Hematopoietic Cell Transplantation Outcomes in Monosomal Karyotype Myeloid Malignancies

Marcelo C. Pasquini; Mei Jie Zhang; Bruno C. Medeiros; Philippe Armand; Zhen Huan Hu; Taiga Nishihori; Mahmoud D. Aljurf; Görgün Akpek; Jean Yves Cahn; Mitchell S. Cairo; Jan Cerny; Edward A. Copelan; Abhinav Deol; César O. Freytes; Robert Peter Gale; Siddhartha Ganguly; Biju George; Vikas Gupta; Gregory A. Hale; Rammurti T. Kamble; Thomas R. Klumpp; Hillard M. Lazarus; Selina M. Luger; Jane L. Liesveld; Mark R. Litzow; David I. Marks; Rodrigo Martino; Maxim Norkin; Richard F. Olsson; Betul Oran; Attaphol Pawarode; Michael A. Pulsipher; Muthalagu Ramanathan; Ran Reshef; Ayman A. Saad; Wael Saber; Bipin N. Savani; Harry C. Schouten; Olle Ringdén; Martin S. Tallman; Geoffrey L. Uy; William A. Wood; Baldeep Wirk; Waleska S. Pérez; Minoo Batiwalla; Daniel J. Weisdorf

doi:10.1016/j.bbmt.2015.08.024

Hematopoietic Cell Transplantation Outcomes in Monosomal Karyotype Myeloid Malignancies

Marcelo C. Pasquini^*, Mei Jie Zhang, Bruno C. Medeiros, Philippe Armand, Zhen Huan Hu, Taiga Nishihori, Mahmoud D. Aljurf, Görgün Akpek, Jean Yves Cahn, Mitchell S. Cairo, Jan Cerny, Edward A. Copelan, Abhinav Deol, César O. Freytes, Robert Peter Gale, Siddhartha Ganguly, Biju George, Vikas Gupta, Gregory A. Hale, Rammurti T. KambleThomas R. Klumpp, Hillard M. Lazarus, Selina M. Luger, Jane L. Liesveld, Mark R. Litzow, David I. Marks, Rodrigo Martino, Maxim Norkin, Richard F. Olsson, Betul Oran, Attaphol Pawarode, Michael A. Pulsipher, Muthalagu Ramanathan, Ran Reshef, Ayman A. Saad, Wael Saber, Bipin N. Savani, Harry C. Schouten, Olle Ringdén, Martin S. Tallman, Geoffrey L. Uy, William A. Wood, Baldeep Wirk, Waleska S. Pérez, Minoo Batiwalla, Daniel J. Weisdorf

^*Corresponding author for this work

Medicine, Hematology Oncology Division

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

30 Scopus citations

Abstract

The presence of monosomal karyotype (MK+) in acute myeloid leukemia (AML) is associated with dismal outcomes. We evaluated the impact of MK+ in AML (MK+AML, n = 240) and in myelodysplastic syndrome (MDS) (MK+MDS, n = 221) on hematopoietic cell transplantation outcomes compared with other cytogenetically defined groups (AML, n = 3360; MDS, n = 1373) as reported to the Center for International Blood and Marrow Transplant Research from 1998 to 2011. MK+ AML was associated with higher disease relapse (hazard ratio, 1.98; P <.01), similar transplantation-related mortality (TRM) (hazard ratio, 1.01; P =90), and worse survival (hazard ratio, 1.67; P <.01) compared with those outcomes for other cytogenetically defined AML. Among patients with MDS, MK+ MDS was associated with higher disease relapse (hazard ratio, 2.39; P <.01), higher TRM (hazard ratio, 1.80; P <.01), and worse survival (HR, 2.02; P <.01). Subset analyses comparing chromosome 7 abnormalities (del7/7q) with or without MK+ demonstrated higher mortality for MK+ disease in for both AML (hazard ratio, 1.72; P <.01) and MDS (hazard ratio, 1.79; P <.01). The strong negative impact of MK+ in myeloid malignancies was observed in all age groups and using either myeloablative or reduced-intensity conditioning regimens. Alternative approaches to mitigate disease relapse in this population are needed.

