PMID- 22499411
OWN - NLM
STAT- MEDLINE
DCOM- 20120917
LR  - 20131121
IS  - 1875-9114 (Electronic)
IS  - 0277-0008 (Linking)
VI  - 32
IP  - 5
DP  - 2012 May
TI  - Possible correlation of sirolimus plasma concentration with sinusoidal 
      obstructive syndrome of the liver in patients undergoing myeloablative allogeneic 
      hematopoietic cell transplantation.
PG  - 441-5
LID - 10.1002/j.1875-9114.2012.01034.x [doi]
AB  - STUDY OBJECTIVES: To determine the frequency of sinusoidal obstructive syndrome 
      (SOS) in patients undergoing allogeneic hematopoietic cell transplantation who 
      received graft-versus-host disease (GVHD) prophylaxis with sirolimus and 
      tacrolimus, and to assess whether the occurrence of SOS correlates with 
      immunosuppressant levels. DESIGN: Retrospective cohort study. SETTING: 
      Hematopoietic cell transplant unit at an academic medical center. PATIENTS: 
      Fifty-nine adults who received myeloablative preparative regimens for 
      transplantation of any hematologic malignancy and received sirolimus and 
      tacrolimus for GVHD prophylaxis between January 1, 2007, and May 1, 2009; all 
      donors and transplant recipients were human leukocyte antigen (HLA) matched for 
      at least HLA-A, -B, -C, and -DRB1. MEASUREMENTS AND MAIN RESULTS: The primary 
      outcome was the occurrence of SOS after hematopoietic cell transplantation. 
      Plasma concentrations of sirolimus and tacrolimus and the summative levels of 
      sirolimus and tacrolimus were then compared in patients who developed SOS with 
      those who did not develop SOS. Trough levels were measured from blood samples 
      collected 30-60 minutes before the morning doses of sirolimus and tacrolimus on 
      days 0-35, or until the development of SOS. Of the 59 patients, 12 (20%) 
      developed SOS. The mean sirolimus level was significantly higher in patients who 
      developed SOS relative to those who did not develop SOS (10.5 vs 8.7 ng/ml, 
      p=0.003). The mean summative trough level of sirolimus and tacrolimus was also 
      significantly higher in those who developed SOS compared with those who did not 
      (19.7 vs 17.1 ng/ml, p=0.003). The mean +/- SD time to the occurrence of SOS was 28 
      +/- 8.7 days. The median time to death was 101 days for patients who developed SOS 
      compared with 433 days for patients who did not develop SOS (p=0.002). 
      CONCLUSION: Sirolimus plasma concentration may correlate with the development of 
      delayed SOS; however, further research is needed to prospectively evaluate the 
      role of sirolimus exposure in the pathogenesis of SOS.
CI  - (c) 2012 Pharmacotherapy Publications, Inc.
FAU - Kiel, Patrick J
AU  - Kiel PJ
AD  - Department of Pharmacy, Indiana University Simon Cancer Center, Indianapolis, 
      Indiana 46202, USA. pkiel@iuhealth.org
FAU - Vargo, Craig A
AU  - Vargo CA
FAU - Patel, Gourang P
AU  - Patel GP
FAU - Rosenbeck, Lindsay L
AU  - Rosenbeck LL
FAU - Srivastava, Shivani
AU  - Srivastava S
LA  - eng
PT  - Journal Article
DEP - 20120412
PL  - United States
TA  - Pharmacotherapy
JT  - Pharmacotherapy
JID - 8111305
RN  - 0 (Immunosuppressive Agents)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Adult
MH  - Cohort Studies
MH  - Female
MH  - Graft vs Host Disease/*prevention & control
MH  - *Hematopoietic Stem Cell Transplantation
MH  - Hepatic Veno-Occlusive Disease/blood/*chemically induced/epidemiology
MH  - Humans
MH  - Immunosuppressive Agents/administration & dosage/adverse 
      effects/*blood/therapeutic use
MH  - Male
MH  - Middle Aged
MH  - Retrospective Studies
MH  - Sirolimus/administration & dosage/adverse effects/*blood/therapeutic use
MH  - Transplantation Conditioning/*methods
MH  - Transplantation, Homologous
MH  - Treatment Outcome
EDAT- 2012/04/14 06:00
MHDA- 2012/09/18 06:00
CRDT- 2012/04/14 06:00
PHST- 2012/04/14 06:00 [entrez]
PHST- 2012/04/14 06:00 [pubmed]
PHST- 2012/09/18 06:00 [medline]
AID - 10.1002/j.1875-9114.2012.01034.x [doi]
PST - ppublish
SO  - Pharmacotherapy. 2012 May;32(5):441-5. doi: 10.1002/j.1875-9114.2012.01034.x. 
      Epub 2012 Apr 12.