Comparison of outcomes of HCT in blast phase of BCR-ABL12 MPN with de novo AML and with AML following MDS

Vikas Gupta; Soyoung Kim; Zhen Huan Hu; Ying Liu; Mahmoud Aljurf; Ulrike Bacher; Amer Beitinjaneh; Jean Yves Cahn; Jan Cerny; Edward Copelan; Shahinaz M. Gadalla; Robert Peter Gale; Siddhartha Ganguly; Biju George; Aaron T. Gerds; Usama Gergis; Betty K. Hamilton; Shahrukh Hashmi; Gerhard C. Hildebrandt; Rammurti T. Kamble; Tamila Kindwall-Keller; Hillard M. Lazarus; Jane L. Liesveld; Mark Litzow; Richard T. Maziarz; Taiga Nishihori; Richard F. Olsson; David Rizzieri; Bipin N. Savani; Sachiko Seo; Melhem Solh; Jeff Szer; Leo F. Verdonck; Baldeep Wirk; Ann Woolfrey; Jean A. Yared; Edwin P. Alyea; Uday R. Popat; Ronald M. Sobecks; Bart L. Scott; Ryotaro Nakamura; Wael Saber

doi:10.1182/bloodadvances.2020002621

Comparison of outcomes of HCT in blast phase of BCR-ABL1² MPN with de novo AML and with AML following MDS

Vikas Gupta
, Soyoung Kim
, Zhen Huan Hu
, Ying Liu
, Mahmoud Aljurf
, Ulrike Bacher
, Amer Beitinjaneh
, Jean Yves Cahn
, Jan Cerny
, Edward Copelan
, Shahinaz M. Gadalla
, Robert Peter Gale
, Siddhartha Ganguly
, Biju George
, Aaron T. Gerds
, Usama Gergis
, Betty K. Hamilton
, Shahrukh Hashmi
, Gerhard C. Hildebrandt
, Rammurti T. Kamble

Tamila Kindwall-Keller, Hillard M. Lazarus, Jane L. Liesveld, Mark Litzow, Richard T. Maziarz, Taiga Nishihori, Richard F. Olsson, David Rizzieri, Bipin N. Savani, Sachiko Seo, Melhem Solh, Jeff Szer, Leo F. Verdonck, Baldeep Wirk, Ann Woolfrey, Jean A. Yared, Edwin P. Alyea, Uday R. Popat, Ronald M. Sobecks, Bart L. Scott, Ryotaro Nakamura, Wael Saber

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

19 Scopus citations

Abstract

Comparative outcomes of allogeneic hematopoietic cell transplantation (HCT) for BCR-ABL1² myeloproliferative neoplasms (MPNs) in blast phase (MPN-BP) vs de novo acute myeloid leukemia (AML), and AML with prior myelodysplastic syndromes (MDSs; post-MDS AML), are unknown. Using the Center for International Blood and Marrow Transplant Research (CIBMTR) database, we compared HCT outcomes in 177 MPN-BP patients with 4749 patients with de novo AML, and 1104 patients with post-MDS AML, using multivariate regression analysis in 2 separate comparisons. In a multivariate Cox model, no difference in overall survival (OS) or relapse was observed in patients with MPN-BP vs de novo AML with active leukemia at HCT. Patients with MPN-BP in remission had inferior OS in comparison with de novo AML in remission (hazard ratio [HR], 1.40 [95% confidence interval [CI], 1.12-1.76]) due to higher relapse rate (HR, 2.18 [95% CI, 1.69-2.80]). MPN-BP patients had inferior OS (HR, 1.19 [95% CI, 1.00-1.43]) and increased relapse (HR, 1.60 [95% CI, 1.31-1.96]) compared with post-MDS AML. Poor-risk cytogenetics were associated with increased relapse in both comparisons. Peripheral blood grafts were associated with decreased relapse in MPN-BP and post-MDS AML (HR, 0.70 [95% CI, 0.57-0.86]). Nonrelapse mortality (NRM) was similar between MPN-BP vs de novo AML, and MPN-BP vs post-MDS AML. Total-body irradiation-based myeloablative conditioning was associated with higher NRM in both comparisons. Survival of MPN-BP after HCT is inferior to de novo AML in remission and post-MDS AML due to increased relapse. Relapse-prevention strategies are required to optimize HCT outcomes in MPN-BP.

