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Background: Lymphoma represents the third most common cancer under 15yrs of age and the most common cancer in adolescents and young adults.(Hochberg/Cairo, BJH 2009) Hodgkin Lymphoma occurs in approximately 7,500 people per yr in the U.S. EBV infection has been suggested to be one of several causative possibilities in its pathogenesis with about 40% of HL being EBV-associated. Autologous T cells directed to LMP1/2 antigens can induce durable responses in high risk patients without significant toxicity.(Bollard, JCO 2014) Although there has been significantly improved outcomes, those with progressive or relapsed disease often require alternative strategies with limited good options.
Objectives: We intend to analyze the toxicity and overall response rate of allogeneic HLA matched donor derived latent membrane protein (LMP) specific-cytotoxic T cell lymphocytes (CTLs) in Children, Adolescents and Young Adults (CAYA) with EBV-associated refractory or relapsed Hodgkin lymphoma (HL) following reduced intensity conditioning and allogeneic hematopoietic stem cell transplantation (AlloSCT) from EBV positive HLA matched sibling or unrelated adult donors.
Methods: EBV positive patients with poor-risk HL will receive a reduced intensity conditioning regimen followed by an allogeneic stem cell transplant from EBV positive HLA matched sibling or unrelated adult donor combined with up to three doses of post AlloSCT allogeneic donor derived LMP specific cytotoxic T-lymphocyte (CTL) infusions (Fig 1A) as previously described.(Bollard et al, Blood 2007)
Results: To date, our first patient has successfully completed therapy – a 20yr old male with EBV+ relapsed/refractory Hodgkin Lymphoma who received his donor EBV-CTL infusion approximately 60 days post AlloSCT from an EBV+ 10/10 MUD donor without adverse effect or complication.
Conclusions: The development of this multicenter LCTC consists of 9 outstanding multidisciplinary academic centers (Fig 1B) that comprise expertise in CAYA clinical and translational lymphoma research, lymphoma biology and biopathology, stem and cell therapy, targeted cell therapy manufacturing (GMP), biostatistics and bioinformatics, and expertise in state and federal regulatory compliance. This consortium is poised to rapidly translate targeted cell therapy in CAYA with high- or poor-risk lymphomas. Further results from this trial will provide critical information to develop future randomized trials investigating the use of donor derived LMP-CTLs.