Original language	English (US)
Pages (from-to)	248-257
Number of pages	10
Journal	Biology of Blood and Marrow Transplantation
Volume	22
Issue number	2
DOIs	https://doi.org/10.1016/j.bbmt.2015.08.024
State	Published - Feb 1 2016

Funding

Additional members from the Writing Committee who offered input different stages of development of this study include Camille N. Abboud, Bruce Camitta, William Drobyski, Sergio Giralt, Vincent Ho, Luis Isola, John Koreth, Mary Laughlin, Ian Lewis, Michael Lil, Selina Luger, Richard Maziarz, Ryan Mattinson, Joseph McGuirk Reinhold Munker, Amandee Salhorta, Salyka Sengsayadeth, Gerard Socié. 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); 2 grants N00014-13-1-0039 and N00014-14-1-0028 from the Office of Naval Research; and grants from *Actinium Pharmaceuticals; Allos Therapeutics, Inc.; *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. 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 United States Government. Financial disclosure: There is nothing to disclose. Conflict of interest statement: There are no conflicts of interest to report. 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); 2 grants N00014-13-1-0039 and N00014-14-1-0028 from the Office of Naval Research ; and grants from *Actinium Pharmaceuticals; Allos Therapeutics, Inc.; *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. 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 United States Government.

Keywords

Acute myeloid leukemia
Allogeneic transplantation
Monosomal karyotype
Myelodysplastic syndrome

ASJC Scopus subject areas

Hematology
Transplantation

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10.1016/j.bbmt.2015.08.024

Cite this

Pasquini, M. C., Zhang, M. J., Medeiros, B. C., Armand, P., Hu, Z. H., Nishihori, T., Aljurf, M. D., Akpek, G., Cahn, J. Y., Cairo, M. S., Cerny, J., Copelan, E. A., Deol, A., Freytes, C. O., Gale, R. P., Ganguly, S., George, B., Gupta, V., Hale, G. A., ... Weisdorf, D. J. (2016). Hematopoietic Cell Transplantation Outcomes in Monosomal Karyotype Myeloid Malignancies. Biology of Blood and Marrow Transplantation, 22(2), 248-257. https://doi.org/10.1016/j.bbmt.2015.08.024

@article{f8d199d1a9324492acbbe129c49a34a1,

title = "Hematopoietic Cell Transplantation Outcomes in Monosomal Karyotype Myeloid Malignancies",

abstract = "The presence of monosomal karyotype (MK+) in acute myeloid leukemia (AML) is associated with dismal outcomes. We evaluated the impact of MK+ in AML (MK+AML, n = 240) and in myelodysplastic syndrome (MDS) (MK+MDS, n = 221) on hematopoietic cell transplantation outcomes compared with other cytogenetically defined groups (AML, n = 3360; MDS, n = 1373) as reported to the Center for International Blood and Marrow Transplant Research from 1998 to 2011. MK+ AML was associated with higher disease relapse (hazard ratio, 1.98; P <.01), similar transplantation-related mortality (TRM) (hazard ratio, 1.01; P =90), and worse survival (hazard ratio, 1.67; P <.01) compared with those outcomes for other cytogenetically defined AML. Among patients with MDS, MK+ MDS was associated with higher disease relapse (hazard ratio, 2.39; P <.01), higher TRM (hazard ratio, 1.80; P <.01), and worse survival (HR, 2.02; P <.01). Subset analyses comparing chromosome 7 abnormalities (del7/7q) with or without MK+ demonstrated higher mortality for MK+ disease in for both AML (hazard ratio, 1.72; P <.01) and MDS (hazard ratio, 1.79; P <.01). The strong negative impact of MK+ in myeloid malignancies was observed in all age groups and using either myeloablative or reduced-intensity conditioning regimens. Alternative approaches to mitigate disease relapse in this population are needed.",

keywords = "Acute myeloid leukemia, Allogeneic transplantation, Monosomal karyotype, Myelodysplastic syndrome",

