Abstract
Background: Anti B cell antibodies have been proposed as a treatment for post-transplant lymphoproliferative disorders (PTLD). Experience in children is limited.
Methods and Results: We report experience (n=40) with use of the chimeric mouse/human antiCD20 monoclonal antibody (rituximab) in pediatric PTLD patients with refractory disease (no response to reduced immunosuppression, progressive or relapsed disease, or concomitant allograft rejection). Initial experience was through a voluntary registry (n=26), and most recent experience is from an onging prospective, non-randomized clinical trial (n=14). Use of chemotherapy or other experimental therapies were an exclusion criteria for both studies. All PTLD were of B cell origin and expressed CD20 and all but 2 (both in registry cohort) were EBV positive. The first cohort (registry) comprised 26 solid organ recipients from 12 centers (heart 11, kidney 6, lung 4, other 5) with mean age of 12.5 years, 29 months (range 2–132) from transplant. Histology revealed these lesions: polymorphic 17, monomorphic 7 (including 1 Burkitts-like), Hodgkins-like 1, unspecified 1. 21/26 received 375mg/m2 x 4 doses. There were no SAE’s. 18 pts (69%) showed CR, and 4 (16%) showed PR. The 4 non-responders comprised the 2 EBV negative cases, the Burkitts-like disease and the earliest onset case (fulminant disease at 2 months post-transplant). At latest follow-up (mean 41 months), 73% survive with one graft loss (kidney). In the prospective clinical trial, 14 patients (to date) with refractory disease were enrolled. The protocol comprises 4 doses of 375mg/m2 (weeks 1–4) with no further treatment for patients with CR or for those with no response. Patients with PR receive 4 further doses (weeks 5–8). The 14 patients were from 5 centers (lung 5, kidney 5, heart 4) with mean age of 6.5 years, 41 months (range 4–120) from transplant. Histology revealed the following: polymorphic 10, monomorphic 3, Hodgkin-like 1. There were no SAE’s. Two are still recieving therapy. Of the other 12, 9 (75%) acheived CR and 10 pts (83%) are alive with one graft loss (kidney) at mean follow-up of 1.5 years. The two deaths were due to fungal pneumonia and complications of elective surgery in a patient in CR (both lung recipients).
Conclusions: These results suggest that rituximab may have an important role to play in management of refractory PTLD in solid organ recipients (CR rate approx. 70–75% with low incidence of graft loss). This group of patients traditionally has high mortality and has been treated with chemotherapy. Rituximab should be considered as first line treatment for refractory polymorphic PTLD in children after solid organ transplantation. Role in monomorphic disease requires further investigation. Use of rituximab as first line therapy is under investigation.
Risk of diffuse large B-cell lymphoma after solid organ transplantation in the United States