Original language	English
Pages (from-to)	4748-4757
Number of pages	10
Journal	Blood advances
Volume	4
Issue number	19
DOIs	https://doi.org/10.1182/bloodadvances.2020002621
State	Published - Oct 13 2020

Bibliographical note

Publisher Copyright:
© 2020 American Society of Hematology. All rights reserved.

Funding

Acknowledgments The CIBMTR was supported primarily by Public Health Service U24CA076518 from the National Cancer Institute, the National Heart, Lung, and Blood Institute, and the National Institute of Allergy and Infectious Diseases of the National Institutes of Health; U24HL138660 from the National Heart, Lung, and Blood Institute and National Cancer Institute; T3HL147741, R21HL140314, and U01HL128568 from the National Heart, Lung, and Blood Institute; HHSH250201700006C, SC1MC31881-01-00, and HHSH250201700007C from the Health Resources and Services Administration; and N00014-18-1-2850, N00014-18-1-2888, and N00014-20-1-2705 from the Office of Naval Research. Additional federal support was provided by P01CA111412, R01CA152108, R01CA215134, R01CA218285, and R01CA231141 from the National Cancer Institute; R01HL126589 from the National Heart, Lung, and Blood Institute; R01AI128775 from the National Institute of Allergy and Infectious Diseases; R01HL129472, R01HL130388, and R01HL131731 from the National Heart, Lung, and Blood Institute; U01AI069197 and U01AI126612 from the National Institute of Allergy and Infectious Diseases; and Biomedical Advanced Research and Development Authority. Support was also provided by Be the Match Foundation, Boston Children’s Hospital, Dana-Farber, Japan Hematopoietic Cell Transplantation Data Center, St. Baldrick’s Foundation, the National Marrow Donor Program, the Medical College of Wisconsin, and from the following commercial entities: AbbVie; Actinium Pharmaceuticals, Inc; Adaptive Biotechnologies; Adienne SA; Allovir, Inc; Amgen, Inc; Anthem, Inc; Astellas Pharma US; AstraZeneca; Atara Biother-apeutics, Inc; bluebird bio, Inc; Bristol Myers Squibb; Celgene Corp; Chimerix, Inc; CSL Behring; CytoSen Therapeutics, Inc; Daiichi Sankyo Co Ltd; Gamida-Cell, Ltd; Genzyme; GlaxoSmithK-line (GSK); HistoGenetics, Inc; Incyte Corporation; Janssen Biotech, Inc; Janssen Pharmaceuticals, Inc; Janssen/Johnson & Johnson; Jazz Pharmaceuticals, Inc; Kiadis Pharma; Kite Pharma; Kyowa Kirin; Legend Biotech; Magenta Therapeutics; Mallinckrodt LLC; Medac GmbH; Merck & Company, Inc; Merck Sharp & Dohme Corp; Mesoblast; Millennium, the Takeda Oncology Co; Miltenyi Biotec, Inc; Novartis Oncology; Novartis Pharmaceuticals Corporation; Omeros Corporation; Oncoimmune, Inc; Orca Biosystems, Inc; Pfizer, Inc; Phamacyclics, LLC; Regeneron Pharmaceuticals, Inc; REGiMMUNE Corp; Sanofi Genzyme; Seattle Genetics; Sobi, The CIBMTR was supported primarily by Public Health Service U24CA076518 from the National Cancer Institute, the National Heart, Lung, and Blood Institute, and the National Institute of Allergy and Infectious Diseases of the National Institutes of Health; U24HL138660 from the National Heart, Lung, and Blood Institute and National Cancer Institute; T3HL147741, R21HL140314, and U01HL128568 from the National Heart, Lung, and Blood Institute; HHSH250201700006C, SC1MC31881-01-00, and HHSH250201700007C from the Health Resources and Services Administration; and N00014-18-1-2850, N00014-18-1-2888, and N00014-20-1-2705 from the Office of Naval Research. Additional federal support was provided by P01CA111412, R01CA152108, R01CA215134, R01CA218285, and R01CA231141 from the National Cancer Institute; R01HL126589 from the National Heart, Lung, and Blood Institute; R01AI128775 from the National Institute of Allergy and Infectious Diseases; R01HL129472, R01HL130388, and R01HL131731 from the National Heart, Lung, and Blood Institute; U01AI069197 and U01AI126612 from the National Institute of Allergy and Infectious Diseases; and Biomedical Advanced Research and Development Authority. Support was also provided by Be the Match Foundation, Boston Children's Hospital, Dana-Farber, Japan Hematopoietic Cell Transplantation Data Center, St. Baldrick's Foundation, the National Marrow Donor Program, the Medical College of Wisconsin, and from the following commercial entities: AbbVie; Actinium Pharmaceuticals, Inc; Adaptive Biotechnologies; Adienne SA; Allovir, Inc; Amgen, Inc; Anthem, Inc; Astellas Pharma US; AstraZeneca; Atara Biotherapeutics, Inc; bluebird bio, Inc; Bristol Myers Squibb; Celgene Corp; Chimerix, Inc; CSL Behring; CytoSen Therapeutics, Inc; Daiichi Sankyo Co Ltd; Gamida-Cell, Ltd; Genzyme; GlaxoSmithKline (GSK); HistoGenetics, Inc; Incyte Corporation; Janssen Biotech, Inc; Janssen Pharmaceuticals, Inc; Janssen/Johnson & Johnson; Jazz Pharmaceuticals, Inc; Kiadis Pharma; Kite Pharma; Kyowa Kirin; Legend Biotech; Magenta Therapeutics; Mallinckrodt LLC; Medac GmbH; Merck & Company, Inc; Merck Sharp & Dohme Corp; Mesoblast; Millennium, the Takeda Oncology Co; Miltenyi Biotec, Inc; Novartis Oncology; Novartis Pharmaceuticals Corporation; Omeros Corporation; Oncoimmune, Inc; Orca Biosystems, Inc; Pfizer, Inc; Phamacyclics, LLC; Regeneron Pharmaceuticals, Inc; REGiMMUNE Corp; Sanofi Genzyme; Seattle Genetics; Sobi, Inc; Takeda Oncology; Takeda Pharma; Terumo BCT; Viracor Eurofins; and Xenikos BV. The views expressed in this article do not reflect the official policy or position of the National Institutes of Health, the Department of the Navy, the Department of Defense, the Health Resources and Services Administration, or any other agency of the US government.

