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

Abstract

<h4>Background</h4>Even after high dose chemotherapy (HDT) and autologous haemopoietic stem cell transplantation, the majority of patients with multiple myeloma eventually relapse.<h4>Aim</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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).<h4>Conclusions</h4>(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.