Chemorefractory diffuse B-LCL has a very poor prognosis with only a remote possibility of durable survival following myeloablative therapy and autologous or allogeneic BMT. In a phase I-II trial evaluating non-myeloablative bone marrow transplantation for hematologic malignancies, 20 evaluable patients had advanced B-LCL. Preparative therapy consisted of cyclophosphamide (CY 150-200 mg/kg), peri-transplant anti-T cell antibody therapy with either equine anti-thymocyte globulin (ATG) (15-30 mg/kg, days -2, -1, +1 or -1, +1, +3, +5) or monoclonal anti-CD2 antibody therapy (MEDI-507; BioTransplant, Charlestown, MA), thymic irradiation (700 cGy) in patients who had not received previous mediastinal therapy and cyclosporine beginning on day -1 with rapid taper to discontinuation by day + 35 in patients without GVHD. In pts with mixed chimerism and no evidence of GVHD, prophylactic donor leukocyte infusions (pDLI) were given beginning on day + 35 post-transplant. Median pt. age was 38 (20 to 62) years. The median number of prior chemoradiotherapy regimens was 3 (2 to 5) and median time from diagnosis to BMT was 12.5 (5 to 115) months. Three pts had received a prior autologous stem cell transplant (AuSCT). Ten pts were in refractory relapse, 7 pts had primary refractory disease, one pt was in a 2nd partial remission (PR) following a 2 month first complete remission (CR) and 2 were in untreated relapse following AuSCT. Ten patients received transplants from HLA matched donors, and 10 from HLA 1 to 3 antigen mismatched donors. No early (day 100) transplant related mortality occurred. One late death from aspergillosis occurred. Three of 10 HLA matched patients received prophylactic pDLI. None of the HLA mismatched patients received DLI. Acute GVHD grade II occurred in 4 of the 8 evaluable HLA matched patients following BMT. One pt developed grade IV acute GVHD and one chronic GVHD following pDLI. Five of 10 HLA mismatched patients developed grade II GVHD. Eight of 19 evaluable patients achieved a response (5 CR, 3 PR) including 3 of 10 HLA matched patients and 5 of 10 HLA mismatched patients. Five patients are alive, and progression free at 13 to 52 months post-transplant: two received an HLA matched transplant and both received pDLI, while 3 pts received an HLA mismatched transplant including one patient who had graft loss at day + 75. Two of the 5 pts have had no acute GVHD while 4 developed chronic GVHD (2 limited, 2 extensive). Durable PFS is achievable in approximately 25% of patients with chemorefractory diffuse B-LCL. These durable remissions occurred in HLA matched pts following pDLI and without DLI in HLA mismatched recipients, and notably, in some pts, without acute or chronic GVHD.
Full conference title:
43rd American Society of Hematology (ASH) Annual Meeting
- ASH 43rd (2001)