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

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Abstract:

Abstract Background: 

Even after high dose chemotherapy (HDT) and autologous haemopoietic stem cell transplantation, the majority of patients with multiple myeloma eventually relapse. Aim: 

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. Methods: 

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. Results: 

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 β-2-microglobulin below 3 µγ/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). Conclusions: 

(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. (Intern Med J 2004; 34: 167−175)

Keywords: CD34+ selection; in vivo purge; multiple myeloma; tandem autotransplantation

Document Type: Research Article

DOI: http://dx.doi.org/10.1111/j.1444-0903.2004.00552.x

Affiliations: 1: Department of Haematology, Institute of Medical and Veterinary Science, 2: Department of Haematology, Flinders Medical Centre and 3: Department of Haematology, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia and 4: Department of Haematology/Oncology, The Queen Elizabeth Hospital, Adelaide, South Australia, 5: Nexell Inc, Irvine, California, USA

Publication date: April 1, 2004

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