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

A 13-year-old splenectomized, multitransfused beta-thalassemia major, male patient received an allogenic BMT from his HLA-compatible brother after suf fering grade III regimen-related pulmonary toxicity. He developed features of CMV pneumonitis with positive pp65 CMV antigenemia involving 2.5% periph eral blood neutrophils from day +46. The patient received intravenous immun oglobulin and ganciclovir 5 mg/kg intravenously twice daily. His neutrophil count was maintained above 1 x 10(9)/l by G-CSF 5 mu g/kg subcutaneously a s and when required. From day 7 onwards following twice daily ganciclovir h is peripheral blood smear started showing isolated cytoplasmic inclusions, 1-3 per neutrophil? 3-5 mu in diameter, involving 2-3% of the neutrophils a nd occasional monocytes, Transmission election microscopy of peripheral blo od neutrophils showed type I and type II intranuclear inclusions. These inc lusions disappeared within 48h of stopping ganciclovir, Inclusions were not seen in three patients who were given prophylactic ganciclovir 5 mg/kg onc e daily for 5 days every week following allogenic BMT after the same condit ioning regimen. These patients were also negative for CMV antigenemia, Deve lopment 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 ev idence of the toxic effect of this drug on blood neutrophils.