Impact of depth of clinical response on outcomes of acute myeloid leukemia patients in first complete remission who undergo allogeneic hematopoietic cell transplantation

Mary Elizabeth Percival; Hai Lin Wang; Mei Jie Zhang; Wael Saber; Marcos de Lima; Mark Litzow; Partow Kebriaei; Hisham Abdel-Azim; Kehinde Adekola; Mahmoud Aljurf; Ulrike Bacher; Sherif M. Badawy; Amer Beitinjaneh; Nelli Bejanyan; Vijaya Bhatt; Michael Byrne; Jean Yves Cahn; Paul Castillo; Nelson Chao; Saurabh Chhabra; Edward Copelan; Corey Cutler; Zachariah DeFilipp; Ajoy Dias; Miguel Angel Diaz; Elihu Estey; Nosha Farhadfar; Haydar A. Frangoul; César O. Freytes; Robert Peter Gale; Siddhartha Ganguly; Lohith Gowda; Michael Grunwald; Nasheed Hossain; Rammurti T. Kamble; Christopher G. Kanakry; Ankit Kansagra; Mohamed A. Kharfan-Dabaja; Maxwell Krem; Hillard M. Lazarus; Jong Wook Lee; Jane L. Liesveld; Richard Lin; Hongtao Liu; Joseph McGuirk; Reinhold Munker; Hemant S. Murthy; Sunita Nathan; Taiga Nishihori; Richard F. Olsson; Neil Palmisiano; Jakob R. Passweg; Tim Prestidge; Olov Ringdén; David A. Rizzieri; Witold B. Rybka; Mary Lynn Savoie; Kirk R. Schultz; Sachiko Seo; Akshay Sharma; Melhem Solh; Roger Strair; Marjolein van der Poel; Leo F. Verdonck; Jean A. Yared; Daniel Weisdorf; Brenda M. Sandmaier

doi:10.1038/s41409-021-01261-6

Impact of depth of clinical response on outcomes of acute myeloid leukemia patients in first complete remission who undergo allogeneic hematopoietic cell transplantation

Mary Elizabeth Percival^*, Hai Lin Wang, Mei Jie Zhang, Wael Saber, Marcos de Lima, Mark Litzow, Partow Kebriaei, Hisham Abdel-Azim, Kehinde Adekola, Mahmoud Aljurf, Ulrike Bacher, Sherif M. Badawy, Amer Beitinjaneh, Nelli Bejanyan, Vijaya Bhatt, Michael Byrne, Jean Yves Cahn, Paul Castillo, Nelson Chao, Saurabh ChhabraEdward Copelan, Corey Cutler, Zachariah DeFilipp, Ajoy Dias, Miguel Angel Diaz, Elihu Estey, Nosha Farhadfar, Haydar A. Frangoul, César O. Freytes, Robert Peter Gale, Siddhartha Ganguly, Lohith Gowda, Michael Grunwald, Nasheed Hossain, Rammurti T. Kamble, Christopher G. Kanakry, Ankit Kansagra, Mohamed A. Kharfan-Dabaja, Maxwell Krem, Hillard M. Lazarus, Jong Wook Lee, Jane L. Liesveld, Richard Lin, Hongtao Liu, Joseph McGuirk, Reinhold Munker, Hemant S. Murthy, Sunita Nathan, Taiga Nishihori, Richard F. Olsson, Neil Palmisiano, Jakob R. Passweg, Tim Prestidge, Olov Ringdén, David A. Rizzieri, Witold B. Rybka, Mary Lynn Savoie, Kirk R. Schultz, Sachiko Seo, Akshay Sharma, Melhem Solh, Roger Strair, Marjolein van der Poel, Leo F. Verdonck, Jean A. Yared, Daniel Weisdorf, Brenda M. Sandmaier

