Iron toxicity and hematopoietic cell transplantation: do we understand why iron affects transplant outcome?

2.

European Association for the Study of the Liver

.

EASL clinical practice guidelines on non-invasive tests for evaluation of liver disease severity and prognosis—2021 update

.

J. Hepatol

.

2021

;

75

(

3

):

659

-

689

.

3.

Angelucci

E

,

Brittenham

GM

,

McLaren

CE

, et al.

Hepatic iron concentration and total body iron stores in thalassemia major

.

N Engl J Med

.

2000

;

343

(

5

):

327

-

331

.

4.

Lucarelli

G

,

Galimberti

M

,

Polchi

P

, et al.

Bone marrow transplantation in patients with thalassemia

.

N Engl J Med

.

1990

;

322

(

7

):

417

-

421

.

5.

Angelucci

E

,

Pilo

F

,

Coates

TD

.

Transplantation in thalassemia: revisiting the pesaro risk factors 25 years later

.

Am J Hematol

.

2017

;

92

(

5

):

411

-

413

.

6.

Li

C

,

Mathews

V

,

Kim

S

, et al.

Related and unrelated donor transplantation for β-thalassemia major: results of an international survey

.

Blood Adv

.

2019

;

3

(

17

):

2562

-

2570

.

7.

Swaminathan

VV

,

Uppuluri

R

,

Patel

S

, et al.

Matched family versus alternative donor hematopoietic stem cell transplantation for patients with thalassemia major: experience from a tertiary referral center in south India

.

Biol Blood Marrow Transplant

.

2020

;

26

(

7

):

1326

-

1331

.

8.

Baronciani

D

,

Angelucci

E

,

Potschger

U

, et al.

Hemopoietic stem cell transplantation in thalassemia: a report from the European Society for Blood and Bone Marrow Transplantation Hemoglobinopathy Registry, 2000-2010

.

Bone Marrow Transplant

.

2016

;

51

(

4

):

536

-

541

.

9.

De la Fuente

J

,

Galimard

JE

,

Dalissier

A

,

Zahrani

MA

,

2024

.

Allogeneic transplantation for sickle cell disease offers high rates of cure with low incidence of severe chronic GVHD in both children and adults: real world data from 2010-2023

.

An analysis of the European Society for Blood and Marrow Transplantation Hemoglobinopathy Working Party

.

Blood

.

2024

;

144

(

suppl 1

):

176

.

10.

Leitch

HA

,

Fibach

E

,

Rachmilewitz

E

.

Toxicity of iron overload and iron overload reduction in the setting of hematopoietic stem cell transplantation for hematologic malignancies

.

Crit Rev Oncol Hematol

.

2017

;

113

:

156

-

170

.

11.

Wermke

M

,

Eckoldt

J

,

Götze

KS

, et al.

Enhanced labile plasma iron and outcome in acute myeloid leukaemia and myelodysplastic syndrome after allogeneic haemopoietic cell transplantation (ALLIVE): a prospective, multicentre, observational trial

.

Lancet Haematol

.

2018

;

5

(

5

):

e201

-

e210

.

12.

Angelucci

E

,

Matthes-Martin

S

,

Baronciani

D

, et al;

EBMT Inborn Error and EBMT Paediatric Working Parties

.

Hematopoietic stem cell transplantation in thalassemia major and sickle cell disease: indications and management recommendations from an international expert panel

.

Haematologica

.

2014

;

99

(

5

):

811

-

820

.

13.

Muretto

P

,

Angelucci

E

,

Lucarelli

G

.

Reversibility of cirrhosis in patients cured of thalassemia by bone marrow transplantation

.

Ann Intern Med

.

2002

;

136

(

9

):

667

-

672

.

14.

Lüftinger

R

,

Zubarovskaya

N

,

Galimard

JE

, et al;

EBMT Pediatric Diseases, Inborn Errors Working Parties

.

Busulfan-fludarabine- or treosulfan- fludarabine-based myeloablative conditioning for children with thalassemia major

.

Ann Hematol

.

2022

;

101

(

3

):

655

-

665

.

