Autologous stem cell transplant is only possible where sufficient numbers of CD34+ stem cells are available for re-infusion following high dose therapy. As a consequence, it is important to establish both those factors that predict successful stem cell mobilisation and the optimal regimen for stem cell mobilisation.
A number of factors have been shown to influence mobilisation and stem cell collection including:
- the number of cycles of prior chemotherapy
- the number of prior chemotherapy regimens
- pelvic radiotherapy
- exposure to chemotherapeutic agents that are ‘stem cell toxic’ e.g. melphalan, carmustine
- lenalidomide (stem cell collection should be considered within the first 4 cycles)
- age (decreasing yield with advancing age)
- platelet count at the time of apheresis (platelet count greater than 200 x 109/L is associated with successful mobilisation).rrrrr
What does the addition of CY achieve vs GCSF alone?
While stem cell mobilisation is possible using G-CSF alone, many transplant centres use cyclophosphamide (CY) in combination with G-CSF on the basis that it has been clearly established that the combination of cyclophosphamide and G-CSF is superior to G-CSF alone or the combination of G-CSF and GM-CSF in terms of the number of CD34+ stem cells and colony-forming units-granulocyte-macrophage (CFU-GM) mobilised, with CY/G-CSF enabling a higher yield of CD34+ stem cells, and a lower number of apheresis procedures to achieve target stem cell yields. This may particularly be the case in patients with risk factors for poor mobilisation. Like mobilisation using G-CSF, the Cy/G-CSF regimen also allows predictable mobilisation (in this case at ~ 10 to 14 days post treatment).r,r,r,r,r,r,r,r,r,r
While the use of cyclophosphamide allows better stem cell collection and reduces the likelihood of collection failure, it prolongs the collection process (relative to G-CSF alone) and increases the risk of febrile neutropenia and other infectious complications. A number of studies have shown no evidence of cyclophosphamide (irrespective of dose) on overall transplant outcome.r There is a suggestion in the era of novel agent induction that the use of cyclophosphamide vs G-CSF alone may impair engraftment, but this needs further confirmation.r
*Evidence for Cyclophosphamide dosage
A number of studies have compared the effectiveness (measured in terms of the likelihood of achieving sufficient CD34+ stem cells for a single or tandem ASCT) and toxicity of high-dose (7 g/m2), intermediate-dose (3 to 4 g/m2) and low-dose (1.2 to 2 g/m2) cyclophosphamide.r,r,r,r
The results of these studies suggest that intermediate-dose (3 to 4 g/m2) cyclophosphamide is as effective as high-dose (7 g/m2) cyclophosphamide but is associated with less clinical toxicity.r,r,r While lower doses of cyclophosphamide (1.2 to 2 g/m2) may be associated with less toxicity and fewer episodes of febrile neutropenia, data regarding the efficacy of stem cell mobilisation with lower doses of cyclophosphamide is less clear, with some studies suggesting equivalent effectiveness in mobilisation, while a number of studies suggest that lower doses of cyclophosphamide may yield lower numbers of CD34+ stem cells and require more apheresis procedures.r,r,r,r