Concomitant zoster myelitis and cerebral leukemia relapse after stem cell transplantation.

Abstract

A 45-year-old woman with acute myeloid leukemia (AML) and granulocytic sarcoma (GS) of the uterine cervix was treated with radiotherapy (45 Gy) and chemotherapy [Adriamycin and cytosine arabinoside (AraC), followed by fludarabine, idarubicin, and AraC ×2]. She received an allogeneic stem cell transplantation (SCT) from her HLA-identical sibling 6 months from diagnosis. Lumbar puncture examinations at diagnosis and at SCT showed no evidence of AML. Six months post-SCT, she presented with right T6 dermatomal varicella zoster (VZV) reactivation (Fig. 1a), with scattered lesions on the right forearm and left chest. This was accompanied by left-sided (contralateral) hemi-body numbness to touch and temperature sensation with a sensory level at T6. Magnetic resonance imaging (MRI) showed transverse myelitis (Fig. 1b). A lumbar puncture showed acellular cerebrospinal fluid (CSF) with strong positivity to VZV by polymerase chain reaction (PCR) (Fig. 1c). She was treated with 1 week of intravenous acyclovir 500 mg every 6 hours with rapid resolution of the skin vesicles, but only partial recovery of numbness. This was followed by progression to paraparesis, retrobulbar optic neuritis, and urinary retention. A repeat CSF assessment showed AML blast cells (Fig. 1d) and persistent VZV PCR positivity (Fig. 1c); and a repeat MRI showed cauda equina leukemic infiltration. A bone marrow biopsy showed concomitant AML relapse with graft rejection. She was treated with intrathecal methotrexate (12 mg ×6 doses), lumbosacral radiotherapy (RT), and chemotherapy reinduction (idarubicin, AraC, and etoposide) with allogeneic stem cells and acyclovir coverage. The CSF was sequentially cleared of VZV and blasts (Fig. 1c), with complete neurological recovery, but a marrow remission was not obtained. She was put on palliative chemotherapy and died of refractory leukemia 5 months later, without any recurrence of zoster or cerebral leukemia. Reactivation of VZV after allogeneic SCT occurs in up to 40% of cases at a median of 200 days post-SCT [1]. Multi-dermatomal, systemic, and central nervous system involvements are reported in up to 30% of cases [2]. The death rate ranged from 0.9 to 2.2% [1, 2], and mortality is attributed to delayed acyclovir treatment, visceral and neural complications, and comorbid conditions. Myelitis accounts for 25% of CNS VZV infections in immunocompromised hosts and skin rash may be absent [3]. Definitive diagnosis requires a combination of clinical, virological, and imaging evidence [4]. Our case illustrated several important points. First, it reaffirms our previous observation of the association between severe VZV reactivation and leukemia relapse after SCT [5]. This may be due to the loss of VZV immune control accompanying the loss of graft and the resurgence of the disease marrow. Second, although the CNS is a leukemia sanctuary site, cerebral leukemia without preceding systemic relapse is uncommon after SCT [6]. Noncutaneous extramedullary granulocytic sarcoma is not reported to be associated with increased incidence of CNS disease [7]. It is possible that the disruption of the blood-brain barrier due to VZV myelitis may have led to transgression of blast cells in the CNS. Finally, although VZV myelitis may require prolonged antiviral treatment [4], any discordant dermatological and neurological response should alert physicians to look out for concomitant pathologies. W. Y. Au (*) Department of Medicine, Queen Mary Hospital, 4/F Professorial Block, Pokfulam Road, Hong Kong SAR, China e-mail: auwing@hotmail.com Tel.: +852-2-8444792 Fax: +852-2-9741165