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363: Tacrolimus Neurotoxicity in Lung Transplant Recipients
Abstracts Results: Data is presented for the 6 most recent studies. The study duration ranged from 5 to 41 days (mean 26 days). The VAD rate was 74.5 ⫹/⫺ 9.6 (mean ⫹/⫺sd) beats per minute (estimated flow 1.04 ⫹/⫺ .13 l/min). There were no thromboembolic events. There was no evidence of devicerelated renal infarction; in two cases there were cortical depressions and fibrosis consistent with old infarcts. Conclusions: In vivo testing of the Penn State Pediatric VAD demonstrated low thrombogenicity in a pediatric animal model using moderate levels of anticoagulation. 361 Retinoid Therapy Is Ineffective in Preventing Cutaneous Malignancy Complicating Lung Transplantation T. Tse, D.C. Chambers, P.M.A. Hopkins. The Prince Charles Hospital, Brisbane, QLD, Australia. Purpose: Cutaneous malignancy is a recognised complication of solid organ transplantation and is particularly prevalent in Australia. Retinoid therapy with acitretin has been shown to be effective for the chemoprophylaxis of cutaneous malignancy in renal, liver and heart transplantation but no studies have been performed in lung transplantation (LT). Known effects of acitretin include immunomodulation, antikeratinization, induction of apoptosis and antiproliferation. Methods and Materials: We retrospectively reviewed our experience with acitretin for LT patients at risk of recurrent cutaneous malignancy. In our program acitretin is indicated for patients with recurrent or aggressive non-melanotic cutaneous malignancy. Results: 12 patients (8.6% of our cohort), 3 female, age 41-67 years, median 5 (3-13) years post LT received a dose of 10-25mg acitretin daily for an average of 25 months (9 months to 4 years). Therapy was well tolerated with only one patient experiencing a severe adverse event (hyperostosis). A total of 84 tumours (7.67/patient/year– 42 squamous cell carcinoma, 18 basal cell carcinoma and 24 intraepidermal carcinoma) were excised from the subjects pre commencement of therapy (median 7 per patient (2-15)). 118 tumours (6.25/patient/year–58 squamous cell carcinoma, 9 basal cell carcinoma, 51 intraepidermal carcinoma) were excised after commencement of acitretin (median 7 per patient (3-23)). The annual incidence of cutaneous malignancy did not decline with commencement of therapy despite an overall accompanying reduction in immunosuppression (p⫽ 0.22). 4 of 12 patients experienced a reduction in annual incidence with acitretin (responders). Use of the antifungal agent voriconazole was lower in responders at 1 in 4 or 25% vs 8 of 8 or 100% in non-responders (p⫽0.01, Fishers exact test). Conclusions: Retinoid therapy is well tolerated but does not significantly reduce the annual incidence of cutaneous malignancy in lung transplant recipients. Voriconazole may attenuate the response to acitretin, although further investigation is warranted. 362 PTLD after Lung Transplantation – Influence of CMV Prophylaxis on Incidence – Multicentre Centre Analysis and Review of the Literature P. Jaksch,1 J. Gottlieb,4 C. Geltner,2 A. Simon,3 J. Ankersmit,1 W. Klepetko.1 1Medical University Vienna, Vienna, Austria; 2LKH Natter, Innsbruck, Austria; 3Medical Univerity Hannover, Hannover, Germany; 4Medical Univerity Hannover, Hannover, Germany. Purpose: Post-transplant non-Hodgkin lymphoma are a severe complication after LuTX. Until now no reliable prophylactic regimen is available and the published incidence varies between 1 and 20%. However, kidney transplant recipients, who received anti-CMV immunoglobulin as CMV prophylaxis, showed a complete absence of lymphomas in the first aftertransplantation year (Effect of CMV prophylaxis with IG or with antiviral drugs on postTX non-Hodgkin lymphoma: a multicentre retrospective analysis. Opelz et al, Lancet Oncol 2007; 8: 212–18). We aimed to elucidate the effect of prophylactic treatment for CMV infection on the incidence of PTLD. Methods and Materials: In a multicentre (Vienna, Hannover, Innsbruck) retrospective study, we analyzed the incidence of post-transplant non-
