Current therapies in APL
Due to advancements in therapies, acute promyelocytic leukemia (APL) is considered the most
curable subtype of acute myeloid leukemia (AML).
1 Standard therapy for APL is
generally a form of vitamin A known as
all-trans retinoic acid (ATRA),
combined with an
anthracycline (a member of a family of chemotherapy drugs
that are also antibiotics). With this treatment, 70% to 80% of patients with
newly diagnosed APL achieve long-term remission and are probably cured.
1
However, despite improvements in therapy, approximately one quarter of these patients relapse
and are often resistant to further treatment with ATRA.
1-3
Second-round therapies used to involve high doses of chemotherapy, which was often toxic and
rarely led to a cure.
Bone marrow transplantation may be successful in
achieving a cure, but it is an option for only a fraction of the younger relapsed patients.
3
Clinical studies of
arsenic trioxide have demonstrated high rates of
complete remission for these patients, meaning there is no evidence of disease, following
treatment.
4,5 According to the National Comprehensive Cancer Network (NCCN)
guidelines for oncology, arsenic trioxide is the standard of care for patients who have
relapsed from, or did not respond to, their initial treatment.
6
Types of APL treatment
ATRA
All-
trans retinoic acid (ATRA) is a non-chemotherapy drug that targets leukemia cells. It is a
relative of vitamin A. Although remission induction may be possible with ATRA alone, combining
ATRA with chemotherapy (with an anthracycline) has been shown to achieve long-term remission
and probably even a cure in 70% to 80% of patients with newly diagnosed APL.
1
Chemotherapy
Chemotherapy is a cancer treatment that uses drugs to stop the growth of cancer cells, either by
killing the cells or by stopping the cells from dividing. Anthracycline is a member of a family
of chemotherapy drugs that are also antibiotics. The anthracyclines act to prevent cell division
by disrupting the structure of the DNA and terminate its function. Daunorubicin and idarubicin
are two commonly used anthracyclines shown to induce complete remission in 60% to 80% of APL
patients.
7-9
Combination chemotherapy is treatment using more than one anticancer drug. For example, APL
patients may be given cytarabine in combination with an anthracycline.
7,10 Cytarabine
belongs to the group of medicines called antimetabolites. It is used to treat various cancers
of the blood, as it interferes with the growth of cancer cells.
Stem cell transplant
Stem cell transplant is a method of giving chemotherapy and replacing blood-forming cells that
are abnormal or destroyed by the cancer treatment. Stem cells (immature blood cells) are removed
from the blood or bone marrow of the patient or a donor and are frozen and stored. After the
chemotherapy is completed, the stored stem cells are thawed and given back to the patient
through an infusion. These reinfused stem cells grow into, and restore, the body's blood cells.
Arsenic trioxide
Arsenic trioxide is the standard of care for APL patients whose disease returns after or does
not respond to initial treatment. Arsenic trioxide may be able to kill leukemia cells, stop
the leukemia cells from dividing, or help the leukemia cells mature into white blood cells.
11-16
>> Click here to find out if therapy with TRISENOX
® (arsenic trioxide) injection may be right for you.
Phases of treatment
Usage of the above types of therapy depends on the treatment phase. APL patients generally
undergo three phases of treatment:
Induction therapy
This treatment is designed to be used as a first step toward shrinking the cancer and in
evaluating response to drugs and other agents. For APL patients, induction therapy typically
consists of ATRA with chemotherapy.
1 Induction therapy is followed by additional
therapy to eliminate whatever cancer remains.
Consolidation therapy
The purpose of this phase is to seek out and kill the residual leukemia cells not killed by
induction therapy. Often, these cells are not detectable, but they are assumed to be present.
This phase of treatment often involves high-dose chemotherapy. Consolidation therapy is also
called intensification therapy.
Maintenance therapy
This therapy is often given to help keep cancer in remission. The purpose of maintenance
therapy is to kill any remaining leukemia cells that may not be active but could begin to regrow
and cause a relapse. The doses of chemotherapy are not as high in this phase as in the first two
phases. It appears that APL patients benefit from maintenance ATRA with or without continuous
low-dose chemotherapy.
7 This combination appears to be associated with the lowest
relapse rate.
7
In between stages of therapy, testing such as reverse
transcriptase-polymerase chain reaction
testing (RT-PCR testing) may be performed to assess disease status.
>> Click here to learn more.
1. Lengfelder E, Saussele S, Weisser A, et al. Treatment concepts of acute promyelocytic leukemia. Crit Rev Oncol Hematol. 2005;56:261-274.
2. Douer D. Advances in the treatment of relapsed acute promyelocytic leukemia. Acta Haematol. 2002;107:1-17.
3. Soignet SL. Clinical experience of arsenic trioxide in relapsed acute promyelocytic leukemia. Oncologist. 2001;6 Suppl 2:11-16.
4. Soignet SL, Frankel SR, Douer D, et al. United States multicenter study of arsenic trioxide in relapsed acute promyelocytic leukemia. J Clin Oncol. 2001;19:3852-3860.
5. Soignet SL, Maslak P, Wang Z-G, et al. Complete remission after treatment of acute promyelocytic leukemia with arsenic trioxide. N Engl J Med. 1998;339:1341-1348.
6. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology: Acute Myeloid Leukemia — v.2.2007.
7. Lowenberg B, Griffin JD, Tallman MS. Acute myeloid leukemia and acute promyelocytic leukemia. Hematology Am Soc Hematol Educ Program. 2003:82-101.
8. Bernard J, Weil M, Boiron M, et al. Acute promyelocytic leukemia: results of treatment by daunorubicin. Blood. 1973;41:489-496.
9. Avvisati G, Mandelli F, Petti MC, et al. Idarubicin (4-demethoxydaunorubicin) as single agent for remission induction of previously untreated acute promyelocytic leukemia: a pilot study of the Italian cooperate group GIMEMA. Eur J Haematol. 1990;44:257-260.
10. Petti MC, Avvisati G, Amadori S, et al. Acute promyelocytic leukemia: clinical aspects and results of treatment in 62 patients. Haematologica. 1987;72:151-155.
11. Grignani F, Fagioli M, Alcalay M, et al. Acute promyelocytic leukemia: from genetics to treatment. Blood. 1994;83:10-25.
12. Douer D, Tallman MS. Arsenic trioxide: new clinical experience with an old medication in hematologic malignancies. J Clin Oncol. 2005;23:2396-2410.
13. Davison K, Mann KK, Miller WH Jr. Arsenic trioxide: mechanisms of action. Semin Hematol. 2002;39(2 Suppl 1):3-7.
14. Miller WH Jr. Molecular targets of arsenic trioxide in malignant cells. Oncologist. 2002;7Suppl 1:14-19.
15. Hayakawa F, Privalsky ML. Phosphorlyation of PML by mitogen-activated protein kinases plays a key role in arsenic trioxide-mediated apoptosis. Cancer Cell. 2004;5:389-401.
16. Mann KK, Miller WH Jr. Death by arsenic: implications of PML sumoylation. Cancer Cell. 2004;5:307-309.