Inamoto, Yoshihiro

AU - Hamilton, Betty

AU - Hashmi, Shahrukh K.

AU - Kamble, Rammurti T.

AU - Bacher, Ulrike

AU - Hildebrandt, Gerhard C.

AU - Stiff, Patrick J.

AU - McGuirk, Joseph

AU - Aldoss, Ibrahim

AU - Beitinjaneh, Amer M.

AU - Muffly, Lori

AU - Vij, Ravi

AU - Olsson, Richard F.

AU - Byrne, Michael

AU - Schultz, Kirk R.

AU - Aljurf, Mahmoud

AU - Seftel, Matthew

AU - Savoie, Mary Lynn

AU - Savani, Bipin N.

AU - Verdonck, Leo F.

AU - Cairo, Mitchell S.

AU - Hossain, Nasheed

AU - Bhatt, Vijaya Raj

AU - Frangoul, Haydar A.

AU - Abdel-Azim, Hisham

AU - Al Malki, Monzr

AU - Munker, Reinhold

AU - Rizzieri, David

AU - Khera, Nandita

AU - Nakamura, Ryotaro

AU - Ringdén, Olle

AU - Van Der Poel, Marjolein

AU - Murthy, Hemant S.

AU - Liu, Hongtao

AU - Mori, Shahram

AU - De Oliveira, Satiro

N1 - 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.

PY - 2020/5/1

Y1 - 2020/5/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85086041901&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85086041901&partnerID=8YFLogxK

U2 - 10.3324/HAEMATOL.2019.220756

DO - 10.3324/HAEMATOL.2019.220756

M3 - Article

C2 - 31558669

AN - SCOPUS:85086041901

VL - 105

SP - 1329

EP - 1338

IS - 5

ER -

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

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