Influence of Serum Ferritin on Transplant-related Outcomes and Complications in Children Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

Yoon Jung Lee; Hyung Rae Cho; Keun Wook Bae; Meerim Park; Kyung Nam Koh; Joon Sup Song; Ho Joon Im; Jong Jin Seo

doi:10.5045/kjh.2009.44.4.227

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Lee, Cho, Bae, Park, Koh, Song, Im, and Seo: Influence of Serum Ferritin on Transplant-related Outcomes and Complications in Children Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

Original Article

Korean J Hematol 2009;44(4):227-236.

Published online: 20 December 2009

DOI: https://doi.org/10.5045/kjh.2009.44.4.227

Influence of Serum Ferritin on Transplant-related Outcomes and Complications in Children Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

Yoon Jung Lee, M.D.¹, Hyung Rae Cho, M.D.¹, Keun Wook Bae, M.D.¹, Meerim Park, M.D.¹, Kyung Nam Koh, M.D.¹, Joon Sup Song, M.D.², Ho Joon Im, M.D.^1,, Jong Jin Seo, M.D.¹

¹Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

²Kangdong Sacred Heart Hospital, College of Medicine, Hallym University, Seoul, Korea

Correspondence to：Ho Joon Im, M.D. Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine 388-1, Pungnap-2dong, Songpa-gu, Seoul 138-736, Korea Tel: ＋82-2-3010-3371, Fax: ＋82-2-473-3275 E-mail: hojim@amc.seoul.kr

Received 6 August 2009 Revised 25 September 2009 Accepted 25 September 2009

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background

Iron overload, primarily related to RBC transfusions, is a relatively common complication in hematopoietic stem cell transplant (HSCT) recipients. There are emerging data from retrospective studies that iron overload can significantly increase the risk of nonrelapse mortality after allogeneic HSCT.

Methods

One hundred and five children who received allogeneic HSCT between Jan 2004 and Feb 2009 at Asan Medical Center were analyzed. For indirect estimation of body iron stores, we measured serum ferritin serially in HSCT recipients at pre-transplant, 3 months and 1 year post-transplant. We also analyzed prevalence of hyperferritinemia, correlation of iron overload and transplant-related outcomes and complications.

Results

The prevalence of hyperferritinemia (≥1,000 μg/L) at pre-HSCT, 3 months and 1 year post-HSCT were 66.7% (70/105), 78% (71/91) and 40.9% (27/66), respectively. Children with hyper-ferritinemia (≥1,000 μg/L) at 3 months post-HSCT had worse 2-year OS (79% vs 95%; P=0.023) than those in the low ferritin group (＜1,000 μg/L). Very high levels (VHL) of ferritin (≥3,000 μg/L) at 3 months post-HSCT were associated with increased incidence of treatment related mortality (23% vs 2%, P=0.001) and acute graft-versus-host disease (54% vs 26%, P=0.007) in univariate analysis. VHL of ferritin remained significant in multivariate analysis.

Conclusion

Hyperferritinemia at 3 months post-HSCT had adverse impact for transplantation outcome in patients undergoing allogeneic stem cell transplantation. These results suggest that the screening and adequate treatment of iron overload in HSCT recipients might be helpful to improve the HSCT outcomes.

Keywords: Iron overload, Ferritin, Hematopoietic stem cell transplantation, Pediatrics

References

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Fig. 1.

Change of serum ferritin level before and after HSCT.

Fig. 2.

Overall survival (OS) according to serum ferritin level at pre-HSCT.

Fig. 3.

Overall survival (OS) according to serum ferritin level at 3 months post-HSCT.

Fig. 4.

Cumulative incidence of treatment related mortality (A) and acute graft-versus-host disease (B) according to serum ferritin level at 3 months post-HSCT.

Table 1.

