Allogeneic hematopoietic cell transplant for AML: No impact of pre-transplant extramedullary disease on outcome

S. D. Goyal; M. J. Zhang; H. L. Wang; G. Akpek; E. A. Copelan; C. Freytes; R. P. Gale; M. Hamadani; Y. Inamoto; R. T. Kamble; H. M. Lazarus; D. I. Marks; T. Nishihori; R. F. Olsson; R. Reshef; D. S. Ritchie; W. Saber; B. N. Savani; A. Seber; T. C. Shea; M. S. Tallman; B. Wirk; D. W. Bunjes; S. M. Devine; M. De Lima; D. J. Weisdorf; G. L. Uy

doi:10.1038/bmt.2015.82

Allogeneic hematopoietic cell transplant for AML: No impact of pre-transplant extramedullary disease on outcome

S. D. Goyal, M. J. Zhang, H. L. Wang, G. Akpek, E. A. Copelan, C. Freytes, R. P. Gale, M. Hamadani, Y. Inamoto, R. T. Kamble, H. M. Lazarus, D. I. Marks, T. Nishihori, R. F. Olsson, R. Reshef, D. S. Ritchie, W. Saber, B. N. Savani, A. Seber, T. C. SheaM. S. Tallman, B. Wirk, D. W. Bunjes, S. M. Devine, M. De Lima, D. J. Weisdorf, G. L. Uy

Medicine - Hematology, Oncology, Transplant

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

23 Scopus citations

Abstract

The impact of extramedullary disease (EMD) in AML on the outcomes of allogeneic hematopoietic cell transplantation (alloHCT) is unknown. Using data from the Center for International Blood and Marrow Transplant Research, we compared the outcomes of patients who had EMD of AML at any time before transplant, with a cohort of AML patients without EMD. We reviewed data from 9797 AML patients including 814 with EMD from 310 reporting centers and 44 different countries, who underwent alloHCT between and 1995 and 2010. The primary outcome was overall survival (OS) after alloHCT. Secondary outcomes included leukemia-free survival (LFS), relapse rate and treatment-related mortality (TRM). In a multivariate analysis, the presence of EMD did not affect either OS (hazard ratio 1.00, 95% confidence interval (CI) 0.91-1.09), LFS (0.98, 0.89-1.09), TRM (relative risk 0.92, 95% CI 0.80-1.16, P=0.23) or relapse (relative risk=1.03, 95% CI, 0.92-1.16; P=0.62). Furthermore, the outcome of patients with EMD was not influenced by the location, timing of EMD, or intensity of conditioning regimen. The presence of EMD in AML does not affect transplant outcomes and should not be viewed as an independent adverse prognostic feature.

Original language	English (US)
Pages (from-to)	1057-1062
Number of pages	6
Journal	Bone marrow transplantation
Volume	50
Issue number	8
DOIs	https://doi.org/10.1038/bmt.2015.82
State	Published - Aug 8 2015

