Preemptive therapy of EBV-related lymphoproliferative disease after pediatric haploidentical stem cell transplantation.
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.
Comoli
P
P
Laboratory of Transplant Immunology and Pediatric Hematology/Oncology, Fondazione IRCCS Policlinico S. Matteo, University of Pavia, Pavia, Italy. pcomoli@smatteo.pv.it
Basso
S
S
Zecca
M
M
Pagliara
D
D
Baldanti
F
F
Bernardo
M E
ME
Barberi
W
W
Moretta
A
A
Labirio
M
M
Paulli
M
M
Furione
M
M
Maccario
R
R
Locatelli
F
F
D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D058846:Antibodies, Monoclonal, Murine-Derived; D015703:Antigens, CD / Q000097:blood; D000998:Antiviral Agents / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D020031:Epstein-Barr Virus Infections / Q000517:prevention & control*; D005260:Female; D004854:Herpesvirus 4, Human; D006801:Humans; D007223:Infant; D008212:Lymphocyte Depletion; D008232:Lymphoproliferative Disorders / Q000517:prevention & control* / Q000821:virology; D008297:Male; D000069283:Rituximab; D033581:Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D013601:T-Lymphocytes / Q000276:immunology*; D019172:Transplantation Conditioning
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D015703:Antigens, CD; D000998:Antiviral Agents; D000069283:Rituximab