Rapamycin Inhibits Proliferation of Epstein-Barr Virus–Positive B-cell Lymphomas Through Modulation of Cell-Cycle Protein Expression

Vaysberg, Maria; Balatoni, Cynthia E.; Nepomuceno, Ronald R.; Krams, Sheri M.; Martinez, Olivia M.

doi:10.1097/01.tp.0000260142.38619.9c

Cited by 70 publications

(55 citation statements)

References 28 publications

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“…The decision was made to initially discontinue sirolimus in the short term because the patient had ulcerations, and sirolimus has been shown to impede wound healing compared with tacrolimus. 1 Although sirolimus has antiangiogenic and antitumor properties mostly associated with inhibition of the growth of EBVtransformed B lymphocytes in vitro, 2 there have been no conclusive prospective studies addressing the use of sirolimus in the treatment or prevention of PTLD. In this patient, the approach to reduce immunosuppression was individualized and, given that his PTLD was non-EBV-related, along with the existing significant social and financial barriers, the decision was made to continue the more affordable tacrolimus and prednisone.…”

Section: Departments Of Amentioning

confidence: 99%

Folliculotropic Mycosis Fungoides as a Posttransplant Lymphoproliferative Disorder

Spence-Shishido¹,

Streicher²,

George

et al. 2015

Pediatrics

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Posttransplant lymphoproliferative disorder (PTLD) is a known complication of solid organ transplantation. The majority are B cell in origin and related to Epstein-Barr virus infection. T-cell PTLD is much less common; most are Epstein-Barr virus negative and have a worse prognosis. Primary cutaneous Tcell lymphoma (CTCL) as a presentation of PTLD is rare. CTCL has a less favorable prognosis in transplant patients compared with that in immunecompetent patients. Herein, we report a case of a 13-year-old boy who developed folliculotropic mycosis fungoides, a rare subtype of CTCL, subsequent to renal transplantation. To our knowledge, this is the first report of this type of PTLD in a pediatric patient.

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Section: Departments Of Amentioning

confidence: 99%

Folliculotropic Mycosis Fungoides as a Posttransplant Lymphoproliferative Disorder

Spence-Shishido¹,

Streicher²,

George

et al. 2015

Pediatrics

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“…Inhibition of mTOR has shown preclinical activity against chronic lymphocytic leukemia, 12 Hodgkin's lymphoma (HL), 13 anaplastic large-cell lymphoma, 13 diffuse large B-cell lymphoma (DLBCL), 14 primary effusion lymphoma, 15 post-transplantation lymphoproliferative disease, 16 and acute lymphoblastic leukemia, 17,18 among others. Furthermore, two mTOR inhibitors, temsirolimus and everolimus, have demonstrated promising clinical activity against relapsed or refractory mantle-cell lymphoma.…”

Section: Introductionmentioning

confidence: 99%

Improved Survival in Lymphoma Patients Receiving Sirolimus for Graft-Versus-Host Disease Prophylaxis After Allogeneic Hematopoietic Stem-Cell Transplantation With Reduced-Intensity Conditioning

Armand

Gannamaneni

Kim

et al. 2008

JCO

104

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A B S T R A C T PurposeInhibitors of the mammalian target of rapamycin (mTOR) kinase have shown clinical activity in several lymphoma subtypes. Sirolimus, an mTOR inhibitor, also has activity in the treatment and prophylaxis of graft-versus-host disease (GVHD) after allogeneic hematopoietic stem-cell transplantation (HSCT). We hypothesized that the use of sirolimus for GVHD prophylaxis in patients with lymphoma might lead to improved survival after transplantation through a decreased incidence of disease progression. Patients and MethodsWe retrospectively analyzed 190 patients who underwent transplantation for lymphoma. We compared the outcomes of patients who received sirolimus for GVHD prophylaxis with those of patients who received transplantation with a combination of a calcineurin inhibitor and methotrexate without sirolimus. ResultsOverall survival (OS) after transplantation was significantly superior in the sirolimus group, which was confirmed in multivariable analysis. The benefit was restricted to patients undergoing reduced-intensity conditioning (RIC) HSCT (3-year OS, 66% for sirolimus group v 38% for no-sirolimus group; P ϭ .007; hazard ratio [HR] for mortality in multivariable analysis ϭ 0.5, P ϭ .042). Patients who received sirolimus had a similar incidence of nonrelapse mortality but a decreased incidence of disease progression compared with patients who did not receive sirolimus (3-year cumulative incidence of progression, 42% v 74%, respectively; P Ͻ .001; HR for progression in multivariable analysis ϭ 0.4, P ϭ .01). The effect of sirolimus persisted after adjusting for the occurrence of GVHD. No such survival advantage was apparent in a similar comparison of patients who underwent transplantation for diseases other than lymphoma. ConclusionThis study suggests that sirolimus can independently decrease the risk of lymphoma progression after RIC HSCT, paving the way for prospective clinical trials.

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“…In addition to its immunosuppressive effects, it also displays antiangiogenic and anti-tumour properties, and this make it a potentially attractive agent for patients in remission from PTLD, particularly those who develop chronic allograft rejection as a consequence of a reduction of immunosuppression. Rapamycin inhibits the growth of EBV-transformed B lymphocyte lines in-vitro by arresting cell cycle in the G1 phase (Vaysberg M et al, 2007). There are no prospective studies addressing the use of rapamycin in the treatment or prevention of PTLD.…”

Section: Rapamycinementioning

confidence: 99%

Post Transplant Lymphoproliferative Disorders After Liver Transplantation

Marino¹,

Aversa²,

Stragliotto³

et al. 2012

Liver Transplantation - Technical Issues and Complications

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Rapamycin Inhibits Proliferation of Epstein-Barr Virus–Positive B-cell Lymphomas Through Modulation of Cell-Cycle Protein Expression

Abstract: The results presented here elucidate key targets of RAPA-induced cell cycle arrest, provide insight into the growth pathways of EBV+ B-cell lymphomas, and demonstrate the potential for RAPA as a therapeutic option in the treatment of PTLD and other EBV+ lymphomas.

Cited by 70 publications

References 28 publications

Folliculotropic Mycosis Fungoides as a Posttransplant Lymphoproliferative Disorder

Folliculotropic Mycosis Fungoides as a Posttransplant Lymphoproliferative Disorder

Improved Survival in Lymphoma Patients Receiving Sirolimus for Graft-Versus-Host Disease Prophylaxis After Allogeneic Hematopoietic Stem-Cell Transplantation With Reduced-Intensity Conditioning

Post Transplant Lymphoproliferative Disorders After Liver Transplantation

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