Abstract

Background

Chronic transfusion support plays a key role in survival and quality of life for patients with hematological disorders. However, transfusion-related iron overload (TRIO) is a significant cause of morbidity and mortality in these patients.Adequate iron overload (IO) screening and use of iron chelators, if necessary, is now standard practice in chronically transfused individuals such as hemoglobinopathy patients. Screening practices for IO for patients receiving multiple red blood cell (RBC) transfusions for other reasons (e.g. cancer) are unknown.

Objective

This two part study aimed to detect pediatric (Jaffer et al., 2012) and adult populations at risk for TRIO and to evaluate and compare current screening practices.

Methods

Children (≤ 18 years) and adults (> 18 years) receiving at least 1 RBC transfusion from January 1, 2008 to December 31, 2011 at a tertiary care academic institution were identified using a transfusion registry database. Only those receiving chronic RBC transfusions were included in the study. Chronic transfusion was defined as ≥20 units of RBC or ≥ 20 RBC transfusions dosed at 15ml/kg within 12 consecutive months where transfusions were not given in the setting of an operating room, trauma or surgical procedures, not given 7 days prior/post-surgical procedures and not all given in one day. An adjudicator resolved study inclusion ambiguity. The analysis excluded hemoglobinopathy patients.

Medical records were reviewed to collect patient demographics, diagnosis, and to evaluate IO screening practices and frequency of iron chelation therapy.

Results

A total of 343 patients met the eligibility criteria: 27 pediatric and 316 adult patients, with mean ages of 8.1 years (SD 5.7) and 62 years (SD 12.6), respectively. Table 1 summarizes demographics, number of transfusions, and IO screening and results. Ferritin levels were checked for 12 (44%) pediatric and 227 (72%) adult patients: 2 (17%) pediatric and 30 (13%) adult patients had values<500 μg indicating no further TRIO screening was required. In the pediatric population, 81% had a cancer diagnosis, and just under a third were tested for ferritin, whereas 64% of the adults had cancer, with nearly two-thirds tested for ferritin. A statistically significant difference was observed in the percentage of pediatric and adult cancer patients screened for IO. Of those cancer patients screened, ferritin level > 500 occurred in 71% of pediatric and 85% of adult patients, with an iron chelator reported in 1 adult. Total RBC transfusions ranged from 20 to 44 with a median of 26.5 for pediatrics and 20 to 176 with a median of 31 for adults.

Table 1
 Pediatric Adult 
 Cancer n=22 Other n=5 Cancer n=201 Other n=115 
Female
Male
Age-mean(SD) 
7
15
8.4 (6.18) 
0
5
7.2 (2.95) 
87
114
59.0 (15.95) 
48
67
67.2 (16.4) 
RBC Transfusions
median(Q1-Q3) 
26.5 (22-34) 28 (27-52) 31 (25-44) 50 (29-72) 
Estimated Tranfusional Iron Burden (g)
median(Q1-Q3) 
7.95 (6.6-10.2) 8.4(8.1-15.6) 9.3 (7.5-13.2) 15 (8.7-21.6) 
8.1 (6.6-10.5) 10.5 (7.8-16.5) 
No. with Ferritin screen ordered
n(%) 
7/22 (31.82) 5/5 (100) 123/201 (61.19)
(p=0.008)* 
104/115 (90.43)
(p=1.00)*  
Most recent FL** (for those with Ferritin Screen ordered)
median(Q1-Q3) 
1552 (362-4165) 1981 (1249-2625) 1671 (702-2732) 1976 (1205-3491) 
No. with Ferritin >500 n(%) 5/7 (71.43) 5/5 (100) 104/123 (84.55) 93/104 (89.42) 
No. receiving IC therapy n(%) 0/5 (0) 2/5(40) 1/104 (0.96) 33/93 (35.48) 
 Pediatric Adult 
 Cancer n=22 Other n=5 Cancer n=201 Other n=115 
Female
Male
Age-mean(SD) 
7
15
8.4 (6.18) 
0
5
7.2 (2.95) 
87
114
59.0 (15.95) 
48
67
67.2 (16.4) 
RBC Transfusions
median(Q1-Q3) 
26.5 (22-34) 28 (27-52) 31 (25-44) 50 (29-72) 
Estimated Tranfusional Iron Burden (g)
median(Q1-Q3) 
7.95 (6.6-10.2) 8.4(8.1-15.6) 9.3 (7.5-13.2) 15 (8.7-21.6) 
8.1 (6.6-10.5) 10.5 (7.8-16.5) 
No. with Ferritin screen ordered
n(%) 
7/22 (31.82) 5/5 (100) 123/201 (61.19)
(p=0.008)* 
104/115 (90.43)
(p=1.00)*  
Most recent FL** (for those with Ferritin Screen ordered)
median(Q1-Q3) 
1552 (362-4165) 1981 (1249-2625) 1671 (702-2732) 1976 (1205-3491) 
No. with Ferritin >500 n(%) 5/7 (71.43) 5/5 (100) 104/123 (84.55) 93/104 (89.42) 
No. receiving IC therapy n(%) 0/5 (0) 2/5(40) 1/104 (0.96) 33/93 (35.48) 
*

p-value: result comparing the same diagnosis group between pediatric and adult patients

**

Normal ferritin range 140 - 400 μg/L

Conclusion

Despite high rates of RBC transfusion, screening for TRIO was inconsistent. Although information regarding reasons for not screening for TRIO or not treating with chelation therapy was not collected, the possibilities include a lack of awareness of the risk of TRIO and lack of access to ferriscan and/or to oral iron chelator in Canada for conditions other than hemoglobinopathy and a select subset of MDS cases. Considering TRIO presents an additional, yet unidentified, co-morbidity of cancer therapy and that the therapy (e.g. anthracyclines) may potentiate the end organ effect of TRIO, it is vital to develop strategies to evaluate cancer patients at risk for TRIO and ensure they have access to appropriate iron chelation therapy. Research is needed to explore the comorbidities associated with failure to treat TRIO and to identify barriers to treatment so cancer patients can receive optimal care.

Disclosures:

Leber:Novartis Canada: Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau. Heddle:Canadian Blood Services and Health Canada: Research Funding.

Author notes

*

Asterisk with author names denotes non-ASH members.