Funders	Funder number
Celgene Corp, Chimerix, Inc
Dana-Farber Cancer Institute
Department of the Navy
Magenta Therapeutics
Mallinckrodt LLC
Match Foundation
Mesoblast
US Government or NYU
National Institutes of Health (NIH)	HHSH250201700007C, SC1MC31881-01-00, T3HL147741
U.S. Department of Defense
Office of Naval Research Naval Academy	R01AI128775, U01AI069197, U01AI126612
National Heart, Lung, and Blood Institute (NHLBI)	U24HL138660, R01HL129472, R01HL130388, R01HL131731, R01HL126589, U01HL128568, R21HL140314
National Childhood Cancer Registry – National Cancer Institute	P01CA111412, R01CA231141, R01CA218285, U24CA076518, R01CA215134, R01CA152108
National Institute of Allergy and Infectious F32-AI286447 Cydney N. Johnson Diseases National Institute of Allergy and Infectious R01AI168214 Jason W. Rosch Diseases National Institute of Allergy and Infectious P30 Cydney N. Johnson Diseases National Institute of Allergy and Infectious R00-AI166116 Christopher D. Radka Diseases National Institute of Allergy and Infectious T32-AI106700 Cydney N. Johnson Diseases National Institute of Allergy and Infectious R01AI192221 Jason W. Rosch Diseases National Inst...
Health Resources and Services Administration	N00014-20-1-2705, N00014-18-1-2850, N00014-18-1-2888
Be The Match Foundation
Bristol-Myers Squibb
Celgene
Children's Hospital Boston
U.S. Public Health Service
Bristol-Myers Squibb Canada
Medical College of Wisconsin
Merck Sharp and Dohme
Biomedical Advanced Research and Development Authority

