UCLA Campus    |   UCLA Health    |   School of Medicine Translate:
UCLA Health It Begins With U

Physicians Update


Physicians Update

Spring 2013

Hematopoietic-Stem-Cell Transplantation

Among Oldest Forms of Cancer Immunotherapy

Hematopoietic-Stem-Cell TransplantationTargeted therapies that mobilize the body’s immune system to attack cancer cells continue to emerge as promising weapons in the arsenal of cancer treatment options. But the idea behind cancer immunotherapy is not a new one. More commonly known as bone-marrow transplantation (BMT), hematopoietic-stem-cell transplantation (HSCT) has been performed in the United States for more than 40 years to support patients undergoing treatment for cancers such as acute myeloid leukemia (AML), multiple myeloma or lymphoma.

“Few immune therapies have the track record and demonstrated efficacy that we observe with HSCT,” says Gary Schiller, MD, director of the Hematologic Malignancies/Stem Cell Transplant Unit at UCLA. “It is the most common immune therapy done in the world for cancer and is the immune therapy for which there is the greatest experience.”

In fact, more than 60,000 HSCTs are performed internationally each year, according to Dr. Schiller. Approximately half of transplanted hematopoietic stem cells (those capable of reconstituting bone marrow and blood) are autologous, in which the recipient acts as his or her own donor. The other half are allogeneic, in which stem cells are donated from related (usually a sibling with closely matched human leukocyte antigens) or unrelated adults or from the umbilical-cord blood of a newborn. Both procedures are done to replace bone marrow damaged or destroyed by chemo or radiation therapies delivered to treat malignancies with healthy bone-marrow stem cells. Allogeneic HSCTs, however, also serve another purpose.

“Allogeneic HSCTs deliver an immunoreactive organ, which is more likely to favorably impact the disease,” Dr. Schiller explains. “When using allogeneic stem cells, the chemo and radiation therapies do not necessarily need to completely kill every last malignant cell because some of the heavy lifting will be done by the donor’s immune system.”

The procedure carries major risks. Infection and graft-versus-host disease, an inflammatory condition in which the immune cells of the donor attack the recipient’s tissues, are major complications of allogeneic HSCT. Newer strategies, however, have led to fewer complications and improved outcomes.

“We have become better at identifying and matching potential donors; we have begun to reduce the chemo and radiation therapy we use to treat malignancies because we are more skilled in harnessing the immune effect of donor cells; and we have more effective antibiotics that we use to prevent infections,” Dr. Schiller says.

This image illustrates in detail the characteristic morphologic features of the myeloid response following G-CSF stem cell mobilization.This image illustrates in detail the characteristic morphologic features of the myeloid response following G-CSF stem cell mobilization. Photo: American Society of Hematology

These developments have enabled physicians to expand allogeneic HSCTs to broader populations of patients for whom the risks of transplantation might have previously been too great. For example, “mini-transplant” procedures have been developed that require smaller doses of chemo and radiation therapies. This enables HSCT to be conducted in the elderly, patients with co-morbid conditions and those who would otherwise be considered too weak to undergo a conventional treatment regimen. Use of “mini-transplant” strategies has so far produced mixed results.

“Early results suggest that a greater number of patients relapse using this approach,” Dr. Schiller says. “We do not yet fully understand the reason for this, however, which could be that older people have different kinds of cancer. They certainly have more resistant leukemia, in general, than younger people.”

Patients with severe organ dysfunction, those on dialysis and people for whom no donor can be identified are still not appropriate candidates for allogeneic HSCT. In addition, HSCT has not demonstrated efficacy in the treatment of many solid tumors (breast, lung or colon cancer, for example). Despite its current limitations, HSCT will continue to expand beyond the cancer care continuum, according to Dr. Schiller, including the treatment of autoimmune and other diseases.

“As one of the oldest and largest transplant centers in the region, we have seen very favorable outcomes using HSCT,” Dr. Schiller says. “We will use our broad experience and lessons learned as we continue to build the evidence base for this and related techniques, but we need more available donors so that we can help more patients.”

Add a comment

Please note that we are unable to respond to medical questions through the comments feature below. For information about health care, or if you need help in choosing a UCLA physician, please contact UCLA Physician Referral Service (PRS) at 1-800-UCLA-MD1 (1-800-825-2631) and ask to speak with a referral nurse. Thank you!

comments powered by Disqus