Abstract
Epstein-Barr virus (EBV) is associated with several malignancies, including post-transplant lymphoproliferative disorder (PTLD). Conventional treatments for PTLD are often successful, but risk organ rejection and cause significant side effects. EBV-specific cytotoxic T lymphocytes (CTLs) generated in vitro from peripheral blood lymphocytes provide an alternative treatment modality with few side effects, but autologous CTLs are difficult to use in clinical practice. Here we report the establishment and operation of a bank of EBV-specific CTLs derived from 25 blood donors with human leucocyte antigen (HLA) types found at high frequency in European populations. Since licensure, there have been enquiries about 37 patients, who shared a median of three class I and two class II HLA types with these donors. Cells have been infused into ten patients with lymphoproliferative disease, eight of whom achieved complete remission. Neither patient with refractory disease was matched for HLA class II. Both cases of EBV-associated non-haematopoietic sarcoma receiving cells failed to achieve complete remission. Thirteen patients died before any cells could be issued, emphasizing that the bank should be contacted before patients become pre-terminal. 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.
Highlights
Results of matching for cytotoxic T lymphocytes (CTLs) infused are given as number of human leucocyte antigen (HLA)-A, B, C, DR and DQB1 matches respectively (Table III), so that, for example 1,0,2,1,0 indicates a single matched allele/antigen at HLA-A and DR, two alleles/antigens matched at HLA-C and none matched at HLA-B and DQB1
One HLA class II match, based on our previous findings that response rates correlated with number of matches and CD4 cell counts, it was the final decision of the treating clinicians whether to proceed to infusion
It seems plausible that this poor HLA class II matching contributed to these two patients (Patients 3, 9) being the only ones with post-transplant lymphoproliferative disorder (PTLD) to show no clinical response
Summary
Progressive disease, died Complete response Not yet transplanted, CTLs not yet infused Partial response, fatal infection Complete response Complete response Progressive disease – died Complete response Complete response for PTLD, but spindle cell tumour progressed. PTLD, post-transplant proliferative disorder; CNS, central nervous system; VUD, volunteer unrelated donor; PBSCT, peripheral blood stem cell transplant; GVHD, graft-versus-host disease; CML, chronic myeloid leukaemia; EBV, Epstein-Barr virus; HLA, human leucocyte antigen; CTLs, cytotoxic T lymphocytes. The case was originally discussed with the bank and it was decided not to infuse cells in view of the lack of an evidence base for the use of CTLs in this condition.
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