Severe Cytomegalovirus Reactivation in Patient with Low-Grade Non-Hodgkin’s Lymphoma after Standard Chemotherapy

Abstract

Clinically significant cytomegalovirus (CMV) reactivation is not uncommon in patients with severe immunodeficiency secondary to underlying medical disorders or following aggressive immunosuppressive therapy. However, it is less frequently found in patients with low-grade haematological malignancies after nonintensive chemotherapy. We treated a patient at our centre for stage IVB follicular lymphoma with standard chemotherapy who successively developed CMV colitis associated with a CMV viral load of >3 million copies/ml. Four lines of antiviral treatment were necessary to obtain biochemical remission with undetectable CMV levels, with an initially insufficient response to valganciclovir despite therapeutic pre- and posttreatment levels. Subsequently, our patient also developed an infection with Pneumocystis jirovecii pneumonia (PJP) as further evidence of severe immune compromise. This case report demonstrates the importance of including investigations for less common sources of infection when confronted with a patient with a low-grade haematological malignancy and a pyrexia of unknown origin.

Real-world evidence of cytomegalovirus reactivation in non-Hodgkin lymphomas treated with bendamustine-containing regimens

“…Clinical manifestations and severity of CMV reactivation vary among patients treated with bendamustine, from no symptoms to severe CMV disease and death [ 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 ], as also described in our cohort. In symptomatic patients, various antiviral agents are employed, such as ganciclovir and VGCV at 900 or 1,800 mg/daily [ 46 ].…”

“…CMV reactivation develops early in bendamustine administration usually after the third cycle of therapy, as documented in several case reports [ 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 ]; however, no significant differences in long-term cumulative incidence of reactivation were registered in our cohort between patients who received less than three courses of bendamustine and subjects who had more than three cycles of therapy, while in multivariate analysis the number of cycles of bendamustine increased the risk of CMV reactivation in treatment-naïve patients who received bendamustine as first-line therapy. This augmented susceptibility to viral reactivation might be caused by an impairment in T cell immunity, such as decreased circulating levels of CMV-specific CD8 + cytotoxic lymphocytes and CD4 + T cells [ 19 , 28 , 31 , 34 , 42 , 43 ].…”

“…CMV reactivation in NHL patients has been anecdotically reported after bendamustine exposure often in older subjects with iNHL including FL, MCL, or MALT [ 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 ]. Most of those cases are refractory or relapsed iNHL, and they usually received bendamustine with or without rituximab as second or above line of therapy developing CMV disease after the third cycle of treatment.…”

“…In NHL, CMV reactivation is a frequent cause of mortality, and prophylaxis might be warranted in patients at risk, such as patients with high antigenemia burden, recurrent CMV reactivation, and antiviral-associated toxicities [ 24 ]. In older iNHL (FL, MZL, and Waldenström macroglobulinemia) treated with bendamustine-containing regimens, the risk of CMV reactivation is increased (HR, 3.98; 95% CI, 1.40–11.26) compared to patients treated without bendamustine [ 18 ]; in particular, CMV reactivation is frequent in patients treated with bendamustine as third line or above therapy and exposed to corticosteroids [ 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 ]. Similarly, in our cohort, incidence of CMV reactivation was higher in patients aged >60 years; however, similar rates of reactivation were documented between indolent and aggressive diseases, or between bendamustine course as first-line therapy and second-line or above treatment (26 vs 11% respectively; P = 0.1361).…”

Disseminated cytomegalovirus disease after bendamustine: a case report and analysis of circulating B- and T-cell subsets

“…To our knowledge, this is the first report of a disseminated CMV disease following treatment with bendamustine. While several case studies of localized CMV disease have been reported [12], no disseminated infection post-bendamustine has been described.…”