Retrospective, Nested, Case-Control Study of the Association between Transfusion Frequency and Potential Complications of Iron Overload in Patients with Myelodysplastic Syndrome and Other Acquired Hematopoietic Disorders.
Authors: Delea Thomas E. , Hagiwara May , Phatak Pradyumna D. 
Published: October 2019

Abstract
Background Patients with myelodysplastic syndrome (MDS) and other acquired hematopoietic disorders frequently require chronic transfusion therapy. Although red cell transfusions are known to cause iron overload, data on the risk of iron-related complications in these patients are limited.
Methods We conducted a retrospective, case-control study of the association between complications of iron overload and exposure to transfusions among patients in a large US health-insurance claims database with a diagnosis of MDS and other hematopoietic disorders (ICD-9-CM 238.7: neoplasm of uncertain behavior of other lymphatic and hematopoietic tissues) between 1997 and 2004. Patients with <1 year of claims data prior to this diagnosis (“diagnosis date”), <40 years of age as of diagnosis date, with potential complications of iron overload prior to the diagnosis date, or with diagnoses of thalassemia (ICD-9-CM 282.4) or sickle cell disease (ICD-9-CM 282.6), or were excluded. Complications included: cardiomyopathy/heart failure (ICD-9-CM 425, 428), conduction/rhythm disorders (ICD-9-CM 426, 427), diabetes (ICD-9-CM 250 or antidiabetes medication), and liver disease (ICD-9-CM 571, 572.2, 572.3, 572.8 573.0, 573.8, 573.9, 789.1, 789.5, v427). Cases were defined as subjects with complications of iron overload after the diagnosis date and were compared with a corresponding number of controls (patients without complications) with respect to receipt of transfusions, controlling for other demographic and clinical characteristics (e.g., age, sex, region, plan type, comorbidities, medical care utilization and expenditures), using multivariate conditional logistic regression.
Results A total of 7113 patients met inclusion criteria. From these, we identified 511 patients with one or more complications after the diagnosis date and a corresponding number of controls. Patients with complications were older (mean age 60 vs 56 years, p<.0001) and had more comorbidities (mean Charlson index 2.8 vs 1.4, p<.0001) than those without complications. Mean (max) follow-up was 6.8 (46.0) months. Among those with complications, 22% received one or more transfusion post-diagnosis, compared with 5% of those without complications.
Few patients in either group (<1%) received deferoxamine. After controlling for demographic and clinical characteristics using multivariate conditional logistic regression, risk of potential complications of iron overload was significantly associated with receipt of transfusions (Odds ratio [OR]=2.909, p=.0008). Results for specific potential complications were as follows: cardiomyopathy or heart failure (OR 1.616, p=.2955), conduction/rhythm disorders (OR=4.135, p<.0005), diabetes (OR=5.063, p=.0025), and liver disease (OR=3.325, p=.0008). Risk of complications also was associated with the number of transfusion episodes (unique days on which transfusions were received) (OR=1.096, p=.0483).
Conclusions In patients with MDS and other acquired hematopoietic disorders, patients receiving transfusions are at increased risks of potential complications of iron overload. Iron chelation therapy may be appropriate especially for those with a relatively favorable prognosis.