Status:
Ready to upload
Record number:
1905
Adverse Occurrence type:
MPHO Type:
Estimated frequency:
At the time this paper published (2001, Haut), umbilical cord blood (UCB) was considered a source of EBV-uninfected stem cells, therefore, much less concern for EBV associated post-transplant lymphoproliferative disorder (PTLD) as compared with 65% of patients who develop PTLD with primary immunodeficiencies transplanted with unrelated HLA mismatched, T cell-depleted grafts. There are still not many publications regarding the association with UCB transplants and the occurrence of EBV related PTLD.
A more recent study (Tong 2017) which was performed as multicenter retrospective research, studied outcomes from 79 UCB transplants for hematologic malignancies and compared them to outcomes of 96 allogeneic hematopoietic cell transplants (HCT) using unrelated peripheral blood stem and progenitor cell transplants (PBSPC). There was a lower incidence of Epstein-Barr virus (EBV) transmission/ viremia and PTLD in those patients treated with the UCB transplants. The cumulative incidence of EBV viremia and PTLD within 3 years after transplantation in the UCB group was significantly lower than in the unrelated PBSCT group. Omitting anti-thymocyte globulin (ATG) in the conditioning regimen and graft versus host disease (GvHD) prophylaxis in the UCB transplants may be the cause of these results. Several studies reported that T lymphocyte depletion ex-vivo or in-vivo for prophylaxis of GvHD in HCT recipients has been associated with an increased incidence of EBV viremia and PTLD.
Another report (Ballen 2010) using double UCT found 18 secondary malignancies in 98 patients (18%) at a median of 134 days after transplantation. Sixteen of those second malignancies were EBV-associated PTLD and 14 of those EBV-associated PTLD cases were donor-derived, 2 were undetermined. Known risk factors for PTLD include EBV infection, HLA mismatch, use of ATG, T cell depletion, and chronic graft-versus-host disease. This study noted that the addition of rituximab to the conditioning might decrease the incidence of PTLD.
Reported cases indicate that EBV-associated PTLD occurs in 2% of umbilical cord blood transplantations. The incidence increases to 21% when ATG is added to nonmyeloablative conditioning.
Time to detection:
The patient and recipient who had juvenile chronic myelogenous leukemia (JCML) developed EBV-associated PTLD 139 days following UCB-derived stem cell infusion.
Alerting signals, symptoms, evidence of occurrence:
The recipient developed hepatosplenomegaly with mildly elevate transaminases with normal coagulation studies and bilirubin. IgM for EBV was negative. Soon after, he developed massive cervical lymphadenopathy in the neck and nasopharynx and upper airway obstruction. Lymph node biopsy showed a clonal B cell proliferation consistent with PTLD and EBV was detected by immunohistochemical stains positive for EBV latent membrane protein (LMP). Virtually all B cells present showed cytoplasmic staining for EBV LMP.
Demonstration of imputability or root cause:
HLA typing was performed on the affected cellular proliferation from the liver and spleen found in the recipient during autopsy. This HLA typing was compared with the known recipient HLA typing and the umbilical cord blood unit (UCB) and the DRB1 0411 HLA allele was identified from the donor. Additionally, testing for EBV by PCR was performed on a DNA sample from the UCB which had been stored at the time of original collection. Approximately 1 copy of EBV DNA was detected per 100,000 cells. This cumulative evidence is highly suggestive of donor/UCT as the source of EBV.
The mother's or the donor's EBV infection status before the transplant is unknown (Haut 2001). There is also no information regarding transfusions after the transplantation. Based on these results, it cannot be conclusively proven that the umbilical cord blood was the source of the EBV infection in this case. However, the presence of EBV DNA in the UCB clearly indicates the potential for EBV transmission through UCB transplant.
Imputability grade:
2 Probable
Groups audience:
Keywords:
References:
Suggest new keywords:
Ebstein Barr Virus (EBV)
Umbilical Cord Transplant (UCT)
Post-transpant lymphoproliferative disorder (PTLD)
Bone Marrow Transplant
Reference attachment:
Suggest references:
Detection of EBV DNA in the cord blood donor for a patient developing Epstein–Barr virus-associated lymphoproliferative disorder following mismatched unrelated umbilical cord blood transplantation. Haut PR, et al. Bone Marrow Transplantation (2001) 27, 761–765
Tong J, Xuan L, Sun Y, et al. Umbilical Cord Blood Transplantation without Antithymocyte Globulin Results in Similar Survival but Better Quality of Life Compared with Unrelated Peripheral Blood Stem Cell Transplantation for the Treatment of Acute Leukemia-A Retrospective Study in China. Biol Blood Marrow Transplant 2017; 23:1541.
Ballen KK, Cutler C, Yeap BY, et al. Donor-derived second hematologic malignancies after cord blood transplantation. Biol Blood Marrow Transplant 2010; 16:1025.
Noroozi-Aghideh A, Kheirandish M. Human cord blood-derived viral pathogens as the potential threats to the hematopoietic stem cell transplantation safety: A mini review. World J Stem Cells. 2019 Feb 26;11(2):73-83. doi: 10.4252/wjsc.v11.i2.73. PMID: 30842806; PMCID: PMC6397803.
Claudio G. Brunstein, Daniel J. Weisdorf, Todd DeFor, Juliet N. Barker, Jakub Tolar, Jo-Anne H. van Burik, John E. Wagner; Marked increased risk of Epstein-Barr virus-related complications with the addition of antithymocyte globulin to a nonmyeloablative conditioning prior to unrelated umbilical cord blood transplantation. Blood 2006; 108 (8): 2874–2880. doi: https://doi.org/10.1182/blood-2006-03-011791
Note:
Some pieces on information missing; quite old article. Is there anything more recent that can be added to this? Important topic, very little published on this? Can we make didactic use of this? Most of the other entries in the library are quite old too and address the topic of PTLD rather than the scenario od donor relared transmission, which has not been looked at in detail. There is a debate around the rationale and best strategy for EBV "screening" in the context of cord blood donation.; there is confusion about IgG, IgM, DNA as the necessary markers and the magnitude of risk of maternal viraemia or vertical transmisison of EBV..... . I it possible to touch in any of these, even if briefly?? Or esle, just do the review of this article. Thank you (ines)
Addition from Melissa: 544 and 249 are both EBV via HPC - agree would be best to see which is most appropriate and combine this into one of those other two. One can email Evi and Claudia to ask for the records to be opened to editing when decided.
Expert comments for publication:
Although UCB transplants can be associated with many complications of stem cell transplantation, these procedures may still have decreased frequency of associated EBV-related PTLD development if T cell depletion or use of ATG is omitted (Brunstein 2006), there is no prior donor or recipient EBV seropositive infection, there is related HLA matching, and finally, no chronic graft-versus-host disease develops. The optimal approach to EBV screening in the context of umbilical cord blood donation is controversial--mom is being tested, EBV is common, and the optimal infectious disease marker is unclear. Studies indicate that if recipient's blood EBV DNA is monitored and appropriately treated, the risk of EBV-related PTLD seems to be aligned with that of other HPC treatments. Noorozi-aghideh et al in WJSC (2019) has a thorough review of HPC-related infections, including EBV.