CAR-T therapy in solid transplant recipients with post-transplant lymphoproliferative disease: case report and literature review

Hernani, Rafael; Sancho, Asunción; Amat, Paula; Hernández‐Boluda, Juan Carlos; Pérez, Ariadna; Piñana, José Luís; Carretero, Carlos; Goterris, Rosa; Gómez, Montse; Saus, Ana; Ferrer, Blanca; Teruel, Ana Isabel; Terol, María José; Solano, Carlos

doi:10.1016/j.retram.2021.103304

Cited by 14 publications

(15 citation statements)

References 24 publications

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“…The observations that chemotherapy lymphodepleting agents prior to CAR T-cell administration could act later as immunosuppressants and that B-cell aplasia and hypogammaglobulinemia caused by CAR T cells could decrease the risk of acute graft rejection suggest that stopping immunosuppressants 2-4 weeks prior to CAR T-cell collection and resuming it after 4-12 weeks of CAR T-cell infusion may be safe with careful monitoring of the graft function and for B-cell immune reconstitution. 69,70 When the B cells start to recover, the risk of humeral acute graft rejection begins to rise; however, resuming immunosuppression could still impair the CAR T-cell activity. Luttwak et al 71 reported three patients with SOT EBV-negative monomorphic DLBCL PTLD refractory to chemoimmunotherapy who received CAR T-cell therapy while continuing treatment with calcineurin inhibitors.…”

Section: Car T-cell Therapymentioning

confidence: 99%

“…Thus, dealing with immunosuppressants at that time require the expertise of the transplant team and the cellular therapy group to balance between preservation of the CAR T‐cell activity and prevention of acute graft rejection and GvHD. The observations that chemotherapy lymphodepleting agents prior to CAR T‐cell administration could act later as immunosuppressants and that B‐cell aplasia and hypogammaglobulinemia caused by CAR T cells could decrease the risk of acute graft rejection suggest that stopping immunosuppressants 2–4 weeks prior to CAR T‐cell collection and resuming it after 4–12 weeks of CAR T‐cell infusion may be safe with careful monitoring of the graft function and for B‐cell immune reconstitution 69,70 . When the B cells start to recover, the risk of humeral acute graft rejection begins to rise; however, resuming immunosuppression could still impair the CAR T‐cell activity.…”

Section: Introductionmentioning

confidence: 99%

“…It is unknown if having PTLD can increase the risk of typical CAR T‐cell therapy adverse events such as cytokine‐release syndrome (CRS) and neurotoxicity. Several cases of using autologous CD19‐directed CAR T cells in PTLD patients were reported with mixed results and various grades of CRS and neurotoxicity and degrees of graft rejection 69–75 …”

Section: Introductionmentioning

confidence: 99%

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Post‐transplant lymphoproliferative disorder: Update on treatment and novel therapies

2023

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Post-transplant lymphoproliferative disorder (PTLD) is rare and heterogeneous lymphoid proliferations that occur as a result of immunosuppression following solid organ transplant (SOT) and haematopoietic stem cell transplant (HSCT) with the majority being driven by EBV. Although some histologies are similar to lymphoid neoplasms seen in immunocompetent patients, treatment of PTLD may be different due to difference in pathobiology and higher risk of treatment complications. The most common treatment approach in SOT PTLD after failing immunosuppression reduction (RIS) takes into consideration a risk-stratified sequential algorithm with rituximab +/− chemotherapy based on phase 2 studies. In HSCT PTLD, RIS alone and chemotherapy are usually ineffective making rituximab +/− RIS as the gold standard of frontline treatment. In this review, we give an update on the treatment of PTLD beyond RIS. We highlight the most recent studies that attempted to incorporate more aggressive chemotherapy regimens and novel treatments into the traditional risk-stratified sequential approach. We also discuss the role of EBV-cytotoxic T lymphocytes in treatment of EBV-driven PTLD. Other novel agents with potential role in PTLD will be discussed in addition to the challenges that could arise with chimeric antigen receptor T-cell therapy and immune checkpoint inhibitors in this population.