^*Corresponding author for this work

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10 Scopus citations

Abstract

Acute myeloid leukemia (AML) patients often undergo allogeneic hematopoietic cell transplantation (alloHCT) in first complete remission (CR). We examined the effect of depth of clinical response, including incomplete count recovery (CRi) and/or measurable residual disease (MRD), in patients from the Center for International Blood and Marrow Transplantation Research (CIBMTR) registry. We identified 2492 adult patients (1799 CR and 693 CRi) who underwent alloHCT between January 1, 2007 and December 31, 2015. The primary outcome was overall survival (OS). Multivariable analysis was performed to adjust for patient-, disease-, and transplant-related factors. Baseline characteristics were similar. Patients in CRi compared to those in CR had an increased likelihood of death (HR: 1.27; 95% confidence interval: 1.13–1.43). Compared to CR, CRi was significantly associated with increased non-relapse mortality (NRM), shorter disease-free survival (DFS), and a trend toward increased relapse. Detectable MRD was associated with shorter OS, shorter DFS, higher NRM, and increased relapse compared to absence of MRD. The deleterious effects of CRi and MRD were independent. In this large CIBMTR cohort, survival outcomes differ among AML patients based on depth of CR and presence of MRD at the time of alloHCT. Further studies should focus on optimizing post-alloHCT outcomes for patients with responses less than CR.

Original language	English (US)
Pages (from-to)	2108-2117
Number of pages	10
Journal	Bone Marrow Transplantation
Volume	56
Issue number	9
DOIs	https://doi.org/10.1038/s41409-021-01261-6
State	Published - Sep 2021

Funding

Acknowledgements The CIBMTR is supported primarily by Public Health Service 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); U24HL138660 from NHLBI and NCI; OT3HL147741 and U01HL128568 from the NHLBI; HHSH250201700006C and HHSH250201700007C from the Health Resources and Services Administration (HRSA); and N00014-20-1-2705 and N00014-20-1-2832 from the Office of Naval Research; Additional federal support is provided by P01CA111412, R01CA152108, R01CA215134, R01CA218285, R01CA231141, R01AI128775, R01HL126589, R01HL129472, R01HL130388, R01HL131731, U01AI069197, U01AI126612, UG1HL06924, and BARDA. Support is also provided by Be the Match Foundation, Boston Children’s Hospital, Dana Far-ber, St. Baldrick’s Foundation, Stanford University, the Medical College of Wisconsin the National Marrow Donor Program, and from the following commercial entities: Actinium Pharmaceuticals, Inc.; Adienne SA; Allovir, Inc.; Amgen, Inc.; Angiocrine Bioscience; Astellas Pharma US; bluebird bio, Inc.; Bristol Myers Squibb Co.; Celgene Corp.; CSL Behring; CytoSen Therapeutics, Inc.; Daiichi Sankyo Co., Ltd.; ExcellThera; Fate Therapeutics; Gamida-Cell, Ltd.; Genentech Inc; Incyte Corporation; Janssen/Johnson & Johnson; Jazz Pharmaceuticals, Inc.; Kiadis Pharma; Kite, a Gilead Company; Kyowa Kirin; Legend Biotech; Magenta Therapeutics; Merck Sharp & Dohme Corp.; Millennium, the Takeda Oncology Co.; Miltenyi Bio-tec, Inc.; Novartis Pharmaceuticals Corporation; Omeros Corporation; Oncoimmune, Inc.; Orca Biosystems, Inc.; Pfizer, Inc.; Pharmacyclics, LLC; Sanofi Genzyme; Stemcyte; Takeda Pharma; Vor Biopharma; Xenikos BV. 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 US Government.

