Clinical study of post-transplant lymphoproliferative disorder in children treating with rituximab after hematopoietic stem cell transplantation

Abstract

Objective To discuss the early-stage-diagnosis about post-transplant lymphoproliferative disorder (PTLD) of hematopoietic stem cell transplantation (HSCT) and the effect of treating with rituximab in PTLD. Methods A total of 4 cases of children who received unrelated allogeneic HSCP from January 2011 to June 2015 in Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University were selected into this study. Among them, 2 cases were boys, 2 cases were girls; the age was 3.4-7.1 years old. Inclusion criteria in this study: children received unrelated allogeneic HSCT and diagnosed as PTLD through clinical experience or biopsy proven. Exclusion criteria: original disease or secondary tumor recurred after allogeneic HSCT. All of the 4 cases received intravenous fluid infusion rituximab (375 mg/m2, once a week × 4 weeks) treatment once after the diagnosis of PTLD. Polymerase chain reaction (PCR) was used to monitor the level of Epstein Barr virus (EBV)-DNA after transplantation. The laboratory results and clinical manifestations such as level of EBV-DNA, lymphadenectasis and antiadoncus before and after treated with rituximab of 4 patients were collected. The study protocol was approved by the Ethical Review Board of Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University. Informed consent was obtained from the parents of those children. Results Four cases of patients all had lymphadenectasis, strong positive of EBV-DNA, and 1 case had progress of nasal congestion and dyspnea, 2 cases had fever. One of 4 cases was diagnosed as simplex lymphoma by pathological, one was pleomorphic lymphoma, one was Langerhans cell change, and another one didn't receive biopsy detection. Besides, all the 3 pathological specimens were EBV positive. After the diagnosis of PTLD, 2 cases stopped using immunosuppressants quickly, 1 case used tacrolimus after stopping the use of cyclosporine A (CsA), 1 case stopped using tacrolimus one and half months. After using rituximab (375 mg/m2, once a week × 4 weeks) for treatment, lymphadenectasis and antiadoncus of 4 cases all disappeared, and EBV-DNA changed into negative, and all the 4 cases were effective treated by rituximab. Among them, 1 case of PTLD recurred 6 months after treatment, and then used rituximab again, it still took effect. Conclusions The treatment of rituximab in PTLD is effective. With recurrence of PTLD, using rituximab takes effect as well. Due to the small sample size of this study, the relevant statistical analysis was not carried out. However, the exact effect of rituximab in the treatment of PTLD still need a large sample, multi-center randomized controlled study to further confirm. As to children with PTLD, monitoring the evidence of allogeneic HSCT engraftment after the reduction of immunosuppression and treatment of rituximab is an important measure to guarantee the success of transplantation. Key words: Lymphoproliferative disorders, posttransplant; Rituximab; Hematopoietic stem cell transplantation