Transfusion and Apheresis Science 49 (2013) 295–301

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Transfusion and Apheresis Science

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The oral iron chelator deferasirox might improve survivalin allogeneic hematopoietic cell transplant (alloHSCT) recipientswith transfusional iron overload

1473-0502/$ - see front matter � 2013 Elsevier Ltd. All rights reserved.http://dx.doi.org/10.1016/j.transci.2013.07.004

⇑ Corresponding author. Address: Department of Hematology, Facultyof Medicine, Erciyes University, Kayseri 38039, Turkey. Tel.: +903522076666; fax: +90 3524379348.

E-mail address: serdarsvgn@gmail.com (S. Sivgin).

Serdar Sivgin a,⇑, Suleyman Baldane b, Gulsah Akyol a, Muzaffer Keklik a, Leylagül Kaynar a,Fatih Kurnaz a, Cigdem Pala a, Gokmen Zararsiz c, Mustafa Cetin a, Bulent Eser a, Ali Unal a

a Dedeman Stem Cell Transplantation Hospital, Department of Hematology, Faculty of Medicine, Erciyes University, Kayseri, Turkeyb Department of Internal Medicine, Faculty of Medicine, Erciyes University, Kayseri, Turkeyc Department of Biostatistics, Faculty of Medicine, Erciyes University, Kayseri, Turkey

a r t i c l e i n f o a b s t r a c t

Article history:Received 24 December 2012Accepted 3 July 2013

Keywords:Allogeneic haematopoietic stem celltransplantationDeferasiroxIron overloadSurvival

Introduction: Iron overload (IO) has been shown to be an important cause of mortality andmorbidity in patients who underwent allogeneic hematopoietic stem cell transplantation(alloHSCT). This study aimed to evaluate the possible effect of oral iron-chelation treat-ment (deferasirox) on survival in alloHSCT recipients in the posttransplant period.Materials and methods: A total of 80 alloHSCT recipients with IO were analyzed, retrospec-tively. Pretransplant and posttransplant data were obtained from the patients’ files.Patients were divided into two groups. Group 1; patients who did not receive any chelatortreatment due to side effects or compliance problems. These patients were treated by phle-botomy. Group 2 consisted of patients who received deferasirox treatment.Results: The median treatment duration with deferasirox was 122 days (min–max:91–225). The iron chelating treatment significantly reduced serum ferritin levels administeredat a dosage of 20–30 mg/kg/day (p < 0.001). The median OS in Group 1 was found 16.0(min–max:1.0–63.0) months and 25.0 (min–max:3.0–72.0) months in Group 2. In univar-iate and multivariate analysis, patients in Group 1 showed poorer OS compared to those inGroup 2 with an increase in risk of death (HR:3.22, min–max:1.67–6.23, p = 0.001 andHR:3.51,, min–max:1.75–6.99, p < 0.001; respectively). The median DFS in Group 1 wasfound 11.0 (min–max:3.0–24.0) months and 22.0 (min–max:8.0–43.0) months in Group2. The difference was found statistically significant (p = 0.023). The other factors that wefound significant difference in multivariate analysis between groups were; presence ofacute GVHD (patients with aGVHD had increased risk of death compared to patients with-out aGVHD (HR:2.49, min–max: 1.32–4.69, p = 0.005), chronic GVHD (HR:2.57, min–max:1.23–5.41, p = 0.013), median interval to tx (HR: 2.23, min–max:1.17–4.26,p = 0.015) and HLA match (HR:3.01, min–max:1.35–6.73, p = 0.007)Conclusion: Oral deferasirox (Exjade) treatment may improve survival in patients with ironoverload who underwent alloHSCT.

� 2013 Elsevier Ltd. All rights reserved.

