Evaluation of risk of symptomatic cytomegalovirus reactivation in myeloma patients treated with tandem autologous stem cell transplantation and novel agents: a single‐institution study

Abstract

The introduction of proteasome inhibitors and/or immunomodulators in the treatment of myeloma has led to an increase in viral infections, particularly in the Herpesviridae family. Previous studies about the risk of cytomegalovirus (CMV) reactivation after autologous stem cell transplantation (ASCT) have examined the clinical outcome after the first ASCT; however, only 1 study to date has investigated the risk of CMV reactivation after a second transplantation. To address this issue, we performed a retrospective chart review on 78 consecutive myeloma patients (median age 56 years) who underwent a tandem non-CD34(+) selected ASCT after induction treatment with either conventional chemotherapy (n = 42) or with novel agents (n = 36), respectively. All subjects had been mobilized and conditioned with cyclophosphamide plus granulocyte colony-stimulating factor and melphalan alone, respectively. CMV DNA load in the blood has been determined by polymerase chain reaction in the case of a clinical suspicion of CMV reactivation; therefore, routine monitoring was not performed. Considering the outcome of both the first and the second transplantations, we observed a total of 13 episodes of symptomatic CMV reactivation (13/156, 8%), in 12 subjects (12/78, 15%), all successfully treated. Eight subjects experienced a CMV reactivation after the first ASCT (8/78, 10%); however, only 1 of them (1/8, 12%) experienced a CMV reactivation after the second transplantation. Conversely, 4 CMV reactivations (6%) were observed after the second transplantation in the group of 70 patients who did not experience a CMV reactivation after the first ASCT. No statistically significant difference was observed between first and second ASCT (8/78, 10% vs. 5/78, 6%; P = 0.767). Univariate analysis showed that a pre-transplant treatment with novel agents was the only baseline factor significantly associated with the occurrence of post-ASCT CMV symptomatic reactivation after the first transplant (odds ratio [OR]: 9.897; 95% confidence interval [CI]: 1.154-84.840; P = 0.021) but not after the second transplant (OR: 5.125; 95% CI: 0.546-48.119; P = 0.115). No end-organ disease or primary infection was documented. Our data suggest that second transplantation does not increase the risk of CMV reactivation in our patient population, when compared with the first one, and confirm the role of a pre-transplant treatment with novel agents as a risk factor for CMV symptomatic reactivation.

Cytomegalovirus reactivation after autologous stem cell transplantation in myeloma and lymphoma patients: A single-center study

“…Cumulative incidence of TRM was significantly affected by the occurrence of a symptomatic CMV reactivation (5-fold risen, Figure 1), although only one death was directly attributable to CMV (respiratory distress caused by interstitial pneumonia), whereas the remaining two were caused by a gram negative bacterial co-infection, indirectly favored by the graft failure consequent to CMV reactivation. The global incidence of CMV reactivation and of end-organ disease observed in our study were substantially similar to our previously reports [14,15,17] , but also to the others published studies in which it of reactivation.…”

“…However, the recent large use of immunotherapeutic drugs for the treatment of lymphomas and the introduction of proteasome inhibitors in the treatment of myeloma has determined an increase of viral infections also outside allogeneic transplantation setting, as for ASCT. In the last years, some studies have been published by our and others groups in order to better characterize the incidence of and the risk factors for CMV infection in ASCT of both in lymphoma and myeloma patients [13][14][15][16][17] . However, considering the low number of patients studied and to the multicenter nature of some previous studies (potential bias for the period were excluded from this analysis.…”

Cytomegalovirus infection in autologous stem cell transplant recipients in the era of rituximab

“…Kim et al identified CMV reactivation more common in recipients of tandem transplant as compared to single transplants [15]. However, Marchesi et al did not show increased risk of CMV reactivation with tandem ASCT [16]. More studies are needed to study the effect of second and tandem transplants in the occurrence of CMV reactivation after ASCT.…”

Cytomegalovirus infection in hematologic malignancy settings other than the allogeneic transplant

“…In fact, the reported increase of CMV infection/reactivation occurrence in lymphoma patients undergoing ASCT after treatment with Rituximab needs further confirmation . On the contrary, the evidence about the impact of Bortezomib in myeloma patients is more persuasive, and these data need to be confirmed by larger prospective studies. Nevertheless, even though CMV reactivation still represents an important complication, most cases are successfully managed with a specific antiviral treatment (often administered within outpatient clinical settings).…”

“…However, it also favoured the occurrence of new infectious complications, particularly by opportunistic pathogens, including viral infections . Regarding CMV, several studies have been performed aimed at exploring the incidence and clinical impact of CMV infection/reactivation in patients undergoing ASCT in the era of intensive and pleiotropic immunosuppressive therapy . Table summarizes the main reports published during the last 20 years.…”