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Section: Car T-cell Therapymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Post‐transplant lymphoproliferative disorder: Update on treatment and novel therapies

2023

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“…Furthermore, the use of CAR-T-cell (CAR-T) therapy in BCC resulted in partial tumor regression [ 234 ]. A number of case reports have also documented the use of CAR-T therapy in post-transplant lymphoproliferative disorders in SOTRs [ 235 , 236 , 237 , 238 , 239 , 240 , 241 , 242 , 243 ]. As our understanding of CAR-T therapy improves, its diverse applications continue to grow.…”

Section: Regulatory T Cell Therapiesmentioning

confidence: 99%

Human Regulatory T Cells: Understanding the Role of Tregs in Select Autoimmune Skin Diseases and Post-Transplant Nonmelanoma Skin Cancers

Oparaugo

Ouyang

Nguyen

et al. 2023

IJMS

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Regulatory T cells (Tregs) play an important role in maintaining immune tolerance and homeostasis by modulating how the immune system is activated. Several studies have documented the critical role of Tregs in suppressing the functions of effector T cells and antigen-presenting cells. Under certain conditions, Tregs can lose their suppressive capability, leading to a compromised immune system. For example, mutations in the Treg transcription factor, Forkhead box P3 (FOXP3), can drive the development of autoimmune diseases in multiple organs within the body. Furthermore, mutations leading to a reduction in the numbers of Tregs or a change in their function facilitate autoimmunity, whereas an overabundance can inhibit anti-tumor and anti-pathogen immunity. This review discusses the characteristics of Tregs and their mechanism of action in select autoimmune skin diseases, transplantation, and skin cancer. We also examine the potential of Tregs-based cellular therapies in autoimmunity.

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“…In another report, a kidney transplant patient with high-burden refractory PTLD was enrolled in a clinical trial of CAR T-cell treatment ( ChiCTR1800019622 ) combined with PD-1 inhibitor induction, followed by PD-1 inhibitor maintenance therapy. Here, IST was not discontinued and the patient achieved PR [ 123 ].…”

Section: Treatmentmentioning

confidence: 99%

Recent Advances in Adult Post-Transplant Lymphoproliferative Disorder

Markouli

Ullah

Omar

et al. 2022

Cancers

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PTLD is a rare but severe complication of hematopoietic or solid organ transplant recipients, with variable incidence and timing of occurrence depending on different patient-, therapy-, and transplant-related factors. The pathogenesis of PTLD is complex, with most cases of early PLTD having a strong association with Epstein–Barr virus (EBV) infection and the iatrogenic, immunosuppression-related decrease in T-cell immune surveillance. Without appropriate T-cell response, EBV-infected B cells persist and proliferate, resulting in malignant transformation. Classification is based on the histologic subtype and ranges from nondestructive hyperplasias to monoclonal aggressive lymphomas, with the most common subtype being diffuse large B-cell lymphoma-like PTLD. Management focuses on prevention of PTLD development, as well as therapy for active disease. Treatment is largely based on the histologic subtype. However, given lack of clinical trials providing evidence-based data on PLTD therapy-related outcomes, there are no specific management guidelines. In this review, we discuss the pathogenesis, histologic classification, and risk factors of PTLD. We further focus on common preventive and frontline treatment modalities, as well as describe the application of novel therapies for PLTD and elaborate on potential challenges in therapy.

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CAR-T therapy in solid transplant recipients with post-transplant lymphoproliferative disease: case report and literature review

Cited by 14 publications

References 24 publications

Post‐transplant lymphoproliferative disorder: Update on treatment and novel therapies

Post‐transplant lymphoproliferative disorder: Update on treatment and novel therapies

Human Regulatory T Cells: Understanding the Role of Tregs in Select Autoimmune Skin Diseases and Post-Transplant Nonmelanoma Skin Cancers

Recent Advances in Adult Post-Transplant Lymphoproliferative Disorder

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