Distinct EBV and CMV reactivation patterns following antibody-based immunosuppressive regimens in patients with severe aplastic anemia.
The natural history of EBV and CMV reactivation and the potential for serious complications following antibody-based immunosuppressive treatment for bone marrow failure syndromes in the absence of transplantation is not known. We monitored blood for EBV and CMV reactivation by polymerase chain reaction (PCR) weekly in 78 consecutive patients (total of 99 immunosuppressive courses) with aplastic anemia. Four regimens were studied: (1) HC, horse ATG/cyclosporine; (2) HCS, horse ATG/CsA/sirolimus; (3) RC, rabbit ATG/CsA; and (4) CP, alemtuzumab. There were no cases of EBV or CMV disease, but EBV reactivation occurred in 82 (87%) of 94 and CMV reactivation in 19 (33%) of 57 seropositive patients after starting immunosuppression. The median peak EBV copies were higher in the RC group when compared with HC, HCS, and alemtuzumab (P < .001). The median duration of PCR positivity for EBV was higher in the RC group compared with HC, HCS, and alemtuzumab (P = .001). Subclinical reactivation of both EBV and CMV is common and nearly always self-limited in patients with bone marrow failure receiving immunosuppression; different regimens are associated with different intensity of immunosuppression as measured by viral load and lymphocyte count; and viral reactivation patterns differ according to immunosuppressive regimens.
Scheinberg
Phillip
P
Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA. scheinbp@nhlbi.nih.gov
Fischer
Steven H
SH
Li
Li
L
Nunez
Olga
O
Wu
Colin O
CO
Sloand
Elaine M
EM
Cohen
Jeffrey I
JI
Young
Neal S
NS
John Barrett
A
A
D000293:Adolescent; D000328:Adult; D000368:Aged; D000074323:Alemtuzumab; D000741:Anemia, Aplastic / Q000097:blood* / Q000150:complications / Q000188:drug therapy / Q000821:virology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000008:administration & dosage / Q000009:adverse effects; D000961:Antilymphocyte Serum / Q000008:administration & dosage / Q000009:adverse effects*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D016572:Cyclosporine / Q000008:administration & dosage / Q000009:adverse effects; D003587:Cytomegalovirus; D003586:Cytomegalovirus Infections / Q000097:blood* / Q000139:chemically induced; D004279:DNA, Viral / Q000097:blood; D020031:Epstein-Barr Virus Infections / Q000097:blood* / Q000139:chemically induced; D005260:Female; D004854:Herpesvirus 4, Human; D006736:Horses; D006801:Humans; D007165:Immunosuppression Therapy / Q000009:adverse effects; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D008991:Monitoring, Physiologic; D016133:Polymerase Chain Reaction; D011817:Rabbits; D020123:Sirolimus / Q000008:administration & dosage / Q000009:adverse effects; D013997:Time Factors; D014775:Virus Activation / Q000187:drug effects*
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D000961:Antilymphocyte Serum; D000970:Antineoplastic Agents; D004279:DNA, Viral; D007166:Immunosuppressive Agents; D000074323:Alemtuzumab; D016572:Cyclosporine; D020123:Sirolimus