15.

Locatelli

F

,

Thompson

AA

,

Kwiatkowski

JL

, et al.

Betibeglogene autotemcel gene therapy for non-β0/β0 benotype β-ghalassemia

.

N Engl J Med

.

2022

;

386

(

5

):

415

-

427

.

16.

Baronciani

D

,

Casale

M

,

De Franceschi

L

,

Graziadei

G

.

Selecting ß- thalassemia patients for gene therapy: a decision-making algorithm

.

Hemasphere

.

2021

;

5

(

5

):

e555

.

17.

Koenecke

C

,

Göhring

G

,

de Wreede

LC

, et al;

MDS Subcommittee of the Chronic Malignancies Working Party of the European Society for Blood and Marrow Transplantation

.

Impact of the revised International Prognostic Scoring System, cytogenetics and monosomal karyotype on outcome after allogeneic stem cell transplantation for myelodysplastic syndromes and secondary acute myeloid leukemia evolving from myelodysplastic syndromes: a retrospective multicenter study of the European Society of Blood and Marrow Transplantation

.

Haematologica

.

2015

;

100

(

3

):

400

-

408

.

18.

Gagelmann

N

,

Eikema

DJ

,

Stelljes

M

, et al.

Optimized EBMT transplant-specific risk score in myelodysplastic syndromes after allogeneic stem-cell transplantation

.

Haematologica

.

2019

;

104

(

5

):

929

-

936

.

19.

Bigarella

CL

,

Liang

R

,

Ghaffari

S

.

Stem cells and the impact of ROS signaling

.

Development

.

2014

;

141

(

22

):

4206

-

4218

.

20.

Pilo

F

,

Angelucci

E

.

A storm in the niche: iron, oxidative stress and haemopoiesis

.

Blood Rev

.

2018

;

32

(

1

):

29

-

35

.

21.

Naoum

FA

,

Espósito

BP

,

Ruiz

LP

, et al.

Assessment of labile plasma iron in patients who undergo hematopoietic stem cell transplantation

.

Acta Haematol

.

2014

;

131

(

4

):

222

-

226

.

22.

Duca

L

,

Cappellini

MD

,

Baronciani

D

, et al.

Non-transferrin-bound iron and oxidative stress during allogeneic hemopoietic stem cell transplantation in patients with or without iron overload

.

Am J Hematol

.

2018

;

93

(

9

):

E250

-

E252

.

23.

Angelucci

E

.

How I manage iron overload in the hematopoietic cell transplantation setting

.

Blood

.

2025

;

145

(

4

):

372

-

382

.

24.

Chai

X

,

Li

D

,

Cao

X

, et al.

ROS-mediated iron overload injures the hematopoiesis of bone marrow by damaging hematopoietic stem/progenitor cells in mice

.

Sci Rep

.

2015

;

5

:

10181

.

25.

Okabe

H

,

Suzuki

T

,

Uehara

E

,

Ueda

M

,

Nagai

T

,

Ozawa

K

.

The bone marrow hematopoietic microenvironment is impaired in iron-overloaded mice

.

Eur J Haematol

.

2014

;

93

(

2

):

118

-

128

.

26.

Nomani

H

,

Bayat

G

,

Sahebkar

A

, et al.

Atrial fibrillation in β-thalassemia patients with a focus on the role of iron-overload and oxidative stress: a review

.

J Cell Physiol

.

2019

;

234

(

8

):

12249

-

12266

.

27.

Naoum

FA

,

Espósito

BP

,

Zotarelli Filho

IJ

.

Impact of labile plasma iron and iron chelation on the viability of cultured mononuclear cells from patients undergoing autologous hematopoietic stem cell transplantation

.

Blood Res

.

2017

;

52

(

2

):

135

-

136

.

28.

Visani

G

,

Guiducci

B

,

Giardini

C

,

Loscocco

F

,

Ricciardi

T

,

Isidori

A

.

Deferasirox improves hematopoiesis after allogeneic hematopoietic SCT

.

Bone Marrow Transplant

.

2014

;

49

(

4

):

585

-

587

.

