Intrathecal rituximab for EBV-associated post-transplant lymphoproliferative disorder with central nervous system involvement unresponsive to intravenous rituximab-based treatments: a prospective study

Wu, Meiqing; Sun, Jing; Zhang, Y; Huang, Fen; Zhou, Hongsheng; Zhang, Fan; Xuan, Li; Yu, Guopan; Guo, Xutao; Dai, Min; Feng, Ru; Liu, Qianshi

doi:10.1038/bmt.2015.281

Cited by 13 publications

(8 citation statements)

References 15 publications

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“…Based on the diagnostic value of EBV DNA in plasma and PBMC, it is important to note that early biopsy of brain lesions needs to be considered for post-transplant patients who developed brain mass lesions with ring enhancement in order to accurately diagnose CNS-PTLD. Since recent studies reported that the intrathecal administration of rituximab was effective for CNS-PTLD [10], early biopsy after MRI may be a promising diagnostic modality for the provision of specific therapy.…”

Section: Discussionmentioning

confidence: 99%

Central nervous system post-transplant lymphoproliferative disorder after allogeneic hematopoietic stem cell transplantation: The Nagasaki transplant group experience

Sakamoto

Itonaga

Taguchi

et al. 2019

Leukemia Research Reports

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A 17-year-old male received allogeneic transplantation for acute lymphoblastic leukemia, and presented with generalized seizures due to a solitary brain lesion with massive necrosis on day +621. Epstein–Barr virus (EBV) DNA copies were below the cut-off value in plasma. Stereotactic biopsy of the cerebral lesion confirmed the diagnosis of post-transplant lymphoproliferative disorder (PTLD) with large atypical cells positive for CD20 and EBER. In order to diagnose primary central nervous system PTLD, the biopsy should be applied as early as possible when brain lesion with necrosis develops in post-transplant patients regardless of EBV-DNA in plasma.

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Section: Discussionmentioning

confidence: 99%

Central nervous system post-transplant lymphoproliferative disorder after allogeneic hematopoietic stem cell transplantation: The Nagasaki transplant group experience

Sakamoto

Itonaga

Taguchi

et al. 2019

Leukemia Research Reports

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“…For the present case, all conventional treatment options have been used: cessation of immunosuppression, intravenous rituximab, cytotoxic T‐cell therapy, and chemotherapy. In addition, intrathecal rituximab was also administered as several publications support its use …”

Section: Discussionmentioning

confidence: 99%

Successful nivolumab therapy in an allogeneic stem cell transplant child with post‐transplant lymphoproliferative disorder

Kassa¹,

Reményi²,

Sinkó³

et al. 2018

Pediatric Transplantation

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| INTRODUC TI ONPTLD is a significant cause of morbidity and mortality after allogeneic HSCT, mainly caused by EBV infection. It usually develops within few months after HSCT when cellular immune response is lacking so cytotoxic T cells are not able to control B cells harboring EBV. In the early course of PTLD, lymphoid proliferation is polyclonal; however, monoclonal diseases, such as high-grade lymphomas, can also develop. PTLD typically presents as a disseminated disease with fever, lymphadenopathy, and hepatitis. PTLDs most often involve lymphoid tissues, but extralymphatic involvement may occur as well.Primary CNS PTLD is an extremely rare condition following HSCT. The few case reports reveal difficulties both in diagnosis and therapy and confirm very poor prognosis. Effective strategy against EBV infection in the HSCT setting is based on weekly quantitative PCR scanning and timely introduced pre-emptive therapy. Treatment options for PTLD are reduction in immunosuppressive therapy, rituximab, cytotoxic EBV-specific T-cell infusion, and donor lymphocyte infusion. After failure of the abovementioned treatment modalities, systemic chemotherapy with or Abstract Primary CNS PTLD is an extremely rare complication after allogeneic HSCT. At our centre, an 11-year-old patient developed nausea, vomiting, and diplopy on day +82 following HSCT. On brain MRI, multiple white matter lesions were seen. Histology showed a diffuse large B-cell lymphoma with high load of EBV in tissue. Despite stopping immunosuppression, treatment with EBV-specific cytotoxic T cells, systemic rituximab, HD-MTX, and intrathecal chemotherapy, progression was observed. With a combination of HD-MTX and cytarabine, only a partial response could be achieved.

