Humanized anti-CD20 monoclonal antibody (Rituximab) in post transplant B-lymphoproliferative disorder: A retrospective analysis on 32 patients

Background: B-lymphoproliferative post-transplant disorder (BLPD) is a seve re complication of organ and bone marrow transplantation. The reduction of immuno-suppressive therapy or surgery for localized disease may cure some B LPDs. Other therapeutic approaches such as chemotherapy and antiviral drugs are toxic and of limited efficacy. Adoptive immunotherapy with donor T-cel l infusions has yielded promising results but is, at the present time, easi ly applicable only: in bone marrow-transplanted patients. Anti-B-cell Murin e monoclonal antibodies (MoAbs) have proven effective but are no longer ava ilable for human use. We report the activity of a humanized anti CD 20 Mo A b (Rituximab-MABTHERA(R) Roche) in 32 episodes of BLPD treated in 14 French centers. Patients and methods: Between November 1997 and September 1998, 32 patients were diagnosed with BLPD. Twenty-six patients had undergone solid organ tr ansplants (liver 8, kidney 8, heart 4, lung 3, heart lung 1, kidney-pancrea s 1, liver-kidney 1) and six patients had received bone marrow transplantat ions. The median age of the patients was 34 years (3-67 years) and the medi an delay between graft and tumor 5 months (1-156 months). In organ recipien ts, tumors were classified as polymorphic and monomorphic in 10 and 15 case s. respectively; 4 of 6 bone marrow transplant recipients were treated with out pathology documentation because of a rise in EBV load, fever and lymph node enlargement. Tumors were associated with EBV in 22 of 26 tested cases. Rituximab was used as first-line therapy in 30 patients (after reduction o f immunosuppressive treatment in 27 patients) and as salvage therapy in 2 p atients (after failure of chemotherapy). The median time from diagnosis of BLPD to treatment with Rituximab was 14 days (1-110 days), Two patients rec eived eight infusions, twenty-six patients foul infusions, one patient thre e infusions and three patients two infusions of 375 mg/m(2). Results: The tolerance of rituximab was good. The overall response rate was 69%, with 20 complete responses and 2 partial responses. In solid organ tr ansplant the response rate was 65% (15 CR and 2 PR) while it was 83% in bon e marrow-transplanted patients (5 CSR). With a median follow-up of 8 months (1-16 months) 24 patients are still alive. The one-year protected survival is 73%. Of the 22 patients who achieved response. 15 patients (11 solid or gan transplant and 4 bone marrow transplant) are alive with no evidence of disease, 4 patients relapsed a median of 7 months (3 10 months) after treat ment and 3 died while in CR of concurrent diseases. Of the 10 patients a ho did not respond to Rituximab 5 are alive with no evidence of disease after salvage therapy. Conclusions: The use of rituximab appears to be a safe and relatively effic ient therapy in BLPDs. The results need to be confirmed in a prospective mu lticentric trial.