Toxoplasmosis in patients with hematologic malignancies

Abstract

Toxoplasmosis is one of the most common parasitic infections [1] and is caused by a protozoan, Toxoplasma gondii . Clinically signifi cant toxoplasmosis is a well-recognized opportunistic infection usually due to reactivation of a latent infection [2]. Adults with intact immunity usually have a self-limited infection; however, in immunocompromised patients, it can cause a life-threatening central nervous system (CNS) or disseminated infection. Th e frequency of this opportunistic infection in patients treated with antineoplastic chemotherapy in the modern era is unknown, as most series were published in patients with bone marrow transplant, and before the widespread use of trimethoprim – sulfamethoxazole prophylaxis or the advent of immunotherapy, including rituximab (R) [3 – 5]. Here we report a case of CNS toxoplasmosis after treatment with R and bendamustine (B) in a patient with Waldenstr o m macroglobulinemia (WM), and describe three other cases of toxoplasmosis in patients with hematologic malignancies treated at our institution from 2000 to 2013. A 79-year-old female presented with progressive fatigue and dyspnea on exertion for the past year. She noted easy bruising and several episodes of epistaxis over the preceding 2 months. Physical examination revealed palpable lymphadenopathy. Excisional lymph node biopsy demonstrated that the lymph node architecture was partially eff aced by an infi ltrate of neoplastic lymphoplasmacytoid cells that were positive for CD20, bcl-2 and immunoglobulin kappa light chains, suggesting a diagnosis of lymphoplasmacytic lymphoma. Laboratory studies showed hemoglobin 7.7 g/dL (12.0 – 15.5 g/dL), M-spike 4.6 g/dL, immunoglobulin M (IgM) 6910 mg/dL (37 – 286 mg/dL) and viscosity of 3.2 cP ( 1.5 cP). Bone marrow biopsy showed a hypercellular marrow with 60% involvement by lymphoplasmacytic lymphoma; monoclonal kappa light chain-restricted B-cell lymphocytes were present. Th e diagnosis of WM with hyperviscosity syndrome was made. After initial therapeutic apheresis, she was treated with B and R (BR) at 90 mg/m 2 /day (day 1 and 2) and 375 mg/m 2 (day 1) of body surface area, respectively, every 4 weeks. Following the completion of four cycles of BR, hemoglobin was 10.9 g/dL, M-spike was 1.9 g/dL and IgM was 2690 mg/dL, and observation was recommended. At that time, she was able to perform all activities of daily living independently and had a steady improvement in energy levels. Eight weeks after her last chemotherapy cycle, her family noted intermittent episodes of mild cognitive dysfunction which progressed to frank confusion and visual hallucinations. Th ere were no reported falls, seizures or symptoms suggestive of infection, including fevers and chills. She was admitted to our institution for further work-up. On initial examination, vital signs were normal. Mucous membranes were dry. Lymph nodes, heart, lung, abdomen and extremities were unremarkable. Her pupils were equal, round and reactive to light. She was restless and only partially oriented to person (only able to say her fi rst name), but not oriented to time or place. Strength, sensation, coordination and gait could not be evaluated, but refl exes were brisk throughout, with Babinski fl exor bilaterally. Laboratory examination revealed hemoglobin of 12.5 g/ dL, leukocyte count 6.4 10 9 /L, with normal absolute neutrophil and lymphocyte counts. Serum viscosity and IgM levels were 1.2 cP and 2760 mg/dL, respectively. Fungal, human immunodefi ciency virus (HIV) and syphilis serologies were negative. Magnetic resonance imaging (MRI) showed innumerable peripherally enhancing lesions of variable size, many at the gray – white junction. A mild to moderate mass eff ect was noted on the right frontal horn (Figure 1). Cerebrospinal fl uid (CSF) analysis showed glucose of 51 mg/dL (blood sugar 93 mg/dL), total protein of 239 mg/dL (0 – 35 mg/dL) and a cell count of 239 cells/ μ L (94% lymphocytes). Cytology was negative for malignancy, and fl ow cytometry showed no monotypic B-cells. CSF cultures were negative for bacteria, fungi and mycobacteria. CSF polymerase chain reaction (PCR) was positive for T. gondii . Th erapy with both intravenous trimethoprim – sulfamethoxazole and oral pyrimethamine with folinic acid was initiated due to concerns about erratic oral intake. Intravenous trimethoprim – sulfamethoxazole was later changed to sulfadiazine when oral therapy could be given reliably. Follow-up examination and MRI 6 weeks later