scholarly journals All-trans retinoic acid for the treatment of newly diagnosed acute promyelocytic leukemia. Japan Adult Leukemia Study Group [see comments]

Blood ◽  
1995 ◽  
Vol 85 (5) ◽  
pp. 1202-1206 ◽  
Author(s):  
A Kanamaru ◽  
Y Takemoto ◽  
M Tanimoto ◽  
H Murakami ◽  
N Asou ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Mortality Rate ◽  
Acute Promyelocytic Leukemia ◽  
Promyelocytic Leukemia ◽  
Early Mortality ◽  
Newly Diagnosed ◽  
Free Survival ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Significant Difference

We conducted a multicenter trial of treatment with all-trans retinoic acid (ATRA) for newly diagnosed acute promyelocytic leukemia (APL) in the AML-92 study and compared it with our previous study with standard intensive chemotherapy, the AML-89 study, in the view of complete remission (CR) rate, incidence of early death, and event-free survival (EFS). Patients were scheduled to receive oral ATRA 45 mg/m2 daily until CR. If patients had leukocyte counts above 3 x 10(9)/L at the start of therapy, they received daunorubicine (DNR) 40 mg/m2 for 3 days and behenoyl cytosine arabinoside (BHAC) 200 mg/m2 for 5 days in addition to ATRA. During the ATRA therapy, if patients showed myeloblast plus promyelocyte counts higher than 1 x 10(9)/L in the peripheral blood, they received additional DNR and BHAC in the same schedule, as well. A total of 110 patients were entered into the study. Median age was 43 years (range, 16 to 74). Twenty-eight (26%) of 109 patients (one died before the start of therapy) received ATRA alone. Ninety-seven patients (89%) achieved CR; 48 of 49 (98%) aged less than 40 years, 44 of 52 (84%) aged between 40 and 69, and 5 of 8 (63%) aged above 70 achieved CR, respectively; 25 of 28 (89%) with ATRA alone, 46 of 51 (90%) with ATRA plus initial chemotherapy and 26 of 30 (87%) with ATRA plus later chemotherapy attained CR, respectively. Nine (8%) patients died within 28 days after the start of therapy. In contrast, 44 of 62 patients (71%) attained CR, and 13 (21%) died within 28 days in the AML-89 study with the combination of DNR, BHAC, 6-mercaptopurine and prednisolone. Seven developed retinoic acid syndrome and one died of it in the present study. Other toxicities associated with this drug included cheilitis, desquamation, muscle pain, and hypertriglyceridemia. Predicted 23 months EFS for all ATRA-treated patients and disease-free survival (DFS) in the CR cases were 75% and 81%, respectively, in a median follow-up period of 21 months. Compared to the AML-89 study, there was a highly significant difference in remission rate (P = .004), EFS (P = .0007), and also early mortality rate (P = .02). Present results demonstrated that ATRA with or without chemotherapy gives a statistical improvement in CR rate and early mortality rate, as well as superior survival in newly diagnosed APL.

scholarly journals Efficacy and Safety of Daily All-Trans Retinoic Acid Monotherapy As Maintenance Therapy for Acute Promyelocytic Leukemia

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3898-3898
Author(s):  
Yoo Jin Lee ◽  
Seo-Yeon Ahn ◽  
Jae-Cheol Jo ◽  
Yunsuk Choi ◽  
Ji Hyun Lee
Keyword(s):  
Retinoic Acid ◽  
Maintenance Therapy ◽  
Acute Promyelocytic Leukemia ◽  
Promyelocytic Leukemia ◽  
Newly Diagnosed ◽  
Free Survival ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Significant Difference ◽  
Ecog Ps

