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Clinical utility of cyclosporin C2 monitoring after lung transplantation (LTX)
The Journal of Heart and Lung Transplantation Volume 21, Number 1
Abstracts
compared with an historical control group of 37 patients (Group II) undergoing BLT through the standard clamshell incision. In Group I 2 patients required transverse sternotomy to institute cardio-pulmonary by pass due to hemodynamic instability. The difference between the cold ischemic time of the first and second transplanted lung was not statistically significant between the two groups (75 ⫹/- 14 min vs 72 ⫹/- 15 min.). Postoperative vital capacity measured 3 weeks after the transplant was significantly different between group I and II (66 ⫹/- 16% vs 40 ⫹/- 10% predicted). No wound related complication was observed in Group I; in Group II there were 17 complications related to the surgical approach: sternal ostemyelitis due to Ps Coepacea in 3 patients with cystic fibrosis (surgical debridement and closure with a muscle flap), migration of the Kirschner wire in 3 (removal of the wire), sternal override in 3 (surgical correction and fixation), prolonged pain in 8 (medical treatment). The bilateral sequential antero-lateral thoracotomy is a safe and less invasive approach for BLT; it reduces the incidence of chest wall complications and contributes to improve respiratory function in the early postoperative period. 245 IMPACT OF RECIPIENT AGE AND PROCEDURE TYPE ON SURVIVAL FOLLOWING LUNG TRANSPLANTATION FOR INTERSTITIAL PULMONARY FIBROSIS D.M. Meyer,1 L.E. Bennett,2 F. Torres,3 M.E. Jessen,1 R.J. Novick,4 1Cardiovascular and Thoracic Surgery, University of Texas Southwestern Medical Center, Dallas, TX; 2United Network for Organ Sharing, Richmond, VA; 3St. Paul Medical Center, Dallas, TX; 4London Health Sciences Center, London, Ontario, Canada Whether to perform single (SLT) or bilateral sequential (BSLT) lung transplantation in patients with interstitial pulmonary fibrosis (IPF) is controversial. Some centers use recipient age (⬍50 years) as a criterion to select BSLT over SLT, but the rationale for this approach is not established. 821 patients (636 SLT/185 BSLT), aged 30-69 years, transplanted for IPF in the US between 1994 and 2000, were reported to the United Network for Organ Sharing. Survival was compared by procedure type within 3 age groups (30-49, 50-59, 60-69 years) using the Kaplan-Meier method. Multivariate logistic regression analysis was used to calculate risk-adjusted mortality within 1 month post-transplant and proportional hazards regression was used to calculate riskadjusted mortality after 1 month. Survival in recipients aged 30-49 and in those aged 50-59 was significantly better with SLT than BSLT (P⫽0.02, P⫽0.03, respectively, see Table). When post-transplant survival was reanalyzed contingent upon survival to 3 months, no significant difference in survival by procedure type (SLT vs BSLT) was detected for any age group. The multivariate analyses of survival, adjusting for other known risk factors (CMV status, ventilator dependence, pulmonary artery pressures, graft ischemic time, donor age, etc.), yielded similar results. Patient Age
Procedure
30–49
SLT
30–49 50–59
BSLT SLT
50–59
BSLT
n
1 month survival (%)
3 month survival (%)
1 year survival (%)
3 year survival (%)
14 5 85 28 9 80
90.9
85.4
74.0
63.8
77.1 89.5
68.7 83.0
64.4 69.8
46.2 53.6
81.7
70.1
55.5
46.7
143
Patients less than 60 years of age transplanted for IPF appear to have better survival with SLT than with BSLT. While the basis for this observation is unclear, events occurring in the early period (first 3 months) after transplantation may play a role. Further studies will be needed, but these data do not appear to support the preferential use of BSLT for younger patients with IPF. 246 CLINICAL UTILITY OF CYCLOSPORIN C2 MONITORING AFTER LUNG TRANSPLANTATION (LTX) A.R. Glanville, P.M. Hopkins, C.L. Aboyoun, P.N. Chhajed, M.L. Plit, M.A. Malouf, The Lung Transplant Unit, St Vincent’s Hospital, Sydney, Australia Background: Cyclosporin (CyA) toxicity is associated with renal dysfunction, which occurs in 36 % of LTX recipients at 5 years, 4 % of whom need dialysis. Reducing CyA to “subtherapeutic” trough (C0) levels risks emergence of acute & chronic allograft rejection. Although area under the curve (AUC) monitoring correlates with efficacy and toxicity it is not always practicable. Limited sampling strategies favour the 2-hour post dose concentration (C2) as the best single point surrogate measure of CyA AUC. Aim: To assess the utility of C2 monitoring after LTX. Methods: We prospectively evaluated 45 patients for conversion from traditional C0 monitoring to C2 monitoring. 