author = "Pasquini, {Marcelo C.} and Zhang, {Mei Jie} and Medeiros, {Bruno C.} and Philippe Armand and Hu, {Zhen Huan} and Taiga Nishihori and Aljurf, {Mahmoud D.} and G{\"o}rg{\"u}n Akpek and Cahn, {Jean Yves} and Cairo, {Mitchell S.} and Jan Cerny and Copelan, {Edward A.} and Abhinav Deol and Freytes, {C{\'e}sar O.} and Gale, {Robert Peter} and Siddhartha Ganguly and Biju George and Vikas Gupta and Hale, {Gregory A.} and Kamble, {Rammurti T.} and Klumpp, {Thomas R.} and Lazarus, {Hillard M.} and Luger, {Selina M.} and Liesveld, {Jane L.} and Litzow, {Mark R.} and Marks, {David I.} and Rodrigo Martino and Maxim Norkin and Olsson, {Richard F.} and Betul Oran and Attaphol Pawarode and Pulsipher, {Michael A.} and Muthalagu Ramanathan and Ran Reshef and Saad, {Ayman A.} and Wael Saber and Savani, {Bipin N.} and Schouten, {Harry C.} and Olle Ringd{\'e}n and Tallman, {Martin S.} and Uy, {Geoffrey L.} and Wood, {William A.} and Baldeep Wirk and P{\'e}rez, {Waleska S.} and Minoo Batiwalla and Weisdorf, {Daniel J.}",

note = "Publisher Copyright: {\textcopyright} 2016 American Society for Blood and Marrow Transplantation.",

year = "2016",

month = feb,

day = "1",

doi = "10.1016/j.bbmt.2015.08.024",

language = "English (US)",

volume = "22",

pages = "248--257",

journal = "Biology of Blood and Marrow Transplantation",

issn = "1083-8791",

publisher = "Elsevier Inc.",

number = "2",

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Pasquini, MC, Zhang, MJ, Medeiros, BC, Armand, P, Hu, ZH, Nishihori, T, Aljurf, MD, Akpek, G, Cahn, JY, Cairo, MS, Cerny, J, Copelan, EA, Deol, A, Freytes, CO, Gale, RP, Ganguly, S, George, B, Gupta, V, Hale, GA, Kamble, RT, Klumpp, TR, Lazarus, HM, Luger, SM, Liesveld, JL, Litzow, MR, Marks, DI, Martino, R, Norkin, M, Olsson, RF, Oran, B, Pawarode, A, Pulsipher, MA, Ramanathan, M, Reshef, R, Saad, AA, Saber, W, Savani, BN, Schouten, HC, Ringdén, O, Tallman, MS, Uy, GL, Wood, WA, Wirk, B, Pérez, WS, Batiwalla, M & Weisdorf, DJ 2016, 'Hematopoietic Cell Transplantation Outcomes in Monosomal Karyotype Myeloid Malignancies', Biology of Blood and Marrow Transplantation, vol. 22, no. 2, pp. 248-257. https://doi.org/10.1016/j.bbmt.2015.08.024

TY - JOUR

T1 - Hematopoietic Cell Transplantation Outcomes in Monosomal Karyotype Myeloid Malignancies

AU - Pasquini, Marcelo C.

AU - Zhang, Mei Jie

AU - Medeiros, Bruno C.

AU - Armand, Philippe

AU - Hu, Zhen Huan

AU - Nishihori, Taiga

AU - Aljurf, Mahmoud D.

AU - Akpek, Görgün

AU - Cahn, Jean Yves

AU - Cairo, Mitchell S.

AU - Cerny, Jan

AU - Copelan, Edward A.

AU - Deol, Abhinav

AU - Freytes, César O.

AU - Gale, Robert Peter

AU - Ganguly, Siddhartha

AU - George, Biju

AU - Gupta, Vikas

AU - Hale, Gregory A.

AU - Kamble, Rammurti T.

AU - Klumpp, Thomas R.

AU - Lazarus, Hillard M.