1. Introduction

Transfusional iron overload (IO) increases the risk ofinfections, veno-occlusive disease and hepatic dysfunctionin the post transplant period. The current data established

296 S. Sivgin et al. / Transfusion and Apheresis Science 49 (2013) 295–301

that IO was associated with increased the risk ofnonrelapse-mortality following HCT and might influencethe risk of acute and chronic graft versus host disease(GVHD) [1–3]. The main cause for HCT recipients develop-ing IO, both allogeneic and autologous could be consideredas exposure to RBC transfusions, both during the initialtreatment of their disease and in the post transplant peri-od. The data for administration of iron-chelating agents inhematological disorders (thalassemia, myelodysplasticsyndrome, aplastic anemia) confirmed the efficacy andsafety profiles of the treatment modalities [4–7]. On theother hand; evidence of the efficacy of chelation therapyfor reducing the morbidity and mortality associated withiron overload has widely been obtained from studies ofpatients with b-thalassemia major [8,9]. It is, however,currently it remains unclear whether the data can betranslated directly into practical use for alloHSCT recipi-ents because of limited evaluation and experience in thispopulation [10].

2. Patients and methods

This study was performed in Erciyes Stem Cell Trans-plantation Hospital, Erciyes University, Kayseri, Turkey;retrospectively. A total of 80 alloHSCT recipients with IOwho underwent alloHSCT from April 2004 to August2011 were included in the study. During the chemotherapyor supportive care period before HSCT, ferritin level wasmeasured monthly, and an iron-chelating agent wasstarted when the serum ferritin level was over 1000 ng/ml. Ferritin levels obtained within one month prior toHSCT was used for the analysis.

Patients with a pretransplant ferritin level P1000 ng/ml were included in the study. The patients were dividedinto two groups. In Group 1; patients with IO and whodid not receive chelator treatment because of poor compli-ance (non-treatment group) were included; and in Group2; patients with IO and who received deferasirox treat-ment (treatment group) were included. These two groupswere compared for posttransplant prognosis and survivalwhich could be related with complications of iron burden.Patients with a serum ferritin level <1000 ng/ml were ex-cluded from the study. We retrospectively reviewed med-ical records related to complications of alloHSCT, includingabnormality in liver function test, veno-occlusive disease(VOD), sepsis, CMV or other viral infections, acute respira-tory distress syndrome (ARDS), GVHD, transplant-relatedmortality (TRM), disease-free survival (DFS) and overallsurvival (OS). Platelet engrafment was defined as; theday on which platelet count exceeds 20,000/mm3 and neu-trophil engraftment; the day on which neutrophil countexceeds 500/mm3 for at least 3 days consecutively. All pa-tients’ data were obtained from the patient files by thesame physicians. The study was approved by the local ethiccommittee of Erciyes University.

3. Treatment and prophylaxis strategy

Treatment and prophylaxis regimens were obtainedfrom patient files and standard recorded criteria. All pa-

tients that underwent alloHSCT were accommodated insingle, central hepa-filtered rooms until time of discharge.Cyclosporin was administered as prophylactic regimen forGVHD. Cyclosporin was started as intravenously at adosage of 3 mg/kg per day, for 3 weeks, and later orallyat 4–5 mg/kg as maintenance therapy. Dose adjustmentwas made according to the plasma cyclosporin level, GVHDpresence and any reported side-effects. In the first 4 weeksof the post-transplant period, antibacterial (moxifloxacin1 � 400 mg/day) and antiviral (valacyclovir 1 � 500 mg/day) prophylactic regimens were administered. For anti-fungal prophylaxis, fluconazole 2 � 200 mg/day was givenin the post-transplant period until 75th day following thetransplant. Trimethoprim and sulfametoxazol treatmentwas given at a dose of 160 mg and 800 mg, respectively,twice a day, twice weekly for Pneumocystis jirovecii pro-phylaxis after the engraftment was achieved until day180. Patients were followed by weekly visits for the firstmonth and biweekly for 3 months. CMV-IFAT and CMV-PCR tests were performed in all visits until day 100. Pre-emptive treatment was administered in patients for whomCMV viremia was suspected.

