Some studies suggest patients with high-risk disease should be treated with intensified doses of anthracycline, or intermediate/ high-dose Ara-C or As2O3 as an early consolidation, so as to decrease the risk of relapse.However, a higher cumulative dose of anthracycline may lead to cardiac toxicity, especially for children.
Full Answer
How is high-risk acute promyelocytic leukemia (APL) treated?
On the basis of these data, we recommend treating high-risk APL with ATRA 45 mg/m 2 and ATO 0.15 mg/kg/d until clinical remission and administering one dose of GO 6 mg/m 2 on day 1 or shortly thereafter.
Are ATRA and ATO alone sufficient to treat high-risk acute promyelocytic leukemia (APL)?
ATRA and ATO alone are insufficient for the treatment of high-risk APL, and there seems to be a benefit from substantial cytoreduction early during induction. Cytotoxic chemotherapy with idarubicin was added to a combination of corticosteroids, ATRA, and ATO to treat 23 high-risk patients in the Australian APML4 study.
When are diuretics indicated in the treatment of acute promyelocytic leukemia (APL)?
Although the general notion is to use diuretics in patients with symptoms (hypoxia, peripheral edema), throughout APL induction, we advocate preemptive use of diuretics intending to keep the fluid balance even. Coagulopathy Complex coagulopathy in APL consists of consumptive coagulation and fibrinolysis, resulting in major bleeding complications.
What are the controversial issues in the treatment of acute myeloid leukemia (APL)?
These controversial issues include the optimal dose and schedule of both all- trans -retinoic acid and arsenic trioxide, the optimal regimen for high-risk APL, the need for intrathecal prophylaxis, the use of prophylactic corticosteroids, and the need for maintenance therapy after consolidation.
How do you treat high risk APL?
Summary: High-risk APL, traditionally defined by an initial white cell count exceeding 10 × 10⁹/l, has proven to be almost as amenable to disease eradication as low-risk and intermediate-risk APL, provided treatment includes ATRA, ATO and some chemotherapy.
How do you treat relapsed acute promyelocytic leukemia?
Treatment of relapsed/advanced APL includes the use of arsenic trioxide (ATO), gemtuzumab ozogamicin, and hematopoietic stem cell transplantation. ATO is currently the most effective therapeutic agent in relapsed APL.
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.
Which vitamin is used in the treatment of acute promyelocytic leukemia?
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 is relapsed acute promyelocytic leukemia?
Acute promyelocytic leukaemia (APL) treatment If you don't go into remission, this is known as refractory APL. If you do go into remission, but the cancer comes back, this is known as a relapse. This is especially rare if you were treated with ATRA and arsenic trioxide.
Can acute promyelocytic leukemia be cured?
Because of advances in diagnostic techniques and modern treatments, APL is today considered to be the most curable subtype of acute myeloid leukemia in adults, with complete remission rates of 90 percent and cure rates of approximately 80 percent and even higher among low-risk patients.
Why does ATRA work in APL?
The story of ATRA in the treatment of APL shows that by targeting the molecules critical to the pathogenesis of certain diseases, cells can be induced to return to normal. Differentiation therapy is therefore a practical method of treating human cancer that has shown consistent effectiveness in trials.
Why is DIC in acute promyelocytic leukemia?
In acute promyelocytic leukemia (APL), TF is secreted directly into the bloodstream by the membranes of the promyelocyte blast cells, which initiates the coagulation cascade causing DIC (Mc- Cance & Huether). An estimated 85% of patients diagnosed with APL will develop DIC (Ezzone, 2000; Holmes-Gobel, 2000).
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).
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.
Is ATRA cytotoxic?
Drug Type: ATRA is an anti-cancer ("antineoplastic" or "cytotoxic") chemotherapy drug.
Which vitamin can be use as a cure of leukemia and why?
Since the 1970s, researchers have taken an interest in high-dose vitamin C and its therapeutic potential for treating cancer. New research shows how vitamin C might stop leukemic stem cells from multiplying, and thus block some forms of blood cancer from advancing.
What is the treatment for acute promyelocytic leukemia?
The current recommendations for treatment of patients with newly diagnosed acute promyelocytic leukemia (APL) include all- trans -retinoic acid (ATRA) and anthracycline-based chemotherapy for remission induction, anthracycline-based chemotherapy for consolidation, and ATRA with low-dose chemotherapy for maintenance. 1 Use of ATRA during consolidation has not been explored.
What is ATRA used for?
All- trans -retinoic acid (ATRA) increases the efficacy of chemotherapy when used for induction and maintenance treatment of acute promyelocytic leukemia (APL), but its role in consolidation is unknown. Since November 1996, 426 patients with newly diagnosed APL have received induction therapy with ATRA and idarubicin. Before November 1999 (LPA96 study), consolidation therapy consisted of 3 courses of anthracycline monochemotherapy. After November 1999 (LPA99 study), patients with intermediate and high risks of relapse received consolidation therapy with ATRA and increased doses of anthracyclines. Of the 384 patients who achieved complete remission (90%), 382 proceeded to consolidation therapy. Seven patients died in remission (1.8%). The 3-year cumulative incidence of relapse for patients in the LPA96 and LPA99 studies was 17.2% and 7.5%, respectively ( P = .008). Patients treated with ATRA in consolidation therapy showed an overall reduction in the relapse rate from 20.1% to 8.7% ( P = .004). In intermediate-risk patients the rate decreased from 14.0% to 2.5% ( P = .006). This improved antileukemic efficacy also translated into significantly better disease-free and overall survival. A risk-adapted strategy combining anthracycline monochemotherapy and ATRA for induction and consolidation therapy of newly diagnosed APL results in improved antileukemic efficacy and a high degree of compliance.
