A single course of all-trans retinoic acid plus arsenic trioxide reached a long-term survival in a patient with newly diagnosed acute promyelocytic leukemia: a suggestion for reduction of treatment courses?

2013 ◽  
Vol 91 (5) ◽  
pp. 470-471 ◽  
Author(s):  
Jinsong Yan ◽  
Xueyu Chen ◽  
Jing Shao
Keyword(s):  
Retinoic Acid ◽  
Arsenic Trioxide ◽  
Acute Promyelocytic Leukemia ◽  
Promyelocytic Leukemia ◽  
Newly Diagnosed ◽  
Term Survival ◽  
Long Term Survival ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid

Front-Line Therapy with Arsenic Trioxide/All-Trans-Retinoic Acid Combination and Chemotherapy Improves Cure Rates in Newly Diagnosed Patients with Acute Promyelocytic Leukemia

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2970-2970
Author(s):  
Jiong Hu ◽  
Yuan-fang Liu ◽  
Chuan-feng Wu ◽  
Guang-biao Zhou ◽  
Zhi-Xiang Shen ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Arsenic Trioxide ◽  
Acute Promyelocytic Leukemia ◽  
Promyelocytic Leukemia ◽  
Newly Diagnosed ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Healthy Donors

Abstract BACKGROUND: In this study, we analyzed the clinical benefit and safety of upfront use of all-trans-retinoic acid (ATRA), arsenic trioxide (ATO) and chemotherapy in patients with newly-diagnosed acute promyelocytic leukemia (APL) during Apr 2001 and Dec 2005. METHODS: A total of 85 patients were treated with ATRA and ATO as induction therapy, followed by consolidation/maintenance therapy composed of ATRA, ATO and chemotherapy. All patients were followed-up to evaluate the long-term efficacy and safety. RESULTS: A total of 81 (95.3%) patients entered complete remission (CR) with a median of 27 days. Among these 81 patients, 4 patients relapsed and 2 patients died from the disease with a median follow-up of 70 months (15–87). The 5-year leukemia-free survival (5-yr-LFS) and overall survival (5-yr-OS) for all patients were 89.2±3.4% and 91.7±3.0% while for patients who achieved CR (n=81), the 5-yr-LFS and 5-yr-OS were 96.2±2.1% and 96.2±2.1% respectively. With careful monitoring of in vivo arsenic levels in 33 evaluable long-term survivors, we demonstrated that the serum and urine arsenic concentrations were within safety limits, although a slight but significantly increase in arsenic levels was observed as compared to healthy donors. Overall, no obvious arsenic associated long-term toxicity was documented in these patients. CONCLUSIONS: Use of up-front ATRA/ATO/chemotherapy combination treatment in newly-diagnosed APL has proven relatively safe and has lead to a significant improvement in long-term LFS/OS.

Long-Term Efficacy of Low-Dose All-Trans Retinoic Acid Plus Individually Adapted Chemotherapy Induction Followed by Arsenic Trioxide Based Post-Remission Therapy in Adults with Newly Diagnosed Acute Promyelocytic Leukemia

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1480-1480
Author(s):  
Yinjun Lou ◽  
Jie Jin
Keyword(s):  
Retinoic Acid ◽  
Arsenic Trioxide ◽  
Acute Promyelocytic Leukemia ◽  
Low Dose ◽  
Early Death ◽  
Promyelocytic Leukemia ◽  
Newly Diagnosed ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid

Abstract Abstract 1480 Acute promyelocytic leukemia (APL) is a distinct subtype of acute myelogenous leukemia (AML), which usually presents with pancytopenia, coagulopathies and bleeding. Molecular studies have revealed that it was caused by leukemogenic PML-RARA fusion gene resulting from a specific chromosomal translocation t(15;17). The administration of target agent all-trans-retinoic acid (ATRA) combined with anthracycline-based chemotherapy for induction and consolidation followed by ATRA plus low-dose chemotherapy maintenance is the standard strategies for patients with newly diagnosed APL. However, despite the high cure rate, early death and leukemia relapse are the two main important obstacles. We evaluated the efficacy of low-dose All-trans-retinoic acid (ATRA) plus individually adapted chemotherapy for induction followed by arsenic trioxide (ATO) based post-remission therapy in newly diagnosed acute promyelocytic leukemia (APL). From January 2004 to September 2011, 109 patients with APL were enrolled the study. The complete remission (CR) rate was 96.3%. The early death rate was 0.9%. Two arms were assigned according to post-remission protocols: ATO group cases were treated with standard chemotherapy, ATO, and ATRA. Without ATO group cases were subsequently treated with chemotherapy and ATRA only. Patients were monitored by reverse transcriptase-polymerase chain reaction (RT-PCR) during and after treatment. The six-year relapse-free survival (RFS) was significantly better for patients in ATO group than in without ATO group, 94.4% versus 50.6% (P < 0.0001) and the six-year overall survival (OS) rate was 95.7% versus 64.1%, in two groups (P = 0.003). This study shows that low-dose ATRA plus tailored chemotherapy is effective in induction therapy, and the addition of ATO to post-remission therapy significantly improves the long-term outcome. Disclosures: No relevant conflicts of interest to declare.