AU - Luger, Selina M.

AU - Liesveld, Jane L.

AU - Litzow, Mark R.

AU - Marks, David I.

AU - Martino, Rodrigo

AU - Norkin, Maxim

AU - Olsson, Richard F.

AU - Oran, Betul

AU - Pawarode, Attaphol

AU - Pulsipher, Michael A.

AU - Ramanathan, Muthalagu

AU - Reshef, Ran

AU - Saad, Ayman A.

AU - Saber, Wael

AU - Savani, Bipin N.

AU - Schouten, Harry C.

AU - Ringdén, Olle

AU - Tallman, Martin S.

AU - Uy, Geoffrey L.

AU - Wood, William A.

AU - Wirk, Baldeep

AU - Pérez, Waleska S.

AU - Batiwalla, Minoo

AU - Weisdorf, Daniel J.

PY - 2016/2/1

Y1 - 2016/2/1

N2 - The presence of monosomal karyotype (MK+) in acute myeloid leukemia (AML) is associated with dismal outcomes. We evaluated the impact of MK+ in AML (MK+AML, n = 240) and in myelodysplastic syndrome (MDS) (MK+MDS, n = 221) on hematopoietic cell transplantation outcomes compared with other cytogenetically defined groups (AML, n = 3360; MDS, n = 1373) as reported to the Center for International Blood and Marrow Transplant Research from 1998 to 2011. MK+ AML was associated with higher disease relapse (hazard ratio, 1.98; P <.01), similar transplantation-related mortality (TRM) (hazard ratio, 1.01; P =90), and worse survival (hazard ratio, 1.67; P <.01) compared with those outcomes for other cytogenetically defined AML. Among patients with MDS, MK+ MDS was associated with higher disease relapse (hazard ratio, 2.39; P <.01), higher TRM (hazard ratio, 1.80; P <.01), and worse survival (HR, 2.02; P <.01). Subset analyses comparing chromosome 7 abnormalities (del7/7q) with or without MK+ demonstrated higher mortality for MK+ disease in for both AML (hazard ratio, 1.72; P <.01) and MDS (hazard ratio, 1.79; P <.01). The strong negative impact of MK+ in myeloid malignancies was observed in all age groups and using either myeloablative or reduced-intensity conditioning regimens. Alternative approaches to mitigate disease relapse in this population are needed.

AB - The presence of monosomal karyotype (MK+) in acute myeloid leukemia (AML) is associated with dismal outcomes. We evaluated the impact of MK+ in AML (MK+AML, n = 240) and in myelodysplastic syndrome (MDS) (MK+MDS, n = 221) on hematopoietic cell transplantation outcomes compared with other cytogenetically defined groups (AML, n = 3360; MDS, n = 1373) as reported to the Center for International Blood and Marrow Transplant Research from 1998 to 2011. MK+ AML was associated with higher disease relapse (hazard ratio, 1.98; P <.01), similar transplantation-related mortality (TRM) (hazard ratio, 1.01; P =90), and worse survival (hazard ratio, 1.67; P <.01) compared with those outcomes for other cytogenetically defined AML. Among patients with MDS, MK+ MDS was associated with higher disease relapse (hazard ratio, 2.39; P <.01), higher TRM (hazard ratio, 1.80; P <.01), and worse survival (HR, 2.02; P <.01). Subset analyses comparing chromosome 7 abnormalities (del7/7q) with or without MK+ demonstrated higher mortality for MK+ disease in for both AML (hazard ratio, 1.72; P <.01) and MDS (hazard ratio, 1.79; P <.01). The strong negative impact of MK+ in myeloid malignancies was observed in all age groups and using either myeloablative or reduced-intensity conditioning regimens. Alternative approaches to mitigate disease relapse in this population are needed.

KW - Acute myeloid leukemia

KW - Allogeneic transplantation

KW - Monosomal karyotype

KW - Myelodysplastic syndrome

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Hematopoietic Cell Transplantation Outcomes in Monosomal Karyotype Myeloid Malignancies

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