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Humanized anti-CD20 monoclonal antibody (Rituximab) in post transplant B-lymphoproliferative disorder: a
Background:
B-lymphoproliferative post-transplant disorder (BLPD) is a severe complication of organ and bone marrow transplantation. The reduction of immuno-suppressive therapy or surgery for localized disease may cure some BLPDs. Other therapeutic approaches such as chemotherapy and antiviral drugs are toxic and of limited efficacy. Adoptive immunotherapy with donor T-cell infusions has yielded promising results but is, at the present time, easily applicable only in bone marrow-transplanted patients. Anti-B-cell Murine monoclonal antibodies (MoAbs) have proven effective but are no longer available for human use. We report the activity of a humanized anti CD 20 Mo Ab (Rituximab-MABTHERA 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 transplants (liver 8, kidney 8, heart 4, lung 3, heart lung 1, kidney-pancreas 1, liver-kidney 1) and six patients had received bone marrow transplantations. The median age of the patients was 34 years (3-67 years) and the median delay between graft and tumor 5 months (1-156 months). In organ recipients, tumors were classified as polymorphic and monomorphic in 10 and 15 cases, respectively; 4 of 6 bone marrow transplant recipients were treated without 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 of immunosuppressive treatment in 27 patients) and as salvage therapy in 2 patients (after failure of chemotherapy). The median time from diagnosis of BLPD to treatment with Rituximab was 14 days (1-110 days). Two patients received eight infusions, twenty-six patients four infusions, one patient three infusions and three patients two infusions of 375 mg/m2.
Results:
The tolerance of rituximab was good. The overall response rate was 69%, with 20 complete responses and 2 partial responses. In solid organ transplant the response rate was 65% (15 CR and 2 PR) while it was 83% in bone marrow-transplanted patients (5 CR). With a median follow-up of 8 months (1-16 months) 24 patients are still alive. The one-year projected survival is 73%. Of the 22 patients who achieved response, 15 patients (11 solid organ 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 treatment and 3 died while in CR of concurrent diseases. Of the 10 patients who 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 efficient therapy in BLPDs. The results need to be confirmed in a prospective multicentric trial.