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Preemptive Therapy of EBV‐Related Lymphoproliferative Disease after Pediatric Haploidentical Stem Cell Transplantation
Author(s) -
Comoli P.,
Basso S.,
Zecca M.,
Pagliara D.,
Baldanti F.,
Bernardo M. E.,
Barberi W.,
Moretta A.,
Labirio M.,
Paulli M.,
Furione M.,
Maccario R.,
Locatelli F.
Publication year - 2007
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/j.1600-6143.2007.01823.x
Subject(s) - medicine , rituximab , hematopoietic stem cell transplantation , immunology , transplantation , lymphoproliferative disorders , epstein–barr virus , cd20 , cytotoxic t cell , stem cell , lymphoma , virus , biology , genetics , biochemistry , chemistry , in vitro
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.