Ultrastructural changes in peripheral blood neutrophils in a patient receiving ganciclovir for CMV pneumonitis following allogenic bone marrow transplantation

Abstract

A 13-year-old splenectomized, multitransfused β-thalassemia major, male patient received an allogenic BMT from his HLA-compatible brother after suffering grade III regimen-related pulmonary toxicity. He developed features of CMV pneumonitis with positive pp65 CMV antigenemia involving 2.5% peripheral blood neutrophils from day +46. The patient received intravenous immunoglobulin and ganciclovir 5 mg/kg intravenously twice daily. His neutrophil count was maintained above 1 × 10⁹/l by G-CSF 5 μg/kg subcutaneously as and when required. From day 7 onwards following twice daily ganciclovir his peripheral blood smear started showing isolated cytoplasmic inclusions, 1–3 per neutrophil, 3–5 μ in diameter, involving 2–3% of the neutrophils and occasional monocytes. Transmission election microscopy of peripheral blood neutrophils showed type I and type II intranuclear inclusions. These inclusions disappeared within 48 h of stopping ganciclovir. Inclusions were not seen in three patients who were given prophylactic ganciclovir 5 mg/kg once daily for 5 days every week following allogenic BMT after the same conditioning regimen. These patients were also negative for CMV antigenemia. Development of type I and type II intranuclear inclusions in blood neutrophils in patients receiving ganciclovir therapy has not been reported previously, and the striking light microscopic changes provide simple morphological evidence of the toxic effect of this drug on blood neutrophils.