Epstein-barr virus DNAemia monitoring for the management of post-transplant lymphoproliferative disorder

Kalra, Amit; Roessner, Cameron; Jupp, Jennifer; Williamson, Tyler; Tellier, Raymond; Chaudhry, Ahsan; Khan, Faisal; Taparia, Minakshi; Jiménez-Zepeda, Víctor H.; Stewart, Douglas A.; Daly, Andrew; Storek, Jan

doi:10.1016/j.jcyt.2018.02.367

Cited by 22 publications

(21 citation statements)

References 36 publications

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“…The rate of increase of EBV copy number has been suggested to be important in initiating pre‐emptive treatment . In our institute, we use pre‐emptive rituximab for EBV DNA levels more than 300 000 IU/mL in whole blood as this cutoff has been demonstrated by Kalra et al to minimize unnecessary rituximab administration and also results in near zero mortality due to PTLD.…”

Section: Discussionmentioning

confidence: 99%

Low rates of acute and chronic GVHD with ATG and PTCy in matched and mismatched unrelated donor peripheral blood stem cell transplants

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Al‐Shaibani

et al. 2019

European J of Haematology

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Introduction:We evaluated the combination of ATG and PTCy for GVHD prophylaxis in matched and mismatched unrelated PBSCTs for high-risk hematological malignancies. Methods:We treated 102 patients with reduced intensity conditioning (RIC) with fludarabine, busulfan, and TBI 200 cGy. GVHD prophylaxis included rabbit ATG (thymoglobulin at total dose of 4.5 mg/kg divided over days −3 to −1), PTCy (50 mg/ kg/day on day +3 and on day +4), and cyclosporine. Clinical and outcome data were collected retrospectively.Results: Among 102 patients, 76 patients received 10/10 MUD transplants and 26 patients received 9/10 mismatched transplants. The median age was 59 years. At a median follow-up of 15 months (range 0.6 to −33 months), the 1-year OS in MUD and MMUD cohort was 75% and 50%, respectively (P = 0.027). The corresponding oneyear PFS was 67% and 35%, respectively (P = 0.0024). The incidence of grade 3-4 acute GVHD was 11.8% in MUD and 3.8% in MMUD group, and that of NIH stage moderate/severe chronic GVHD in the 2 groups was 10.5% and 7.6%, respectively.Cytomegalovirus (CMV) reactivation was seen in 49% patients. The cumulative incidence of relapse was 21.1% in the MUD group and 42.3% in the MMUD group. Conclusion:Our experience shows that PTCy and ATG can be combined for GVHD prophylaxis in matched unrelated donor PBSCTs with low rates of Gr3-4 acute GVHD and chronic GVHD, and acceptable relapse rates. K E Y W O R D S ATG, graft-versus-host disease, post-transplant cyclophosphamide 1 | INTRODUC TI ON Post-transplant cyclophosphamide (PTCy) for GVHD prophylaxis in the setting of matched related (MRD), matched and mismatched unrelated (MUD and MMUD), and haplo-identical (HI) transplants has been associated with low rates of acute and chronic GVHD. 1-3 Similarly, ATG has been used extensively for GVHD prophylaxis for MUD transplants with beneficial effects in reducing acute and chronic GVHD. 4,5 There is little published data on combining ATG with PTCy for GVHD prophylaxis in MUD peripheral blood stem cell | 487 PREM Et al.

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Section: Discussionmentioning

confidence: 99%

Low rates of acute and chronic GVHD with ATG and PTCy in matched and mismatched unrelated donor peripheral blood stem cell transplants

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Al‐Shaibani

et al. 2019

European J of Haematology

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“…Cytomegalovirus (CMV) disease prevention was with CMV safe blood products and CMV antigenemia/DNAemia monitoring with preemptive therapy using typically ganciclovir or valganciclovir 9 . Epstein‐Barr virus (EBV) post‐transplant lymphoproliferative disease (PTLD) management was with rituximab given initially as regular therapy (for biopsy‐proven PTLD), between 2012 and 2015 as prompt therapy (for PTLD suspected based on clinical/radiological findings and EBV DNAemia), 22 and since 2015 as preemptive therapy for EBV DNAemia > 300 000 IU/mL blood 23 …”

Section: Methodsmentioning

confidence: 99%

Hematopoietic cell transplant outcomes after myeloablative conditioning with fludarabine, busulfan, low‐dose total body irradiation, and rabbit antithymocyte globulin

Ousia

Kalra

Williamson

et al. 2020

Clinical Transplantation

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“…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%

“…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%

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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Epstein-barr virus DNAemia monitoring for the management of post-transplant lymphoproliferative disorder

Cited by 22 publications

References 36 publications

Low rates of acute and chronic GVHD with ATG and PTCy in matched and mismatched unrelated donor peripheral blood stem cell transplants

Low rates of acute and chronic GVHD with ATG and PTCy in matched and mismatched unrelated donor peripheral blood stem cell transplants

Hematopoietic cell transplant outcomes after myeloablative conditioning with fludarabine, busulfan, low‐dose total body irradiation, and rabbit antithymocyte globulin

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

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