Intensive chemotherapy with blood progenitor transplantation for primary resistant multiple myeloma

Abstract

This study assessed the feasibility and effect of blood progenitors as the only source of haemopoietic support for myeloablative therapy for patients with primary resistant multiple myeloma and markedly infiltrated bone marrow. 17 patients with advanced, primary resistant myeloma received a priming regimen of cyclophosphamide (3 g/m2) and etoposide (900 mg/m2) with GM-CSF. During haematological recovery, at least 2 x 10(6) CD34+ mononuclear cells/kg were collected from each patient with 4-12 leukaphereses. High-dose chemotherapy was then given which consisted of thiotepa (750 mg/m2), busulfan (10 mg/kg) and cyclophosphamide (120 mg/kg) followed by reinfusion of the blood progenitors. Haemopoietic reconstitution was rapid with recovery of granulocytes to > 1.0 x 10(9)/l after a median of 10 d and of platelets to 50 x 10(9)/l after a median of 29 d. The myeloma responded in 10/17 patients for a projected median duration of at least 12 months. Survival was prolonged significantly in comparison with the outcome of control patients who did not receive intensive treatment. Blood progenitors, assessed from the number of CD34+ cells, produced early haemopoietic recovery after myeloablative therapy that induced sustained control of advanced and resistant multiple myeloma.

Response to induction chemotherapy is not essential to obtain survival benefit from high-dose melphalan and autotransplantation in myeloma

“…8,9,15,16 They show that patients with primary refractory disease receiving high-dose therapy fare better than those not undergoing high-dose therapy, 8,9 and that the outcome of patients with refractory relapse treated with high-dose therapy is significantly worse than those with primary refractory disease treated similarly. 15,16 These data have significant practical implications.…”

“…18,20 The response rate of our primary refractory group to high-dose melphalan and autotransplantation is higher than that reported by the MD Anderson group. 8,9 There could be several reasons for this. One is that we proceeded directly to autotransplantation without trying salvage induction regimens or prolonging induction therapy beyond the minimum required to demonstrate lack of response in any given patient.…”

“…4,[21][22][23] The MD Anderson group has, for the patients they have reported, usually employed regimens other than 200 mg/m 2 melphalan. 8,9 We have also used immunoelectrophoresis rather than immunofixation to define CR -which may overestimate the proportion of patients in CR.…”

“…Dose-intensive therapy has been shown to improve the outcome of these patients in comparison with those treated conventionally. 8,9 There are no data comparing the outcome of patients with disease responding to induction chemotherapy (chemosensitive) and that of those with disease not responding adequately to induction chemotherapy (primary refractory) after autotransplantation. There is a prevalent perception that the outcome of patients with primary refractory disease is considerably worse than that of those with chemosensitive disease despite an autograft.…”

Prognostic factors for survival after autologous transplantation: a single centre experience in 133 multiple myeloma patients

“…Dimopoulos et al 29 have published that refractory patients had better outcome after transplantation than after conventional chemotherapy. Terpos et al 20 reported no significant differences in PFS and OS in patients who achieved CR or PR prior to transplantation compared to patients with MR, NR or refractory disease prior to transplantation.…”