Abstract
Introduction/Background: Reduced-intensity conditioning (RIC) and nonmyeloablative (NMA) regimens have enabled patients with cardiovascular disease (CVD) to undergo allogeneic stem cell transplantation (allo-HSCT). However, little is known about long-term outcomes, including cardiovascular (CV) complications. Methods: We retrospectively studied 99 consecutive patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) who underwent allo-HSCT between September 1, 2013, and November 30, 2020. Overall survival (OS), progression-free survival (PFS), nonrelapse mortality (NRM), cumulative incidence of relapse, and cumulative incidence of acute and chronic graft-versus-host disease (GvHD) were compared in patients with and without CV risk factors or disease. Results: Preexisting CVD was present in 34 of 99 patients (34%). CVD patients more commonly had reduced-intensity conditioning (91% vs. 60%, p = 0.001) and unrelated donors (56% vs. 35%, p = 0.04). Early adverse cardiac events occurred more frequently in the CVD versus no-CVD group (38% vs. 14%), particularly arrhythmias (21% vs. 5%; p = 0.04). CVD patients tended to have poorer OS and PFS outcomes (HR = 1.98, [1.00, 3.92]; HR = 1.89, [0.96–3.72], respectively). OS rate at 1, 2, and 3 years for CVD versus no-CVD patients was 66% versus 72%, 55% versus 64%, and 46% versus 62%, respectively. Causes of death in the CVD and no-CVD groups were infections (53% vs. 28%), relapsed disease (32% vs. 52%), and CV events (10% vs. 3%). Conclusion: Based on these data, predictive models to identify patients with CVD with higher risk of post-allo-HSCT complications and mortality and strategies to mitigate these risks should be developed.
Journal Section:
Interdisciplinary Perspectives in Hematology
References
1.
Wingard
JR
, Majhail
NS
, Brazauskas
R
, Wang
Z
, Sobocinski
KA
, Jacobsohn
D
, et al. Long-term survival and late deaths after allogeneic hematopoietic cell transplantation
. J Clin Oncol
. 2011
;29
(16
):2230
–9
. 2.
Majhail
NS
, Tao
L
, Bredeson
C
, Davies
S
, Dehn
J
, Gajewski
JL
, et al. Prevalence of hematopoietic cell transplant survivors in the United States
. Biol Blood Marrow Transpl
. 2013
;19
(10
):1498
–501
. 3.
Tichelli
A
, Bhatia
S
, Socié
G
. Cardiac and cardiovascular consequences after haematopoietic stem cell transplantation
. Br J Haematol
. 2008
;142
(1
):11
–26
. 4.
Hertenstein
B
, Stefanic
M
, Schmeiser
T
, Scholz
M
, Göller
V
, Clausen
M
, et al. Cardiac toxicity of bone marrow transplantation: predictive value of cardiologic evaluation before transplant
. J Clin Oncol
. 1994
;12
(5
):998
–1004
. 5.
Kupari
M
, Volin
L
, Suokas
A
, Timonen
T
, Hekali
PRT
, Ruutu
T
. Cardiac involvement in bone marrow transplantation: electrocardiographic changes, arrhythmias, heart failure and autopsy findings
. Bone Marrow Transpl
. 1990
;5
(2
):91
–8
.6.
Bhatia
S
, Francisco
L
, Carter
A
, Sun
CL
, Baker
KS
, Gurney
JG
, et al. Late mortality after allogeneic hematopoietic cell transplantation and functional status of long-term survivors: report from the Bone Marrow Transplant Survivor study
. Blood
. 2007
;110
(10
):3784
–92
. 7.
Yeh
J
, Whited
L
, Saliba
RM
, Rondon
G
, Banchs
J
, Shpall
E
, et al. Cardiac toxicity after matched allogeneic hematopoietic cell transplant in the posttransplant cyclophosphamide era
. Blood Adv
. 2021
;5
(24
):5599
–607
. 8.
Baker
JK
, Shank-Coviello
J
, Zhou
B
, Dixon
J
, McCorkle
R
, Sarpong
D
, et al. Cardiotoxicity in hematopoietic stem cell transplant: keeping the beat
. Clin Lymphoma Myeloma Leuk
. 2020
;20
(4
):244
–51.e4
. 9.