ASJC Scopus subject areas

Hematology

Access to Document

10.1182/bloodadvances.2020002621

Cite this

Gupta, V., Kim, S., Hu, Z. H., Liu, Y., Aljurf, M., Bacher, U., Beitinjaneh, A., Cahn, J. Y., Cerny, J., Copelan, E., Gadalla, S. M., Gale, R. P., Ganguly, S., George, B., Gerds, A. T., Gergis, U., Hamilton, B. K., Hashmi, S., Hildebrandt, G. C., ... Saber, W. (2020). Comparison of outcomes of HCT in blast phase of BCR-ABL1² MPN with de novo AML and with AML following MDS. Blood advances, 4(19), 4748-4757. https://doi.org/10.1182/bloodadvances.2020002621

@article{9fd68c5cdcc34daaa7831d0091ab99ae,

title = "Comparison of outcomes of HCT in blast phase of BCR-ABL12 MPN with de novo AML and with AML following MDS",

abstract = "Comparative outcomes of allogeneic hematopoietic cell transplantation (HCT) for BCR-ABL12 myeloproliferative neoplasms (MPNs) in blast phase (MPN-BP) vs de novo acute myeloid leukemia (AML), and AML with prior myelodysplastic syndromes (MDSs; post-MDS AML), are unknown. Using the Center for International Blood and Marrow Transplant Research (CIBMTR) database, we compared HCT outcomes in 177 MPN-BP patients with 4749 patients with de novo AML, and 1104 patients with post-MDS AML, using multivariate regression analysis in 2 separate comparisons. In a multivariate Cox model, no difference in overall survival (OS) or relapse was observed in patients with MPN-BP vs de novo AML with active leukemia at HCT. Patients with MPN-BP in remission had inferior OS in comparison with de novo AML in remission (hazard ratio [HR], 1.40 [95\% confidence interval [CI], 1.12-1.76]) due to higher relapse rate (HR, 2.18 [95\% CI, 1.69-2.80]). MPN-BP patients had inferior OS (HR, 1.19 [95\% CI, 1.00-1.43]) and increased relapse (HR, 1.60 [95\% CI, 1.31-1.96]) compared with post-MDS AML. Poor-risk cytogenetics were associated with increased relapse in both comparisons. Peripheral blood grafts were associated with decreased relapse in MPN-BP and post-MDS AML (HR, 0.70 [95\% CI, 0.57-0.86]). Nonrelapse mortality (NRM) was similar between MPN-BP vs de novo AML, and MPN-BP vs post-MDS AML. Total-body irradiation-based myeloablative conditioning was associated with higher NRM in both comparisons. Survival of MPN-BP after HCT is inferior to de novo AML in remission and post-MDS AML due to increased relapse. Relapse-prevention strategies are required to optimize HCT outcomes in MPN-BP.",