S121 Hodgkin lymphoma in LuTX recipients transplanted between 1989 and 2008 (n⫽2112)). All patients received antiviral drugs (ganciclovir/valganciclovir) for a minimum of three months in combination with anti-CMV IG for prevention of CMV infections. The incidence was compared with published papers (n⫽2178) with regard to CMV prophylaxis and induction therapy. Results: During the first post-transplant year, 19 patients developed B-celllymphoma (incidence of 0,9%) and 14 patients developed PTLD thereafter (incidence of 0,6%)(overall incidence of 1,5%). Risk factor for early PTLD was the use of induction therapy with ATG. In all published papers, were CMV prophylaxis was defined, antiviral therapy for a minimum of 3 months (gan/val) was used. Comparing patient cohorts, including our data, who received CMV-hyperimmunoglobuline vs. none the incidence of PTLD was 1,5% vs. 4,6% (p⬍0,05). Conclusions: These findings suggest that prophylactic anti-CMV IG may reduce the incidence of postTX lymphomas. Prophylactic treatment with antiviral drugs does not reduce the risk of post-transplant lymphoma. Analysis of larger registry data or prospective studies are necessary to confirm this theory. 363 Tacrolimus Neurotoxicity in Lung Transplant Recipients L.J. Stuckey,1 R. Florn,2 C. Bartos,2 H. McCullough,2 M.K. Han,2 K.R. Flaherty,2 V.N. Lama,2 S. Gay,2 T. Ojo,2 F.J. Martinez,2 A.C. Chang,3 R. Mahidhara,3 J. Lin,3 K.M. Chan.2 1University of Michigan Health Systems, Ann Arbor, MI; 2University of Michigan Health Systems, Ann Arbor, MI; 3University of Michigan Health Systems, Ann Arbor, MI. Purpose: There has been a trend of tacrolimus (TAC) replacing cyclosporine microemulsion (CSA) in maintenance immunosuppression regimens primarily due to efficacy. Even though TAC and CSA have similar safety profiles, neurotoxicity seems to occur more frequently in TAC-treated patients. Reported incidence of neurotoxicity in lung transplant recipients is low (4%). Since TAC was added to our protocol in the fall of 2005, we describe the incidence of TAC-induced neurotoxicity in our lung transplant recipients. Methods and Materials: We conducted a retrospective chart review of lung transplant recipients. Patients transplanted between 9/05-5/09 who were initiated on TAC at transplant were included. All patients received azathioprine and prednisone. Patients who survived less than 30 days were excluded from analysis. TAC-induced neurotoxicity was defined as neurological symptoms causing a switch to CSA. Variables examined included baseline characteristics, pre-transplant neurological diagnosis (stroke, seizures, depression, anxiety, etc), CMV status, induction, renal function, albumin, and TAC levels at transplant, which were all analyzed by an univariate model. Results: 99 pts were transplanted over the last 3.5 years. 12 pts (12.1%) developed symptoms that lead to the discontinuation of TAC. Median onset was 88 days (13-413 days). Symptoms included seizures, hallucinations, altered mental status, headaches, and severe tremors. 3 pts (25%) had documented PRES on MRI. At the time of the event, 2 pts (25%) were on voriconazole, while 4 pts (33%) received treatment for rejection within 2 months. All symptoms subsided after discontinuation of TAC. The only variable that demonstrated a significant difference between the pts with and without neurotoxicity was age (55 yrs vs. 47.4 yrs, p⫽0.0002). Conclusions: Our single center experience demonstrates a higher incidence of TAC-induced neurotoxicity in lung transplant recipients than previously reported. Even though our data is limited, older recipients seem to be at a greater risk of developing neurotoxicity from TAC. 364 Posterior Reversible Encephalopathy Syndrome after Lung Transplantation L. Hatos-Agyi,1 A. Scheed,1 M. Keplinger,2 P. Jaksch,1 W. Klepetko.1 1 Medical University of Vienna, Vienna, Austria; 2Medical University of Vienna, Vienna, Austria.
