Prolonged survival after intensive therapy and purged ABMT in patients with multiple myeloma

Despite numerous strategies, the cure of multiple myeloma remains a difficu lt challenge. Recent approaches hare involved dose-intensive therapy follow ed by stem cell transplantation, most often with autologous stem cells (ASC T). Although ASCT is of benefit, it is not considered curative. Between 198 8 and 1995, we utilized an aggressive three-drug conditioning regimen follo wed by ABR-IT using marrow purged with either 4-hydroperoxycyclophosphamide (4-HC) or mafosphamide (MAF), Twenty-nine of 42 patients who had first rec eived VAD (14 patients) or VAD followed by cyclophosphamide (7 g/m(2) i.v.) + dexamethasone (40 mg/day p.o. x 4) + GM-CSF (15 patients) met the eligib ility criteria needed to undergo bone marrow harvest and ABR;IT, ie less th an or equal to 10% marrow plasma cells and greater than or equal to 50% dec rease in paraprotein level. Alpha-interferon maintenance therapy was given post ABMT. Median followup is 7.5 years (range 5.0-11.25), Six early and tw o late non-relapse deaths occurred; 15 patients have relapsed. Seven patien ts remain in continuous CR (five) or PR (two), including three with stage I IIB disease at diagnosis. One patient developed a soft tissue sarcoma 8 Sea rs post ASCT. Although this protocol produced excessive toxicity compared w ith current approaches, the results demonstrate that dose-intensive therapy and ASCT can produce durable remission in this disease. Further developmen t of dose-intensive strategies is warranted.