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> Medical
> Treatment
> Mini-transplants

Non-myeloablative Transplants


Until recently, an allogeneic stem cell transplant for a patient aged
55 or older was relatively rare because the rigorous pre-transplant
conditioning required is generally not well tolerated by these patients.
(Recall that the preparation for a stem cell transplant involves very
high doses of chemotherapy drugs and/or radiation.) For the same
reasons, patients with poor overall health, especially those with poorly
functioning internal organs, were also thought to be poor candidates for
allogeneic stem cell transplantation. Now, however, transplant
physicians are developing less strenuous pre-transplant conditioning
regimens that may be suitable for a wider range of patients.

Although this new procedure is commonly called a mini-transplant, the
term used by physicians is a non-myeloablative transplant. This more
accurate medical term also very descriptive: myelo is a Greek word
meaning marrow and ablate means to destroy. Thus, a non-myeloablative
transplant is one that does not completely destroy the patient’s
diseased marrow. Patients being conditioned for a non-myeloablative
transplant receive lowered doses of chemotherapy drugs, typically about
50% of the "normal" dose.

How non-myeloablative transplants work

Underlying non-myeloablative transplants is a phenomenon called the
graft-versus-malignancy (GVM) effect, in which the recipient’s new
immune system (originating from the donated stem cells) destroys any
cancer cells remaining in the patient. The GVM effect is also observed
in traditional myeloablative stem cell transplants, where it destroys
the few remaining cancer cells that may have survived the high-dose
pre-transplant conditioning. In the mid-1990s, physicians began to
explore whether the GVM effect was strong enough to cure diseases in
patients who had not undergone standard myeloablative conditioning.
After first successfully testing non-myeloablative transplants in dogs
and other laboratory animals, physicians began performing non-myeloablative
transplants in humans.

Preliminary results showed that indeed, non-myeloablative transplants
can work, and that recipients can function with "mixed chimerism"
for several months or more post-transplant. Mixed chimerism refers to
the period following a non-myeloablative transplant when blood and
marrow cells from both the donor and recipient coexist within the
recipient’s body. Eventually, the goal is for most, if not all, of the
recipient’s blood and marrow cells to be of donor origin. But even if a
recipient remains in a state of mixed chimerism for a long time,
physicians believe that the GVM effect will effectively control the
recipient’s disease as long as the donor-derived cells remain dominant.

A developing procedure

Sufficient numbers of non-myeloablative transplants have been
performed to conclude that it may be an appropriate treatment for
patients who may otherwise be unsuitable for fully myeloablative stem
cell transplantation due to advanced age or poor health. However, the
procedure has some important characteristics that may limit the number
of patients who might benefit from it.

First, the GVM effect underlying the non-myeloablative transplant
procedure is strongest in treating patients with chronic myelogenous
leukemia (CML). Patients with other malignancies also benefit from the
GVM effect, but to lesser degrees. Second, as the name implies, the GVM
effect operates on malignant (cancerous) diseases. It’s not known
whether non-myeloablative transplants will be effective for patients
with nonmalignant diseases. Finally, there is no GVM effect at all in
autologous transplantation (which uses the patient’s own stem cells) and
syngeneic transplantation (which uses stem cells from an identical
twin). In these cases, the recipient’s restored immune system does not
recognize the remaining cancer cells as being foreign bodies and so does
not destroy them. Thus, non-myeloablative transplants will likely only
be an option in allogeneic transplantation — transplants that use
unrelated or related donors — for malignant diseases.

The patient’s decision

Because this procedure is very new, its risks and benefits have not
yet been clearly established. One clear advantage, however, is that a
transplant may now be an appropriate option for individuals in their
60’s and 70’s who would have been excluded in the past by most
transplant programs because of their age. One disadvantage is that the
procedure is so new that physicians do not have any long-term survival
data on non-myeloablative transplant recipients. So they cannot yet
compare survival rates of these patients with those receiving fully
myeloablative stem cell transplants or with those receiving chemotherapy
or other non-transplant treatments.

Patients interested in exploring the possibilities of a non-myeloablative
transplant must locate a transplant center investigating the procedure
through a clinical trial. (Clinical trials are experimental studies
designed to test a new treatment’s safety and effectiveness.) To locate
transplant centers performing experimental non-myeloablative
transplants, contact the National Cancer Institute at 1-800-4-CANCER.
One can also search on the Internet for the locations of clinical trials
at the NCI’s website: http://cancertrials.nci.nih.gov/


Donation And Transplant Process
Of Stem Cell Transplants
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