ASJC Scopus subject areas

Hematology
Transplantation

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10.1038/s41409-021-01261-6

Cite this

Percival, M. E., Wang, H. L., Zhang, M. J., Saber, W., de Lima, M., Litzow, M., Kebriaei, P., Abdel-Azim, H., Adekola, K., Aljurf, M., Bacher, U., Badawy, S. M., Beitinjaneh, A., Bejanyan, N., Bhatt, V., Byrne, M., Cahn, J. Y., Castillo, P., Chao, N., ... Sandmaier, B. M. (2021). Impact of depth of clinical response on outcomes of acute myeloid leukemia patients in first complete remission who undergo allogeneic hematopoietic cell transplantation. Bone Marrow Transplantation, 56(9), 2108-2117. https://doi.org/10.1038/s41409-021-01261-6

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title = "Impact of depth of clinical response on outcomes of acute myeloid leukemia patients in first complete remission who undergo allogeneic hematopoietic cell transplantation",

abstract = "Acute myeloid leukemia (AML) patients often undergo allogeneic hematopoietic cell transplantation (alloHCT) in first complete remission (CR). We examined the effect of depth of clinical response, including incomplete count recovery (CRi) and/or measurable residual disease (MRD), in patients from the Center for International Blood and Marrow Transplantation Research (CIBMTR) registry. We identified 2492 adult patients (1799 CR and 693 CRi) who underwent alloHCT between January 1, 2007 and December 31, 2015. The primary outcome was overall survival (OS). Multivariable analysis was performed to adjust for patient-, disease-, and transplant-related factors. Baseline characteristics were similar. Patients in CRi compared to those in CR had an increased likelihood of death (HR: 1.27; 95% confidence interval: 1.13–1.43). Compared to CR, CRi was significantly associated with increased non-relapse mortality (NRM), shorter disease-free survival (DFS), and a trend toward increased relapse. Detectable MRD was associated with shorter OS, shorter DFS, higher NRM, and increased relapse compared to absence of MRD. The deleterious effects of CRi and MRD were independent. In this large CIBMTR cohort, survival outcomes differ among AML patients based on depth of CR and presence of MRD at the time of alloHCT. Further studies should focus on optimizing post-alloHCT outcomes for patients with responses less than CR.",

author = "Percival, {Mary Elizabeth} and Wang, {Hai Lin} and Zhang, {Mei Jie} and Wael Saber and {de Lima}, Marcos and Mark Litzow and Partow Kebriaei and Hisham Abdel-Azim and Kehinde Adekola and Mahmoud Aljurf and Ulrike Bacher and Badawy, {Sherif M.} and Amer Beitinjaneh and Nelli Bejanyan and Vijaya Bhatt and Michael Byrne and Cahn, {Jean Yves} and Paul Castillo and Nelson Chao and Saurabh Chhabra and Edward Copelan and Corey Cutler and Zachariah DeFilipp and Ajoy Dias and Diaz, {Miguel Angel} and Elihu Estey and Nosha Farhadfar and Frangoul, {Haydar A.} and Freytes, {C{\'e}sar O.} and Gale, {Robert Peter} and Siddhartha Ganguly and Lohith Gowda and Michael Grunwald and Nasheed Hossain and Kamble, {Rammurti T.} and Kanakry, {Christopher G.} and Ankit Kansagra and Kharfan-Dabaja, {Mohamed A.} and Maxwell Krem and Lazarus, {Hillard M.} and Lee, {Jong Wook} and Liesveld, {Jane L.} and Richard Lin and Hongtao Liu and Joseph McGuirk and Reinhold Munker and Murthy, {Hemant S.} and Sunita Nathan and Taiga Nishihori and Olsson, {Richard F.} and Neil Palmisiano and Passweg, {Jakob R.} and Tim Prestidge and Olov Ringd{\'e}n and Rizzieri, {David A.} and Rybka, {Witold B.} and Savoie, {Mary Lynn} and Schultz, {Kirk R.} and Sachiko Seo and Akshay Sharma and Melhem Solh and Roger Strair and {van der Poel}, Marjolein and Verdonck, {Leo F.} and Yared, {Jean A.} and Daniel Weisdorf and Sandmaier, {Brenda M.}",

note = "Publisher Copyright: {\textcopyright} 2021, The Author(s), under exclusive licence to Springer Nature Limited.",

year = "2021",

month = sep,

doi = "10.1038/s41409-021-01261-6",

language = "English (US)",

volume = "56",

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journal = "Bone Marrow Transplantation",

