A 51-year-old patient with refractory CLL elected to participate in a trial of nonmyeloablative trans- plantation from an HLA-matched unrelated donor. He received low-dose fludarabine/TBI, with infusion of donor PBPC and cyclosporin (CsA)/MMF. Early post transplant he experienced explosive tumor growth with respiratory insufficiency. After immunosuppression discontinuation and rituximab administration, no response was observed. This prompted treatment with cyclophosphamide (2 g/m(2)/day x 2), paclitaxel (250 mg/m(2) over 24 h), doxorubicin (50 mg/m(2)), solumedrol (500 mg/day), and a second dose of rituximab, from days +11 to +14. A rapid response was achieved. Chemotherapy did not cause an obvious compromise of donor stem cell engraftment or establishment of stable donor chimerism.