Bibliographical note

Funding Information:
We acknowledge the following contributing co-authors for their contributions to this manuscript: Kirk R Schultz, Mark R Litzow, Philip L McCarthy, Mahmoud D Aljurf, Mitchell S Cairo, William A Wood, Celalettin Ustun, Thomas R Klumpp, Edwin M. Horwitz, Jyotishankar Raychaudhuri, Bruce M Camitta, Yi-Bin Chen, Peter H Wiernik, Tsiporah B Shore, Selina M Luger, Ashish Bajel, Harry C Schouten, Grace H Ku, Maxim Norkin, Faiz Anwer, Asmita Mishra, Attaphol Pawarode, Amelia Langston, Mitchell Sabloff, Ann E Woolfrey, Hans-Jochem Kolb, Edmund K Waller, Usama Gergis, John Koreth, Reinhold Munker, Joseph McGuirk, William R Drobyski, Bita Jalilizeinali and H Jean Khoury. Geoffrey L Uy’s contribution is supported by NCI grant K23 CA140707. The CIBMTR is supported by Public Health Service Grant/Cooperative Agreement U24-CA076518 from the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Diseases (NIAID); a Grant/Cooperative Agreement 5U10HL069294 from NHLBI and NCI; a contract HHSH250201200016C with Health Resources and Services Administration (HRSA/DHHS); two grants N00014-12-1-0142 and N00014-13-1-0039 from the Office of Naval Research; and grants from *Actinium Pharmaceuticals, Allos Therapeutics, Inc. and *Amgen, Inc. Anonymous donation to the Medical College of Wisconsin, Ariad, Be the Match Foundation, *Blue Cross and Blue Shield Association, *Celgene Corporation, Chimerix, Inc., Fred Hutchinson Cancer Research Center, Fresenius-Biotech North America, Inc., *Gamida Cell Teva Joint Venture Ltd., Genentech, Inc., *Gentium SpA, Genzyme Corporation, GlaxoSmithKline, Health Research, Inc., Roswell Park Cancer Institute, HistoGenetics, Inc., Incyte Corporation, Jeff Gordon Children’s Foundation, Kiadis Pharma, The Leukemia & Lymphoma Society, Medac GmbH, The Medical College of Wisconsin, Merck & Co, Inc., Millennium: The Takeda Oncology Co., *Milliman USA, Inc., *Miltenyi Biotec, Inc., National Marrow Donor Program, Onyx Pharmaceuticals, Optum Healthcare Solutions, Inc., Osiris Therapeutics, Inc., Otsuka America Pharmaceutical, Inc., Perkin Elmer, Inc., *Remedy Informatics, *Sanofi US, Seattle Genetics, Sigma-Tau Pharmaceuticals, Soligenix, Inc., St Baldrick’s Foundation, StemCyte, A Global Cord Blood Therapeutics Co., Stemsoft Software, Inc., Swedish Orphan Biovitrum, *Tarix Pharmaceuticals, *TerumoBCT, *Teva Neuroscience, Inc., *THERAKOS, Inc., University of Minnesota, University of Utah and *Wellpoint, Inc. *Corporate members. 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.

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© 2015 Macmillan Publishers Limited.

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Goyal, S. D., Zhang, M. J., Wang, H. L., Akpek, G., Copelan, E. A., Freytes, C., Gale, R. P., Hamadani, M., Inamoto, Y., Kamble, R. T., Lazarus, H. M., Marks, D. I., Nishihori, T., Olsson, R. F., Reshef, R., Ritchie, D. S., Saber, W., Savani, B. N., Seber, A., ... Uy, G. L. (2015). Allogeneic hematopoietic cell transplant for AML: No impact of pre-transplant extramedullary disease on outcome. Bone marrow transplantation, 50(8), 1057-1062. https://doi.org/10.1038/bmt.2015.82

Goyal, SD, Zhang, MJ, Wang, HL, Akpek, G, Copelan, EA, Freytes, C, Gale, RP, Hamadani, M, Inamoto, Y, Kamble, RT, Lazarus, HM, Marks, DI, Nishihori, T, Olsson, RF, Reshef, R, Ritchie, DS, Saber, W, Savani, BN, Seber, A, Shea, TC, Tallman, MS, Wirk, B, Bunjes, DW, Devine, SM, De Lima, M, Weisdorf, DJ & Uy, GL 2015, 'Allogeneic hematopoietic cell transplant for AML: No impact of pre-transplant extramedullary disease on outcome', Bone marrow transplantation, vol. 50, no. 8, pp. 1057-1062. https://doi.org/10.1038/bmt.2015.82

