Transfusion Related Alloimmunization In Children: Epidemiology and Effects Of Chemotherapy (TRACE-EC Study)

Pediatric hematology/oncology patients require numerous transfusions during myelosuppressive chemotherapy which may lead to red cell (RC) alloantibody formation. However, transfusion related alloimmunization in children has not been studied except in the neonatal and hemoglobinopathy populations. Variability of RC alloimmunization rates by cancer diagnosis has not been described and the immunosuppressive effect of chemotherapy on alloimmunization is unknown. One study has shown a reduction in IgM and IgG in pediatric leukemia patients receiving chemotherapy (Martín Ibáñez et al Allergol Immunopathol 2003); hence, one could hypothesize that chemotherapy could suppress the alloimmune response. This study aimed to: 1) report the rate of alloimmunization in children receiving RC transfusions, 2) compare these rates between oncology and non-oncology patients, and 3) compare these rates based on cancer diagnosis and stage.

TRACE-EC was a retrospective observational study using a large database containing patient blood utilization information from 3 academic hospitals. Patient inclusion criteria included: age ≥ 4 months and ≤ 17 years old at the time of receiving ³ 1 non-autologous RC transfusion between April 2002 and November 2011. Diagnoses were identified using ICD10 codes. Patients with immune disorders were excluded. Study patient cohort included patients with malignancies and recipients of hematopoietic stem cell transplant (HSCT) to treat a malignancy; control cohort included non-oncology patients who met the inclusion criteria. Patient and blood utilization data were extracted from the database, and chemotherapy data were obtained by retrospective review of patient medical records. Study patients were stratified for analysis based on cancer diagnosis and stage (surrogate for chemotherapy intensity). Cancer stage was categorized as low level (I, II, standard risk) and high level (III, IV, V, high risk). Control patients with hemoglobinopathy were analyzed separately due to their high alloimmunization rate (Aygun et al. Transfusion 2002).

There were 1253 patients in the study: 944 in control group; 309 in study group. Females made up 49% of control group and 43% of study group. Mean age was 8.6 years (SD 6.4) in control group, and 7.2 years (SD 5.5) in study group. The frequency of alloimmunization and RC utilization by diagnosis in control and study groups is summarized in Table 1. Overall, a statistical difference in the frequency of alloimmunization was not demonstrated between control patients (4.3%) and study patients (5.5%), p=0.40. When hemoglobinopathy patients were removed from the control group, frequency of alloimmunization decreased to 3.8% (p=0.19). Alloimmunization occurred in 5.4% (10/186) and 5.7% (7/123) of patients with a high level and low level cancer stage respectively, p=0.91. HSCT recipients had a higher rate of alloimmunization than non-HSCT but this was not statistically significant (11.4% vs. 4.5% respectively, p=0.07). Alloimmunization occurred in 4.9% of patients with hematologic malignancies and 7.1% of patients with solid tumors (p=0.44).

This is the first study that has looked at the frequency of alloimmunization in transfused pediatric patients by diagnostic category and cancer stage. The study confirmed high alloimmunization rates in hemoglobinopathy patients. No difference in the frequency of alloimmunization was observed based on cancer diagnosis, stage, or HSCT status. Further studies are needed to assess the effect on alloimmunization of the high RC utilization rate shown in cancer patients and HSCT recipients.

Heddle: Health Canada: Research Funding; Canadian Blood Services: Membership on an entity’s Board of Directors or advisory committees, Research Funding; CIHR: Research Funding.