29.

Olivieri

J

,

Mancini

G

,

Goteri

G

, et al.

Reversal of poor graft function with iron-chelating therapy after allogeneic transplantation for severe aplastic anemia

.

Leuk Lymphoma

.

2016

;

57

(

4

):

965

-

968

.

30.

Forni

GL

,

Podestà

M

,

Musso

M

, et al.

Differential effects of the type of iron chelator on the absolute number of hematopoietic peripheral progenitors in patients with β-thalassemia major

.

Haematologica

.

2013

;

98

(

4

):

555

-

559

.

31.

Deeg

HJ

,

Spaulding

E

,

Shulman

HM

.

Iron overload, hematopoietic cell transplantation, and graft-versus-host disease

.

Leuk Lymphoma

.

2009

;

50

(

10

):

1566

-

1572

.

32.

Angelucci

E

,

Muretto

P

,

Nicolucci

A

, et al.

Effects of iron overload and hepatitis C virus positivity in determining progression of liver fibrosis in thalassemia following bone marrow transplantation

.

Blood

.

2002

;

100

(

1

):

17

-

21

.

33.

Coates

TD

,

Carson

S

,

Wood

JC

,

Berdoukas

V

.

Management of iron overload in hemoglobinopathies: What is the appropriate target iron level?

Ann N Y Acad Sci

.

2016

;

1368

(

1

):

95

-

106

.

34.

Puliyel

M

,

Mainous III

,

AG

,

Berdoukas

V

,

Coates

TD

.

Iron toxicity and its possible association with treatment of cancer: lessons from hemoglobinopathies and rare, transfusion-dependent anemias

.

Free Radic Biol Med

.

2015

;

79

:

343

-

351

.

35.

Cattoni

A

,

Capitoli

G

,

Casagranda

S

, et al.

Iron overload following hematopoietic stem cell transplantation: prevalence, severity, and management in children and adolescents with malignant and nonmalignant diseases

.

Transplant Cell Ther

.

2023

;

29

(

4

):

271.e1

-

271271.e12

.

36.

Vallejo

C

,

Batlle

M

,

Vázquez

L

, et al;

Subcommittee of Non-Infectious Complications of the Grupo Español de Trasplante Hematopoyético

.

Phase IV open-label study of the efficacy and safety of deferasirox after allogeneic stem cell transplantation

.

Haematologica

.

2014

;

99

(

10

):

1632

-

1637

.

37.

Jaekel

N

,

Lieder

K

,

Albrecht

S

, et al.

Efficacy and safety of deferasirox in non-thalassemic patients with elevated ferritin levels after allogeneic hematopoietic stem cell transplantation

.

Bone Marrow Transplant

.

2016

;

51

(

1

):

89

-

95

.

38.

Inati

A

,

Kahale

M

,

Sbeiti

N

, et al.

One-year results from a prospective randomized trial comparing phlebotomy with deferasirox for the treatment of iron overload in pediatric patients with thalassemia major following curative stem cell transplantation

.

Pediatr Blood Cancer

.

2017

;

64

(

1

):

188

-

196

.

39.

Sivgin

S

,

Baldane

S

,

Akyol

G

, et al.

The oral iron chelator deferasirox might improve survival in allogeneic hematopoietic cell transplant (alloHSCT) recipients with transfusional iron overload

.

Transfus Apher Sci

.

2013

;

49

(

2

):

295

-

301

.

40.

Angelucci

E

,

Muretto

P

,

Lucarelli

G

, et al;

Italian Cooperative Group for Phlebotomy Treatment of Transplanted Thalassemia Patients

.

Phlebotomy to reduce iron overload in patients cured of thalassemia by bone marrow transplantation

.

Blood

.

1997

;

90

(

3

):

994

-

998

.

41.

Neuberger

J

,

Patel

J

,

Caldwell

H

, et al;

Guidelines on the use of liver biopsy in clinical practice from the British Society of Gastroenterology, the Royal College of Radiologists and the Royal College of Pathology

.

Gut

.

2020

;

69

(

8

):

1382

-

1403

.