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Updated: Jul 14, 2026
Expanding Cytotoxic T Lymphocytes from Umbilical Cord Blood that Target Cytomegalovirus, Epstein-Barr Virus, and Adenovirus
Published on: May 7, 2012
Preemptive therapy of EBV-related lymphoproliferative disease after pediatric haploidentical stem cell
1Laboratory of Transplant Immunology and Pediatric Hematology/Oncology, Fondazione IRCCS Policlinico S. Matteo, University of Pavia, Pavia, Italy. pcomoli@smatteo.pv.it
Insights
Routine Epstein-Barr virus (EBV) surveillance and rituximab treatment are safe but only partly effective for preventing EBV-related post-transplant lymphoproliferative disease (PTLD) after haplo-HSCT. Donor EBV-specific cytotoxic T-lymphocytes (CTLs) offer a permanent rescue for PTLD patients progressing under rituximab.
Area of Science:
- Immunology
- Hematology
- Oncology
Background:
- Epstein-Barr virus (EBV)-related post-transplant lymphoproliferative disease (PTLD) poses a significant challenge after hematopoietic stem cell transplantation (HSCT).
- Current treatment strategies for EBV-related PTLD following HSCT remain unsatisfactory, necessitating novel therapeutic approaches.
Purpose of the Study:
- To prospectively evaluate the efficacy of routine EBV surveillance and preemptive rituximab treatment in preventing PTLD.
- To assess the impact of these interventions on pediatric recipients undergoing T-cell depleted HSCT from HLA-haploidentical donors.
Main Methods:
- A prospective trial involving 27 pediatric patients receiving extensively T-cell depleted HSCT from HLA-haploidentical donors.
- Routine surveillance for EBV DNA positivity, with preemptive treatment using rituximab for sustained viral DNA levels.
- Monitoring for EBV load, B-cell populations, and PTLD development; subsequent treatment with EBV-specific cytotoxic T-lymphocytes (CTLs) for refractory cases.
Main Results:
- Of 27 patients, 12 developed EBV DNA positivity, with 8 requiring rituximab treatment, which was well-tolerated and cleared EBV DNA.
- Four patients showed EBV rebound under rituximab, with 3 developing overt PTLD; these patients were successfully treated with EBV-specific CTLs.
- CTL therapy restored EBV-specific T-cell frequency and led to durable remission in patients with PTLD progressing despite rituximab.
Conclusions:
- Preemptive rituximab therapy is safe but only partially effective in preventing PTLD in haplo-HSCT recipients.
- EBV-specific CTLs provide a potentially curative option for patients who develop PTLD refractory to rituximab treatment.
- This study highlights the importance of advanced cellular therapies in managing refractory EBV-related PTLD post-HSCT.
Abstract:
The treatment of Epstein-Barr virus (EBV)-related post-transplant lymphoproliferative disease (PTLD) after hematopoietic stem cell transplantation (HSCT) is still unsatisfactory. We conducted a prospective trial to evaluate the impact of routine EBV surveillance and preemptive treatment with the anti-CD20 monoclonal antibody rituximab on the development of PTLD in pediatric recipients of extensively T-cell depleted HSCT from an HLA-haploidentical relative. Twenty-seven patients were included in the surveillance program, 12 developed EBV DNA positivity, with 8 of 12 presenting with sustained viral DNA levels requiring treatment with rituximab. Treatment was well tolerated, and induced clearance of EBV DNA in all patients. However, 4/8 patients showed a new increase in EBV load, coincident with the emergence of CD20(-)/CD19(+) B cells in peripheral blood, accompanied by overt PTLD in 3 patients. The latter cleared PTLD after receiving donor EBV-specific cytotoxic T-lymphocytes (CTLs), and persist in remission at a median 30-month follow-up. EBV-specific T-cell frequency, undetectable at time of EBV DNA positivity, was restored by T-cell therapy to levels comparable with controls. We conclude that preemptive therapy with rituximab is safe, but only partly effective in haplo-HSCT recipients. Patients who progress to PTLD under rituximab treatment can be rescued permanently by infusion of EBV-specific CTLs.
