Sirolimus therapy in liver transplant patients: an initial experience at a single center.
Sirolimus (SRL) is an mTOR inhibitor that has been shown, in contrast to calcineurin inhibitors (CNI), to inhibit cancers in experimental models. Since February 2005, we introduced SRL in liver transplant patients in group a, in whom the primary disease was hepatocellular carcinoma (HCC) associated with hepatitis B virus (HBV), hepatitis C virus (HCV), alcoholic or autoimmune liver cirrhosis, and group b, HCC-negative patients who developed posttransplantation cancers de novo. Of 18 patients in group a, 11 received SRL ab initio (subgroup a1), starting for 10 patients at 66.1+/-29.2 days after surgical healing and after 10 days in 1 case; the remaining 7 patients (subgroup a2) received SRL at 31.2+/-24.2 months. Three patients in group b, included 1 with Kaposi's sarcoma, 1 with bladder cancer, and 1 with thyroid cancer. In this group, SRL was introduced at 80.8+/-40.4 months. In all patients but one, who received a single 5 mg loading dose, SRL was started at 2 mg/d and adjusted to 6 to 8 ng/mL blood levels. CNI drugs, present as primary therapy, were gradually tapered to low levels and eventually stopped. The following observations were drawn from this initial experience: (1) 4/21 (19.0%) patients had to discontinue SRL because of early and late side effects: thrombocytopenia (n=2) and headache with leukopenia and leg edema associated with knee joint arthralgia (n=2); (2) 14 patients (11 in group a and 3 in group b) are still on SRL monotherapy; (3) 1 HCC recurrence and 1 de novo pancreatic adenocarcinoma were observed at 14 and 16 months, respectively (at the time of transplantation, both patients were beyond the MIlan HCC criteria), and (4) 1 patient, from subgroup a1, died after 99 days due to pneumonitis and possible relation to SRL lung toxicity. In conclusion, SRL appeared to be an effective immunosuppressant that could be used as monotherapy in liver transplant patients. Any conclusion on SRL anticancer effects can only come from randomized large studies after long follow-up.
Nocera
A
A
Transplant Immunology Unit, San Martino Hospital, Genoa, Italy. arcangelo.nocera@hsanmartino.it
Andorno
E
E
Tagliamacco
A
A
Morelli
N
N
Bottino
G
G
Ravazzoni
F
F
Casaccia
M
M
Barocci
S
S
Alice
S
S
Santori
G
G
Ghirelli
R
R
Valente
U
U
D000740:Anemia / Q000453:epidemiology; D006528:Carcinoma, Hepatocellular / Q000601:surgery / Q000821:virology; D006509:Hepatitis B / Q000150:complications; D006526:Hepatitis C / Q000150:complications; D006801:Humans; D006937:Hypercholesterolemia / Q000453:epidemiology; D015228:Hypertriglyceridemia / Q000453:epidemiology; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use; D008113:Liver Neoplasms / Q000601:surgery / Q000821:virology; D016031:Liver Transplantation / Q000276:immunology*; D012189:Retrospective Studies; D020123:Sirolimus / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
D007166:Immunosuppressive Agents; D020123:Sirolimus