Cytomegalovirus (CMV) infections and CMV-specific cellular immune reconstitution following reduced intensity conditioning allogeneic stem cell transplantation with Alemtuzumab

• Published in: Bone marrow transplantation (Basingstoke) Vol. 36; no. 9; pp. 797 - 802
• Main Authors: LAMBA, R, CARRUM, G, MYERS, G. D, BOLLARD, C. M, KRANCE, R. A, HESLOP, H. E, BRENNER, M. K, POPAT, U
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 01.11.2005
• Subjects: Adult; Aged; Alemtuzumab; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal, Humanized; Antibodies, Neoplasm - administration & dosage; Antigenemia; Antigens, Viral - blood; Biological and medical sciences; Bone marrow; Bone marrow, stem cells transplantation. Graft versus host reaction; CD8 antigen; Complications and side effects; Conditioning; Cytomegalovirus; Cytomegalovirus infections; Cytomegalovirus Infections - blood; Cytomegalovirus Infections - drug therapy; Cytomegalovirus Infections - immunology; Cytotoxicity; Diagnosis; Drug therapy; Female; Foscarnet; Ganciclovir; Graft vs Host Disease - etiology; Graft vs Host Disease - prevention & control; Graft vs Host Disease - virology; Health risks; Hematologic and hematopoietic diseases; Hematologic Neoplasms - blood; Hematologic Neoplasms - complications; Hematologic Neoplasms - immunology; Hematologic Neoplasms - therapy; Histocompatibility antigen HLA; Humans; Immune reconstitution; Infections; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphocytes; Lymphocytes T; Male; Medical sciences; Middle Aged; Monoclonal antibodies; Recovery of Function - drug effects; Recovery of Function - immunology; Recurrent infection; Risk factors; Stem Cell Transplantation; Stem cells; T-Lymphocytes, Cytotoxic - immunology; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Transplantation; Transplantation Conditioning - methods; Transplantation, Homologous; Virus Activation - drug effects; Virus Activation - immunology; Viruses; United States; Stem cell; Hematopoietic cell; Homograft; Cellular immunity; Monoclonal antibody; Betaherpesvirinae; Cancerology; Graft; Complication; CAMPATH; Human; Cytomegalovirus; Hematology; Herpesviridae; Immune reconstitution; Malignant hemopathy; Alemtuzumab; Non myeloablative treatment; CMV; Infection; Virus; Immunomodulator; Treatment; Viral disease; Alemtuzumab RIC-SCT; Immunosuppressive agent
• ISSN: 0268-3369; 1476-5365
• DOI: 10.1038/sj.bmt.1705121

We studied the incidence and recurrence of Cytomegalovirus (CMV) infection and reactivation in 38 recipients of Alemtuzumab reduced intensity conditioning-stem cell transplantation, and used CMV-HLA tetramer studies to discover if these events correlated with recovery of circulating CMV-specific CD8+ T cells (cytotoxic T lymphocyte (CTLs)). The cumulative incidence of CMV infection was 60% at 1 year (95% CI, 45-78%) with a median reactivation time of 24 days (range 5-95 days). All patients with CMV reactivation received Ganciclovir or Foscarnet, and only one developed CMV disease. More strikingly, only 8/21 patients had relapse of CMV antigenemia. Tetramer analysis in 13 patients showed that 11 reconstituted CMV CTLs (7/11 by day 30 and 10/11 by day 90). The development of CMV infection was accompanied by a >5-fold rise of CMV CTLs. Recurrence of CMV infection occurred only in the patients who failed to generate a CTL response to the virus. Hence, recipients of SCT using Alemtuzumab-RIC are initially profoundly immunosuppressed and have a high incidence of early CMV reactivation. However, in the majority of patients, infection is transient, and antiviral T cell reconstitution is rapid. Monitoring with CMV-specific CTLs may help identify the subset of patients at risk from recurrent infection or disease.