Clinical characteristics of 105 pediatric allogeneic HSCT recipients

Clinical characteristics	No. of patients
Gender
Male	67
Female	38
Underlying diseases
Hematologic malignancies	81
AML		42
ALL		28
MDS		6
ABL		3
CML		2
Non-malignant diseases	24
Aplastic anemia		10
Immunodeficiency		4
Fanconi anemia		3
Metabolic disease		3
HLH		3
Pure red cell anemia		1
Donors
Sibling	25
Unrelated	80
Conditioning
With TBI	29
Without TBI	76
Myeloablation
Yes	86
No	19
VOD
Yes	6
No	99
aGVHD (≥Grade 2)
Yes	33
No	69
cGVHD
Yes	37
No	58

Abbreviations: AML, indicates acute myeloblastic leukemia; ALL, acute lymphoblastic leukemia; MDS, myelodysplastic syndrome; ABL, acute biphenotypic leukemia; CML, chronic myeloblastic leukemia; HLH, hemophagoctic lymphohistiocytosis; VOD, venoocclusive disease; aGVHD, acute graft-versus-host-disease; cGVHD, chronic graft-versus-host disease.

Table 2.

Number of packed red cell transfusions by serum ferritin level

	Serum ferritin
	Low (＜1,000 μg/L)	High (≥1,000 μg/L	P-value
Pre-HSCT	6.7±4.3	16.8±13.3	＜0.005
3 months post-HSCT	3.1±1.8	6.0±5.4	0.021
1 year post-HSCT	3.9±3.1	9.9±9.0	＜0.005

Table 3.

Clinical characteristics of pediatric allogeneic HSCT recipients according to serum ferritin level at pre-HSCT and 3 months, 1 year post-HSCT

	Serum ferritin
Characteristic	Pre-HSCT			3 months post-HSCT			1 year post-HSCT
	Low	High	P-value	Low	High	P-value	Low	High	P-value
Gender			0.082			0.597			0.823
Male	23	44		12	48		24	20
Female	12	26		8	23		15	7
Underlying diseases			0.025			0.24			1
Hematologic malignancies	22	59		13	56		30	21
Non-malignant diseases	13	11		7	15		9	6
Donors			0.063			0.227			0.078
Sibling	7	18		7	14		12	3
Unrelated	28	52		13	57		27	24
Conditioning			0.01			0.002			0.006
With TBI	4	25		0	23		4	11
Without TBI	31	45		20	48		35	16
Myeloablation			0.424			0.55			0.729
Yes	27	59		17	55		34	22
No	8	11		3	16		5	5

Abbreviation: TBI, indicates total body irradiation.

Table 4.

Complications after HSCT according to serum ferritin level

	No. of patients/Evaluable patients
	Pre-HSCT			3 months post-HSCT			1 year post-HSCT
	Low	High	P-value	Low	High	P-value	Low	High	P-value
VOD	3/35	3/70	0.661	0/20	3/71	0.591	0/39	1/27	0.409
aGVHD	13/34	20/68	0.501	6/20	25/71	0.792	9/39	9/27	0.408
cGVHD	13/33	24/62	1	4/20	33/70	0.039	12/39	13/27	0.199
CMV reactivation	13/35	25/70	1	7/20	26/71	1	10/39	10/27	0.416
CMV disease	2/35	4/70	1	0/20	5/71	0.349	0/39	1/27	0.409
ARDS	2/35	2/70	0.407	1/20	2/71	0.53

Abbreviations: Low, serum ferritin level ＜1,000 μg/L; High, serum ferritin level ≥1,000 μg/L; VOD, indicates veno-occlusive disease; aGVHD, acute graft-versus-host disease; cGVHD, chronic graft-versus-host disease; CMV, cytomegalovirus; ARDS, acute respiratory distress syndrome.

Table 5.

Causes of treatment-related mortality in patients with hyperferritinemia (≥1,000 μg/L) at 3 months after HSCT

Causes of death	No.
cGVHD	3
Fungal infection	2
VOD	1
Post transplant BO	1
Total	7

Abbreviations: cGVHD indicates chronic graft-versus-host disease; VOD, veno-occlusive disease; BO, bronchiolitis obliterance.

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