valganciclovir and Waldenstrom-Macroglobulinemia

Bendamustine, used for the treatment of indolent B-cell non-Hodgkin lymphoma and chronic lymphocytic leukemia, is known to cause prolonged myelosuppression and lymphocytopenia and has been associated with the risk of developing serious and fatal infections. While reports of localized CMV infections in asymptomatic patients exist, disseminated CMV disease has not been described.. We report the first case of disseminated CMV infection in a 75-year-old male diagnosed with lymphoplasmacytic lymphoma/Waldenström macroglobulinemia with massive bone marrow infiltration. Despite 6-cycle R-bendamustine chemotherapy resulted in a good partial response, the patient developed persistent fever and severe weight loss. Analysis of cerebrospinal fluid and peripheral blood revealed the presence of CMV-DNA, while the fundus oculi examination revealed bilateral CMV retinitis. Treatment with induction and maintenance drugs was complicated by neutropenia and deterioration of renal function with electrolyte imbalance. From an immunological standpoint, we observed a profound imbalances in phenotype and function of B- and T-cell subsets, with a high proportion of circulating total, activated CD69+ and CD80+ B-cells, a low γ/δ T-cell frequency with a high proportion of CD69- and CD38-expressing cells, and hyperactivated/exhausted CD4+ and CD8+ T-cell phenotypes unable to face CMV challenge.. We hereby describe a severe form of disseminated CMV disease after R-bendamustine treatment. Our observations strongly support the careful clinical monitoring of CMV reactivation/infection in oncologic patients undergoing this therapeutic regimen.

Topics: Aged; Antineoplastic Agents, Alkylating; Antiviral Agents; B-Lymphocytes; Bendamustine Hydrochloride; CD8-Positive T-Lymphocytes; Cytomegalovirus Infections; Cytomegalovirus Retinitis; Humans; Male; T-Lymphocyte Subsets; Valganciclovir; Waldenstrom Macroglobulinemia

A 64-year-old man with a 2-week history of fatigue and fever presented to the medical admissions unit. He had a background of lymphoplasmacytic lymphoma and had recently completed a course of fludarabine-based chemotherapy. CT of the abdomen demonstrated an increase in spleen size and it was thought that his fevers were most likely due to disease recurrence or high-grade transformation. A bone marrow trephine was organised, which showed no evidence of lymphoma and positron emission tomography-CT demonstrated an area of increased avidity at the gastro-oesophageal junction. An oesophagogastroduodenoscopy was recommended, which revealed ulceration within the oesophagus and stomach. Biopsy of the lesions and immunohistochemistry confirmed a diagnosis of cytomegalovirus oesophagitis. He was treated with intravenous ganciclovir followed by oral valganciclovir for a total of 3 weeks. His fever resolved and he was discharged home approximately 8 weeks after he first presented.

Topics: Antineoplastic Agents; Antiviral Agents; Biopsy; Cytomegalovirus Infections; Diagnosis, Differential; Endoscopy, Digestive System; Esophagitis; Ganciclovir; Humans; Immunocompromised Host; Male; Middle Aged; Positron-Emission Tomography; Tomography, X-Ray Computed; Valganciclovir; Vidarabine; Waldenstrom Macroglobulinemia