Introduction Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloid leukemia with a unique chromosomal translocation t(15;17), causing promyelocytic leukemia gene fusion with the retinoic acid receptor α gene (PML-RARα). Therapeutic All-trans retinoic acid (ATRA) converts PML-RARα into transcriptional activator, induces APL differentiation. ATRA added during all treatment period have been reported to improve the outcomes of newly diagnosed APL. However, the benefits of maintenance therapy for patients with acute promyelocytic leukemia (APL) who achieved molecular complete remission (CRmol) are uncertain. In this study, we evaluated the efficacy and toxicity of daily ATRA monotherapy comparing with ATRA for 15 days with or without additional chemotherapy. Materials and Methods A retrospective data on 129 patients with newly diagnosed APL was conducted between February 2007 and August 2014. Induction and consolidation therapy were based on PETHEMA protocol. Among 113 patients (87.6%) who achieved CRmol following induction and 3 cycles of consolidation chemotherapy, 35 patients were treated daily with ATRA monotherapy (ATRAdaily), 39 with intermittent ATRA monotherapy for 15 days every 3 months (ATRA15), and 39 with ATRA plus continuous low-dose 6 mercaptopurine and methotrexate chemotherapy (ATRA/CT) for 2 years as a maintenance therapy. Event-free survival was defined as the time of CRmol to the development of events, which were defined by relapse, death, and toxicity that required hospitalization or dose reduction. Results The median age of patients was 46 years (range, 18-80 years). There was no significant difference among the three groups (ATRAdaily, ATRA15, and ATRA/CT) in terms of age, sex, ECOG PS, WBC count, platelet count, fibrinogen, prothrombin time, and Sanz risk score. Among the 12 relapsed patients during maintenance therapy, 3 presented molecular relapse and 9 hematologic relapse. Six (15.4%) relapses were observed in the ATRA15 group, whereas 2 (5.7%) and 4 (10.3%) relapses were observed in the ATRAdaily and ATRA/CT groups, respectively. At a median follow-up of 75.3 months (range: 9.0-140.4 months) from CRmol, the 5-year relapse free survival (RFS) for patients receiving maintenance therapy with ATRAdaily was higher than that of the patients in the ATRA15 or ATRA/CT groups without a statistically significant difference, 93.0 ± 4.8%, 84.6 ± 5.8%, and 88.0 ± 5.7%, respectively (P = 0.447). The 5-year overall survival (OS) rate was 92.7 ± 5.1%, 94.6 ± 3.7%, and 91.2 ± 5.0% for the ATRAdaily, ATRA15, and ATRA/CT groups, respectively (P = 0.601). However, ATRA/CT group frequently had myelosuppression (n = 11, 28.2%). The 5-year EFS rate was 81.5 ± 7.6%, 86.4 ± 5.7%, and 51.7 ± 8.2% for the ATRAdaily, ATRA15, and ATRA/CT groups, respectively (P < 0.001). In the multivariate analysis, maintenance therapy in the ATRA/CT group compared to ATRAdaily showed a significantly lower EFS (HR = 2.14, 95% CI = 1.06-4.31, P = 0.023). ECOG PS ≥ 2 was also associated with lower EFS (P = 0.033). Sanz risk score was the only adverse prognostic factor for RFS, and OS (HR = 6.20, 95% CI = 1.29-29.90, P = 0.023; HR=5.30, 95% CI = 1.10-25.63, P = 0.038). Conclusions In conclusion, in the present study, ATRAdaily as a maintenance therapy for patients with newly diagnosed APL who achieved CRmol showed non-inferiority compared with ATRA/CT in terms of RFS and OS. In addition, ATRAdaily maintenance therapy can be a feasible and effective choice in terms of myelosuppression or hepatotoxicity. In the future, well-conducted systematic studies of long term survivorship, quality of life, and treatment-related complications are needed to confirm these observations. Figure Disclosures No relevant conflicts of interest to declare.

Insights into the All-trans-Retinoic Acid and Arsenic Trioxide Combination Treatment for Acute Promyelocytic Leukemia: A Meta-Analysis

2015 ◽  
Vol 134 (2) ◽  
pp. 101-108 ◽  
Author(s):  
Hongbing Ma ◽  
Jing Yang
Keyword(s):  
Retinoic Acid ◽  
Mortality Rate ◽  
Combination Therapy ◽  
Arsenic Trioxide ◽  
Meta Analysis ◽  
Promyelocytic Leukemia ◽  
Early Mortality ◽  
Newly Diagnosed ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid

