The use of sirolimus as a rescue therapy in pediatric intestinal transplant recipients

Abstract

To review our experience with SRL as a second-line therapy in our series of 45 SBTx recipients (1997-2009). Retrospective review of five children converted to SRL: 3 M/2 F; median of three yr old (range 20 months-18 yr); rescue indications, adverse events with SRL, resolution of tacrolimus-related side effects, incidence of rejection, PTLD, or GVHD were summarized. Tacrolimus was discontinued (average 13 months after transplant) because of refractory hemolytic anemia in four patients with decreased renal function and because of advanced renal failure and unclear neutropenia in one. PTLD and GVHD had been previously diagnosed in two. Tacrolimus-related side effects disappeared in all five although other immunosuppressants and splenectomy were used simultaneously or later in most of them. Adverse events reported after the conversion were infections (tuberculosis and Pneumocystis carinii in two) and mild hypertriglyceridemia. No rejection, GVHD, or PTLD episode was observed. Four patients are alive with excellent quality of life (median follow-up 18 months). Sirolimus is a safe rescue therapy in SBTx children when tacrolimus is not well tolerated. Renal function and hematologic disorders seem to improve, although other simultaneous strategies could be also involved. Further studies could demonstrate its efficacy as a first-line treatment.

Autoimmune hemolytic anemia: An unusual presentation of hemophagocytic lymphohistiocytosis in a pediatric post–liver transplant patient

“…With rituximab, one should consider the risk of additional immunosuppression in patients who are already immunosuppressed, such as our patient. In AIHA, it is also recommended to run lower levels of serum tacrolimus or to consider switching to sirolimus, which seems to have less of an effect on the thymus . For this reason, we decided to initially run lower levels of tacrolimus and also considered switching to therapy to sirolimus.…”

Targeting the PI3K/AKT/mTOR Signaling Axis in Children with Hematologic Malignancies

“…This approach has been recently shown to improve PTLD in many cases, occasionally inducing a complete remission. [210][211][212][213] ALPS is a disorder of abnormal lymphocyte survival caused by defective Fas-mediated apoptosis. [135,214,215] Children with ALPS often present with lymphoproliferation (massive lymphadenopathy and/or splenomegaly) and autoimmune disease (most commonly autoimmune cytopenias).…”

Pneumocystis jirovecii pneumonia in non-HIV-infected patients

“…PJP has been reported following renal [50], cardiac [51] and intestinal [45] transplantation. Lymphocytopenia, particularly CD4 þ lymphocytopenia, has been identified as a risk factor for development of PJP following renal transplantation [52], with infection reported in the late transplant period (median 19 months following renal transplantation) [53].…”