Functional hyperactivity of monocytes after bone marrow transplantation: possible relevance for the development of post-transplant complications or relapse.
Bone marrow transplant (BMT) complications such as graft-versus-host disease (GVHD), veno-occlusive disease (VOD) and cytomegalovirus (CMV) infection are associated with high levels of circulating tumour necrosis factor-alpha (TNF), much of which may be monocyte derived. We therefore studied monocyte activation after BMT in 36 patients (18 allografts and 18 autografts); plasma neopterin and in vitro secretion of superoxide, neopterin and TNF by peripheral blood monocytes were assessed. Monocyte respiratory burst was raised at regeneration but returned to near-normal within 7 days. Plasma neopterin, and in vitro secretion of neopterin and TNF, were greater than twice normal at regeneration and remained raised for up to 6 weeks after BMT. Plasma neopterin was higher following allogeneic BMT than autologous BMT and was independent of GVHD or VOD. Low levels were seen in one patient who failed to engraft. There is evidence of increased activation of monocytes at the time of and for several weeks after engraftment post-BMT. Abnormal monocyte activation may predispose to, rather than result from, the development of complications in the early post-transplant period.
Castenskiold
E C
EC
Department of Haematology, Royal London Hospital, UK.
Kelsey
S M
SM
Collins
P W
PW
Coldwell
R D
RD
Allen
P D
PD
Side
L E
LE
Makin
H L
HL
Goldstone
A H
AH
Newland
A C
AC
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D015415:Biomarkers; D001708:Biopterins / Q000031:analogs & derivatives / Q000378:metabolism; D016026:Bone Marrow Transplantation / Q000276:immunology*; D002066:Busulfan / Q000008:administration & dosage; D002330:Carmustine / Q000008:administration & dosage; D002478:Cells, Cultured; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D003561:Cytarabine / Q000008:administration & dosage; D004198:Disease Susceptibility / Q000276:immunology; D005260:Female; D006086:Graft vs Host Disease / Q000097:blood; D006504:Hepatic Veno-Occlusive Disease / Q000097:blood; D006801:Humans; D007938:Leukemia / Q000628:therapy; D008223:Lymphoma / Q000628:therapy; D008297:Male; D008558:Melphalan / Q000008:administration & dosage / Q000627:therapeutic use; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology*; D019798:Neopterin; D011034:Podophyllotoxin / Q000008:administration & dosage; D016897:Respiratory Burst; D013481:Superoxides / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014916:Whole-Body Irradiation
D015415:Biomarkers; D014409:Tumor Necrosis Factor-alpha; D003561:Cytarabine; D013481:Superoxides; D001708:Biopterins; D019798:Neopterin; D003520:Cyclophosphamide; D002066:Busulfan; D011034:Podophyllotoxin; D008558:Melphalan; D002330:Carmustine