Autologous stem cell transplantation and apheresis

Autologous stem cell transplantation is the transplantation of the patient’s own hematopoietic stem cells after high dose chemotherapy. This is most commonly performed in patients with multiple myeloma. Stem cell transplantation has traditionally been and is still performed to a low degree with bone marrow transplant; however, this procedure is painful and associated with high risks.

Since approximately 20 years stem cells are isolated from the peripheral blood. Since stem cells under normal circumstances are present in the blood only in very small numbers, they need to be mobilized from the bone marrow prior to collection from the blood by a procedure called apheresis. During apheresis blood is passed via infusion lines into an apparatus outside of the body where the stem cells are separated from the blood by centrifugation. They are collected in a bag, conserved and frozen for subsequent transplantation. The whole procedure takes several hours (3-4h) and resembles dialysis.

Apheresis is performed before high dose chemotherapy. At the appropriate interval the stem cells are infused back to the patient and find their way into the bone marrow where they start to reconstitute the patient’s blood and immune system (engraftment). This process usually takes between 10-21 days during which the patient is at high risk for serious infections and bleeding complications.

Current standard therapy for stem cell mobilization requires repeated daily injections of G-CSF (granulocyte-colony stimulating factor) for 4-5 days. G-CSF is a naturally occurring protein and essential for the maintenance and proliferation of stem cells in the bone marrow. After injection of the synthetic, recombinant G-CSF protein to volunteers or patients the stem cells are mobilized from the bone marrow into the peripheral blood where they are harvested for subsequent transplantation; in some patients this apheresis must be repeated on subsequent days because of collection of insufficient numbers of stem cells on one day. The application of G-CSF is cumbersome for the patient because of the repeated injections apheresis procedure and is associated with side effects (like bone pain).

More recent pharmacological approaches to mobilize stem cells from the bone marrow into the peripheral blood include antagonists of the chemokine receptor CXCR4 like POL6326. POL6326 offers distinct advantages for the patient and the hospital because the mobilization occurs more rapidly and in a very predictable way. Moreover, the infusion of POL6326 and subsequent apheresis takes place on the same day. Therefore, POL6326 has the potential to become a novel stand alone therapy for stem cell mobilization and may eventually abrogate the use of G-CSF.