chimeric anti-CD20 monoclonal antibody
post transplant B lymphoproliferative
Springer Online Journal Archives 1860-2000
Abstract Background:B-lymphoproliferative post-transplant disorder (BLPD)is a severe complication of organ and bone marrow transplantation. Thereduction of immuno-suppressive therapy or surgery for localized disease maycure some BLPDs. Other therapeutic approaches such as chemotherapy andantiviral drugs are toxic and of limited efficacy. Adoptive immunotherapy withdonor T-cell infusions has yielded promising results but is, at the presenttime, easily applicable only in bone marrow-transplanted patients. Anti-B-cellMurine monoclonal antibodies (MoAbs) have proven effective but are no longeravailable for human use. We report the activity of a humanized anti CD 20 MoAb (Rituximab–MABTHERA® Roche) in 32 episodes of BLPD treated in 14French centers. Patients and methods:Between November 1997 and September 1998,32 patients were diagnosed with BLPD. Twenty-six patients had undergone solidorgan transplants (liver 8, kidney 8, heart 4, lung 3, heart lung 1,kidney-pancreas 1, liver-kidney 1) and six patients had received bone marrowtransplantations. The median age of the patients was 34 years (3–67years) and the median delay between graft and tumor 5 months (1–156months). In organ recipients, tumors were classified as polymorphic andmonomorphic in 10 and 15 cases, respectively; 4 of 6 bone marrow transplantrecipients were treated without pathology documentation because of a rise inEBV load, fever and lymph node enlargement. Tumors were associated with EBVin 22 of 26 tested cases. Rituximab was used as first-line therapy in 30patients (after reduction of immunosuppressive treatment in 27 patients) andas salvage therapy in 2 patients (after failure of chemotherapy). The mediantime from diagnosis of BLPD to treatment with Rituximab was 14 days(1–110 days). Two patients received eight infusions, twenty-six patientsfour infusions, one patient three infusions and three patients two infusionsof 375 mg/m2. Results:The tolerance of rituximab was good. The overall responserate was 69%, with 20 complete responses and 2 partial responses. Insolid organ transplant the response rate was 65% (15 CR and 2 PR) whileit was 83% in bone marrow-transplanted patients (5 CR). With a medianfollow-up of 8 months (1–16 months) 24 patients are still alive. Theone-year projected survival is 73%. Of the 22 patients who achievedresponse, 15 patients (11 solid organ transplant and 4 bone marrow transplant)are alive with no evidence of disease, 4 patients relapsed a median of 7months (3–10 months) after treatment and 3 died while in CR ofconcurrent diseases. Of the 10 patients who did not respond to Rituximab 5 arealive with no evidence of disease after salvage therapy. Conclusions:The use of rituximab appears to be a safe andrelatively efficient therapy in BLPDs. The results need to be confirmed in aprospective multicentric trial.
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