author = "Vikas Gupta and Soyoung Kim and Hu, \{Zhen Huan\} and Ying Liu and Mahmoud Aljurf and Ulrike Bacher and Amer Beitinjaneh and Cahn, \{Jean Yves\} and Jan Cerny and Edward Copelan and Gadalla, \{Shahinaz M.\} and Gale, \{Robert Peter\} and Siddhartha Ganguly and Biju George and Gerds, \{Aaron T.\} and Usama Gergis and Hamilton, \{Betty K.\} and Shahrukh Hashmi and Hildebrandt, \{Gerhard C.\} and Kamble, \{Rammurti T.\} and Tamila Kindwall-Keller and Lazarus, \{Hillard M.\} and Liesveld, \{Jane L.\} and Mark Litzow and Maziarz, \{Richard T.\} and Taiga Nishihori and Olsson, \{Richard F.\} and David Rizzieri and Savani, \{Bipin N.\} and Sachiko Seo and Melhem Solh and Jeff Szer and Verdonck, \{Leo F.\} and Baldeep Wirk and Ann Woolfrey and Yared, \{Jean A.\} and Alyea, \{Edwin P.\} and Popat, \{Uday R.\} and Sobecks, \{Ronald M.\} and Scott, \{Bart L.\} and Ryotaro Nakamura and Wael Saber",

year = "2020",

month = oct,

day = "13",

doi = "10.1182/bloodadvances.2020002621",

language = "English",

volume = "4",

pages = "4748--4757",

number = "19",

}

Gupta, V, Kim, S, Hu, ZH, Liu, Y, Aljurf, M, Bacher, U, Beitinjaneh, A, Cahn, JY, Cerny, J, Copelan, E, Gadalla, SM, Gale, RP, Ganguly, S, George, B, Gerds, AT, Gergis, U, Hamilton, BK, Hashmi, S, Hildebrandt, GC, Kamble, RT, Kindwall-Keller, T, Lazarus, HM, Liesveld, JL, Litzow, M, Maziarz, RT, Nishihori, T, Olsson, RF, Rizzieri, D, Savani, BN, Seo, S, Solh, M, Szer, J, Verdonck, LF, Wirk, B, Woolfrey, A, Yared, JA, Alyea, EP, Popat, UR, Sobecks, RM, Scott, BL, Nakamura, R & Saber, W 2020, 'Comparison of outcomes of HCT in blast phase of BCR-ABL1² MPN with de novo AML and with AML following MDS', Blood advances, vol. 4, no. 19, pp. 4748-4757. https://doi.org/10.1182/bloodadvances.2020002621

TY - JOUR

T1 - Comparison of outcomes of HCT in blast phase of BCR-ABL12 MPN with de novo AML and with AML following MDS

AU - Gupta, Vikas

AU - Kim, Soyoung

AU - Hu, Zhen Huan

AU - Liu, Ying

AU - Aljurf, Mahmoud

AU - Bacher, Ulrike

AU - Beitinjaneh, Amer

AU - Cahn, Jean Yves

AU - Cerny, Jan

AU - Copelan, Edward

AU - Gadalla, Shahinaz M.

AU - Gale, Robert Peter

AU - Ganguly, Siddhartha

AU - George, Biju

AU - Gerds, Aaron T.

AU - Gergis, Usama

AU - Hamilton, Betty K.

AU - Hashmi, Shahrukh

AU - Hildebrandt, Gerhard C.

AU - Kamble, Rammurti T.

AU - Kindwall-Keller, Tamila

AU - Lazarus, Hillard M.

AU - Liesveld, Jane L.

AU - Litzow, Mark

AU - Maziarz, Richard T.

AU - Nishihori, Taiga

AU - Olsson, Richard F.

AU - Rizzieri, David

AU - Savani, Bipin N.

AU - Seo, Sachiko

AU - Solh, Melhem

AU - Szer, Jeff

AU - Verdonck, Leo F.

AU - Wirk, Baldeep

AU - Woolfrey, Ann

AU - Yared, Jean A.

AU - Alyea, Edwin P.

AU - Popat, Uday R.

AU - Sobecks, Ronald M.

AU - Scott, Bart L.

