High dose therapy and stem cell transplantation

• Autologous SCT after high dose melphalan (HDM; 200mg/m2) achieves high CR rates (25-80%) after initial therapy with a VAD-type regimen and PBSC harvest; median duration of response 2-3 years; treatment of choice for patients <65 years; best responders have best survival, median >5 years; improved progression free survival (32 vs. 20 mo) and overall survival (54 vs. 42mo) in large randomised study1; side effects: myelosuppression, infection, delayed regeneration; not curative.

• Addition of TBI to melphalan 140mg/m2 with autologous SCT adds toxicity but no benefit; no convincing benefit for 'double/tandem' autografts though may be of value for those converted to CR after second procedure; no benefit from stem cell purification procedures.

• Intermediate dose melphalan (60-80mg/m2) + G-CSF offers an alternative consolidation treatment for patients with failed PBSC mobilisation.

• Allogeneic SCT: applicable to fit patients <50 years; transplant-related mortality with standard conditioning regimens (fflp3)0) is high (~33%) due to infection and GvHD; 35-45% long term survival (>5 years); ~33% chance of durable remission and possible cure; ~33% chance of survival with recurrence; evidence of graft vs. myeloma effect; non-myeloablative regimens (fflp3)0) reduce toxicity, increase age limit but reduce response rate; allogeneic SCT should be discussed with all patients <55 with a suitable sibling donor.

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