Fludarabine-based low toxicity conditioning for allogeneic peripheral blood stem cell transplantation

The curative potential of allogeneic transplantation is based on the effect of chemo/radiotherapy-conditioning and the graft-versus-leukaemia reaction. Transplant-related toxicity is of concern in heavily pretreated or elderly patients. Therefore, allogeneic transplantation has been restricted usually to patients younger than age 55. We started a phase II trial for patients with advanced malignancies (myelodysplastic syndromes, lymphomas, chronic leukaemias, multiple myeloma, metastatic melanoma and renal cell carcinoma) up to age 65 using fludarabine 5 x 30 mg/m(2), BCNU 2 x 150 mg/m(2) and melphalan 110 mg/m(2) for conditioning. PBSCT grafts from matched related donors were transplanted and cyclosporin A and mini-methotrexate were used for GVHD prophylaxis. Until now II patients have been transplanted with the diagnosis: AML/MDS, OMF, CLL or other low grade lymphomas, multiple myeloma, and metastatic melanoma and metastatic renal cell carcinoma. Conditioning was well tolerated with little mucositis only. All patients engrafted day +10 and showed complete or partial response of their disease, except for one patient with melanoma progressing after partial response. Acute GVHD developed in 4 patients, with mild skin reaction in 3 patients, and grade IV acute intestinal GvHD in 1 patient with AML/MDS. Donor chimerism was complete in the majority of patients evaluated. This regimen is active in a variety of malignant diseases and allows allogeneic immunotherapy with reduced toxicities. Especially older patients with concomitant diseases may benefit from this approach.