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“…35,36 Quantification of EBV-DNA in the CSF is informative for CNS involvement. 16 Quantification of EBV-CTLs, using HLA tetramers, enzymelinked immune-spot, or flow-cytometry-based intracellular cytokine staining, are also promising methods, [37][38][39] but current assays are costly, complex, time-consuming and nonstandardized.…”

Section: How Should Ebv-dna Be Monitored and Ebv-dnaemia Be Managed?mentioning

confidence: 99%

“…57 Intrathecal administration is required due to the low penetrance of rituximab across the blood-brain barrier. 16 Intrathecal rituximab (on a sequential dose-escalation schedule (10,20,30,40, and 50 mg, weekly), starting from 7-15 days after intravenous rituximab-based treatment) resulted in a good response for CNS involvement after the failure of intravenous rituximab-based treatment. 16,56 Intravenous rituximab failed in Case 5, while intrathecal administration finally rescued the patient.…”

Section: First-line Treatmentmentioning

confidence: 99%

“…11 EBV-PTLD following allo-HSCT is almost exclusively of donor origin and generally develops during the second to fourth month after transplantation. 4,6,13–17 However, no characteristic signature of oncogene expression or mutation in EBV-PTLD has been identified. 8 Sporadically, EBV invades T or NK cells and leads to T-/NK- EBV-PTLD.…”

Section: What Is the Pathogenesis Of Ebv-ptld?mentioning

confidence: 99%

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Management of Epstein–Barr virus-related post-transplant lymphoproliferative disorder after allogeneic hematopoietic stem cell transplantation

Liu

Feng

2020

Therapeutic Advances in Hematology

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Epstein–Barr virus-related post-transplant lymphoproliferative disorder (EBV-PTLD) is a rare but life-threatening complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). T-cell immunodeficiency after transplantation and EBV primary infection/reactivation play major roles in the pathogenesis. Unspecific clinical manifestations make the diagnosis difficult and time consuming. Moreover, this fatal disease usually progresses rapidly, and leads to multiple organ dysfunction or death if not treated promptly. Early diagnosis of EBV-DNAemia or EBV-PTLD generally increases the chances of successful treatment by focusing on regular monitoring of EBV-DNA and detection of symptomatic patients as early as possible. Rituximab ± reduction of immunosuppression (RI) is currently the first-line choice in preemptive intervention and targeted treatment. Unless patients are suffering from severe graft versus host disease (GvHD), it is better to combine rituximab with RI. Once a probable diagnosis is made, the first-line treatment should be initiated rapidly, along with, or ahead of, biopsy, although histopathologic confirmation is requisite. In addition, EBV-specific cytotoxic T lymphocytes (EBV-CTLs) or donor lymphocyte infusion (DLI) has shown promise in cases of suboptimal response. Chemotherapy ± rituximab might lend more opportunities to refractory/relapsed patients, who might also benefit from ongoing clinical trials. Herein, we discuss our clinical experience in detail based on the current literature and our five cases.

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Intrathecal rituximab for EBV-associated post-transplant lymphoproliferative disorder with central nervous system involvement unresponsive to intravenous rituximab-based treatments: a prospective study

Cited by 13 publications

References 15 publications

Central nervous system post-transplant lymphoproliferative disorder after allogeneic hematopoietic stem cell transplantation: The Nagasaki transplant group experience

Central nervous system post-transplant lymphoproliferative disorder after allogeneic hematopoietic stem cell transplantation: The Nagasaki transplant group experience

Successful nivolumab therapy in an allogeneic stem cell transplant child with post‐transplant lymphoproliferative disorder

Management of Epstein–Barr virus-related post-transplant lymphoproliferative disorder after allogeneic hematopoietic stem cell transplantation

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