@article{085e026996e94635b49bf5cd2e8f0243,

title = "Allogeneic hematopoietic cell transplant for AML: No impact of pre-transplant extramedullary disease on outcome",

abstract = "The impact of extramedullary disease (EMD) in AML on the outcomes of allogeneic hematopoietic cell transplantation (alloHCT) is unknown. Using data from the Center for International Blood and Marrow Transplant Research, we compared the outcomes of patients who had EMD of AML at any time before transplant, with a cohort of AML patients without EMD. We reviewed data from 9797 AML patients including 814 with EMD from 310 reporting centers and 44 different countries, who underwent alloHCT between and 1995 and 2010. The primary outcome was overall survival (OS) after alloHCT. Secondary outcomes included leukemia-free survival (LFS), relapse rate and treatment-related mortality (TRM). In a multivariate analysis, the presence of EMD did not affect either OS (hazard ratio 1.00, 95% confidence interval (CI) 0.91-1.09), LFS (0.98, 0.89-1.09), TRM (relative risk 0.92, 95% CI 0.80-1.16, P=0.23) or relapse (relative risk=1.03, 95% CI, 0.92-1.16; P=0.62). Furthermore, the outcome of patients with EMD was not influenced by the location, timing of EMD, or intensity of conditioning regimen. The presence of EMD in AML does not affect transplant outcomes and should not be viewed as an independent adverse prognostic feature.",

author = "Goyal, {S. D.} and Zhang, {M. J.} and Wang, {H. L.} and G. Akpek and Copelan, {E. A.} and C. Freytes and Gale, {R. P.} and M. Hamadani and Y. Inamoto and Kamble, {R. T.} and Lazarus, {H. M.} and Marks, {D. I.} and T. Nishihori and Olsson, {R. F.} and R. Reshef and Ritchie, {D. S.} and W. Saber and Savani, {B. N.} and A. Seber and Shea, {T. C.} and Tallman, {M. S.} and B. Wirk and Bunjes, {D. W.} and Devine, {S. M.} and {De Lima}, M. and Weisdorf, {D. J.} and Uy, {G. L.}",

note = "Funding Information: We acknowledge the following contributing co-authors for their contributions to this manuscript: Kirk R Schultz, Mark R Litzow, Philip L McCarthy, Mahmoud D Aljurf, Mitchell S Cairo, William A Wood, Celalettin Ustun, Thomas R Klumpp, Edwin M. Horwitz, Jyotishankar Raychaudhuri, Bruce M Camitta, Yi-Bin Chen, Peter H Wiernik, Tsiporah B Shore, Selina M Luger, Ashish Bajel, Harry C Schouten, Grace H Ku, Maxim Norkin, Faiz Anwer, Asmita Mishra, Attaphol Pawarode, Amelia Langston, Mitchell Sabloff, Ann E Woolfrey, Hans-Jochem Kolb, Edmund K Waller, Usama Gergis, John Koreth, Reinhold Munker, Joseph McGuirk, William R Drobyski, Bita Jalilizeinali and H Jean Khoury. Geoffrey L Uy{\textquoteright}s contribution is supported by NCI grant K23 CA140707. The CIBMTR is supported by Public Health Service Grant/Cooperative Agreement U24-CA076518 from the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Diseases (NIAID); a Grant/Cooperative Agreement 5U10HL069294 from NHLBI and NCI; a contract HHSH250201200016C with Health Resources and Services Administration (HRSA/DHHS); two grants N00014-12-1-0142 and N00014-13-1-0039 from the Office of Naval Research; and grants from *Actinium Pharmaceuticals, Allos Therapeutics, Inc. and *Amgen, Inc. Anonymous donation to the Medical College of Wisconsin, Ariad, Be the Match Foundation, *Blue Cross and Blue Shield Association, *Celgene Corporation, Chimerix, Inc., Fred Hutchinson Cancer Research Center, Fresenius-Biotech North America, Inc., *Gamida Cell Teva Joint Venture Ltd., Genentech, Inc., *Gentium SpA, Genzyme Corporation, GlaxoSmithKline, Health Research, Inc., Roswell Park Cancer Institute, HistoGenetics, Inc., Incyte Corporation, Jeff Gordon Children{\textquoteright}s Foundation, Kiadis Pharma, The Leukemia & Lymphoma Society, Medac GmbH, The Medical College of Wisconsin, Merck & Co, Inc., Millennium: The Takeda Oncology Co., *Milliman USA, Inc., *Miltenyi Biotec, Inc., National Marrow Donor Program, Onyx Pharmaceuticals, Optum Healthcare Solutions, Inc., Osiris Therapeutics, Inc., Otsuka America Pharmaceutical, Inc., Perkin Elmer, Inc., *Remedy Informatics, *Sanofi US, Seattle Genetics, Sigma-Tau Pharmaceuticals, Soligenix, Inc., St Baldrick{\textquoteright}s Foundation, StemCyte, A Global Cord Blood Therapeutics Co., Stemsoft Software, Inc., Swedish Orphan Biovitrum, *Tarix Pharmaceuticals, *TerumoBCT, *Teva Neuroscience, Inc., *THERAKOS, Inc., University of Minnesota, University of Utah and *Wellpoint, Inc. *Corporate members. 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. Publisher Copyright: {\textcopyright} 2015 Macmillan Publishers Limited.",

