Morbidity and mortality from EBV-induced post-transplant lymphoproliferative disease (EBV+ PTLD) can complicate solid organ transplant (SOT), particularly in those seronegative prior to transplant and in lung/small bowel graft recipients. EBV+ PTLD ranges from early lesions that can respond to decreases in immune suppression to rapidly progressive, monoclonal, diffuse large B-cell lymphomas (DLBCLs). Combination chemotherapy can induce remissions in 40%-50% of cases but relapses are common.

We report treatment results in 13 SOT patients (pts) with EBV-specific cytotoxic T lymphocytes (EBV-CTLs) derived from a third party donor, i.e. someone other than themselves or their SOT donor. EBV-CTLs were matched with the pt for ≥ 2/10 HLA alleles at high resolution (HLA – A, B, C or DR) including the HLA allele required for EBV antigen recognition (the restricting HLA allele). Each cycle included 3 weekly intravenous infusions of 1 – 2 x 10⁶/kg cells followed by a 3 week period of observation. Pts who failed to achieve CR could receive additional cycles from the same donor (pts with SD or PR), switch to therapy with cells from a different donor (POD), or be referred for alternative therapy.

The median age at time of treatment was 19.1 years with median time for development of EBV lymphoma 36.4 months (180-5330 days) after SOT. The median time from diagnosis of PTLD to initial cell therapy was 13.9 months (36-4230 days) reflecting the duration of prior treatment. All pts had failed prior rituximab. Eleven (11) of 13 pts had received additional multi-agent chemotherapy (median of 2 regimens) and/or radiation therapy (n=5) prior to treatment with EBV CTLs. At the time of treatment 6 had ≥3/ sites of disease. Of the seven with 1 or 2 involved sites, five had CNS lesions.

There were no immediate infusion related adverse reactions observed. No patient experienced suppression of blood counts and none showed evidence of organ rejection related to infusion of the EBV CTLs. After the first cycle of cells 3/13 pts achieved a CR or PR. After a median of 2 cycles of cells (range 1-6 cycles) 1 CR and 6 PRs by Lugano criteria were obtained for an overall response rate of 54% (CR+PR). Taken together, our findings show that adoptive immunotherapy with banked EBV-CTLs was well tolerated and may offer clinical benefit to pts with EBV+PTLD after SOT.

CITATION INFORMATION: Prockop S, Doubrovina E, Sauter C, Suser S, O'Reilly R. Banked EBV-Specific T-Cells for Treatment of Rituximab Refractory EBV+ B-Cell Lymphoma in Solid Organ Transplantation Recipients. Am J Transplant. 2016;16 (suppl 3).

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