Laboratory Assessment of Patients with Hypereosinophilic Syndrome

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Abstract

Eosinophil-depleting therapies have shown benefit in women of childbearing age. Although the risks and benefits of these agents in pregnant women with hypereosinophilia have not been established, this study suggests that eosinophils are not required for normal human development. We followed up a patient with hypereosinophilic syndrome who became pregnant while receiving benralizumab (monoclonal antibody against IL-5R) on a clinical trial and delivered a healthy baby without eosinophils. The mother was a 36-year-old woman with hypereosinophilic syndrome and severe eosinophilic gastrointestinal involvement. She was unexpectedly found to be pregnant at a routine benralizumab administration visit (week 128). After discussion with the National Institutes of Health Institutional Review Board, the National Institutes of Health Investigational New Drug sponsor, and AstraZeneca, she was allowed to continue benralizumab therapy. At 38 weeks of gestation, she delivered a healthy baby girl by primary cesarean section for failure to progress. APGAR scores were 8 and 9 at 1 and 5 minutes, respectively. Physical examination of the neonate was entirely normal. Complete blood cell count at birth showed a white blood cell count of 22,500/L with 0 eosinophils/L. Newborn screening revealed a mildly elevated thyroid-stimulating hormone level (with normal free T4 level) that decreased over the ensuing months. The patient elected not to breast-feed. The baby's growth and development have been within normal limits. She has been healthy (no sick visits) without eczema, food allergy, or other evidence of atopic disease. Babys absolute eosinophil count remained undetectable until age 7 months at which time it was 228/L. Repeat absolute eosinophil count at age 1 year was 258/L. Platelets began to rise at age 1 month, peaking at age 7 months at 723 k/L before returning to near-normal values (492 k/L) at 1 year. The remainder of her complete blood cell count has been consistently within normal limits. Peripheral blood smear review and flow cytometric analysis of whole blood at age 1 year confirmed the presence of phenotypically normal eosinophils. Although limited to a single case, the current report clearly demonstrates that eosinophils are not essential for normal human development in utero through age 1 year. The 7-month delay in detectable peripheral eosinophils is consistent with the nonhuman primate postpartum data but slightly longer than the 3 to 6 months reported in benralizumab-treated patients following discontinuation of therapy. Elevated eosinophil counts at age 3 months have been associated with atopic disease in childhood. It is interesting that, despite a strong family history of early atopic disease, the child has had no evidence of atopy to date. Although the transient increase in platelet count remains unexplained, reactive thrombocytosis is common in the first 2 years of life and typically resolves spontaneously without clinical consequences. This is a first report of the case of a healthy child born to a mother receiving benralizumab throughout pregnancy and supports the hypothesis that eosinophils are not essential for normal human development. Although no safety signals were identified, more data are clearly needed to establish the risks and benefits of benralizumab and other eosinophil-depleting therapies in pregnancy.