4. Statistical analysis

SPSS Statistics 20.0 (IBM-SPSS Inc., Chicago, IL) softwarewas used for data analysis. Shapiro–Wilk’s test was usedand histograms, q–q plots were examined to assess thedata normality. To compare te differences between groups,a two-sided independent samples t test or Mann–WhitneyU tests were used for continuous variables and Chi-Squareanalysis were used for categorical variables. Values are ex-pressed as frequencies and percentages or median and25th-75th percentiles. Spearman’s test was used for corre-lation analysis. Survival probabilities were estimated usingKaplan–Meier method and comparisons were performedusing Log-rank test. Moreover, univariate and multivariatecox regression analysis were applied to identify the mostsignificant risk factors. To determine the independent riskfactors, variables significant at p < 0.20 on univariate anal-ysis were included into multivariate model and backwardstepwise selection was applied by using Wald statistic atp < 0.10 stringency level. Also, hazard ratios were givenwith 95% confidence intervals. p < 0.05 was considered sta-tistically significant.

5. Results

A total of 80 patients with IO who underwent alloHSCTwere included in the study. Of the patients 37(46.25%)were in were in Group 1 and 43(53.75%) were in Group2. The distribution of the diagnosis in Group 1 were; acutemyeloid leukemia(AML) in 19(51.4%) patients, acute lym-phoid leukemia(ALL) in 7(18.9%), aplastic anemia(AA) in8(21.6%), lymphoma in 2(5.4%) and myelodysplastic syn-drome in 1(2.7%) patient. In Group 2; AML in 26(60.5%) pa-tients, ALL in 11(25.6%), aplastic anemia in 3(7.0%), andmyelodysplastic syndrome(MDS) in 3(7.0%) patients. Themost common conditioning regimens were; CY/Bu in46(57.5%), Cy/TBI in 15(18.8%), ATG/Flu/Cy in 9 (11.3%),

S. Sivgin et al. / Transfusion and Apheresis Science 49 (2013) 295–301 297

Flu/Cy in 4(5.0%), ATG/Flu/Bu in 3 (3.8%) and other regi-mens in 3(3.8%) of the patients. The patient characteristicsare listed in Table 1.

The median treatment duration with deferasirox wasfound 122 days (min–max:91–225). The iron chelatingtreatment significantly reduced serum ferritin levels at adose of 20–30 mg/kg/day (p < 0.001). There was a reduc-tion in post-transplant transferrin saturation (TS), serumiron (Fe), aspartate transaminase (AST), gamma-glutamyltransferase (GGT) and total bilirubin levels, but the differ-ences were not statistically significant (p > 0.05). The ironparameters and other laboratory data of the patients inthe treatment group are shown in Table 2.

6. Renal and hepatic function tests

Serum creatinine levels of all patients were analyzedbefore and after treatment with deferasirox. No patienthad renal dysfunction due to side effects during the treat-ment period. The median creatinin levels before and aftertreatment was found to be 0.85 mg/dl (min–max:0.70–1.10) and 0.89 mg/dl (min–max:0.66–1.10), respectively.There was no statistically significant difference for creati-nin levels at the end of the treatment (p > 0.05). Incrementsin serum creatinine were transient and returned to base-line without any dose modification in our patients. Patientswith a high LFT for seven days during treatment under-went liver biopsy to exclude GVHD. The data for GVHD isshown in Table 3. The liver enzymes ALT, AST and totalbilirubins decreased after the treatment, but only the dif-ference in ALT was statistically significant (p < 0.05). Themost common adverse effects were nausea in 8(18.6%) pa-tients and vomiting in 3 (7%).

Table 1Patient characteristics.

