The significance of cytomegalovirus viremia at day 100 or more following allogeneic hematopoietic stem cell transplantation

We conducted a single‐center retrospective review of patients who had received allogeneic hematopoietic stem cell transplantation (HSCT) between January 2003 and December 2007, to assess the incidence and risk factors for late CMV infection and evaluate its effects on outcomes. Twenty of 49 HSCT recipients (41%) developed CMV infection at day ≥100 after transplant. Univariable analysis showed that having a matched unrelated donor, having early CMV infection, having a diagnosis of lymphoma, and receipt of antithymocyte globulin were risks for developing late CMV. On multivariable analysis, the occurrence of CMV prior to day 100 and lymphoma conferred a significant risk for late CMV infection. Of the 20 patients with late CMV infection, two patients manifested CMV disease (10%). Despite the relatively low incidence of CMV disease, patients with late CMV infection had a 4.8‐fold increased risk of death compared to patients without late CMV. Identifying patients at increased risk for developing late CMV infection may be important for prompting more intensive monitoring of infection late after HSCT, particularly because this manifestation of CMV is associated with poorer outcomes.

[1]  M. Boeckh,et al.  Immune monitoring with iTAg MHC Tetramers for prediction of recurrent or persistent cytomegalovirus infection or disease in allogeneic hematopoietic stem cell transplant recipients: a prospective multicenter study. , 2010, Blood.

[2]  B. Sandmaier,et al.  Defining the intensity of conditioning regimens: working definitions. , 2009, Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.

[3]  N. Mahmud,et al.  Fludarabine/i.v. BU conditioning regimen: myeloablative, reduced intensity or both? , 2008, Bone Marrow Transplantation.

[4]  H. Nakasone,et al.  Clinical features of late cytomegalovirus infection after hematopoietic stem cell transplantation , 2008, International journal of hematology.

[5]  P. Ljungman,et al.  Allogeneic stem cell transplantation: low immunoglobulin levels associated with decreased survival , 2008, Bone Marrow Transplantation.

[6]  M. Labopin,et al.  Risk factors for fatal infectious complications developing late after allogeneic stem cell transplantation , 2007, Bone Marrow Transplantation.

[7]  P. Ljungman,et al.  Evaluation of intervention strategy based on CMV-specific immune responses after allogeneic SCT , 2007, Bone Marrow Transplantation.

[8]  E. Shpall,et al.  Risk factors associated with late cytomegalovirus reactivation after allogeneic stem cell transplantation for hematological malignancies , 2007, Bone Marrow Transplantation.

[9]  N. Mahmud,et al.  Comparable kinetics of myeloablation between fludarabine/full-dose busulfan and fludarabine/melphalan conditioning regimens in allogeneic peripheral blood stem cell transplantation , 2006, Bone Marrow Transplantation.

[10]  D. Follmann,et al.  Persisting posttransplantation cytomegalovirus antigenemia correlates with poor lymphocyte proliferation to cytomegalovirus antigen and predicts for increased late relapse and treatment failure. , 2004, Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.

[11]  G. Papanicolaou,et al.  Cytomegalovirus in hematopoietic stem cell transplant recipients: Current status, known challenges, and future strategies. , 2003, Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.

[12]  W. Leisenring,et al.  Late cytomegalovirus disease and mortality in recipients of allogeneic hematopoietic stem cell transplants: importance of viral load and T-cell immunity. , 2002, Blood.

[13]  S. Rowland-Jones,et al.  Cytomegalovirus reactivation following allogeneic stem cell transplantation is associated with the presence of dysfunctional antigen-specific CD8+ T cells. , 2002, Blood.

[14]  P. Griffiths,et al.  Definitions of cytomegalovirus infection and disease in transplant recipients. , 2002, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[15]  A. Verma,et al.  Allogeneic blood cell transplantation following reduced-intensity conditioning is effective therapy for older patients with myelofibrosis with myeloid metaplasia. , 2002, Blood.

[16]  M. Boeckh,et al.  High risk of death due to bacterial and fungal infection among cytomegalovirus (CMV)-seronegative recipients of stem cell transplants from seropositive donors: evidence for indirect effects of primary CMV infection. , 2002, The Journal of infectious diseases.

[17]  J. Mary,et al.  Prolonged immune deficiency following allogeneic stem cell transplantation: risk factors and complications in adult patients , 2001, British journal of haematology.

[18]  C. Pannuti,et al.  Extended antigenemia surveillance and late cytomegalovirus infection after allogeneic BMT , 2001, Bone Marrow Transplantation.

[19]  R. Tedder,et al.  Extended routine polymerase chain reaction surveillance and pre‐emptive antiviral therapy for cytomegalovirus after allogeneic transplantation , 2000, British journal of haematology.

[20]  H. Einsele,et al.  Risk factors for treatment failures in patients receiving PCR-based preemptive therapy for CMV infection , 2000, Bone Marrow Transplantation.

[21]  J. Tarrand,et al.  Late cytomegalovirus pneumonia in adult allogeneic blood and marrow transplant recipients. , 1999, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[22]  E D Thomas,et al.  1994 Consensus Conference on Acute GVHD Grading. , 1995, Bone marrow transplantation.

[23]  H. Einsele,et al.  Lymphocytopenia as an unfavorable prognostic factor in patients with cytomegalovirus infection after bone marrow transplantation. , 1993, Blood.

[24]  M. Boeckh,et al.  Cytomegalovirus antigen detection in peripheral blood leukocytes after allogeneic marrow transplantation. , 1992, Blood.

[25]  S. Riddell,et al.  Cytotoxic T-lymphocyte response to cytomegalovirus after human allogeneic bone marrow transplantation: pattern of recovery and correlation with cytomegalovirus infection and disease. , 1991, Blood.

[26]  K. Sullivan,et al.  Chronic graft-versus-host disease and other late complications of bone marrow transplantation. , 1991, Seminars in hematology.