Long-term follow up of sequential mobilisation and autologous transplantation with CD34-selected cells in multiple myeloma: a multimodality approach.

Abstract

Even after high dose chemotherapy (HDT) and autologous haemopoietic stem cell transplantation, the majority of patients with multiple myeloma eventually relapse. The aim of the present study was to study the -feasibility and outcome of delivering a regimen including in vivo and in vitro purging and double HDT in patients with multiple myeloma. Thirty-four patients with advanced multiple myeloma were enrolled in a program of vincristine, doxorubicin and dexamethasone chemotherapy, high dose cyclophosphamide/granulocyte macrophage colony stimulating factor (GM-CSF) stem cell mobilisation, CD34 selection of harvested stem cells (in vitro purging), double HDT (cyclophosphamide/epirubicin in the first, busulphan/melphalan in the second) rescued by CD34(+)-selected cells, the second rescue using cells harvested following the first HDT (in vivo purging) and interferon maintenance. Forty-four per cent of patients completed the program. Fifty-three per cent of withdrawals were as a result of insufficient stem cells. This correlated to previous chemotherapy. Therapy-related mortality was 6%. CD34(+) selection achieved more than a 2-log reduction of CD38(++) cells; in vivo purging achieved 80%. Although similar numbers of CD34(+) cells were reinfused at both HDT, platelet recovery was slower after the second HDT. Additional complete remissions were achieved after each phase of therapy, 3% at the end of vincristine, doxorubicin and dexamethasone and 33% after completing planned HDT. Factors associated with longer overall survival included age less than 60 years (P = 0.044), serum beta-2-microglobulin below 3 micro gamma/L at entry (P = 0.042) and less than 2 months between the two HDT (P = 0.024). The only factor associated with a longer event-free survival was less than 2 months between HDT on study (P = 0.038). (i) dose intensification with two HDT delivered within 2 months might be associated with a better patient outcome, (ii) early mobilisation should be incorporated in multiple myeloma HDT programs and (iii) higher CD34(+) doses may be required for tandem transplants.