A higher death rate during consolidation therapy was also observed in the IC-APL. These results show that daunorubicin and idarubicin have similar antileukaemic efficacy in terms of primary resistance, molecular persistence, as well as molecular and haematological relapse rates when combined with ATRA in treatment of APL.
Full Answer
Is triple induction of idarubicin and atra effective for newly diagnosed APL?
In an attempt to build on the proven benefits of ATRA and idarubicin, 14–16 and to exploit the potent antileukemic efficacy of ATO, the Australasian Leukaemia and Lymphoma Group (ALLG) initiated a single-arm, phase 2 study using triple induction with ATRA, idarubicin, and ATO for patients with newly diagnosed APL.
What is the optimal dose of idarubicin for high-risk APL?
When GO was unavailable, the MD Anderson trial allowed for one dose of idarubicin at 12 mg/m 2. The 5-year EFS, DFS, and OS for 54 high-risk patients were 81%, 89%, and 86%, respectively. 7 A similar regimen was also used in 28 patients with high-risk APL in the UK AML17 trial; however, GO was used at 6 mg/m 2 instead of 9 mg/m 2.
What are the treatment options for APL that doesn't go away?
The most common options for maintenance therapy are ATRA alone, or ATRA along with chemo (6-mercaptopurine (6-MP) and/or methotrexate). Maintenance therapy is typically given for about a year. Treating APL that doesn't go away or comes back
Is idarubicin a Novartis product?
J.R. served as a statistician for the ALLG during the APML4 study, but has since joined Novartis (ATRA, idarubicin, and ATO are not Novartis products). The remaining authors declare no competing financial interests.
How does ATRA work for APL?
All-Trans Retinoic Acid (ATRA) This drug, a vitamin A derivative, has become a standard component of induction therapy for APL. ATRA targets and eliminates the PML/RARα abnormality. This treatment causes a marked decrease in the concentration of leukemic blast cells in the marrow, and a remission frequently follows.
How does ATRA work in AML?
Conclusion: All-trans retinoic acid (ATRA) can enhance the anti-leukemia effect of ABT-199 on AML cell lines by inhibiting cell proliferation as seen by the cell cycle arrest of AML cells in G1 phase, promoting apoptosis and inducing differentiation.
What is the chemo drug ATRA?
ATRA is a form of vitamin A that is typically part of the initial (induction) treatment of APL. It is given either along with chemo, or along with arsenic trioxide for the initial treatment of APL.
What type of leukemia is treated with arsenic?
Arsenic trioxide is a chemotherapy drug and is also called Trisenox or ATO. It is a treatment for a type of acute myeloid leukaemia called acute promyelocytic leukaemia (APL).
How is APL different from AML?
APL is a rare sub-type of acute myeloid leukaemia (AML). When you have APL, the bone marrow is not able to make enough normal blood cells. APL is treated in a very different way from other forms of AML, if a patient with APL is given standard treatment, there is a risk of serious problems with their clotting system.
How do you treat APL leukemia?
The most important drugs for treating APL are non-chemo drugs called differentiating agents, like all-trans-retinoic acid (ATRA). Other treatments might include chemotherapy (chemo) and transfusions of platelets or other blood products.
How does ATRA and arsenic work in APL?
Both of the medications in ATRA + Arsenic Trioxide are designed to reduce the number of APL cells by triggering leukemic promyelocytes to die. Goals of therapy: ATRA + Arsenic Trioxide is given to eliminate leukemic cells for patients with low-to-intermediate risk APL.
What ATRA means?
A nutrient that the body needs in small amounts to function and stay healthy. ATRA is made in the body from vitamin A and helps cells to grow and develop, especially in the embryo.
Is ATRA and tretinoin the same?
Tretinoin is also called all trans retinoic acid (ATRA) and its brand name is Vesanoid. It belongs to a group of drugs called retinoids, these are similar to vitamin A.
How does ATO work in APL?
ATRA and ATO are not chemotherapy drugs, but drugs called differentiating agents. They encourage the promyelocytic cells to differentiate (mature) into normal white blood cells. They also have complementary actions in that ATRA breaks down the PML-RARA gene and ATO encourages the abnormal APL cells to self-destruct.
How does arsenic treat Apml?
The arsenic-based cure of acute promyelocytic leukemia promotes cytoplasmic sequestration of PML and PML/RARA through inhibition of PML body recycling. Blood (2012) 120 (4): 847–857. Arsenic in the form of arsenic trioxide (ATO) is used as a therapeutic drug for treatment of acute promyelocytic leukemia (APL).
Is APL a type of AML?
Acute promyelocytic leukemia (APL) is a unique subtype of acute myeloid leukemia (AML) in which cells in the bone marrow that produce blood cells (red cells, white cells and platelets) do not develop and function normally.
Abstract
The treatment of acute promyelocytic leukemia has improved considerably after recognition of the effectiveness of all- trans -retinoic acid (ATRA), anthracycline-based chemotherapy, and arsenic trioxide (ATO). Here we report the use of all 3 agents in combination in an APML4 phase 2 protocol.
Introduction
Acute promyelocytic leukemia (APL) is a discrete subtype of acute myeloid leukemia characterized by a t (15;17) translocation, rearrangement of the PML and RARA genes, and formation of an abnormal chimeric retinoic acid receptor transcription factor (PML-RARA).
