ALLOGENEIC BLOOD OR MARROW TRANSPLANTATION FOR CHRONIC LYMPHOCYTIC-LEUKEMIA - TIMING OF TRANSPLANTATION AND POTENTIAL EFFECT OF FLUDARABINEON ACUTE GRAFT-VERSUS-HOST DISEASE

The outcome of allogeneic haemopoietic transplants including the rate of immune complications for patients with chronic lymphocytic leukaemi a (CLL) refractory to or relapsing after chemotherapy with fludarabine was analysed. Fifteen patients with advanced CLL who received allogen eic transplantation were prospectively analysed. All patients had prev iously received chemotherapy with fludarabine for 3-15 courses; 12 wer e refractory. The median number of circulating CD4(+) and CD8(+) lymph ocytes at the time of transplant was 0.49x10(9)/l and 0.23x10(9)/l, re spectively. One patient was transplanted from a one HLA-antigen mismat ched unrelated donor. Three others received a one or two antigen misma tched graft and 11 had HLA-identical sibling donors. Patients received cyclosporine or tacrolimus in addition to methotrexate or methylpredn isolone for prophylaxis of acute graft-versus-host disease (aGVHD). Fo urteen patients engrafted; one patient had graft failure, but recovere d after therapy with intravenous immunoglobulin. 13 (87%) achieved com plete remission (CR). Nine (53%) remain alive and in CR with a median follow-up of 36 (range 3-60) months. None developed visceral graft-ver sus-host disease. These data compared favourably to published reports in other leukaemia patients and for patients with CLL who received a c omparable immunosuppressive therapy but without prior fludarabine expo sure. This data indicates that allogeneic haemopoietic transplantation can induce durable remission in patients with CLL refractory to fluda rabine and that it is reasonable to delay transplantation until failur e of fludarabine therapy. It also suggests that prior exposure to flud arabine may decrease the incidence of severe aGVHD, possibly through i ts immunosuppressive effects. Further studies are warranted to evaluat e this observation.