Anti–B-Cell Monoclonal Antibody Treatment of Severe Posttransplant B-Lymphoproliferative Disorder: Prognostic Factors and Long-Term Outcome

Abstract

B-lymphoproliferative disorder (BLPD) is a rare but severe complication of organ and bone marrow transplantation (BMT). Profound cytotoxic T-cell deficiency is thought to allow the outgrowth of Epstein-Barr virus–transformed B cells. When possible, reduction of immunosuppressive treatment or surgery for localized disease may cure BLPD. Therapeutic approaches using chemotherapy or antiviral drugs have limited effects on survival. Adoptive immunotherapy with donor T-cell infusions has given promising results in BMT recipients. We previously reported that administration of two monoclonal anti–B-cell antibodies (anti-CD21 and anti-CD24) could contribute to the control of oligoclonal BLPD. Here we report the long-term results of treatment with these monoclonal anti–B-cell antibodies for cases of severe BLPD. In an open multicenter trial, 58 patients in whom aggressive B-cell lymphoproliferative disorder developed after BMT (n = 27) or organ (n = 31) transplantation received 0.2 mg/kg/d of specific anti-CD21 and anti-CD24 murine monoclonal antibodies (MoAbs) for 10 days. The treatment was well tolerated. Thirty-six of the 59 episodes of BLPD in the 58 patients presented complete remission (61%). The relapse rate was low (3 of 36, 8%). Multivariate analysis identified the following risk factors for partial or no response to anti–B-cell MoAb therapy: multivisceral disease (P ≤ .005), central nervous system involvement (P ≤ .05), and late onset of BLPD (P ≤ .005). The overall long-term survival was 46% (median follow-up, 61 months); it was lower among BMT patients (35%) than organ transplant patients (55%). None of the patients who had received BMT for hematological malignancy survived for 1 year. Eight of these 11 patients presented monoclonal BLPD. Tumor burden was the only other variable that contributed significantly to poor survival. Thus, as assessed from this long-term study, the use of anti–B-cell MoAbs therefore appears to be a safe and relatively effective therapy for severe posttransplant BLPD. © 1998 by The American Society of Hematology.

Post cardiac transplantation lymphoproliferative disorder presenting as t(8;14) Burkitt leukaemia/lymphoma treated with low intensity chemotherapy and rituximab

“…Early reports suggested that these potentially malignant lymphoid proliferations responded to reduced immune suppression in children and normal intensive B cell lymphoma therapy in adults [10,11]. Immunotherapy with early B cell antibodies was also explored with some success [12]. Over the last 10 years it has become clear that PTLD is amenable to treatment.…”

De novo malignancies after liver transplantation: A major cause of late death

“…41 The potential for exacerbation of rejection with interferon, toxicity with chemotherapy, and logistic problems with cell-based therapy make antibody therapy attractive. With the unavailability of anti-CD21 and anti-CD24 monoclonal antibodies, 48 anti-CD20 monoclonal antibody therapy has been used instead and recently was reported to be of some benefit in post-LT PTLD. 49 Chemotherapy may be necessary for refractory PTLD.…”

Review of Epstein–Barr virus and post‐transplant lymphoproliferative disorder post‐solid organ transplantation (Review Article)

“…[100][101][102] Factors shown to predict a favourable response to rituximab include a short duration between organ transplantation and onset of PTLD, localised disease, absence of CNS involvement, and a normal serum LDH level. 102,103 Rituximab has been used simultaneously with other treatments including chemotherapy or sirolimus (as monotherapy to prevent allograft rejection) which appear promising with improved response rates. 104,105 Preemptive treatment with rituximab has been evaluated in HSCT recipients (but not in SOT recipients) with high EBV viral load, demonstrating a decrease in incidence of PTLD from 49% to 18% compared to a historical cohort.…”