Methods
This trial was approved by human research ethics committees in all participating ALLG and Australian & New Zealand Children's Haematology/Oncology Group centers, and was registered at the Australian New Zealand Clinical Trials Registry ( www.anzctr.org.au) as ACTRN12605000070639. Patients were accrued between November 2004 and September 2009.
Results
A total of 129 patients from 27 Australian centers were registered.
Discussion
The potential mechanisms of the striking antileukemic activity of ATO in APL have been studied extensively. ATO can induce both differentiation and apoptosis of APL cells in a dose-dependent manner.
Acknowledgments
The authors thank Andrew Wei (ALLG Acute Leukaemia and Myelodysplasia Disease Group Chair) for helpful comments regarding the manuscript; Richard Fisher and Jenny Beresford (Centre for Biostatistics and Clinical Trials) for assistance with the statistical analysis; and the nurses, data coordinators, and patients who participated.
Authorship
Contribution: H.J.I. was the principal investigator and takes primary responsibility for the manuscript; H.J.I., K.B., M.H., P.B., F.F., J.R., and J.F.S. designed the study; H.J.I., K.B., M.H., A.G., F.F., C.T., K.T., R.F., M.S., J.T., J.S., J.M., J.B., and J.F.S. recruited the patients; S.G.S., A.C., and A.H.
Why is it important to treat APL?
Prompt diagnosis and treatment of acute promyelocytic leukemia (APL), the M3 subtype of acute myeloid leukemia (AML), is very important because patients with APL can quickly develop life-threatening blood-clotting or bleeding problems if not treated. In fact, treatment might need to be started even if the diagnosis of APL is suspected ...
What is the treatment for APL?
The treatment of APL typically differs from the treatment of most other types of AML. The most important drugs for treating APL are non-chemo drugs called differentiating agents, like all-trans-retinoic acid (ATRA). Other treatments might include chemotherapy (chemo) and transfusions of platelets or other blood products.
What happens to APL after remission?
Once APL is in remission, consolidation is needed to keep it in remission and try to get rid of the remaining leukemia cells. Which drugs are used depends on what was given for induction, as well as other factors. Patients typically get some of the same drugs they got during remission, although the doses and timing of treatment might be different. Some of the options include:
What is the first step in the treatment of APL?
Induction. The goal of induction, the first part of treatment, is to get the number of leukemia cells to very low levels, putting the APL into remission. The most important drug in the initial treatment of APL is all-trans-retinoic acid (ATRA). This is usually combined with one of these:
Is ATO a non-chemo drug?
Arsenic trioxide (ATO), another non-chemo drug. For some people at higher risk of APL coming back after treatment, the targeted drug gemtuzumab ozogamicin (Mylotarg) might be added as well. Chemotherapy with an anthracycline drug (daunorubicin or idarubicin). For some people at high risk of their APL coming back after treatment, ...
Does ATRA need maintenance therapy?
People who have a lower risk of the leukemia coming back and who have a good response to ATRA plus ATO might not need maintenance therapy, although this is still being studied. The most common options for maintenance therapy are ATRA alone, or ATRA along with chemo (6-mercaptopurine (6-MP) and/or methotrexate).
Abstract
All- trans retinoic acid (ATRA) plus anthracycline chemotherapy is the reference treatment of newly diagnosed acute promyelocytic leukemia (APL), whereas the role of cytosine arabinoside (AraC) remains disputed.
Introduction
Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloid leukemia characterized by its morphology, t (15;17) translocation leading to PML-RARa fusion gene, and by a life-threatening coagulopathy.
Methods
Eligibility criteria for both studies were a diagnosis of de novo APL with demonstration of the t (15;17) or PML/RAR rearrangement, no cardiac contraindication to anthracycline chemotherapy, and a signed informed consent.
Results
In LPA 99 trial, 410 consecutive patients younger than 65 with newly diagnosed APL from 74 institutions from Spain, Argentina, the Netherlands, and Czech Republic were registered between September 1999 and August 2004. Median follow-up was 67 months.
Discussion
The 2 trials (LPA 99 and APL 2000) analyzed together here shared many similarities including frontline treatment with ATRA and anthracycline-based chemotherapy followed by anthracycline-based consolidation treatment and a maintenance treatment combining intermittent ATRA and continuous 6-mercaptopurine and methotrexate, which are now widely considered as references in the treatment of APL.
Acknowledgments
This study was supported in part by the program Hospitalier de Recherche Clinique and the CHU of Lille-France, the Association pour la Recherche sur le Cancer and the Ligue Contre le Cancer (Comité du Nord), grant 2006/0137 from the Fundación para la Investigación Hospital Universitario La Fe-Ayudas Bancaja, and grant RD06/0020/0031from the Red Temática de Investigación Cooperativa en Cáncer..
COMPANION ARTICLES
Treatment of Acute Promyelocytic Leukemia With No or Minimal Chemotherapy: Now a Reality in Common Clinical Practice. September 22, 2018
COMPANION ARTICLES
Treatment of Acute Promyelocytic Leukemia With No or Minimal Chemotherapy: Now a Reality in Common Clinical Practice. September 22, 2018
