High incidence of cytomegalovirus infection after nonmyeloablative stem cell transplantation: potential role of Campath-1H in delaying immune reconstitution

Abstract

Nonmyeloablative conditioning is increasingly used for transplantation in a wide range of diseases, but little is known about its impact on the incidence of infections and immune reconstitution. We examined the pattern and outcome of cytomegalovirus (CMV) infections monitored by polymerase chain reaction-based assays and treated preemptively in 101 patients following nonmyeloablative conditioning containing in vivo Campath-1H. Fifty-one patients (50%) had a CMV infection at a median of 27 days after transplantation with a probability of 84.8% in patients at risk of CMV infection. The probability of recurrence of CMV infection before and after 100 days was 53.6% and 46.6%, respectively, and was more common in unrelated donor transplant recipients. All 3 patients who developed CMV disease died of this complication. The 2 patients with late CMV disease had grade III to IV graft-versus-host-disease (GVHD), which occurred de novo in only 4% of patients and in another 10% following donor lymphocyte infusions. The median time to CD4 ؉ T-cell count more than 200/L was 9 months in the 48 patients studied. The probabilities of overall survival and nonrelapse mortality at 18 months were 65% and 27.8%, respectively, with no significant difference in survival between CMV-infected and -uninfected patients. The use of Campath-1H appeared to be associated with a low incidence of GVHD but a high incidence of CMV infections and prolonged immune paresis. (Blood. 2002;99:4357-4363)

Cytomegalovirus infection and disease after reduced intensity conditioning allogeneic stem cell transplantation: single-centre experience

“…7,14,15,[28][29][30] In addition, relevant changes of patients' characteristics over time led to higher proportion of high-risk patients for CMV-I and CMV-D in the quantPCR period [data not shown], mostly higher proportions of unrelated and mismatched donors (31% in the quantPCR period vs 11% in the pp65Ag period, Po0.01) and in vivo T-cell depleting (20 vs 8%, respectively, Po0.01). 4,9,14,19,31,32 Several observations in this study support that CMV infection and disease are still a frequent and serious complication, with a significant incidence of CMV-D (11%), similar to that observed earlier in alloHSCT-RIC patients. 3,9,31 Of note, 48% of the cases of CMV-D occurred late post transplant (after day þ 100).…”

“…In this study, we report a median onset of CMV-I of 57 days, which seems to be delayed compared with RIC regimens based on in vivo T-cell depletion. 4 We also observed that more than half of the patients (24 of 44, 54%) who developed a CMV-I without disease had a recurrence. This observation, in addition to the high rate of late (after day þ 100) episodes of CMV-I and CMV-D (63 and 48%, respectively) have substantial implications.…”

“…3 However, RIC regimens that include in vivo T-cell depletion with antithymocyte globulin (ATG), and, more importantly, with alemtuzumab, may lead to high incidence of CMV-I after HSCT, but CMV-D may be prevented with close monitorization and pre-emptive anti-CMV therapy. [4][5][6][7] On the other hand, non-T-cell depleted RIC regimens may lead to a high incidence of extensive chronic GVHD and, thus, potentially to a high risk of late (after 3-4 months post-HSCT) CMV-I and CMV-D. Thus, CMV-I and CMV-D may still be a major cause of morbidity and mortality in alloHSCT-RIC setting.…”

Valganciclovir as CMV reactivation prophylaxis in patients receiving alemtuzumab for marrow failure syndromes

“…Alemtuzumab has been scarcely investigated in bone marrow failure syndromes given the specific risk of opportunistic infection from viruses (especially CMV reactivation) and other intracellular pathogens [1,[5][6][7] that would synergize and increase the risk of bacterial complications due to the concomitant neutropenia, especially in SAA. Another concern could be the fear of marrow toxicity deriving from both CMV reactivation and anti-CMV agents.…”

Unrelated cord blood transplantation in a girl with Hoyeraal–Hreidarsson syndrome

“…Patients receiving highly immunosuppressive RIC regimens (particularly those containing fludarabine regimens) may be prone to an increased incidence of viral infections such as CMV and EBV. 9 However, with early detection and treatment, death due to reactivation can be avoided.…”