Variables Group 1 Non-treatment(n = 37)

Age (years) 30.16 ± 11.00Gender (female/male) 19(51.4)/18(48.6)

Acute GVHD (yes/no) 12(32.4)/25(67.6)

Chronic GVHD (yes/no) 14(37.8)/23(62.2)

Relapse (yes/no) 11(29.7)/26(70.3)

Presence of infection (yes/no) 34(91.9)/3(8.1)

Preparative regimen (myeloablative/nonmyeloablative)

24(64.9)/13(35.1)

HLA match (full match/miss match) 31(83.8)/6(16.2)

Median interval to tx (h12/i 12 months) 22(59.5)/15(40.5)

Peritransplant mortality (yes/no) 7(18.9)/30(81.1)

Gender match (matched/mismatched) 25(67.6)/12(32.4)

Exitus (yes/no) 28(75.7)/9(24.3)

7. Deferasirox treatment and survival after HSCT

The median OS in Group 1 was found 16.0 (min–max:1.0–63.0) months and 25.0 (min–max:3.0–72.0)months in Group 2. A total of 42 patients, 28 (75.7%) inGroup 1 and 14 (32.6%) in Group 2 died in the posttrans-plant period. The causes of death in Group 1 were; infec-tions in 10 (27.0%) cases, relapsed disease in 5(13.5%)cases, chronic GVHD in 5 (13.5%) cases, engraftment failurein 4 (10.8%) cases and other causes in the remaining 4(10.8%) cases. In Group 2; 8 (18.6%) cases died due to infec-tions, 2 (4.7%) cases due to relapsed disease, GVHD in 2(4.7%) cases and other causes in the remaining 2 (4.7%)cases. In univariate and multivariate analysis, patients inGroup 1 showed poorer OS compared to those in Group 2with an increase in risk of death (HR: 3.22, min–max:1.67–6.23, p = 0.001 and HR: 3.51,, min–max:1.75–6.99, p < 0.001; respectively). The other factors that wefound significant difference in multivariate analysis be-tween groups were; presence of acute GVHD (patientswith aGVHD had increased risk of death compared topatients without aGVHD (HR:2.49, min–max: 1.32–4.69,p = 0.005), chronic GVHD (HR: 2.57, min–max: 1.23–5.41,p = 0.013), median interval to tx (HR: 2.23,min–max:1.17–4.26, p = 0.015) and HLA match (HR:3.01,min–max:1.35–6.73, p = 0.007)

The median DFS in Group 1 was found 11.0 (3.0–24.0)months and 22.0 (8.0–43.0) months in Group 2. The differ-ence was statistically significant (p = 0.023). In evaluatingDFS; univariate and multivariate analysis showed that pa-tients in Group 1 had significantly lower DFS comparedwith patients in Group 2 (HR:2.99, min–max: 1.10–8.11,p = 0.031 and HR:3.11, min–max:1.14–8.44, p = 0.026;respectively). Among patient characteristics; age was the

group Group 2 treatment group(n = 43)

p Total

31.05 ± 9.27 0.697 30.64 ± 10.0519(44.2)/24(55.8) 0.678 38(47.5)/

42(52.5)12(27.9)/31(72.1) 0.845 24(30.0)/

56(70.0)16(37.2)/27(62.8) 0.999 30(37.5)/

50(62.5)6(14.0)/37(86.0) 0.148 17(21.3)/

63(78.7)36(83.7)/7(16.3) 0.326 70(87.5)/

10(12.5)39(90.7)/4(9.3) 0.011 63(78.8)/

17(21.2)36(83.7)/7(16.3) 0.999 67(83.8)/

13(16.3)32(74.4)/11(25.6) 0.236 54(67.5)/

26(32.5)1(2.3)/42(97.7) 0.022 8(10.0)/

72(90.0)31(72.1)/12(27.9) 0.845 56(70.0)/

24(30.0)14(32.6)/29(67.4) <0.001 42(52.5)/

38(47.5)

Table 2Laboratory data for the treatment results.