15/45 (33%), (M: F⫽12:3), aged 47⫹/-14 years (range 28-62) @ 3.5⫹/-2.7 (0.2-9.0) years post LTX with C0 in the low therapeutic range (100-200 mcg/L) but abnormal renal function had dosage reductions targeting C2 levels of 300-600mcg/L (Behring/EMIT immunoassay). Diagnoses included cystic fibrosis (n⫽5/14), emphysema (n⫽4/14), pulmonary fibrosis (n⫽5/12) and asthma (n⫽1/ 1). Results: CyA dosage was reduced from 6.4⫹/-7.3(1.2-27.9) to 3.9⫹/-3.7(0.9-12.9) mg/kg/d (p⬍0.05) with a reduction in C2 (n⫽15) levels from 794⫹/-363(299-1416) to 479⫹/-199 (2041029) mcg/L (p⬍0.01) and C0 (n⫽10) from 184⫹/-105(60-368) to 103⫹/-26(62-144) mcg/L (p⬍0.05). Serum creatinine improved from 0.20⫹/-0.07(0.12-0.35) to 0.16⫹/-0.05(0.11-0.25) mmol/L (p⬍0.01). Magnitude of effect varied inversely with time post LTX. Lung function remained stable and no patient developed acute rejection during study follow up of 102⫹/-60 (30-270) days. Conclusions: Conversion to a limited sampling strategy using C2 monitoring is a practical method of facilitating renal preservation by allowing safe dosage alterations of CyA in patients where repeated formal AUC monitoring is not feasible. Short-term risks of allograft rejection appear low. De novo utilisation of C2 monitoring holds promise of improving cost efficiency and reducing the risk of permanent renal dysfunction. 247 THE IMPORTANCE OF AREA UNDER THE CURVE MONITORING OF CYCLOSPORIN IN PATIENTS WITH CYSTIC FIBROSIS AFTER LUNG TRANSPLANTATION J.M. Morton,1 L.M. Kear,1 S. Williamson,1 D. Davis,2 J.M. Potter,2 1Queensland Lung Transplant Unit, The Prince Charles Hospital, Brisbane, Australia; 2Queensland Health Pathology Service, The Prince Charles Hospital, Brisbane, Australia Background: Traditional monitoring for Cyclosporin (CsA) utilises trough concentrations (C0). Recent studies in solid organ
Abstracts
compared with an historical control group of 37 patients (Group II) undergoing BLT through the standard clamshell incision. In Group I 2 patients required transverse sternotomy to institute cardio-pulmonary by pass due to hemodynamic instability. The difference between the cold ischemic time of the first and second transplanted lung was not statistically significant between the two groups (75 ⫹/- 14 min vs 72 ⫹/- 15 min.). Postoperative vital capacity measured 3 weeks after the transplant was significantly different between group I and II (66 ⫹/- 16% vs 40 ⫹/- 10% predicted). No wound related complication was observed in Group I; in Group II there were 17 complications related to the surgical approach: sternal ostemyelitis due to Ps Coepacea in 3 patients with cystic fibrosis (surgical debridement and closure with a muscle flap), migration of the Kirschner wire in 3 (removal of the wire), sternal override in 3 (surgical correction and fixation), prolonged pain in 8 (medical treatment). The bilateral sequential antero-lateral thoracotomy is a safe and less invasive approach for BLT; it reduces the incidence of chest wall complications and contributes to improve respiratory function in the early postoperative period. 245 IMPACT OF RECIPIENT AGE AND PROCEDURE TYPE ON SURVIVAL FOLLOWING LUNG TRANSPLANTATION FOR INTERSTITIAL PULMONARY FIBROSIS D.M. Meyer,1 L.E. Bennett,2 F. Torres,3 M.E. Jessen,1 R.J. Novick,4 1Cardiovascular and Thoracic Surgery, University of Texas Southwestern Medical Center, Dallas, TX; 2United Network for Organ Sharing, Richmond, VA; 3St. Paul Medical Center, Dallas, TX; 4London Health Sciences Center, London, Ontario, Canada Whether to perform single (SLT) or bilateral sequential (BSLT) lung transplantation in patients with interstitial pulmonary fibrosis (IPF) is controversial. Some centers use recipient age (⬍50 years) as a criterion to select BSLT over SLT, but the rationale for this approach is not established. 