From Arthritis to Zoster

Bone marrow stem cell transplants – more accurately called hematopoietic stem cell transplants (HSCT) because transplanted cells can be acquired from sites other than bone marrow – offer a potential cure for hematologic cancers (myelomas, lymphomas, leukemias, etc.) and various blood disorders (aplastic anemia, primary immunodeficiency states, myelodysplasia, etc.).

HSCT has also been employed in the treatment of certain solid tumors like breast or germ cell cancers, but this approach may not be any more effective than traditional methods for these cancers.

Although the technology surrounding HSCT is rapidly evolving, the technique still carries significant complications and mortality.

HSCT can be either autologous (stem cells are harvested from the same individual who will receive them) or allogeneic (stem cells are harvested from another person). Umbilical cord, bone marrow, and peripheral blood are all potential sources for stem cells; due to the relative ease of harvesting and the typically quicker post-transplant recovery of immune cells and platelets, peripheral blood has largely supplanted bone marrow as a source of stem cells (especially in autologous transplants).

While there are no contraindications to autologous HSCT, allogeneic transplants are relatively contraindicated in patients who are older than 50 or who are debilitated. Anyone who has undergone previous HSCT may also be at higher risk for complications if the procedure is repeated.

The main problem with allogeneic HSCT, of course, is the scarcity of compatible donors. Better-matched donors usually confer a longer disease-free survival for transplant recipients. However, HLA-identical or HLA-matched siblings can only be found for approximately 25% of individuals needing HSCT. Therefore, mismatched relatives or matched unrelated donors must be used for the majority of HSCTs. Stem cells harvested from umbilical cord sources may not require HLA typing, because they are not endowed with antigens that are typically found on cells from other sources.

Once stem cells are harvested from the donor – either from bone marrow, peripheral blood, or umbilical cord – they are infused into the recipient, a procedure that requires the use of a central venous catheter and that may take several hours.

Cancer patients undergoing HSCT are usually subjected to an extensive “conditioning” regimen that involves the use of powerful chemotherapeutic agents and whole-body irradiation. This pre-transplant preparation is designed to induce cancer remission and suppress the recipient’s immune system so the transplanted stem cells can be accepted, or “engrafted.”

Similar conditioning protocols are often used in patients receiving allogeneic grafts – even when they are not being treated for cancer – to improve engrafting, but patients who are receiving autologous grafts for conditions that aren’t cancerous often don’t require conditioning.

In certain disease states, such as multiple myeloma, stem cell grafts may mount an immune response against the underlying tumor, so conditioning regimens are frequently tailored to reduce this risk.

Following HSCT, transplant recipients are treated with medications that stimulate new white blood cell growth, prevent infection, and suppress the immune system. The latter treatment is designed to prevent the transplanted stem cells from attacking the recipient’s tissues (graft-vs-host disease).

Complications of HSCT include graft rejection, failure to engraft, and graft-vs-host disease (GVHD). Acute GVHD – that which occurs within 100 days of HSCT – can affect up to 80% of recipients, with the incidence being much higher when unrelated donors are used.

Disease relapse (recurrence of the condition for which HSCT was performed) varies widely, depending on the patient’s underlying illness and the methodology used. In general, relapse occurs in 40 – 75% of individuals receiving autologous transplants and in 10 – 40% of those receiving allogeneic transplants. The higher incidence of relapse in autologous HSCT may be due to inadvertent inclusion of circulating tumor cells in the graft or to a lower graft-vs-tumor effect in autologous transplants (ironically, the GVHD that occurs more frequently in allogeneic transplants – and that can increase mortality following HSCT – also tends to eliminate more of the host’s tumor cells).

As HSCT technology improves, indications for the procedure will probably expand, and complication rates will decrease. Wider availability of antigen-free stem cells – a presumed result of stem cell research – will revolutionize this technique in the not-too-distant future.