Published Ahead of Print on August 3, 2018, as doi:10.3324/haematol.2018.189134. Copyright 2018 Ferrata Storti Foundation.
Diffuse alveolar hemorrhage is most often fatal and is affected by graft source, conditioning regiment toxicity, and engraftment kinetics by Fatma Keklik, Ezzideen Barjes Alrawi, Qing Cao, Nelli Bejanyan, Armin Rashidi, Aleksandr Lazaryan, Patrick Arndt, Erhan H. Dincer, Veronika Bachanova, Erica D. Warlick, Margaret L. MacMillan, Mukta Arora, Jeffrey Miller, Claudio G. Brunstein, Daniel J. Weisdorf, and Celalettin Ustun Haematologica 2018 [Epub ahead of print] Citation: Fatma Keklik, Ezzideen Barjes Alrawi, Qing Cao, Nelli Bejanyan, Armin Rashidi, Aleksandr Lazaryan, Patrick Arndt, Erhan H. Dincer, Veronika Bachanova, Erica D. Warlick, Margaret L. MacMillan, Mukta Arora, Jeffrey Miller, Claudio G. Brunstein, Daniel J. Weisdorf, and Celalettin Ustun. Diffuse alveolar hemorrhage is most often fatal and is affected by graft source, conditioning regiment toxicity, and engraftment kinetics. Haematologica. 2018; 103:xxx doi:10.3324/haematol.2018.189134 Publisher's Disclaimer. E-publishing ahead of print is increasingly important for the rapid dissemination of science. Haematologica is, therefore, E-publishing PDF files of an early version of manuscripts that have completed a regular peer review and have been accepted for publication. E-publishing of this PDF file has been approved by the authors. After having E-published Ahead of Print, manuscripts will then undergo technical and English editing, typesetting, proof correction and be presented for the authors' final approval; the final version of the manuscript will then appear in print on a regular issue of the journal. All legal disclaimers that apply to the journal also pertain to this production process.
Diffuse alveolar hemorrhage is most often fatal and is affected by graft source, conditioning regiment toxicity, and engraftment kinetics Authors:
1
Aleksandr
D. Warlick, J.
1
Fatma Keklik,
1
4
Lazaryan,
3
Ezzideen Barjes
Patrick
Arndt,
Margaret L. MacMillan,
Weisdorf
and
1
1
Alrawi,
3
Erhan
2
Qing Cao, H.
1
Nelli Bejanyan,
Dincer,
Mukta Arora, Jeffrey Miller,
1
Veronika
1
Armin
Rashidi,
1
Bachanova, Erica
1
Claudio G Brunstein,
1
Daniel
Celalettin Ustun
Affiliation: 1
Division of Hematology-Oncology and Transplantation, Department of Medicine, University
of Minnesota, Minneapolis, Minnesota, USA
2
Biostatistics and Bioinformatics, University of Minnesota, Minneapolis, Minnesota, USA.
3
Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine,
University of Minnesota, Minneapolis, Minnesota, USA
4
Division
of
Pediatric
Blood
and
Marrow
Transplantation,
Department
of
Pediatrics, University of Minnesota, Minneapolis, Minnesota, USA
Running Head: Key Words:
Diffuse alveolar hemorrhage after HCT
Diffuse
alveolar
hemorrhage,
allogeneic
hematopoietic
cell
transplantation,
umbilical cord blood, peripheral blood stem cell, bone marrow, engraftment
Word Count:
Abstract, 341 and entire text, 2978
Reference Count:
54
3 Tables, 1 Supplemental Table, and 1 Supplemental Figure Corresponding Author and Address: Celalettin Ustun, MD Associate Professor of Medicine Division of Hematology Oncology and Transplantation Department of Medicine, University of Minnesota 14-142 PWB, 516 Delaware Street SE Minneapolis, MN 55455, USA Tel: 612-624-0123 Fax: 612-625-6919 Email:
[email protected]
1
Abstract Diffuse alveolar hemorrhage after hematopoietic stem cell transplantation is a frequently
fatal complication with no standard therapy. Although significant changes in supportive and
intensive care measures
for hematopoietic
stem cell
transplantation patients
have been
made over the past decades, the impact of these changes on the incidence and outcome of
patients
with
diffuse
alveolar
hemorrhage
has
not
been
examined.
We
analyzed
1228
patients who underwent allogeneic hematopoietic stem cell transplantation between 2008-
2015 at the University of Minnesota to study the incidence, risk factors, and outcomes of
diffuse alveolar hemorrhage. Diffuse alveolar hemorrhage developed in 5% of allogeneic
hematopoietic stem cell transplantation recipients, a median day +30 (range +3 to +168
days)
after
hematopoietic
stem
cell
transplantation.
The
incidence
of
diffuse
alveolar
hemorrhage was significantly greater in recipients of umbilical cord blood versus peripheral
blood
or
marrow
grafts
(HR:
2.08,
95%CI:
1.16-3.74),
p=0.01.
In
multivariate
analysis,
delayed neutrophil engraftment or primary graft failure was a risk factor for diffuse alveolar
hemorrhage in peripheral blood or marrow hematopoietic stem cell transplantation (HR:
5.51,
95%CI:
1.26-24,
p=0.02)
and
delayed
platelet
engraftment
was
associated
with
significantly increased diffuse alveolar hemorrhage in umbilical cord blood hematopoietic
stem cell transplantation (HR: 6.96, 95%CI: 2.39-20-.29, p35 U/L),
8% had
elevated international normalized ratio (INR) >1.5, 25% had elevated partial thromboplastin
time (PTT≥37 sec)-though most were
