Faculty Opinions recommendation of Long-term outcome of acute promyelocytic leukemia treated with all-trans-retinoic acid, arsenic trioxide, and gemtuzumab.

Author(s):  
Wee Joo Chng
Blood ◽  
2008 ◽  
Vol 112 (8) ◽  
pp. 3130-3134 ◽  
Author(s):  
Miguel A. Sanz ◽  
Pau Montesinos ◽  
Edo Vellenga ◽  
Consuelo Rayón ◽  
Javier de la Serna ◽  
...  

Abstract A previous report of the Programa de Estudio y Tratamiento de las Hemopatías Malignas (PETHEMA) Group showed that a risk-adapted strategy combining all-trans retinoic acid (ATRA) and anthracycline monochemotherapy for induction and consolidation in newly diagnosed acute promyelocytic leukemia results in an improved outcome. Here we analyze treatment outcome of an enlarged series of patients who have been followed up for a median of 65 months. From November 1999 through July 2005 (LPA99 trial), 560 patients received induction therapy with ATRA plus idarubicin. Patients achieving complete remission received 3 courses of consolidation followed by maintenance with ATRA and low-dose chemotherapy. The 5-year cumulative incidence of relapse and disease-free survival were 11% and 84%, respectively. These results compare favorably with those obtained in the previous LPA96 study (P = .019 and P = .04, respectively). This updated analysis confirms the high antileukemic efficacy, low toxicity, and high degree of compliance of a risk-adapted strategy combining ATRA and anthracycline monochemotherapy for consolidation therapy.


Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2970-2970
Author(s):  
Jiong Hu ◽  
Yuan-fang Liu ◽  
Chuan-feng Wu ◽  
Guang-biao Zhou ◽  
Zhi-Xiang Shen ◽  
...  

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.


Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1480-1480
Author(s):  
Yinjun Lou ◽  
Jie Jin

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.


Blood ◽  
2010 ◽  
Vol 115 (9) ◽  
pp. 1690-1696 ◽  
Author(s):  
Lionel Adès ◽  
Agnes Guerci ◽  
Emmanuel Raffoux ◽  
Miguel Sanz ◽  
Patrice Chevallier ◽  
...  

AbstractAcute promyelocytic leukemia (APL) is highly curable with the combination of all-trans retinoic acid (ATRA) and anthracycline-based chemotherapy (CT), but very long-term results of this treatment, when CT should be added to ATRA and the role of maintenance treatment, remain uncertain. In our APL93 trial that included 576 newly diagnosed APL patients, with a median follow-up of 10 years, 10-year survival was 77%. Maintenance treatment significantly reduced 10-year cumulative incidence of relapses, from 43.2% to 33%, 23.4%, and 13.4% with no maintenance, maintenance using intermittent ATRA, continuous 6 mercaptopurine plus methotrexate, and both treatments, respectively (P < .001). Maintenance particularly benefited patients with white blood cell (WBC) count higher than 5 × 109/L (5000/μL). Early addition of CT to ATRA significantly improved 10-year event-free survival (EFS), but without significant effect on overall survival (OS). The 10-year cumulative incidence of deaths in complete response (CR), resulting mainly from myelosuppression, was 5.7%, 15.4%, and 21.7% in patients younger than 55, 55 to 65, and older than 65 years, respectively, supporting the need for less myelosuppressive treatments, particularly for consolidation therapy. This study is registered at http://clinicaltrials.gov as NCT00599937.


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