BK virus encephalitis with thrombotic microangiopathy in an allogeneic hematopoietic stem cell transplant recipient.

BK virus (BKV) infection occurs most often in immunocompromised hosts, in the setting of renal or bone marrow transplantation. Hemorrhagic cystitis is the commonest manifestation but in recent years infections in other organ systems have been reported. We report an unusual case of biopsy-proven BKV encephalitis in a hematopoietic stem cell transplant patient who subsequently developed thrombotic microangiopathy. As far as we know, this is the first report of such an association in a transplant patient.

Treatment of brain metastases in patients with HER2+ breast cancer.

Brain metastases are a frequent complication of cancer. However, effective treatments are available. This article aims to review clinical aspects of patients with brain metastases discussing the various treatment options for such patients. It will address the importance and significance of brain metastases in patients with breast cancer and, finally, review the problem of brain metastasis associated with human epidermal growth factor receptor 2-positive (HER2+) breast cancer. With ever-improving survival rates of patients with cancer, there is a greater likelihood that many will develop brain metastases. Treatments such as whole brain or stereotactic radiotherapy and surgery have been shown to be effective against brain metastases. In HER2+ breast cancer, trastuzumab has been shown to be very effective, although it cannot cross the blood-brain barrier. If patients with breast cancer who are being treated with trastuzumab and are responding systemically, develop brain metastases, then patient prognosis does need to be taken into account; however, maintaining treatment with trastuzumab while using available therapies to treat intracranial lesions should be considered as an option.

Second-line chemotherapy with temozolomide in recurrent oligodendroglioma after PCV (procarbazine, lomustine and vincristine) chemotherapy: EORTC Brain Tumor Group phase II study 26972.

BACKGROUND: Oligodendroglial tumors are chemosensitive, with two-thirds of patients responding to PCV combination chemotherapy with procarbazine, lomustine (CCNU) and vincristine. Temozolomide (TMZ), a new alkylating and methylating agent has shown high response rates in recurrent anaplastic astrocytoma. We investigated this drug in recurrent oligodendroglial tumors (OD) and mixed oligoastrocytomas (OA) after prior PCV chemotherapy and radiation therapy. PATIENTS AND METHODS: In a prospective non-randomized multicenter phase II trial patients were treated with TMZ 150 mg/m(2) on days 1-5 in cycles of 28 days for 12 cycles. Eligible patients had a recurrence after prior PCV chemotherapy, with measurable and enhancing disease as shown by magnetic resonance imaging. Pathology and all responses were centrally reviewed. RESULTS: Thirty-two eligible patients were included. In four patients the pathology review did not confirm the presence of an OD or OA. Twelve of 24 patients [50%, 95% confidence interval (CI) 29% to 71%] evaluable for response to first-line PCV chemotherapy had responded to PCV. Temozolomide was in general well tolerated; the most frequent side-effects were hematological. One patient discontinued treatment due to toxicity. In seven of 28 patients (25%, 95% CI 11% to 45%) with histologically confirmed OD an objective response to TMZ was observed. Median time to progression for responding patients was 8.0 months. After 6 and 12 months from the start of treatment, 29% and 11% of patients, respectively, were still free from progression. CONCLUSIONS: TMZ may be regarded as the preferred second-line treatment in OD after failure of PCV chemotherapy. Further studies on TMZ in OD are indicated.

Multicenter phase II trial of temozolomide in patients with glioblastoma multiforme at first relapse.

BACKGROUND: Recurrent glioblastoma multiforme (GBM) is resistant to most therapeutic endeavors, with low response rates and survival rarely exceeding six months. There are no clearly established chemotherapeutic regimens and the aim of treatment is palliation with improvement in the quality of life. PATIENTS AND METHODS: We report an open-label, uncontrolled, multicenter phase II trial of temozolomide in 138 patients (intent-to-treat [ITT] population) with glioblastoma multiforme at first relapse and a Karnofsky performance status (KPS) > or = 70. One hundred twenty-eight patients were histologically confirmed with GBM or gliosarcoma (GS) by independent central review. Chemotherapy-naïve patients were treated with temozolomide 200 mg/m2/day orally for the first five days of a 28-day cycle. Patients previously treated with nitrosourea-containing adjuvant chemotherapy received 150 mg/m2/day for the first five days of a 28-day cycle. In the absence of grade 3 or 4 toxicity, patients on the 150 mg/m2 dose schedule were eligible for a 200 mg/m2 dose on the next cycle. RESULTS: The primary endpoint was six-month progression-free survival assessed with strict radiological and clinical criteria. Secondary endpoints included radiological response and Health-related Quality of Life (HQL). Progression-free survival at six months was 18% (95% confidence interval (CI): 11%-26%) for the eligible-histology population. Median progression-free survival and median overall survival were 2.1 months and 5.4 months, respectively. The six-month survival rate was 46%. The objective response rate (complete response and partial response) determined by independent central review of gadolinium-enhanced magnetic resonance imaging (MRI) scans was 8% for both the ITT and eligible-histology populations, with an additional 43% and 45% of patients, respectively, having stable disease (SD). Objectively assessed response and maintenance of a progression-free status were both associated with HQL benefits (characterized by improvements over baseline in HQL domains). Temozolomide had an acceptable safety profile, with only 9% of therapy cycles requiring a dose reduction due to thrombocytopenia. There was no evidence of cumulative hematologic toxicity. CONCLUSIONS: Temozolomide demonstrated modest clinical efficacy, with an acceptable safety profile and measurable improvement in quality of life in patients with recurrent GBM. The use of this drug should be explored further in an adjuvant setting and in combination with other agents.

Syringomyelia secondary to compression of the cervical spinal cord by an extramedullary lymphoma.

A case of syringomyelia secondary to an extramedullary cervical spinal cord compression by a non-Hodgkin's lymphoma is described. After radiotherapy, the syrinx was no longer seen. The pathogenesis of this type of syrinx is discussed, and the potential benefit of radiotherapy in these cases is suggested.

Uveomeningoencephalitis in a human immunodeficiency virus type 2-seropositive patient.

A 35-year-old woman developed longstanding uveitis and later a uveomeningoencephalitis of unknown origin and died of toxoplasmal brain abscesses. The presence of immunological impairment, human immunodeficiency virus type 2 (HIV-2) seropositivity, and multinucleated cells in the brain led us to suspect neurotropic properties for HIV-2 similar to those of HIV-1.

Crossed optic ataxia: possible role of the dorsal splenium.

An unusual combination of disconnective syndromes is reported: transcortical motor aphasia, left arm apraxia and optic ataxia. Neuropathological examination showed a left parieto-occipital and a subcortical frontal infarct and a lesion of the dorsal part of the posterior two-fifths of the callosum. The frontal lesion caused the transcortical motor aphasia and produced the left arm apraxia. Visuomotor incoordination in the right hemispace was due to the left parieto-occipital infarct, while the crossed optic ataxia in the left hemispace was attributed to the callosal lesion. It is proposed that the pathway that serves crossed visual reaching passes through the dorsal part of the posterior callosum. This case reinforces the growing evidence that fibres in the corpus callosum are arranged in ventro-dorsal functional lamination.