year = "2015",

month = aug,

day = "8",

doi = "10.1038/bmt.2015.82",

language = "English (US)",

volume = "50",

pages = "1057--1062",

journal = "Bone marrow transplantation",

issn = "0268-3369",

publisher = "Nature Publishing Group",

number = "8",

}

TY - JOUR

T1 - Allogeneic hematopoietic cell transplant for AML

T2 - No impact of pre-transplant extramedullary disease on outcome

AU - Goyal, S. D.

AU - Zhang, M. J.

AU - Wang, H. L.

AU - Akpek, G.

AU - Copelan, E. A.

AU - Freytes, C.

AU - Gale, R. P.

AU - Hamadani, M.

AU - Inamoto, Y.

AU - Kamble, R. T.

AU - Lazarus, H. M.

AU - Marks, D. I.

AU - Nishihori, T.

AU - Olsson, R. F.

AU - Reshef, R.

AU - Ritchie, D. S.

AU - Saber, W.

AU - Savani, B. N.

AU - Seber, A.

AU - Shea, T. C.

AU - Tallman, M. S.

AU - Wirk, B.

AU - Bunjes, D. W.

AU - Devine, S. M.

AU - De Lima, M.

AU - Weisdorf, D. J.

AU - Uy, G. L.

N1 - Funding Information: We acknowledge the following contributing co-authors for their contributions to this manuscript: Kirk R Schultz, Mark R Litzow, Philip L McCarthy, Mahmoud D Aljurf, Mitchell S Cairo, William A Wood, Celalettin Ustun, Thomas R Klumpp, Edwin M. Horwitz, Jyotishankar Raychaudhuri, Bruce M Camitta, Yi-Bin Chen, Peter H Wiernik, Tsiporah B Shore, Selina M Luger, Ashish Bajel, Harry C Schouten, Grace H Ku, Maxim Norkin, Faiz Anwer, Asmita Mishra, Attaphol Pawarode, Amelia Langston, Mitchell Sabloff, Ann E Woolfrey, Hans-Jochem Kolb, Edmund K Waller, Usama Gergis, John Koreth, Reinhold Munker, Joseph McGuirk, William R Drobyski, Bita Jalilizeinali and H Jean Khoury. Geoffrey L Uy’s contribution is supported by NCI grant K23 CA140707. The CIBMTR is supported by Public Health Service Grant/Cooperative Agreement U24-CA076518 from the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Diseases (NIAID); a Grant/Cooperative Agreement 5U10HL069294 from NHLBI and NCI; a contract HHSH250201200016C with Health Resources and Services Administration (HRSA/DHHS); two grants N00014-12-1-0142 and N00014-13-1-0039 from the Office of Naval Research; and grants from *Actinium Pharmaceuticals, Allos Therapeutics, Inc. and *Amgen, Inc. Anonymous donation to the Medical College of Wisconsin, Ariad, Be the Match Foundation, *Blue Cross and Blue Shield Association, *Celgene Corporation, Chimerix, Inc., Fred Hutchinson Cancer Research Center, Fresenius-Biotech North America, Inc., *Gamida Cell Teva Joint Venture Ltd., Genentech, Inc., *Gentium SpA, Genzyme Corporation, GlaxoSmithKline, Health Research, Inc., Roswell Park Cancer Institute, HistoGenetics, Inc., Incyte Corporation, Jeff Gordon Children’s Foundation, Kiadis Pharma, The Leukemia & Lymphoma Society, Medac GmbH, The Medical College of Wisconsin, Merck & Co, Inc., Millennium: The Takeda Oncology Co., *Milliman USA, Inc., *Miltenyi Biotec, Inc., National Marrow Donor Program, Onyx Pharmaceuticals, Optum Healthcare Solutions, Inc., Osiris Therapeutics, Inc., Otsuka America Pharmaceutical, Inc., Perkin Elmer, Inc., *Remedy Informatics, *Sanofi US, Seattle Genetics, Sigma-Tau Pharmaceuticals, Soligenix, Inc., St Baldrick’s Foundation, StemCyte, A Global Cord Blood Therapeutics Co., Stemsoft Software, Inc., Swedish Orphan Biovitrum, *Tarix Pharmaceuticals, *TerumoBCT, *Teva Neuroscience, Inc., *THERAKOS, Inc., University of Minnesota, University of Utah and *Wellpoint, Inc. *Corporate members. 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. Publisher Copyright: © 2015 Macmillan Publishers Limited.