Variables Pre-treatment Post-treatment p Normal ranges

Fe (lg/dL) 147.00(88.00–205.00) 118.00(78.00–216.00) 0.750 65–175(lg/dL)TIBC (lg/dL) 274.00(235.00–328.00) 276.00(235.00–348.00) 0.704 225–480 (lg/dL)Ferritin (ng/mL) 2684.20(1777.00–3653.00) 1097.00(824.60–2199.00) <0.001 7.0–276.8 (ng /mL)TS (%) 52.00(34.00–72.70) 43.00(29.00–71.00) 0.299 15–48 (%)ALT (u/L) 50.00(18.00–106.00) 29.00(19.00–59.00) 0.025 10–49 (u/L)AST (u/L) 34.00(24.00–47.00) 26.00(20.00–47.00) 0.229 0–34 (u/L)ALP (u/L) 89.00(72.00–160.00) 98.00(74.00–151.00) 0.664 45–129 (u/L)GGT (u/L) 82.00(43.00–238.00) 75.00(31.00–152.00) 0.131 0–73 (u/L)Total bil. (u/L) 0.69(0.44–1.10) 0.60(0.50–0.88) 0.438 0.3–1.2 (u/L)Direct bil. (mg/dl) 0.15(0.10–0.30) 0.17(0.10–0.26) 0.798 65–175 (u/L)Creatinine (mg/dl) 0.85(0.70–1.10) 0.89(0.66–1.10) 0.500 0.7–1.3 (u/L)

Values are expressed as median(25th–75th percentiles). Abbreviations: ALT: alanine transaminase; ALP: alkaline phosphatase; AST: aspartate transami-nase; GGT: gamma-glutamyl transferase; bil: bilirubin, Fe: iron; TIBC: total iron binding capacity; TS: transferrin saturation.

Table 3Patients’ data of the treatment group.

Number of RBC transfusions (packages, median,min–max)

7 (4–22)

Duration of treatment (median, min–max) 122.00(91.00–225.00)

Causes of mortality N,%Relapsed disease 2(14.3)Acute GVHD 1(7.1)Chronic GVHD 1(7.1)Infections 8(57.1)Other 2(14.3)

Side effects (yes/no) 14(32.6)/29(67.4)

Headache (yes/no) 1(2.3)/42(97.7)Nausea (yes/no) 8(18.6)/35(81.4)Vomiting (yes/no) 3(7.0)/40(93.0)Diarrhea (yes/no) 2(4.6)/41(95.4)Abdominal discomfort (yes/no) 1(2.3)/42(97.7)Hepatotoxicity (yes/no) 1(2.3)/42(97.7)

Values are expressed as n(%) or median(25th–75th percentiles).

298 S. Sivgin et al. / Transfusion and Apheresis Science 49 (2013) 295–301

only parameter for which significant difference was foundbetween groups (p = 0.049). The results are shown in Table4.

8. Peritransplant mortality (PTM)

Peritransplant mortality was defined as death within3 months after transplantation. In Group 1; a total of 7(18.9%) patients died within 100 days of alloHSCT and inGroup 2; one(2.3%) patient died. The difference amonggroups for PTM was statistically significant (p = 0.02).

Spearman correlation analysis established that thereductions in serum ferritin levels were significantly corre-lated with improved OS and DFS (Table 5). In contrast; OSand DFS were significantly correlated with improved ser-um hemoglobin levels after the treatment period.

9. Discussion

Under normal conditions, ferritin levels in the serumare low, but steadily increase in conditions of IO. Therefore,assessment of serum ferritin levels may serve as a simpleand widely used surrogate marker for body iron load. On

the other hand; inflammation, liver damage, infection,and GVHD, all can result in elevated serum ferritin levelsand, therefore should be considered as potential overesti-mation of iron load. Many studies documented the adverseprognostic impact of iron overload in patients undergoingHSCT for haematological malignancies and MDS. In a largeretrospective study, elevated pre-transplantation serumferritin levels were associated with a lower overall and dis-ease-free survival in patients undergoing myeloablativeallogeneic HSCT for acute leukaemia or MDS [11]. Pretrans-plant IO adversely affects survival, relapse-free survival,and mortality following both autologous HSCT [12–14].

