NEW YORKAcute myelogenous leukemia (AML) is an aggressive
disease. But improved diagnosis with cytogenetic examinations and
other special studies have made it possible to select the most
effective induction therapy, Frederick R. Appelbaum, MD, told
patients at a teleconference sponsored by Cancer Care Inc. and the
Leukemia Society of America.
Today, with good supportive care, complete remission can be achieved
in most cases, he said. But consolidation therapy is needed after
that first remission. Without it, most patients relapse.
Probably the hardest decision once a patient has achieved
complete remission is choosing the subsequent therapy, said Dr.
Appelbaum, director of the Clinical Research Center, Fred Hutchinson
Cancer Research Center, and professor and head of the Division of
Medical Oncology, University of Washington School of Medicine. He
pointed out that cytogenetic risk group, age, and general health
often dictate the choice.
The first and standard option for the majority of patients following
complete remission is three or four subsequent cycles of intensive
chemotherapy similar to the kind used for initial inductionan
anthracycline and cytarabine (ara-C).
The M3 subtype of AML, acute promyelocytic leukemia (APL), Dr.
Appelbaum said, is uniquely sensitive to the oral drug, all-trans-retinoic
acid (ATRA). Combined with chemotherapy, ATRA dramatically increases
the cure rate of APL. Randomized trials show that ATRA is useful both
during initial induction and as a maintenance therapy.
Following up first remission with an allogeneic bone marrow
transplant is an option open to AML patients with an HLA-matched
sibling. In the absence of a matched donor, or if the patient is over
55, autologous transplantation is an option, using bone marrow
harvested while the patient is in remission.
Both kinds of transplantation have a far greater likelihood of
producing a cure in patients who have failed first-line therapy than
does further chemotherapy, Dr. Appelbaum said, but the
odds of cure for patients who have failed first-line therapy are not
as good as when they started initial therapy.
More Risky, Most Beneficial
Allogeneic transplants, Dr. Appelbaum said, are more risky but
are also the most beneficial. In Seattle, we recommend allogeneic
transplant for patients who are less than age 55 because, in our
experience, it is the form of therapy that gives patients the very
best chance for long-term survival and ultimate cure.
For older patients or those who dont have a matched sibling,
the alternative is an autologous transplantation. The outcomes
with autologous transplants during first remission are not as good as
with allogeneic transplants, but they are better than with
conventional chemotherapy and are better tolerated by older
patients, Dr. Appelbaum said. Autologous transplants are often
done in patients up to age 65, but most transplant centers will not
use either type of transplantation in patients over age 65, he added.
In the majority of cases, the quality of life following
transplantation is similar to what people enjoyed before they were
ill, Dr. Appelbaum said. But there are exceptions.
Graft-versus-host disease can significantly diminish quality of life
for months or even years, and if patients are planning to have
children, there is a high risk of sterility.
In contrast, the drugs used to treat leukemia in the nontransplant
setting do not, in general, cause permanent sterility in men,
particularly younger men, or increase the risk of fetal malformation
of their children. But they can induce premature menopause in women
in their late 30s or early 40s.
When to Transplant
If allogeneic transplantation is chosen, the next decision is when to
have it. If the disease is in first remission, then it is
preferable to be transplanted fairly soon. There is a realistic
chance that, of course, the patient could relapse in 3 or 6 months if
they choose to wait.
The problem with waiting to see if the chemotherapy worked and only
undergoing transplantation if there is a relapse, Dr. Appelbaum
warned, is that transplantation is not as effective once patients
have relapsed. But people have their reasons for waiting, he acknowledged.
I understand that once in a while there may be important events
coming up, a wedding or graduation, for example, and the patient may
sayI want to wait 6 weeks before I get my transplant, Dr.
Appelbaum said. But in general, if a patient is going to be
transplanted while in first remission, we would recommend that they
be transplanted within 2 months of achieving first remission to get
the very best results.
Dr. Appelbaum urged all AML patients to consider enrolling in
clinical trials, especially the elderly for whom conventional
therapies have been less successful.
Among the new approaches being studied in the treatment of AML, he
said, are the use of targeted chemotherapy that acts only on leukemic
cells and immunologic approaches, including vaccines and donor lymphocytes.
The Southwest Oncology Group recently completed a study of a compound
that prevents the development of drug resistance by stopping proteins
on the surface of some leukemic cells from pumping out
chemotherapeutic agents directed at those cells.
In a later interview with ONI, Dr. Appelbaum explained that the agent
STI 571, which, in early trials, has shown activity in chronic
myelogenous leukemia (CML) [see ONI January 2000, page 1], is not
likely to have activity in AML.
STI 571 is a specific inhibitor of the tyrosine kinase
associated with the abl gene, the gene that is turned on by the
chromosomal translocation seen in chronic myelogenous leukemia,
Dr. Appelbaum said. That abl gene is not activated in the vast
majority of AML cases. Thus, while STI 571 may prove to be of great
use in the treatment of CML, there is no reason to think that it has
or could have any activity in AML.