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Aug 3, 2018 - 2015 at the University of Minnesota to study the incidence, risk factors, and .... schedule of methylprednisolone with the dose of methylprednisolone adjusted per body ... median time-to-engraftment was shorter in PB/BM graft recipients .... animal studies the lung can contribute to platelet production (29-31).
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