A 42-year-old Chinese man with myelodysplastic syndrome (MDS, RAEB-2) underwent cord blood transplantation (CBT) from a Japanese donor in October 2011. The conditioning regimen consisted of total-body irradiation (TBI) (12 Gy), cyclophosphamide (total dose, 120 mg/kg), and cytarabine (total dose, 12 g/m2). Prophylaxis against graft-versus-host disease (GVHD) consisted of cyclosporine (CsA) and a short course of methotrexate. Neutrophil engraftment was prompt, and complete remission was confirmed on day 29. CsA was discontinued on day 189, and no signs of GVHD were observed. Acyclovir (ACV) (1,000 mg/day, orally) was administered from day -7 to 35 as prophylaxis against herpes virus. This was maintained at a reduced dose of 200 mg/day until day 213. The patient's serum immunoglobulin G (IgG) levels remained within the normal limits, and his peripheral post-transplant leukocyte counts remained within the normal range.
On day 241 after CBT, the patient presented with blisters on his face and on day 245, a herpes zoster rash developed on his face, body, and extremities. Other than slight numbness on his legs, he presented no neurological symptoms. His body temperature was 37.5 C. The patient was clinically diagnosed with a systemic VZV infection and intravenous ACV (5 mg/kg three times a day) was promptly administered. The cutaneous lesions were reduced on the 8th day after the initiation of ACV treatment, and the treatment was then switched to oral valaciclovir. However, the patient developed a high fever, paralysis of the lower extremities, ischuria, neck stiffness, and spinal automatism on the second day of valaciclovir treatment. His consciousness was alert and there were no signs of recurrent cutaneous lesions. Head computed tomography showed no abnormal findings. The patient's cerebrospinal fluid (CSF) showed an increased number of mononuclear cells (77/muL), an elevated protein level, and a normal glucose level. The enzyme immunoassay (EIA) values in the patient's CSF and serum were 2.56 and 13.5, respectively, for VZV-IgG, and 5.32 and 3.90 for VZV-IgM. VZV-DNA was not detected in a polymerase chain reaction (PCR). At 5.3, the ratio of VZV-IgG in the serum and CSF was relatively low. The presentation of spinal automatism, paralysis of the lower extremities and ischuria led to a diagnosis of VZV meningitis, myelitis, and radiculitis. Intravenous ACV was resumed at an increased dose (10 mg/kg, three times a day), on the 12th day after the initial diagnosis of the VZV infection. Magnetic resonance imaging (MRI) of the thoracic vertebrae and the lumbosacral spinal cord on days 6 and 7 after the resumption of ACV, respectively, revealed no evident abnormalities.
Seventeen days after the resumption of ACV, a high mononuclear cell count (69/muL) was still present in the patient's CSF, and the patient's paralysis and ischuria showed no improvement. ACV was then switched to foscarnet (90 mg/kg, twice a day) on day 20 after the initial diagnosis. After 12 days of foscarnet treatment, the patient showed a complete recovery from ischuria and was able to walk by himself. The patient's CSF showed a significantly decreased cell count, and foscarnet was discontinued after 51 days of treatment. On day 25 after the discontinuation of foscarnet therapy, the VZV-IgM level in the patient's CSF dropped to negative value of 0.78, whereas the VZV-IgG level in the patient's CSF rose to 7.53; in contrast, the value at time of the patient's diagnosis was 2.56. The patient has been in complete remission without recurrent neurological symptoms for 3.5 years since transplantation.