PMID- 10385089
OWN - NLM
STAT- MEDLINE
DCOM- 19990715
LR  - 20190713
IS  - 0041-1337 (Print)
IS  - 0041-1337 (Linking)
VI  - 67
IP  - 11
DP  - 1999 Jun 15
TI  - Pretransplant chemotherapy reduces inflammatory cytokine production and acute 
      graft-versus-host disease after allogeneic bone marrow transplantation.
PG  - 1478-80
AB  - BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) is known to be a critical 
      effector molecule in the pathogenesis of graft-versus-host disease (GVHD), and 
      elevated levels during bone marrow transplantation (BMT) conditioning are 
      associated with more severe GVHD. Many patients receive chemotherapy prior to 
      BMT, but its effect on subsequent toxicities is controversial. METHODS: We 
      studied the effect of prior chemotherapy on GVHD severity and inflammatory 
      cytokine generation in a well-established murine model of allogeneic BMT 
      (B6-->B6D2F1). RESULTS: Three weeks after a single dose of cyclophosphamide, bone 
      marrow and splenic cellularity was reduced by 50% and the production of TNF-alpha 
      to LPS stimulation by macrophages was also markedly impaired (both before and 
      after total body irradiation). Allogeneic BMT recipients previously treated with 
      cyclophosphamide had significantly less GVHD and improved survival relative to 
      recipients previously pretreated with diluent only. This survival advantage was 
      associated with reduced systemic levels of both TNF-alpha and interleukin-1beta 7 
      days after BMT. This reduction occurred despite equivalent serum levels of 
      lipopolysaccharide, consistent with the reductions in TNF-alpha and 
      interleukin-1beta production by host macrophages after cyclophosphamide 
      pretreatment. CONCLUSIONS: These data support the notion that patients entering 
      BMT conditioning without prior cytotoxic treatment (e.g., patients with chronic 
      myeloid leukemia) may be at increased risk of posttransplant complications 
      associated with excessive inflammatory cytokine production.
FAU - Hill, G R
AU  - Hill GR
AD  - Department of Pediatric Oncology, Dana Farber Cancer Institute, Harvard Medical 
      School, Boston, Massachusetts 02115, USA.
FAU - Cooke, K R
AU  - Cooke KR
FAU - Brinson, Y S
AU  - Brinson YS
FAU - Bungard, D
AU  - Bungard D
FAU - Ferrara, J L
AU  - Ferrara JL
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Transplantation
JT  - Transplantation
JID - 0132144
RN  - 0 (Cytokines)
RN  - 0 (Interleukin-1)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 8N3DW7272P (Cyclophosphamide)
SB  - IM
MH  - Acute Disease
MH  - Animals
MH  - Bone Marrow Transplantation/*immunology
MH  - Cyclophosphamide/therapeutic use
MH  - Cytokines/*biosynthesis
MH  - Graft vs Host Disease/etiology/*prevention & control
MH  - Humans
MH  - Interleukin-1/blood
MH  - Mice
MH  - *Transplantation Conditioning
MH  - Tumor Necrosis Factor-alpha/analysis
EDAT- 1999/06/29 00:00
MHDA- 1999/06/29 00:01
CRDT- 1999/06/29 00:00
PHST- 1999/06/29 00:00 [pubmed]
PHST- 1999/06/29 00:01 [medline]
PHST- 1999/06/29 00:00 [entrez]
AID - 10.1097/00007890-199906150-00015 [doi]
PST - ppublish
SO  - Transplantation. 1999 Jun 15;67(11):1478-80. doi: 
      10.1097/00007890-199906150-00015.