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Percival, ME, Wang, HL, Zhang, MJ, Saber, W, de Lima, M, Litzow, M, Kebriaei, P, Abdel-Azim, H, Adekola, K, Aljurf, M, Bacher, U, Badawy, SM, Beitinjaneh, A, Bejanyan, N, Bhatt, V, Byrne, M, Cahn, JY, Castillo, P, Chao, N, Chhabra, S, Copelan, E, Cutler, C, DeFilipp, Z, Dias, A, Diaz, MA, Estey, E, Farhadfar, N, Frangoul, HA, Freytes, CO, Gale, RP, Ganguly, S, Gowda, L, Grunwald, M, Hossain, N, Kamble, RT, Kanakry, CG, Kansagra, A, Kharfan-Dabaja, MA, Krem, M, Lazarus, HM, Lee, JW, Liesveld, JL, Lin, R, Liu, H, McGuirk, J, Munker, R, Murthy, HS, Nathan, S, Nishihori, T, Olsson, RF, Palmisiano, N, Passweg, JR, Prestidge, T, Ringdén, O, Rizzieri, DA, Rybka, WB, Savoie, ML, Schultz, KR, Seo, S, Sharma, A, Solh, M, Strair, R, van der Poel, M, Verdonck, LF, Yared, JA, Weisdorf, D & Sandmaier, BM 2021, 'Impact of depth of clinical response on outcomes of acute myeloid leukemia patients in first complete remission who undergo allogeneic hematopoietic cell transplantation', Bone Marrow Transplantation, vol. 56, no. 9, pp. 2108-2117. https://doi.org/10.1038/s41409-021-01261-6

Impact of depth of clinical response on outcomes of acute myeloid leukemia patients in first complete remission who undergo allogeneic hematopoietic cell transplantation. / Percival, Mary Elizabeth; Wang, Hai Lin; Zhang, Mei Jie et al.
In: Bone Marrow Transplantation, Vol. 56, No. 9, 09.2021, p. 2108-2117.

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

TY - JOUR

T1 - Impact of depth of clinical response on outcomes of acute myeloid leukemia patients in first complete remission who undergo allogeneic hematopoietic cell transplantation

AU - Percival, Mary Elizabeth

AU - Wang, Hai Lin

AU - Zhang, Mei Jie

AU - Saber, Wael

AU - de Lima, Marcos

AU - Litzow, Mark

AU - Kebriaei, Partow

AU - Abdel-Azim, Hisham

AU - Adekola, Kehinde

AU - Aljurf, Mahmoud

AU - Bacher, Ulrike

AU - Badawy, Sherif M.

AU - Beitinjaneh, Amer

AU - Bejanyan, Nelli

AU - Bhatt, Vijaya

AU - Byrne, Michael

AU - Cahn, Jean Yves

AU - Castillo, Paul

AU - Chao, Nelson

AU - Chhabra, Saurabh

AU - Copelan, Edward

AU - Cutler, Corey

AU - DeFilipp, Zachariah

AU - Dias, Ajoy

AU - Diaz, Miguel Angel

AU - Estey, Elihu

AU - Farhadfar, Nosha

AU - Frangoul, Haydar A.

AU - Freytes, César O.

AU - Gale, Robert Peter

AU - Ganguly, Siddhartha

AU - Gowda, Lohith

AU - Grunwald, Michael

AU - Hossain, Nasheed

AU - Kamble, Rammurti T.

AU - Kanakry, Christopher G.

AU - Kansagra, Ankit

AU - Kharfan-Dabaja, Mohamed A.

AU - Krem, Maxwell

AU - Lazarus, Hillard M.

AU - Lee, Jong Wook

AU - Liesveld, Jane L.

AU - Lin, Richard

AU - Liu, Hongtao

AU - McGuirk, Joseph

AU - Munker, Reinhold

AU - Murthy, Hemant S.

