Increased transplant-related morbidity and mortality in CMV-seropositive patients despite highly effective prevention of CMV disease after allogeneic T-cell–depleted stem cell transplantation

Abstract

We evaluated the efficacy, toxicity, and outcome of preemptive ganciclovir (GCV) therapy in 80 cytomegalovirus (CMV)-seropositive patients allografted between 1991 and 1996 and compared their outcome to 35 seronegative patients allografted during the same period. Both cohorts were comparable with respect to diagnosis and distribution of high- versus standard-risk patients. All patients received a stem cell graft from an HLA-identical sibling donor, and grafts were partially depleted of T cells in 109 patients. Patients were monitored for CMV antigenemia by leukocyte expression of the CMV-pp65 antigen. Fifty-two periods of CMV reactivation occurring in 30 patients were treated preemptively with GCV. A favorable response was observed in 48 of 50 periods, and only 2 patients developed CMV disease: 1 with esophagitis and 1 with pneumonia. Ten of 30 treated patients developed GCV-related neutropenia (less than 0.5 × 109/L), which was associated with a high bilirubin at the start of GCV therapy. Overall survival at 5 years was 64% in the CMV-seronegative cohort and 40% in the CMV-seropositive cohort (P = .01). Increased treatment-related mortality accounted for inferior survival. CMV seropositivity proved an independent risk factor for developing acute graft-versus-host disease, and acute graft-versus-host disease predicted for higher treatment-related mortality and worse overall survival in a time-dependent analysis. We conclude that, although CMV disease can effectively be prevented by preemptive GCV therapy, CMV seropositivity remains a strong adverse risk factor for survival following partial T-cell–depleted allogeneic stem cell transplantation.

Risk factors of Ganciclovir-related neutropenia after allogeneic stem cell transplantation: a retrospective monocentre study on 547 patients

“…In this large series of adult patients presenting with CMV reactivation after Allo-SCT, we found patient age, serum CMV load and ANC value at viral reactivation to be significant predictive factors of neutropenia [17][18][19]. CMV reactivation is a well-known risk factor for mortality after transplantation [20]. Pre-emptive therapy has been shown to improve survival and monitoring of CMV levels is recommended in high-risk patients [21].…”

Validation and extension of the EBMT Risk Score for patients with chronic myeloid leukaemia (CML) receiving allogeneic haematopoietic stem cell transplants

“…Specific aims of this study were: (1) to validate the EBMT Risk Score by applying it to an independent dataset; (2) to investigate adding other variables; and (3) to develop a prognostic score specifically for patients in early first chronic phase (Broers et al, 2000).…”

Respiratory Infections

“…The advent of PCR testing of the blood has further improved the detection of CMV in neutropenic patients and has been associated with improved survival over viral culture [43]. After treatment of patients for CMV, the physician should remain aware that the risk of subsequent bacterial and fungal infections is substantially increased [53,54,77,78].…”