S121 Hodgkin lymphoma in LuTX recipients transplanted between 1989 and 2008 (n⫽2112)). All patients received antiviral drugs (ganciclovir/valganciclovir) for a minimum of three months in combination with anti-CMV IG for prevention of CMV infections. The incidence was compared with published papers (n⫽2178) with regard to CMV prophylaxis and induction therapy. Results: During the first post-transplant year, 19 patients developed B-celllymphoma (incidence of 0,9%) and 14 patients developed PTLD thereafter (incidence of 0,6%)(overall incidence of 1,5%). Risk factor for early PTLD was the use of induction therapy with ATG. In all published papers, were CMV prophylaxis was defined, antiviral therapy for a minimum of 3 months (gan/val) was used. Comparing patient cohorts, including our data, who received CMV-hyperimmunoglobuline vs. none the incidence of PTLD was 1,5% vs. 4,6% (p⬍0,05). Conclusions: These findings suggest that prophylactic anti-CMV IG may reduce the incidence of postTX lymphomas. Prophylactic treatment with antiviral drugs does not reduce the risk of post-transplant lymphoma. Analysis of larger registry data or prospective studies are necessary to confirm this theory. 363 Tacrolimus Neurotoxicity in Lung Transplant Recipients L.J. Stuckey,1 R. Florn,2 C. Bartos,2 H. McCullough,2 M.K. Han,2 K.R. Flaherty,2 V.N. Lama,2 S. Gay,2 T. Ojo,2 F.J. Martinez,2 A.C. Chang,3 R. Mahidhara,3 J. Lin,3 K.M. Chan.2 1University of Michigan Health Systems, Ann Arbor, MI; 2University of Michigan Health Systems, Ann Arbor, MI; 3University of Michigan Health Systems, Ann Arbor, MI. Purpose: There has been a trend of tacrolimus (TAC) replacing cyclosporine microemulsion (CSA) in maintenance immunosuppression regimens primarily due to efficacy. Even though TAC and CSA have similar safety profiles, neurotoxicity seems to occur more frequently in TAC-treated patients. Reported incidence of neurotoxicity in lung transplant recipients is low (4%). Since TAC was added to our protocol in the fall of 2005, we describe the incidence of TAC-induced neurotoxicity in our lung transplant recipients. Methods and Materials: We conducted a retrospective chart review of lung transplant recipients. Patients transplanted between 9/05-5/09 who were initiated on TAC at transplant were included. All patients received azathioprine and prednisone. Patients who survived less than 30 days were excluded from analysis. TAC-induced neurotoxicity was defined as neurological symptoms causing a switch to CSA. Variables examined included baseline characteristics, pre-transplant neurological diagnosis (stroke, seizures, depression, anxiety, etc), CMV status, induction, renal function, albumin, and TAC levels at transplant, which were all analyzed by an univariate model. Results: 99 pts were transplanted over the last 3.5 years. 12 pts (12.1%) developed symptoms that lead to the discontinuation of TAC. Median onset was 88 days (13-413 days). Symptoms included seizures, hallucinations, altered mental status, headaches, and severe tremors. 3 pts (25%) had documented PRES on MRI. At the time of the event, 2 pts (25%) were on voriconazole, while 4 pts (33%) received treatment for rejection within 2 months. All symptoms subsided after discontinuation of TAC. The only variable that demonstrated a significant difference between the pts with and without neurotoxicity was age (55 yrs vs. 47.4 yrs, p⫽0.0002). Conclusions: Our single center experience demonstrates a higher incidence of TAC-induced neurotoxicity in lung transplant recipients than previously reported. Even though our data is limited, older recipients seem to be at a greater risk of developing neurotoxicity from TAC. 364 Posterior Reversible Encephalopathy Syndrome after Lung Transplantation L. Hatos-Agyi,1 A. Scheed,1 M. Keplinger,2 P. Jaksch,1 W. Klepetko.1 1 Medical University of Vienna, Vienna, Austria; 2Medical University of Vienna, Vienna, Austria.