Intermediate-dose intravenous melphalan and blood stem cells mobilized with sequential GM+G-CSF or G-CSF alone to treat AL (amyloid light chain) amyloidosis

AL amyloidosis patients ineligible for dose-intensive melphalan (200 mg/m(2 )) were enrolled on a phase II trial to be treated with two cycles of inter mediate-dose melphalan (IDM 100 mg/m(2)) and mobilized blood stern cells (B SC), For mobilization patients were randomized to either GM-CSF 250 mu g/m( 2) for 3 d followed by G-CSF 10 mu g/ kg for 3 d (GM+G), or G-CSF 10 mu g/k g for 6 d (G-alone), with leukaphereses on days 5, 6 and 7. To minimize mor bidity, we planned to support each cycle with 3.5 x 10(6) CD34(+) cells/kg and had a collection target of 7x10(6) CD34(+) cells/kg. Those who did not achieve the target were treated with one cycle of IDM. 30 patients, a media n of 62 years old and 7 months from diagnosis, were enrolled. Both mobiliza tion regimens were generally well tolerated, and similar in terms of CD34() cells and CFU-GM collected, but only 6/28 patients achieved the collectio n target (GM+G four, G-alone two). Despite a 19% incidence of grade 4 toxic ities, IDM therapy was well tolerated. At a median follow-up of 24 months ( 19-36) 57% of patients had survived, 17% with durable complete haematologic al responses and 40% with improved or stable amyloid organ involvement, inc luding 3/9 patients with predominant cardiac amyloid who are alive 2-3 year s after treatment. The 100 d mortality was 20%. In conclusion, no definitiv e differences were identified between the mobilization regimens and IDM was an active regimen in AL for selected patients.