The data in our study showed that patients in the treat-ment group had significantly improved OS (p < 0.001) nadDFS (p = 0.023) compared to those in non-treatment group.The Kaplan–Meier analysis of the data are shown in Figs. 1and 2; respectively.

Today we know that excessive amounts of iron cancause tissue damage which might cause protein oxidation,membrane lipid peroxidation, and nucleic acid modifica-tion, with conversion of hydrogen peroxide to reactive oxy-gen species [15]. Recent laboratory studies showed thatiron acquisition could be countered as an essential elementfor increased growth and virulence of Aspergillosis species[16]. This could be explained by the fact that iron is anessential element for all pathological microorganisms andthus, iron overload has the potential to increase trans-plant-related mortality (TRM) due to toxic death and lethalinfections in HSCT recipients especially invasive fungalinfections in patients with haematological malignancies[17–19]. In recent reports, a similar association was foundbetween invasive fungal infections and iron overload inallogeneic bone marrow recipients [20,21]. This could leadus to hypothesize that the hypoxic environment could betreated with iron chelating methods including phlebotomywhich would result in decreased risk of systemicinfections.

The analysis of treatment efficacy -on reducing serumiron parameters- showed that patients in the treatmentgroup had significantly lower levels of serum ferritin(p < 0.05).

In our study; despite the fact that presence of infectionwas not among the significant parameters on survival (HR:2.30, min–max:0.71–7.47, p = 0.165 for OS and HR:1.40,

Tab

le4

Uni

vari

ate

and

mul

tiva

riat

epr

ogno

stic

fact

ors

for

over

all

surv

ival

(OS)

and

dise

ase-

free

surv

ival

(DFS

)in

allo

HSC

Tre

cipi

ents

.

Var

iabl

esO

SD

FS

Un

ivar

iate

HR

(95%

CI)

pM

ult

ivar

iate

HR

(95%

CI)

pU

niv

aria

teH

R(9

5%C

I)p

Mu

ltiv

aria

teH

R(9

5%C

I)p

Age

(yea

rs)

1.01

(0.9

8–1.

04)

0.44

9–

–0.

94(0

.88–

1.00

)0.

057

0.94

(0.8

9–1.

00)

0.04

9G

ende

r(f

emal

e/m

ale)

1.80

(0.9

6–3.

35)

0.06

52.

15(1

.12–

4.13

)0.

022

1.57

(0.6

1–4.

09)

0.35

4–

–G

ende

rm

atch

(mis

mat

ched

/mat

ched

)1.

35(0

.72–

2.52

)0.

355

––

1.27

(0.4

7–3.

45)

0.63

5–

–A

cute

GV

HD

(yes

/no)

2.36

(1.2

8–4.

37)

0.00

62.

49(1

.32–

4.69

)0.

005

2.19

(0.8

3–5.

82)

0.11

5–

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hro

nic

GV

HD

(yes

/no)

1.95

(0.9

9–3.

84)

0.05

22.

57(1

.23–

5.41

)0.

013

1.44

(0.5

3–3.

90)

0.47

2–

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edia

nin

terv

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tx(>

12/<

12m

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51(1

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4.66

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004

2.23

(1.1

7–4.

26)

0.01

51.

30(0

.45–

3.72

)0.

628

––

Prep

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ive

regi

men

(mye

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––

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99(0

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)0.

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––

CD

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(<6/

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(0.6

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3.22

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6.99

)<0

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2.99

(1.1

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11)

0.03

13.

11(1

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026

Abb

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S. Sivgin et al. / Transfusion and Apheresis Science 49 (2013) 295–301 299

min–max:0.32–6.12, p = 0.657 for DFS); there was an in-creased risk for mortality in patients with any infectiousevent. We hypothesize that iron-chelation treatment couldprovide a less-toxic environment during and after treat-ment in the posttransplant period and duration of thetreatment should be prolonged according to not only ser-um ferritin levels but also patient compliance.