Cost-Effectiveness Of Arsenic Trioxide + All-Trans Retinoic Acid Compared With All-Trans Retinoic Acid + Idarubicin In The Treatment Of Newly Diagnosed Acute Promyelocytic Leukemia In Canada

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1677-1677
Author(s):  
Jean Lachaine ◽  
Karine Mathurin ◽  
Stephane Barakat
Keyword(s):  
Retinoic Acid ◽  
Cost Effectiveness ◽  
Arsenic Trioxide ◽  
Acute Promyelocytic Leukemia ◽  
Societal Perspective ◽  
Promyelocytic Leukemia ◽  
Newly Diagnosed ◽  
First Line ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid

Abstract Acute promyelocytic leukemia (APL) is a distinct and rare morphological, clinical and pathological subtype of acute myeloid leukemia (AML). It represents approximately 10% to 15% of AML patients. APL is characterized by a high incidence of coagulopathy caused by disseminated intravascular coagulation and/or excessive fibrinolysis and is associated with a high early mortality. Treatment can exacerbate the coagulopathy. Untreated, APL is rapidly fatal, but if promptly diagnosed and treated, it is frequently curable. Although current treatments (all-trans retinoic acid (ATRA), anthracyclines and conventional chemotherapy) are associated with high remission rates, cytotoxic effects of chemotherapy remain a concern in the management of newly diagnosed APL. Trisenox® is a sterile injectable solution of arsenic trioxide (ATO). Trisenox® has been approved in several countries, including Canada, for the induction of remission and consolidation in patients with APL who are refractory to, or have relapsed from, retinoid and anthracycline chemotherapy. Since the first approval of ATO is for the indication of relapsed/refractory APL, the safety and efficacy of ATO during induction and consolidation of newly diagnosed APL patients have been demonstrated. Specifically, Lo-Coco et al. compared the combination of ATO+ATRA to ATRA + idarubicin (IDA) and confirmed that the combination of ATO+ATRA is at least as effective as standard treatment in the first-line setting. The objective of this study was to assess, from a Canadian perspective, the economic impact of the combination of ATO+ATRA in the treatment of newly diagnosed APL. A time-dependent Markov model was constructed to assess the cost-effectiveness of ATO+ATRA compared to ATRA+IDA in the treatment of newly diagnosed APL. The Markov model comprises four health states: event-free survival (EFS), treatment failure/relapse (TF), post-failure (PF) and death. The length of each Markov cycle was one month for the 48-month period of the Lo-Coco et al. study and then of one year. The model continued to run until all patients reached the absorbing state, defined as death. All patients started in the EFS state and could then move to other health states. In the case of treatment relapse/failure, patients were subsequently treated with a salvage induction therapy composed of ATRA and conventional chemotherapy followed by autologous hematopoietic stem cell transplantation (HSCT) as consolidation treatment. The model also takes into account the incidence of treatment-induced adverse events that were significantly different between both treatment arms in the Lo-Coco et al. study(neutropenia, thrombocytopenia, fever episodes, and QTc interval prolongation). The model also allows comparison with the combination of ATRA+IDA+cytarabine, which is also used in Canada. Analyses were conducted from both a Canadian Ministry of Health (MoH) and a societal perspective over a lifetime horizon. In the treatment of newly diagnosed APL, ATRA+ATO is associated with incremental cost-effectiveness ratios (ICERs) of $50,193 per QALY and $46,367 per QALY, from a MoH and societal perspective respectively when compared with ATRA+IDA. According to the deterministic analysis Results, the ICER of ATO+ATRA compared to ATRA+IDA varied from $23,045 / QALY and $60,759 / QALY from a MoH perspective and between $21,294 / QALY and $56,933 / QALY from a societal perspective. Results of the probabilistic sensitivity analysis indicated that the ICER remains below $50,000 in 48.33% and 74.21% of the Monte Carlo simulations from a MoH and a societal perspective respectively. However, ICER remains below $100,000 in 100% of the simulations from both perspectives. The use of Trisenox in the first line therapy of patients with APL provides significant additional clinical benefits and is associated with an ICUR below the ICUR of many other oncology treatments currently in use. Disclosures: Lachaine: Lundbeck Canada: Research Funding. Off Label Use: Arsenic trioxide is not yet approved in Canada for the First-line treatment of acute promyelocytic leukemia. Barakat:Lundbeck Canada: Employment.

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