AU - Nakamura, Ryotaro

AU - Saber, Wael

PY - 2020/10/13

Y1 - 2020/10/13

N2 - Comparative outcomes of allogeneic hematopoietic cell transplantation (HCT) for BCR-ABL12 myeloproliferative neoplasms (MPNs) in blast phase (MPN-BP) vs de novo acute myeloid leukemia (AML), and AML with prior myelodysplastic syndromes (MDSs; post-MDS AML), are unknown. Using the Center for International Blood and Marrow Transplant Research (CIBMTR) database, we compared HCT outcomes in 177 MPN-BP patients with 4749 patients with de novo AML, and 1104 patients with post-MDS AML, using multivariate regression analysis in 2 separate comparisons. In a multivariate Cox model, no difference in overall survival (OS) or relapse was observed in patients with MPN-BP vs de novo AML with active leukemia at HCT. Patients with MPN-BP in remission had inferior OS in comparison with de novo AML in remission (hazard ratio [HR], 1.40 [95% confidence interval [CI], 1.12-1.76]) due to higher relapse rate (HR, 2.18 [95% CI, 1.69-2.80]). MPN-BP patients had inferior OS (HR, 1.19 [95% CI, 1.00-1.43]) and increased relapse (HR, 1.60 [95% CI, 1.31-1.96]) compared with post-MDS AML. Poor-risk cytogenetics were associated with increased relapse in both comparisons. Peripheral blood grafts were associated with decreased relapse in MPN-BP and post-MDS AML (HR, 0.70 [95% CI, 0.57-0.86]). Nonrelapse mortality (NRM) was similar between MPN-BP vs de novo AML, and MPN-BP vs post-MDS AML. Total-body irradiation-based myeloablative conditioning was associated with higher NRM in both comparisons. Survival of MPN-BP after HCT is inferior to de novo AML in remission and post-MDS AML due to increased relapse. Relapse-prevention strategies are required to optimize HCT outcomes in MPN-BP.

AB - Comparative outcomes of allogeneic hematopoietic cell transplantation (HCT) for BCR-ABL12 myeloproliferative neoplasms (MPNs) in blast phase (MPN-BP) vs de novo acute myeloid leukemia (AML), and AML with prior myelodysplastic syndromes (MDSs; post-MDS AML), are unknown. Using the Center for International Blood and Marrow Transplant Research (CIBMTR) database, we compared HCT outcomes in 177 MPN-BP patients with 4749 patients with de novo AML, and 1104 patients with post-MDS AML, using multivariate regression analysis in 2 separate comparisons. In a multivariate Cox model, no difference in overall survival (OS) or relapse was observed in patients with MPN-BP vs de novo AML with active leukemia at HCT. Patients with MPN-BP in remission had inferior OS in comparison with de novo AML in remission (hazard ratio [HR], 1.40 [95% confidence interval [CI], 1.12-1.76]) due to higher relapse rate (HR, 2.18 [95% CI, 1.69-2.80]). MPN-BP patients had inferior OS (HR, 1.19 [95% CI, 1.00-1.43]) and increased relapse (HR, 1.60 [95% CI, 1.31-1.96]) compared with post-MDS AML. Poor-risk cytogenetics were associated with increased relapse in both comparisons. Peripheral blood grafts were associated with decreased relapse in MPN-BP and post-MDS AML (HR, 0.70 [95% CI, 0.57-0.86]). Nonrelapse mortality (NRM) was similar between MPN-BP vs de novo AML, and MPN-BP vs post-MDS AML. Total-body irradiation-based myeloablative conditioning was associated with higher NRM in both comparisons. Survival of MPN-BP after HCT is inferior to de novo AML in remission and post-MDS AML due to increased relapse. Relapse-prevention strategies are required to optimize HCT outcomes in MPN-BP.

UR - https://www.scopus.com/pages/publications/85092401454

UR - https://www.scopus.com/pages/publications/85092401454#tab=citedBy

U2 - 10.1182/bloodadvances.2020002621

DO - 10.1182/bloodadvances.2020002621

M3 - Article

C2 - 33007075

AN - SCOPUS:85092401454

SN - 2473-9529

VL - 4

SP - 4748

EP - 4757

JO - Blood advances

JF - Blood advances

IS - 19

ER -