The data established that long-term red blood celltransfusion for the treatment of various chronic anemiasinevitably lead to the accumulation of iron in the body.During the last decade, several iron chelators have beendeveloped, designed to mobilize tissue iron by formingcomplexes that are excreted in the feces and/or urine. Def-erasirox (Exjade; Novartis Pharma) was developed as aonce-daily oral iron chelator through a rational drug devel-opment program and represents a new class of tridentateiron chelators. Deferasirox is currently approved in manycountries worldwide for the treatment of chronic ironoverload due to blood transfusions in patients agedP2 years.

The efficacy and safety of deferasirox has been evalu-ated in patients with -thalassemia and also in a wide rangeof patients with other underlying anemias, includingmyelodysplastic syndromes (MDS), sickle cell disease(SCD), aplastic anemia (AA), Diamond-Blackfan anemia(DBA), and various other rare anemias [22–25].

The management of posttransplantation IO in adult HCTrecipients has not been well studied. Although long-termfollow-up guidelines recommend screening with serumferritin measurements 1 year post-HCT [26], there are noclear-cut criteria for when and how to treat iron overload.In this manner, treatment options include phlebotomy andiron chelation therapy. Hereby, phlebotomy can be consid-ered the treatment of choice because of its safety and effi-cacy, but it may not be feasible in patients with coexistinganemia.

Recently; Taher et al. [27] conducted a prospectivestudy assessing the efficacy and safety of deferasirox innontransfusion-dependent thalassemia (NTDT) patientswith iron overload. In the study they reported that ironchelation with deferasirox significantly reduced iron over-load in NTDT patients with a frequency of overall adverseevents similar to placebo.

In our study; the starting dosage for deferasirox wasgenerally 20 mg/kg once daily. According to the tolerabilityand level of serum ferritin; deferasirox was administeredup to 30 mg/kg/day. Many of the patients had good compli-ance to deferasirox during administration and side effectswere not different from those mentioned above.

In a recent study; Lee et al. [28] investigated the associ-ation of pre-transplant ferritin level with complicationsand survival after allogeneic HSCT in pediatric population,and evaluated the efficacy of iron-chelating therapy beforeHSCT. As a result; they found that elevated serum ferritinlevel was associated with increased TRM and decreasedsurvival, and the analysis of the IC group suggested thebenefit of iron-chelating therapy to improve the outcomeof HSCT. They used deferoxamine (Desferrioxamine mesy-late, Mayne Pharma Pty Ltd, Melbourne, Australia) as theiron-chelating agent with 30–50 mg/kg, which was infusedfor 8 h subcutaneously, 5–7 times a week.

Table 5Spearman correlation coefficients revealing the correlations between iron parameters and survival in alloHSCT recipients.

Variables Hemoglobin DFe DTIBC DFerritin DTS

Overall survival (months) 0.412** �0.277 �0.141 �0.301* �0.097Disease free survival (months) 0.414** �0.293 �0.162 �0.316* �0.102

* p < 0.05,** p < 0.01.

Fig. 1. Kaplan–Meier analysis of overall survival (OS)) of alloHSCT recipients in both treatment and non-treatment groups. OS was significantly poorer innon-treatment group compared to those in treatment group (p < 0.001).

Fig. 2. Kaplan–Meier analysis of disease-free survival (DFS) of alloHSCT recipients in both treatment and non-treatment groups. DFS was significantlypoorer in non-treatment group compared to those in treatment group (p = 0.023).

300 S. Sivgin et al. / Transfusion and Apheresis Science 49 (2013) 295–301

S. Sivgin et al. / Transfusion and Apheresis Science 49 (2013) 295–301 301

Iron chelation treatment still remains doubtfull partsfor practice in alloHSCT recipients. Further prospectivestudies are needed to ascertain whether deferasirox canimprove the morbidity and mortality of patients undergo-ing alloHSCT.

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