821 patients (636 SLT/185 BSLT), aged 30-69 years, transplanted for IPF in the US between 1994 and 2000, were reported to the United Network for Organ Sharing. Survival was compared by procedure type within 3 age groups (30-49, 50-59, 60-69 years) using the Kaplan-Meier method. Multivariate logistic regression analysis was used to calculate risk-adjusted mortality within 1 month post-transplant and proportional hazards regression was used to calculate riskadjusted mortality after 1 month. Survival in recipients aged 30-49 and in those aged 50-59 was significantly better with SLT than BSLT (P⫽0.02, P⫽0.03, respectively, see Table). When post-transplant survival was reanalyzed contingent upon survival to 3 months, no significant difference in survival by procedure type (SLT vs BSLT) was detected for any age group. The multivariate analyses of survival, adjusting for other known risk factors (CMV status, ventilator dependence, pulmonary artery pressures, graft ischemic time, donor age, etc.), yielded similar results. Patient Age
Procedure
30–49
SLT
30–49 50–59
BSLT SLT
50–59
BSLT
n
1 month survival (%)
3 month survival (%)
1 year survival (%)
3 year survival (%)
14 5 85 28 9 80
90.9
85.4
74.0
63.8
77.1 89.5
68.7 83.0
64.4 69.8
46.2 53.6
81.7
70.1
55.5
46.7
143
Patients less than 60 years of age transplanted for IPF appear to have better survival with SLT than with BSLT. While the basis for this observation is unclear, events occurring in the early period (first 3 months) after transplantation may play a role. Further studies will be needed, but these data do not appear to support the preferential use of BSLT for younger patients with IPF. 246 CLINICAL UTILITY OF CYCLOSPORIN C2 MONITORING AFTER LUNG TRANSPLANTATION (LTX) A.R. Glanville, P.M. Hopkins, C.L. Aboyoun, P.N. Chhajed, M.L. Plit, M.A. Malouf, The Lung Transplant Unit, St Vincent’s Hospital, Sydney, Australia Background: Cyclosporin (CyA) toxicity is associated with renal dysfunction, which occurs in 36 % of LTX recipients at 5 years, 4 % of whom need dialysis. Reducing CyA to “subtherapeutic” trough (C0) levels risks emergence of acute & chronic allograft rejection. Although area under the curve (AUC) monitoring correlates with efficacy and toxicity it is not always practicable. Limited sampling strategies favour the 2-hour post dose concentration (C2) as the best single point surrogate measure of CyA AUC. Aim: To assess the utility of C2 monitoring after LTX. Methods: We prospectively evaluated 45 patients for conversion from traditional C0 monitoring to C2 monitoring. 15/45 (33%), (M: F⫽12:3), aged 47⫹/-14 years (range 28-62) @ 3.5⫹/-2.7 (0.2-9.0) years post LTX with C0 in the low therapeutic range (100-200 mcg/L) but abnormal renal function had dosage reductions targeting C2 levels of 300-600mcg/L (Behring/EMIT immunoassay). Diagnoses included cystic fibrosis (n⫽5/14), emphysema (n⫽4/14), pulmonary fibrosis (n⫽5/12) and asthma (n⫽1/ 1). Results: CyA dosage was reduced from 6.4⫹/-7.3(1.2-27.9) to 3.9⫹/-3.7(0.9-12.9) mg/kg/d (p⬍0.05) with a reduction in C2 (n⫽15) levels from 794⫹/-363(299-1416) to 479⫹/-199 (2041029) mcg/L (p⬍0.01) and C0 (n⫽10) from 184⫹/-105(60-368) to 103⫹/-26(62-144) mcg/L (p⬍0.05). Serum creatinine improved from 0.20⫹/-0.07(0.12-0.35) to 0.16⫹/-0.05(0.11-0.25) mmol/L (p⬍0.01). Magnitude of effect varied inversely with time post LTX. Lung function remained stable and no patient developed acute rejection during study follow up of 102⫹/-60 (30-270) days. Conclusions: Conversion to a limited sampling strategy using C2 monitoring is a practical method of facilitating renal preservation by allowing safe dosage alterations of CyA in patients where repeated formal AUC monitoring is not feasible. Short-term risks of allograft rejection appear low. De novo utilisation of C2 monitoring holds promise of improving cost efficiency and reducing the risk of permanent renal dysfunction. 247 THE IMPORTANCE OF AREA UNDER THE CURVE MONITORING OF CYCLOSPORIN IN PATIENTS WITH CYSTIC FIBROSIS AFTER LUNG TRANSPLANTATION J.M. Morton,1 L.M. Kear,1 S. Williamson,1 D. Davis,2 J.M. Potter,2 1Queensland Lung Transplant Unit, The Prince Charles Hospital, Brisbane, Australia; 2Queensland Health Pathology Service, The Prince Charles Hospital, Brisbane, Australia Background: Traditional monitoring for Cyclosporin (CsA) utilises trough concentrations (C0). Recent studies in solid organ