What is the PETHEMA trial?
A risk-adapted strategy designed by the cooperative group Programa Español de Tratamientos en Hematología (PETHEMA), which was based on the combination of all- trans retinoic acid (ATRA) and anthracycline monochemotherapy for induction and consolidation (PETHEMA LPA99 trial), has previously demonstrated a high antileukemic efficacy and high protocol compliance coupled with moderate toxicity in patients with acute promyelocytic leukemia (APL). 1, 2
Does mitoxantrone reduce toxicity?
In conclusion, the lower dose of mitoxantrone resulted in a significant reduction of toxicity and hospital stay while maintaining the antileukemic activity, and the combination of ATRA, idarubicin, and cytarabine for high-risk acute promyelocytic leukemia significantly reduced the relapse rate in this setting.
Who is the author of CME questions?
The authors and Associate Editor Martin S. Tallman declare no competing financial interests. The CME questions author Désirée Lie, University of California, Irvine, CA, served as a nonproduct speaker for “Topics in Health” for Merck Speaker Services.
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
Is ATRA safe for patients?
Furthermore, the combination of ATRA and arsenic trioxide (ATO) was shown to be safe and effective in frontline treatment and, for patients with low and intermediate risk disease, possibly superior to the standard ATRA and anthracycline-based regimen.
Is trans retinoic acid safe for APL?
Furthermore, the combination of ATRA and arsenic trioxide (ATO) was shown to be safe and effective in frontline treatment and, for patients with low and intermediate risk disease, possibly superior to the standard ATRA and anthracycline-based regimen. However, in spite of this tremendous progress, APL still remains associated with a high incidence of early death due to the frequent occurrence of an abrupt bleeding diathesis. This hemorrhagic syndrome more frequently develops in high-risk APL patients, currently defined as those exhibiting >10 × 10 (9)/L WBC at presentation. In addition to high WBC count, other molecular and immunophenotypic features have been associated with high-risk APL. Among them, the expression in APL blasts of the stem/progenitor cell antigen CD34, the neural adhesion molecule (CD56), and the T cell antigen CD2 help to identify a subset of patients at higher risk of relapse and often the expression of these markers is associated with high WBC count. At the molecular level, the short PML/RARA isoform and FLT3-internal tandem duplication (ITD) mutations have been associated with increased relapse risk. These observations indicate that extended immunophenotypic and molecular characterization of APL at diagnosis including evaluation of CD2, CD56, and CD34 antigens and of FLT3 mutations may help to better design risk-adapted treatment in this disease.
How long has APL been around?
Acute promyelocytic leukemia (APL) as a distinct clinical entity was first described only 50 years ago. The last twenty years are notable for rapid advances in understanding the molecular basis of the disease as well as dramatic improvements in treating APL. A new classification system that stratifies patients by risk has also lead to dramatic improvement in managing the disease. Molecular monitoring for minimal residual disease holds great promise for continued improvement in decreasing relapse risk. We are now able to tailor our therapy based on risk of relapse, and ongoing clinical trials use this risk-adapted framework in an attempt to further improve outcomes.
What are alternative treatment strategies?
Alternate treatment strategies are being tested to both maintain the excellent outcomes observed in low-risk patients and decrease the toxicity of treatment. They are also being applied to current trials in high-risk patients. Investigators at The University of Texas MD Anderson Cancer Center conducted a trial in 82 patients with newly diagnosed APL using only ATRA, ATO, and, in some cases, gemtuzumab ozogamicin, completely eliminating the use of cytotoxic agents.
Abstract
Acute promyelocytic leukemia (APL) has a favorable prognosis. However, results of randomized studies do not necessarily reflect the outcomes of a real-life population.
Introduction
Acute promyelocytic leukemia (APL) is now the most curable subtype of adult acute myeloid leukemia, with a complete remission rate of > 90.
Patients and Methods
We performed a retrospective analysis of 283 adult patients from 20 Polish hospitals. Patients were diagnosed with APL in between April 2005 and December 2017.
Results
Between April 2005 and December 2017, a total of 283 APL patients were registered in 20 Polish hospitals. The median follow-up time was 51 months (range, 1-164 months). The main demographic, clinical, and biological features of the study population are shown in Table 2.
Discussion
This is to our knowledge the first Polish real-life study performed on unselected APL patients. According to the standard of care in Poland, PETHEMA protocols have been used in the treatment of APL patients.
Conclusion
ED is still a problem limiting the chances for cure in APL patients. It is underestimated in prospective clinical trials, as some patients (those with advanced age, poor performance status, bleeding at diagnosis, and s-APL) could not be included.
Acknowledgments
The authors thank all PALG members for data collection and all patients for their collaboration with this study.