Pre‐emptive rituximab for Epstein–Barr virus reactivation after haplo‐hematopoietic stem cell transplantation

Kobayashi, Shogo; Sano, Hideki; Mochizuki, Kazuhiro; Ohara, Yoshihiro; Takahashi, Nobuhisa; Ohto, Hitoshi; Kikuta, Atsushi

doi:10.1111/ped.13336

Cited by 12 publications

(12 citation statements)

References 28 publications

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“…Among them, only one study was conducted in children. Kobayashi et al demonstrated in 2017 that in children with a median age of 8 years (range, 1‐18), rituximab was administered as preemptive therapy, and PTLD did not occur. The median number of doses of rituximab was two based on EBV titers greater than 1000 copies/10 6 of peripheral blood mononuclear cells.…”

Section: Discussionmentioning

confidence: 99%

Successful preemptive therapy with single‐dose rituximab for Epstein‐Barr virus infection to prevent post‐transplant lymphoproliferative disease after pediatric hematopoietic stem cell transplantation

Kim

Kang

Hong

et al. 2019

Transplant Infectious Dis

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oproliferative disease occurs in 1%-3.5% of pediatric patients after undergoing hematopoietic stem cell transplantation (HSCT). 1,2 B cell-related PTLD accounts for a major portion of all PTLD cases, and only 5% of cases are of natural killer T cell or Hodgkin disease origin. 3 The risk factors of PTLD include infection, degree and level of immunosuppressive therapy, genetic susceptibility, and HSCT-related factors. Of them, 50%-70% of all PTLD cases are associated with Epstein-Barr virus (EBV) infection. 3 Uncontrolled EBV-driven B cell proliferation extends the half-life of virally infected cells and leads to malignant transformation. 4 Known prophylaxis and treatments of EBV-related PTLD include the administration of rituximab (CD20 monoclonal antibodies), reduction of immunosuppression, Abstract Background: The efficacy of preemptive treatment containing rituximab to prevent post-transplant lymphoproliferative disease (PTLD) in children has not yet been fully elucidated. Methods:We analyzed 19 pediatric patients who developed high Epstein-Barr virus (EBV) DNAemia (EBV viral load of greater than 40 000 copies/mL) after allogeneic hematopoietic stem cell transplantation (HSCT) and were preemptively administered rituximab. Rituximab was intravenously injected at a dose of 375 mg/m 2 once the EBV viral load was greater than 40 000 copies/mL. Results:In all 19 patients, EBV DNAemia was eradicated after a median of 9 days (range, 3-20 days), and PTLD did not occur. One patient had transient fever, and four patients did not fully recover B cell counts after transplantation. We suggested that delayed B cell recovery was caused by chronic graft-versus-host disease (GVHD) related drugs, not rituximab administration. And there were no other infection-related side effects. Conclusions:In conclusion, preemptive therapy containing rituximab is expected to reduce the incidence of PTLD after HSCT and improve post-transplantation outcomes in children. K E Y W O R D SEpstein-Barr virus, hematopoietic stem cell transplantation, post-transplant lymphoproliferative disease, rituximab

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Section: Discussionmentioning

confidence: 99%

Successful preemptive therapy with single‐dose rituximab for Epstein‐Barr virus infection to prevent post‐transplant lymphoproliferative disease after pediatric hematopoietic stem cell transplantation

Kim

Kang

Hong

et al. 2019

Transplant Infectious Dis

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“…2,8 However, this disease progresses very rapidly and often leaves limited time for diagnosis and treatment; long-term survival of EBV-PTLD remains unsatisfactory. 3,9,10 Based on our five cases (Table 1), we focus mainly on current perspectives and challenges in the management of EBV-PTLD after allo-HSCT.…”

Section: +157mentioning

confidence: 99%

“…2 The incidence of EBV-DNAemia varies from 18.6% to 81.7% depending on the transplantation type, risk factors, assay sensitivity, cut-off values, and so on. 7,10,14,17,30,41 However, it is difficult to define an EBV-DNA load for the initiation of preemptive therapy that produces maximal benefits and limited toxicities. The velocity of rising EBV-DNA seems better for discriminating between recipients who are more likely or unlikely to develop PTLD.…”

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%

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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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“…Rituximab (R) (Rituxan®, Roche, Basel Switzerland) is the first anti-CD20 monoclonal antibody that has demonstrated efficacy in patients with various lymphoid malignancies, including indolent and aggressive forms of B-cell non-Hodgkin's lymphoma and B-cell chronic lymphocytic leukemia [1] . Administered intravenously (IV), it has been shown to be also efficient to treat other hematologic situations such as EBV reactivation, especially after hematopoietic stem cell transplantation (HSCT), [2] or ITP [3] . Finally, survivals of younger patients with CD20-positive Philadelphia-negative ALL are significantly increased when combining IV-R with chemotherapy [4] .…”

Section: Introductionmentioning

confidence: 99%

Subcutaneous rituximab given to patients for other indications than CD20+ B-cell lymphoma: A monocentric study of 20 cases

Péterlin¹,

Guillaume²,

Garnier³

et al. 2018

Leukemia Research Reports

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Pre‐emptive rituximab for Epstein–Barr virus reactivation after haplo‐hematopoietic stem cell transplantation

Abstract: Pre-emptive rituximab therapy could be a useful strategy for EBV-PTLD in TCR-haplo-SCT recipients with low-dose ATG.

Cited by 12 publications

References 28 publications

Successful preemptive therapy with single‐dose rituximab for Epstein‐Barr virus infection to prevent post‐transplant lymphoproliferative disease after pediatric hematopoietic stem cell transplantation

Successful preemptive therapy with single‐dose rituximab for Epstein‐Barr virus infection to prevent post‐transplant lymphoproliferative disease after pediatric hematopoietic stem cell transplantation

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

Subcutaneous rituximab given to patients for other indications than CD20+ B-cell lymphoma: A monocentric study of 20 cases

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