Intrathecal Administration of High-Titer Cytomegalovirus Immunoglobulin for Cytomegalovirus Meningitis

Abstract

Cytomegalovirus (CMV) central nervous system disease after hematopoietic stem cell transplantation (HSCT) is a rare but life-threatening complication. Here, we report a patient who developed CMV meningitis after HSCT and was treated with the combination therapy of intrathecal high-titer CMV immunoglobulin and antiviral drugs. A 38-year-old man with myelodysplastic syndrome received a cord blood transplant after graft failure. On day 147, he was diagnosed with CMV meningitis based on pleocytosis and CMV DNA in the cerebrospinal fluid (CSF). Intravenous ganciclovir, foscarnet, and immunoglobulin were administered; however, CMV DNA in the CSF was continuously detected. The addition of intrathecal high-titer CMV immunoglobulin resulted in CMV DNA in the CSF becoming undetectable. On day 241, CMV DNA in the CSF was detected again, but both intrathecal immunoglobulin and intravenous ganciclovir led to its disappearance. No adverse effects related to intrathecal administration were observed. The intrathecal administration of immunoglobulin may be safe and effective for CMV meningitis.

Intrathecal cytomegalovirus immunoglobulin for CMV encephalitis post allogeneic stem cell transplantation

“…Potential reasons for this include uncertainty regarding dosing. Fujiwara and colleagues [4] demonstrated clearance of CMV in CSF after 3 doses of IT high-titer CMV immunoglobulin; however, they used a different product and gave concomitant foscarnet and ganciclovir. Our patient experienced recurrent renal injury and concurrent treatment with foscarnet would have led to unacceptable renal toxicity, whereas ganciclovir administration was hampered by pancytopenia.…”

“…Cytomegalovirus encephalitis is a rare presentation of CMV disease that has a high mortality [2] , [3] , and as such novel antiviral strategies may be required. One therapeutic strategy proposed has been the intrathecal administration of high-titer CMV immunoglobulin [4] . We report a patient with cytomegalovirus encephalitis with high CSF CMV titer and low peripheral blood CMV titer; treated with intrathecal (IT) CMV specific immunoglobulin (Cytogam).…”

Successful treatment of post‐transplant CMV meningoencephalitis with third‐party CMV virus‐specific T cells: Lessons learned

“…Here, 2 cases of patients successfully treated with third‐party CMV VSTs for CMV meningoencephalitis are reported. Both patients had failed other available medical treatment, including antiviral therapy and intrathecal immunoglobulin administration . Analysis provided some valuable pieces of information: first, CMV VSTs seem to be active in the CNS compartment.…”

“…Both patients had failed other available medical treatment, including antiviral therapy and intrathecal immunoglobulin administration. 9 Analysis provided some valuable pieces of information: first, CMV VSTs seem to be active in the CNS compartment. In patient 2, we demonstrated a dramatic drop in CMV copy number in his CSF accompanied by a peak in lymphocyte number ( Figure 2).…”

“…However, most reported cases in which adoptive T‐cell therapy was used for CMV involved patients with persistent CMV DNAemia (hereafter referred to as viremia) and not with CMV disease. CMV meningoencephalitis is a rare but devastating complication after HSCT and is almost invariably fatal with the usual medical treatment consisting of antiviral therapy and IvIG infusion . Reddy et al reviewed the literature and contributed with 2 cases.…”