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Establishment and operation of a Good Manufacturing Practice-compliant allogeneic Epstein-Barr virus (EBV)-specific cytotoxic cell bank for the treatment of EBV-associated lymphoproliferative disease.

Vickers MA, Wilkie GM, Robinson N, Rivera N, Haque T, Crawford DH, Barry J, Fraser N, Turner DM, Robertson V, Dyer P, Flanagan P, Newlands HR, Campbell J, Turner ML - Br. J. Haematol. (2014)

Bottom Line: Conventional treatments for PTLD are often successful, but risk organ rejection and cause significant side effects.Both cases of EBV-associated non-haematopoietic sarcoma receiving cells failed to achieve complete remission.Thus, this third party donor-derived EBV-specific CTL cell bank can supply most patients with appropriately matched cells and most recipients have good outcomes.

View Article: PubMed Central - PubMed

Affiliation: Scottish National Blood Transfusion Service, Aberdeen, London, UK; University of Aberdeen, Aberdeen, London, UK.

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Related in: MedlinePlus

Timeline of bank summarizing enquiries and outcomes. Months before licensure are shown as negative numbers on the horizontal axis, and months after as positive numbers. Cases are indicated by stacked bars and are ordered by time at which initial contact was made with the bank. *1 indicates a directed donation from the father of the patient; the cytotoxic T lymphocytes (CTLs) were infused after licensure. *2 indicates that the issued CTLs have not yet been infused. *3 indicates that the patients had EBV-associated non-haematopoietic sarcoma, the other recipients had post-transplant proliferative disorder.
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fig01: Timeline of bank summarizing enquiries and outcomes. Months before licensure are shown as negative numbers on the horizontal axis, and months after as positive numbers. Cases are indicated by stacked bars and are ordered by time at which initial contact was made with the bank. *1 indicates a directed donation from the father of the patient; the cytotoxic T lymphocytes (CTLs) were infused after licensure. *2 indicates that the issued CTLs have not yet been infused. *3 indicates that the patients had EBV-associated non-haematopoietic sarcoma, the other recipients had post-transplant proliferative disorder.

Mentions: In the 21 months since licensure, and 3 months post manufacturing certification, but pre-licensure, 37 enquiries were received. The frequency of enquiries increased slightly during this time (Fig1). Twelve of these enquiries resulted in the issue of CTLs (Table III). Nine of the twelve (Patients 1, 3, 4, 7, 8, 9, 10, 11, 12) were cases of PTLD. Of these, one was CD20- and rituximab-resistant (Patient 1), one had concomitant graft-versus-host disease (GVHD) precluding reduction of immunosuppression (Patient 3), one was unfit for chemotherapy because of recent necrotizing fasciitis and multi-organ failure (Patient 4) and six cases had the CTLs used to consolidate reduction of immunosuppression and chemotherapy. Four patients had central nervous system (CNS) disease, where rituximab penetration is known to be poor. Of these nine, seven went into complete remission, while two (Patients 3, 9) had progressive disease and died within weeks of the infusions. Neither of these two had an HLA class II match (see below), although both had three HLA class I matches. Both also had relatively rapidly progressive disease at the time of infusions. In a further two cases (Patients 2, 5), the CTLs were planned to be used as a bridge to allogeneic HSCT for EBV+ lymphoproliferation associated with congenital immunosuppression, although only one of these has been infused at the time of writing.


Establishment and operation of a Good Manufacturing Practice-compliant allogeneic Epstein-Barr virus (EBV)-specific cytotoxic cell bank for the treatment of EBV-associated lymphoproliferative disease.

Vickers MA, Wilkie GM, Robinson N, Rivera N, Haque T, Crawford DH, Barry J, Fraser N, Turner DM, Robertson V, Dyer P, Flanagan P, Newlands HR, Campbell J, Turner ML - Br. J. Haematol. (2014)

Timeline of bank summarizing enquiries and outcomes. Months before licensure are shown as negative numbers on the horizontal axis, and months after as positive numbers. Cases are indicated by stacked bars and are ordered by time at which initial contact was made with the bank. *1 indicates a directed donation from the father of the patient; the cytotoxic T lymphocytes (CTLs) were infused after licensure. *2 indicates that the issued CTLs have not yet been infused. *3 indicates that the patients had EBV-associated non-haematopoietic sarcoma, the other recipients had post-transplant proliferative disorder.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4232001&req=5

fig01: Timeline of bank summarizing enquiries and outcomes. Months before licensure are shown as negative numbers on the horizontal axis, and months after as positive numbers. Cases are indicated by stacked bars and are ordered by time at which initial contact was made with the bank. *1 indicates a directed donation from the father of the patient; the cytotoxic T lymphocytes (CTLs) were infused after licensure. *2 indicates that the issued CTLs have not yet been infused. *3 indicates that the patients had EBV-associated non-haematopoietic sarcoma, the other recipients had post-transplant proliferative disorder.
Mentions: In the 21 months since licensure, and 3 months post manufacturing certification, but pre-licensure, 37 enquiries were received. The frequency of enquiries increased slightly during this time (Fig1). Twelve of these enquiries resulted in the issue of CTLs (Table III). Nine of the twelve (Patients 1, 3, 4, 7, 8, 9, 10, 11, 12) were cases of PTLD. Of these, one was CD20- and rituximab-resistant (Patient 1), one had concomitant graft-versus-host disease (GVHD) precluding reduction of immunosuppression (Patient 3), one was unfit for chemotherapy because of recent necrotizing fasciitis and multi-organ failure (Patient 4) and six cases had the CTLs used to consolidate reduction of immunosuppression and chemotherapy. Four patients had central nervous system (CNS) disease, where rituximab penetration is known to be poor. Of these nine, seven went into complete remission, while two (Patients 3, 9) had progressive disease and died within weeks of the infusions. Neither of these two had an HLA class II match (see below), although both had three HLA class I matches. Both also had relatively rapidly progressive disease at the time of infusions. In a further two cases (Patients 2, 5), the CTLs were planned to be used as a bridge to allogeneic HSCT for EBV+ lymphoproliferation associated with congenital immunosuppression, although only one of these has been infused at the time of writing.

Bottom Line: Conventional treatments for PTLD are often successful, but risk organ rejection and cause significant side effects.Both cases of EBV-associated non-haematopoietic sarcoma receiving cells failed to achieve complete remission.Thus, this third party donor-derived EBV-specific CTL cell bank can supply most patients with appropriately matched cells and most recipients have good outcomes.

View Article: PubMed Central - PubMed

Affiliation: Scottish National Blood Transfusion Service, Aberdeen, London, UK; University of Aberdeen, Aberdeen, London, UK.

Show MeSH
Related in: MedlinePlus