AU - Nathan, Sunita

AU - Nishihori, Taiga

AU - Olsson, Richard F.

AU - Palmisiano, Neil

AU - Passweg, Jakob R.

AU - Prestidge, Tim

AU - Ringdén, Olov

AU - Rizzieri, David A.

AU - Rybka, Witold B.

AU - Savoie, Mary Lynn

AU - Schultz, Kirk R.

AU - Seo, Sachiko

AU - Sharma, Akshay

AU - Solh, Melhem

AU - Strair, Roger

AU - van der Poel, Marjolein

AU - Verdonck, Leo F.

AU - Yared, Jean A.

AU - Weisdorf, Daniel

AU - Sandmaier, Brenda M.

PY - 2021/9

Y1 - 2021/9

N2 - Acute myeloid leukemia (AML) patients often undergo allogeneic hematopoietic cell transplantation (alloHCT) in first complete remission (CR). We examined the effect of depth of clinical response, including incomplete count recovery (CRi) and/or measurable residual disease (MRD), in patients from the Center for International Blood and Marrow Transplantation Research (CIBMTR) registry. We identified 2492 adult patients (1799 CR and 693 CRi) who underwent alloHCT between January 1, 2007 and December 31, 2015. The primary outcome was overall survival (OS). Multivariable analysis was performed to adjust for patient-, disease-, and transplant-related factors. Baseline characteristics were similar. Patients in CRi compared to those in CR had an increased likelihood of death (HR: 1.27; 95% confidence interval: 1.13–1.43). Compared to CR, CRi was significantly associated with increased non-relapse mortality (NRM), shorter disease-free survival (DFS), and a trend toward increased relapse. Detectable MRD was associated with shorter OS, shorter DFS, higher NRM, and increased relapse compared to absence of MRD. The deleterious effects of CRi and MRD were independent. In this large CIBMTR cohort, survival outcomes differ among AML patients based on depth of CR and presence of MRD at the time of alloHCT. Further studies should focus on optimizing post-alloHCT outcomes for patients with responses less than CR.

AB - Acute myeloid leukemia (AML) patients often undergo allogeneic hematopoietic cell transplantation (alloHCT) in first complete remission (CR). We examined the effect of depth of clinical response, including incomplete count recovery (CRi) and/or measurable residual disease (MRD), in patients from the Center for International Blood and Marrow Transplantation Research (CIBMTR) registry. We identified 2492 adult patients (1799 CR and 693 CRi) who underwent alloHCT between January 1, 2007 and December 31, 2015. The primary outcome was overall survival (OS). Multivariable analysis was performed to adjust for patient-, disease-, and transplant-related factors. Baseline characteristics were similar. Patients in CRi compared to those in CR had an increased likelihood of death (HR: 1.27; 95% confidence interval: 1.13–1.43). Compared to CR, CRi was significantly associated with increased non-relapse mortality (NRM), shorter disease-free survival (DFS), and a trend toward increased relapse. Detectable MRD was associated with shorter OS, shorter DFS, higher NRM, and increased relapse compared to absence of MRD. The deleterious effects of CRi and MRD were independent. In this large CIBMTR cohort, survival outcomes differ among AML patients based on depth of CR and presence of MRD at the time of alloHCT. Further studies should focus on optimizing post-alloHCT outcomes for patients with responses less than CR.

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UR - http://www.scopus.com/inward/citedby.url?scp=85104540946&partnerID=8YFLogxK

U2 - 10.1038/s41409-021-01261-6

DO - 10.1038/s41409-021-01261-6

M3 - Article

C2 - 33864019

AN - SCOPUS:85104540946

SN - 0268-3369

VL - 56

SP - 2108

EP - 2117

JO - Bone Marrow Transplantation

JF - Bone Marrow Transplantation

IS - 9

ER -

Impact of depth of clinical response on outcomes of acute myeloid leukemia patients in first complete remission who undergo allogeneic hematopoietic cell transplantation

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