TRANSPLANT-LITE - INDUCTION OF GRAFT-VERSUS-MALIGNANCY USING FLUDARABINE-BASED NONABLATIVE CHEMOTHERAPY AND ALLOGENEIC BLOOD PROGENITOR-CELL TRANSPLANTATION AS TREATMENT FOR LYMPHOID MALIGNANCIES

Purpose: To investigate the use of a nonmyeloablative fludarabine-base d preparative regimen to produce sufficient immunosuppression to allow engraftment of allogeneic stem cells and induction of graft-versus-le ukemia/lymphoma (GVL) as the primary treatment modality for patients w ith chronic lymphocytic leukemia (CLL) and lymphoma. Patients and Meth ods: Fifteen patients were studied. Six patients were in advanced refr actory relapse, and induction therapy had failed in two patients. Pati ents with CLL or low-grade lymphoma received fludarabine 90 to 150 mg/ m(2) and cyclophosphamide 900 to 2,000 mg/m(2). patients with intermed iate-grade lymphoma or in Richter's transformation received cisplatin 25 mg/m(2) daily for 4 days; fludarabine 30 mg/m2; and cytarabine 500 mg/m(2) daily for 2 days. Chemotherapy was followed by allogeneic stem -cell infusion from HLA-identical siblings. Patients with residual mal ignant cells or mixed chimerism could receive a donor lymphocyte infus ion of 0.5 to 2 x 10(8) mononuclear cells/kg 2 to 3 months posttranspl antation if graft-versus-host disease (GVHD) was not present. Results: Eleven patients had engraftment of donor cells, and the remaining fou r patients promptly recovered autologous hematopoiesis. Eight of 11 pa tients achieved a complete response (CR). Five of six patients (83.3%) with chemosensitive disease continue to be alive compared with two of nine Patients (22.2%) who had refractory or untested disease at the t ime of study entry (P = .04). Conclusion: These findings indicate the feasibility of allogeneic hematopoietic transplantation with a nonabla tive preparative regimen to produce engraftment and GVL against lympho id malignancies. The ability to induce remissions with donor lymphocyt e infusion in patients with CLL, Richter's, and low-grade and intermed iate-grade lymphoma is direct evidence of GVL activity against these d iseases. This approach appears to be most promising in patients with c hemotherapy-responsive disease and low tumor burden. J Clin Oncol 16:2 817-2824. (C) 1998 by American Society of Clinical Oncology.