Defilipp
Z
, Duarte
RF
, Snowden
JA
, Majhail
NS
, Greenfield
DM
, Miranda
JL
, et al. Metabolic syndrome and cardiovascular disease following hematopoietic cell transplantation: screening and preventive practice recommendations from CIBMTR and EBMT
. Bone Marrow Transpl
. 2017
;52
(2
):173
–82
. 10.
Armenian
SH
, Sun
CL
, Vase
T
. Cardiovascular risk factors in hematopoietic cell transplantation survivors: role in development of subsequent cardiovascular disease
. Transfuze a Hematol Dnes
. 2013
;19
(1
):52
.11.
Dhopeshwarkar
N
, Iqbal
S
, Wang
X
, Salas
M
. A retrospective study of comorbidities and complications in elderly acute myeloid leukemia patients in the United States
. Clin Lymphoma Myeloma Leuk
. 2019
;19
(8
):e436
–56
. 12.
Assuncao
BMBL
, Handschumacher
MD
, Brunner
AM
, Yucel
E
, Bartko
PE
, Cheng
KH
, et al. Acute leukemia is associated with cardiac alterations before chemotherapy
. J Am Soc Echocardiogr
. 2017
;30
(11
):1111
–8
. 13.
Kattih
B
, Shirvani
A
, Klement
P
, Garrido
AM
, Gabdoulline
R
, Liebich
A
, et al. IDH1/2 mutations in acute myeloid leukemia patients and risk of coronary artery disease and cardiac dysfunction: a retrospective propensity score analysis
. Leukemia
. 2021
;35
(5
):1301
–16
. 14.
Jagasia
MH
, Greinix
HT
, Arora
M
, Williams
KM
, Wolff
D
, Cowen
EW
, et al. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. The 2014 diagnosis and staging working group report
. Biol Blood Marrow Transpl
. 2015
;21
(3
):389
–401.e1
. 15.
Harris
AC
, Young
R
, Devine
S
, Hogan
WJ
, Ayuk
F
, Bunworasate
U
, et al. International, multicenter standardization of acute graft-versus-host disease clinical data collection: a report from the Mount Sinai acute GVHD international Consortium
. Biol Blood Marrow Transpl
. 2016
;22
(1
):4
–10
. 16.
National Cancer Institute (NCI) dictionary [Internet]
. Cardiovascular disease
. Available from: https://www.cancer.gov/publications/dictionaries/cancer-terms/def/cardiovascular-disease17.
United States National Heart, Lung and BI
. The framingham study: an epidemiological investigation of cardiovascular disease; section 34
. 2015
; p. 2
–4
.18.
Varadarajan
R
, Licht
AS
, Hyland
AJ
, Ford
LA
, Sait
SNJ
, Block
AW
, et al. Smoking adversely affects survival in acute myeloid leukemia patients
. Int J Cancer
. 2012
;130
(6
):1451
–8
. 19.
Chelghoum
Y
, Danaíla
C
, Belhabri
A
, Charrin
C
, Le
QH
, Michallet
M
, et al. Influence of cigarette smoking on the presentation and course of acute myeloid leukemia
. Ann Oncol
. 2002
;13
(10
):1621
–7
. 20.
He
J
, Zhu
Z
, Bundy
JD
, Dorans
KS
, Chen
J
, Hamm
LL
. Trends in cardiovascular risk factors in US adults by race and ethnicity and socioeconomic status, 1999-2018
. JAMA J Am Med Assoc
. 2021
;326
(13
):1286
–98
. 21.
Fine
JP
, Gray
RJ
. A proportional hazards model for the subdistribution of a competing risk
. J Am Stat Assoc
. 1999
;94
(446
):496
–509
. 22.
Team
RCR
. A language and environment for statistical computing
. Vienna, Austria
: R Foundation for Statistical Computing
; 2019
.23.
CIBMTR
. Disease risk index (DRI) assignment tool [Internet]
. 2022
. Available from: https://www.cibmtr.org/ReferenceCenter/Statistical/Tools/Pages/DRI.aspx24.
Sorror
ML
, Maris
MB
, Storb
R
, Baron
F
, Sandmaier
BM
, Maloney
DG
, et al. Hematopoietic cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic HCT
. Blood
. 2005
;106
(8
):2912
–9
. 25.
