Conversion to Rapamycin Immunosuppression for Malignancy After Kidney Transplantation: Case Reports

Iaria, Giuseppe; Anselmo, Alessandro; Luca, Linda De; Manuelli, M.; Lucchesi, Carlo; Tariciotti, Laura; Monaco, Anthony P.; Sforza, D.; Nigro, F.; Abruzzese, Elisabetta; Tisone, Giuseppe

doi:10.1016/j.transproceed.2007.05.046

Cited by 19 publications

(13 citation statements)

References 7 publications

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“…According to several independent studies on organ transplant patients who developed PTLD, substitution of the calcineurine inhibitor-based immunosuppressive therapy with an mTORC1 inhibitor resulted in a potent anti-PTLD effect leading to the full resolution of the PTLD lesions in some cases. [37][38][39][40][41][42][43] Perhaps even more strikingly, a similar therapeutic switch in transplant patients who developed the Kaposi sarcoma resulted in a sustained complete remission in all patients. [42][43][44][45] 822 El-Salem et al AJP August 2009, Vol.…”

Section: Discussionmentioning

confidence: 92%

“…2 The potential usage of mTORC1 inhibitors in AIDS patients may raise the concern of further increasing their immunodeficiency. However, transplant patients are also immunocompromised and yet mTORC1 inhibitors have proven efficacious in such patients, [37][38][39][40][41][42][43][44][45] as discussed above. This observation indicates that the direct effects of mTORC1 inhibitors on malignant cells by impairing their proliferation, survival, and angiogenesis, clearly outweigh immunosuppressive properties of the inhibitors.…”

Section: Discussionmentioning

confidence: 99%

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Activation of mTORC1 Signaling Pathway in AIDS-Related Lymphomas

El-Salem

Raghunath

Marzec

et al. 2009

The American Journal of Pathology

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Using immunohistochemistry with antibodies against the phosphoserine residues in both S6rp and 4E binding protein 1, we identified the activation of the mammalian target of rapamycin (mTORC)1 pathway in 29 cases of AIDS-related lymphoma. These cases represented a diverse spectrum of histological types of nonHodgkin lymphoma (24 cases) and classic Hodgkin lymphoma (five cases). mTORC1 was also activated in the hyperplastic but not involuted follicles of HIV-associated lymphadenopathy in eight cases, supporting the notion that mTORC1 activation is a common feature of transformed lymphocytes irrespective of either their reactive or malignant phenotype. We also found that in B-cell lines that represent diffuse large B-cell lymphoma, Burkitt lymphoma, Epstein-Barr virus-infected lymphocytes, and human herpesvirus 8-positive primary effusion lymphoma, inhibitors of Syk, MEK, and, seemingly , phosphoinositide 3 kinases suppressed mTORC1 activation , in particular when these inhibitors were used in combination. These findings indicate that AIDS-related lymphoma and other histologically similar types of lymphomas that are derived from transformed B lymphocytes may display clinical responses to inhibitors that directly target mTORC1 or , possibly , upstream activators of the mTORC1 pathway.

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Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Activation of mTORC1 Signaling Pathway in AIDS-Related Lymphomas

El-Salem

Raghunath

Marzec

et al. 2009

The American Journal of Pathology

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“…However, results were biased by concomitant dose reduction or suspension of CsA. Other small series report success in reduction of PTLD progression when main drug in the ISR was switched for mTORi (21)(22)(23)(24). database showed a temporal association in the increased incidence of PTLD after TAC started to be used in pediatric kidney transplantation.…”

Section: Discussionmentioning

confidence: 99%

Association of Immunosuppressive Maintenance Regimens With Posttransplant Lymphoproliferative Disorder in Kidney Transplant Recipients

et al. 2012

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“…Despite this increased risk of malignancy, only recently has substantial attention been focused on examining potential differences in tumorigenic potential between immunosuppressive regimens (17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27). Recent studies have reported significantly fewer skin malignancies among renal transplant patients receiving sirolimus (SRL) versus other CNI regimens (18 -21, 25).…”

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confidence: 99%