PY - 2015/8/8

Y1 - 2015/8/8

N2 - The impact of extramedullary disease (EMD) in AML on the outcomes of allogeneic hematopoietic cell transplantation (alloHCT) is unknown. Using data from the Center for International Blood and Marrow Transplant Research, we compared the outcomes of patients who had EMD of AML at any time before transplant, with a cohort of AML patients without EMD. We reviewed data from 9797 AML patients including 814 with EMD from 310 reporting centers and 44 different countries, who underwent alloHCT between and 1995 and 2010. The primary outcome was overall survival (OS) after alloHCT. Secondary outcomes included leukemia-free survival (LFS), relapse rate and treatment-related mortality (TRM). In a multivariate analysis, the presence of EMD did not affect either OS (hazard ratio 1.00, 95% confidence interval (CI) 0.91-1.09), LFS (0.98, 0.89-1.09), TRM (relative risk 0.92, 95% CI 0.80-1.16, P=0.23) or relapse (relative risk=1.03, 95% CI, 0.92-1.16; P=0.62). Furthermore, the outcome of patients with EMD was not influenced by the location, timing of EMD, or intensity of conditioning regimen. The presence of EMD in AML does not affect transplant outcomes and should not be viewed as an independent adverse prognostic feature.

AB - The impact of extramedullary disease (EMD) in AML on the outcomes of allogeneic hematopoietic cell transplantation (alloHCT) is unknown. Using data from the Center for International Blood and Marrow Transplant Research, we compared the outcomes of patients who had EMD of AML at any time before transplant, with a cohort of AML patients without EMD. We reviewed data from 9797 AML patients including 814 with EMD from 310 reporting centers and 44 different countries, who underwent alloHCT between and 1995 and 2010. The primary outcome was overall survival (OS) after alloHCT. Secondary outcomes included leukemia-free survival (LFS), relapse rate and treatment-related mortality (TRM). In a multivariate analysis, the presence of EMD did not affect either OS (hazard ratio 1.00, 95% confidence interval (CI) 0.91-1.09), LFS (0.98, 0.89-1.09), TRM (relative risk 0.92, 95% CI 0.80-1.16, P=0.23) or relapse (relative risk=1.03, 95% CI, 0.92-1.16; P=0.62). Furthermore, the outcome of patients with EMD was not influenced by the location, timing of EMD, or intensity of conditioning regimen. The presence of EMD in AML does not affect transplant outcomes and should not be viewed as an independent adverse prognostic feature.

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JO - Bone marrow transplantation

JF - Bone marrow transplantation

IS - 8

ER -

Allogeneic hematopoietic cell transplant for AML: No impact of pre-transplant extramedullary disease on outcome

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