HCT comorbidity index calculator
. 2022
. [Internet]. Available from: http://www.hctci.org/Home/Calculator26.
Armand
P
, Kim
HT
, Logan
BR
, Wang
Z
, Alyea
EP
, Kalaycio
ME
, et al. Validation and refinement of the Disease Risk Index for allogeneic stem cell transplantation
. Blood
. 2014
;123
(23
):3664
–71
. 27.
Alkhaldi
H
, Goloubeva
O
, Rapoport
AP
, Dahiya
S
, Pang
Y
, Ali
MM
, et al. Outcomes of busulfan, fludarabine, and 400 cGy total body irradiation compared with busulfan and fludarabine reduced-intensity conditioning regimens for allogeneic stem cell transplantation in adult patients with hematologic diseases: a single-center experience
. Transpl Proc
. 2023
;55
(1
):214
–24
. 28.
Saber
W
, Opie
S
, Rizzo
JD
, Zhang
MJ
, Horowitz
MM
, Schriber
J
. Outcomes after matched unrelated donor versus identical sibling hematopoietic cell transplantation in adults with acute myelogenous leukemia
. Blood
. 2012
;119
(17
):3908
–16
. 29.
Duarte
RF
, Sánchez-Ortega
I
. HSCT in elderly patients
. In: Carreras
E
, Dufour
C
, Mohty
M
, et al, editors. The EBMT handbook: hematopoietic stem cell transplantation and cellular therapies [Internet]
. 7th ed. Cham (CH)
: Springer
; 2019
. [Chapter 68].30.
Sorror
ML
, Giralt
S
, Sandmaier
BM
, De Lima
M
, Shahjahan
M
, Maloney
DG
, et al. Hematopoietic cell transplantation-specific comorbidity index as an outcome predictor for patients with acute myeloid leukemia in first remission: combined FHCRC and MDACC experiences
. Blood
. 2007
;110
(13
):4606
–13
. 31.
Penack
O
, Peczynski
C
, Mohty
M
, Yakoub-Agha
I
, de la Camara
R
, Glass
B
, et al. Association of pre-existing comorbidities with outcome of allogeneic hematopoietic cell transplantation. A retrospective analysis from the EBMT
. Bone Marrow Transpl
. 2022
;57
(2
):183
–90
. 32.
Birninger
N
, Bornhäuser
M
, Schaich
M
, Ehninger
G
, Schetelig
J
. The hematopoietic cell transplantation-specific comorbidity index fails to predict outcomes in high-risk AML patients undergoing allogeneic transplantation-investigation of potential limitations of the index
. Biol Blood Marrow Transpl
. 2011
;17
(12
):1822
–32
. 33.
Assuncao
BM
, Wang
L
. Leukemia is associated with a high prevalence of major adverse cardiac events after anthracycline-based chemotherapy
. Circulation
. 2018
;134
.34.
Gharib
MI
, Burnett
AK
. Chemotherapy-induced cardiotoxicity: current practice and prospects of prophylaxis
. Eur J Heart Fail
. 2002
;4
(3
):235
–42
. 35.
Coghlan
JG
, Handler
CE
, Kottaridis
PD
. Cardiac assessment of patients for haematopoietic stem cell transplantation
. Best Pract Res Clin Haematol
. 2007
;20
(2
):247
–63
. 36.
Murdych
T
, Weisdorf
DJ
. Serious cardiac complications during bone marrow transplantation at the University of Minnesota, 1977-1997
. Bone Marrow Transpl
. 2001
;28
(3
):283
–7
. 37.
Duléry
R
, Mohty
R
, Labopin
M
, Sestili
S
, Malard
F
, Brissot
E
, et al. Early cardiac toxicity associated with post-transplant cyclophosphamide in allogeneic stem cell transplantation
. JACC CardioOncol
. 2021
;3
(2
):250
–9
. 38.
Pérez-Valencia
AI
, Cascos
E
, Carbonell-Ordeig
S
, Charry
P
, Gómez-Hernando
M
, Rodríguez-Lobato
LG
, et al. Incidence, risk factors, and impact of early cardiac toxicity after allogeneic hematopoietic cell transplant
. Blood Adv
. 2023
;7
(10
):2018
–31
. © 2024 S. Karger AG, Basel
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
2024
You do not currently have access to this content.
