Successful treatment of progressive multifocal ... · Progressive multifocal leukoencephalopathy (PML) is a rare demyelinating disease caused by John Cunningham virus (JCV) infection
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International Journal of Myeloma vol. 10 no. 1 (2020)8
Successful treatment of progressive multifocal leukoencephalopathy with mirtazapine and mefloquine in refractory myeloma
Received: December 22, 2019, accepted: February 21, 20201Department of Hematology, Endocrinology and Metabolism, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan2Department of Clinical Neuroscience, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan3Division of Transfusion Medicine and Cell Therapy, Tokushima University Hospital, Tokushima, Japan
Corresponding author: Hirokazu MIKI, M.D., PhD.Division of Transfusion Medicine and Cell Therapy, Tokushima University Hospital, Tokushima, 2-50-1, Kuramoto-cho, Tokushima 770-8503, JapanE-mail: [email protected]
9International Journal of Myeloma vol. 10 no. 1 (2020)
Mirtazapine and mefloquine for PML
We herein report the efficacy of combination therapy of
mirtazapine and mefloquine for PML that developed in a
patient with MM after autologous peripheral blood stem cell
transplantation (ASCT) and the subsequent long-term oral
administration of cyclophosphamide and prednisolone (CP).
Case Report
A 52-year-old man was diagnosed with MM (IgA-λ type,
International Staging System: 2) in December 20XY. He
received induction chemotherapy consisting of vincristine,
doxorubicin, and dexamethasone for three cycles, and
achieved a partial response (PR). He received high-dose
chemotherapy (melphalan: 200 mg/m2) followed by ASCT
(CD34 positive cells 2.4 × 106 cells/kg) in February 20XY+2,
and achieved very good PR. However, he relapsed in October
20XY+2, and was treated with CP. His disease status remained
stable without progression with continuous CP; however, he
developed apraxia in March 20XY+4, followed by dysmnesia,
visual disturbance, weakness in the right arm, and aphasia. He
was admitted to our hospital in May 20XY+4 (835 days after
ASCT).
On admission, his body temperature was 36.8°C, blood
pressure 125/89 mmHg, pulse rate 68/minute, and oxygen
saturation 99% on room air. He had severe memory impair-
ment (Mini-Mental State Examination score of 5/30), moderate
International Journal of Myeloma vol. 10 no. 1 (2020)10
UDAKA et al.
glucose (50 mg/dL). A polymerase chain reaction (PCR) analy-
sis for JCV in CSF showed positive results (JCV-DNA 1.39 × 102
copies/mL) and the HIV antibody test was negative (Table 1).
Therefore, he was diagnosed with HIV-negative PML. We
stopped CP and started mirtazapine (15 mg/day) with the
continuous infusion of cytarabine (100 mg/day for 5 days)
and high-dose intravenous immunoglobulin. After this combi-
nation therapy, the PCR test for JCV in CSF became negative
with the recovery of CD4-positive lymphocyte counts (176/μL).
However, his neurological symptoms worsened, and the
hyperintense lesion on the FLAIR image expanded to the left
frontal and right parietal lobes (Fig. 2B). After obtaining
informed consent from the patient and his wife under the
approval of the Ethics Committee/Internal Review Board of the
Tokushima University Hospital (permission # 1012), oral admin-
istration of mefloquine (275 mg/week) was initiated 3 months
after the diagnosis of PML. His neurological symptoms
gradually improved after the combination of mefloquine and
mirtazapine without apparent adverse events, and he was
discharged in August 20XY+4 (940 days after ASCT). Unfor-
tunately, a laboratory examination showed an increase in
M- protein, and an anti-MM treatment, involving CP, thalido-
mide, and high-dose dexamethasone, was started along with
mirtazapine and mefloquine in October 20XY+4. His neuro-
logical symptoms remained stable without progression,
and MRI showed a marked reduction in white matter lesions
(Fig. 2C, 2D). He died due to MM progression in August
20XY+6 (Fig. 3).
Discussion
The present case demonstrated that PML may occur in
immunocompromised MM patients after ASCT. PML must be
considered in immunodeficient patients after ASCT with
neurological symptoms, and relevant diagnostic examinations
need to be performed. In addition to the discontinuation
of immunosuppressive therapy, several drugs have been
attempted in the treatment of HIV-negative PML. However,
no specific antiviral treatment for JCV has been established.
Cytarabine, a chemotherapeutic drug, has been demonstrated
Figure 1. Brain MRI findings of the patient at the diagnosis of PML. A: T1-weighted image (T1WI). Note that the lesion basically demonstrates hypointense signals but there is subtle hyper intense signals in the advancing edge. B: T2-weighted image (T2WI). C: Fluid attenuated inver-sion recovery (FLAIR) image. D: Diffusion-weighted image (DWI). E: T1-weighted image of the brain after the gadolinium injection (Gd-T1).
11International Journal of Myeloma vol. 10 no. 1 (2020)
Mirtazapine and mefloquine for PML
Figure 2. Follow-up brain MRI imaging of the patient (FLAIR). A: MRI of the brain in May 20XY+4 (at the diagnosis of PML). B: MRI in June 20XY+4. C: MRI in May 20XY+5. D: MRI in April 20XY+6.
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