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 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; Acute Leukemia Committee of the CIBMTR

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

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 journal › Article › Academic › peer-review

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 language	English
Pages (from-to)	1329-1338
Number of pages	10
Journal	Haematologica-the Hematology Journal
Volume	105
Issue number	5
Early online date	26 Sept 2019
DOIs	https://doi.org/10.3324/haematol.2019.220756
Publication status	Published - 1 May 2020

Keywords

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

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10.3324/haematol.2019.220756Licence: CC BY-NC

1 Erratum / corrigendum / retractions

Erratum: 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
Lazaryan, A., Dolan, M., Zhang, M. J., Wang, H. L., Kharfan-Dabaja, M. A., Marks, D. I., Bejanyan, N., Copelan, E., Majhail, N. S., Waller, E. K., Chao, N., Prestidge, T., Nishihori, T., Kebriaei, P., Inamoto, Y., Hamilton, B., Hashmi, S. K., Kamble, R. T., Bacher, U., Hildebrandt, G. C., & 31 othersStiff, P. J., McGuirk, J., Aldoss, I., Beitinjaneh, A. M., Muffly, L., Vij, R., Olsson, R. F., Byrne, M., Schultz, K. R., Aljurf, M., Seftel, M., Savoie, M. L., Savani, B. N., Verdonck, L. F., Cairo, M. S., Hossain, N., Bhatt, V. R., Frangoul, H. A., Abdel-Azim, H., Al Malki, M., Munker, R., Rizzieri, D., Khera, N., Nakamura, R., Ringdén, O., Van Der Poel, M., Murthy, H. S., Liu, H., Mori, S., De Oliveira, S. & Acute Leukemia Committee of the CIBMTR, 1 Aug 2021, In: Haematologica-the Hematology Journal. 106, 8, p. 2295-2296 2 p.
Research output: Contribution to journal › Erratum / corrigendum / retractions › Academic

Open Access

Cite this

Lazaryan, A., Dolan, M., Zhang, M.-J., Wang, H.-L., Kharfan-Dabaja, M. A., Marks, D. I., Bejanyan, N., Copelan, E., Majhail, N. S., Waller, E. K., Chao, N., Prestidge, T., Nishihori, T., Kebriaei, P., Inamoto, Y., Hamilton, B., Hashmi, S. K., Kamble, R. T., Bacher, U., ... 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-the Hematology Journal, 105(5), 1329-1338. https://doi.org/10.3324/haematol.2019.220756

Lazaryan, Aleksandr ; Dolan, Michelle ; Zhang, Mei-Jie 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. In: Haematologica-the Hematology Journal. 2020 ; Vol. 105, No. 5. pp. 1329-1338.

@article{a2af6e1ec1fc498391b648db1609abf8,

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. 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.",

keywords = "MINIMAL RESIDUAL DISEASE, ACUTE MYELOID-LEUKEMIA, MONOSOMAL KARYOTYPE, TRANSLOCATIONS, PROGNOSIS, THERAPY, IKZF1",

author = "Aleksandr Lazaryan and Michelle Dolan and Mei-Jie Zhang and Hai-Lin Wang 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 and {Acute Leukemia Committee of the CIBMTR}",

note = "Copyright {\textcopyright} 2019, Ferrata Storti Foundation.",

year = "2020",

month = may,

day = "1",

doi = "10.3324/haematol.2019.220756",

language = "English",

volume = "105",

pages = "1329--1338",

journal = "Haematologica-the Hematology Journal",

issn = "0390-6078",

publisher = "Ferrata Storti Foundation",

number = "5",

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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, Al Malki, M, Munker, R, Rizzieri, D, Khera, N, Nakamura, R, Ringdén, O, van der Poel, M, Murthy, HS, Liu, H, Mori, S, De Oliveira, S & 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-the Hematology Journal, 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. / Lazaryan, Aleksandr; Dolan, Michelle; Zhang, Mei-Jie et al.
In: Haematologica-the Hematology Journal, Vol. 105, No. 5, 01.05.2020, p. 1329-1338.

Research output: Contribution to journal › Article › Academic › 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

AU - Acute Leukemia Committee of the CIBMTR

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. 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.

AB - 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.

KW - MINIMAL RESIDUAL DISEASE

KW - ACUTE MYELOID-LEUKEMIA

KW - MONOSOMAL KARYOTYPE

KW - TRANSLOCATIONS

KW - PROGNOSIS

KW - THERAPY

KW - IKZF1

U2 - 10.3324/haematol.2019.220756

DO - 10.3324/haematol.2019.220756

M3 - Article

C2 - 31558669

SN - 0390-6078

VL - 105

SP - 1329

EP - 1338

JO - Haematologica-the Hematology Journal

JF - Haematologica-the Hematology Journal

IS - 5

ER -

Lazaryan A, Dolan M, Zhang MJ, Wang HL, Kharfan-Dabaja MA, Marks DI 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-the Hematology Journal. 2020 May 1;105(5):1329-1338. Epub 2019 Sept 26. 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

Abstract

Keywords

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Research output

Erratum: 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

Cite this