Background: This study aimed to compare the curative effects of the combination therapy of all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO, As2O3) with ATRA monotherapy on newly diagnosed acute promyelocytic leukemia (APL). Methods: The studies were retrieved from PubMed, EMBASE, Cochrane Library, ChinaInfo and China National Knowledge Infrastructure (CNKI) databases from the inception to June 20, 2014. Thereafter, the eligible studies were selected based on the predefined criteria, and the literature quality was assessed. The meta-analysis was conducted using Review Manager 5.2 software. The pooled effect size was relative risk (RR) and its 95% confidence interval (CI). Results: A total of 8 studies containing 480 cases were included, among which 264 were assigned to the ATRA + ATO group and the other 216 to the ATRA group. The meta-analysis showed that ATRA + ATO combination therapy significantly improved the complete remission (CR) rate (RR = 1.09, 95% CI = 1.03-1.16, p = 0.004), decreased the early mortality rate (RR = 0.42, 95% CI = 0.20-0.9, p = 0.03) and relapse rate (RR = 0.17, 95% CI = 0.07-0.42, p < 0.0001), but increased the high risk of liver dysfunction (RR = 2.43, 95% CI = 1.72-3.41, p < 0.00001), comparing with ATRA monotherapy. Conclusions: The ATRA + ATO combination therapy may be more effective for newly diagnosed APL with a higher CR rate but lower early mortality rate and relapse rate. However, the risks of liver damage should be of concern.

All-trans retinoic acid and early mortality in acute promyelocytic leukemia

2013 ◽  
Vol 37 (10) ◽  
pp. 1391-1392 ◽  
Author(s):  
Armin Rashidi ◽  
Ranjit K. Goudar ◽  
Farzaneh Sayedian ◽  
Jeffrey A. Vos ◽  
Teresa A. Goldin ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Acute Promyelocytic Leukemia ◽  
Promyelocytic Leukemia ◽  
Early Mortality ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid

scholarly journals All-trans-retinoic acid, idarubicin, and IV arsenic trioxide as initial therapy in acute promyelocytic leukemia (APML4)

Blood ◽  
2012 ◽  
Vol 120 (8) ◽  
pp. 1570-1580 ◽  
Author(s):  
Harry J. Iland ◽  
Ken Bradstock ◽  
Shane G. Supple ◽  
Alberto Catalano ◽  
Marnie Collins ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Arsenic Trioxide ◽  
Acute Promyelocytic Leukemia ◽  
Substantial Reduction ◽  
Initial Therapy ◽  
Promyelocytic Leukemia ◽  
Free Survival ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Clinical Trials Registry

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. For induction, ATO was superimposed on an ATRA and idarubicin backbone, with scheduling designed to exploit antileukemic synergy while minimizing cardiotoxicity and the severity of differentiation syndrome. Consolidation comprised 2 cycles of ATRA and ATO without chemotherapy, followed by 2 years of maintenance with ATRA, oral methotrexate, and 6-mercaptopurine. Of 124 evaluable patients, there were 4 (3.2%) early deaths, 118 (95%) hematologic complete remissions, and all 112 patients who commenced consolidation attained molecular complete remission. The 2-year rate for freedom from relapse is 97.5%, failure-free survival 88.1%, and overall survival 93.2%. These outcomes were not influenced by FLT3 mutation status, whereas failure-free survival was correlated with Sanz risk stratification (P[trend] = .03). Compared with our previously reported ATRA/idarubicin-based protocol (APML3), APML4 patients had statistically significantly improved freedom from relapse (P = .006) and failure-free survival (P = .01). In conclusion, the use of ATO in both induction and consolidation achieved excellent outcomes despite a substantial reduction in anthracycline exposure. This trial was registered at the Australian New Zealand Clinical Trials Registry (www.anzctr.org.au) as ACTRN12605000070639.

Potential curability of newly diagnosed acute promyelocytic leukemia without use of chemotherapy: the example of liposomal all-trans retinoic acid

Blood ◽  
2005 ◽  
Vol 105 (3) ◽  
pp. 1366-1367 ◽  
Author(s):  
Elihu Estey ◽  
Charles Koller ◽  
Apostolia M. Tsimberidou ◽  
Susan O'Brien ◽  
Miloslav Beran ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Acute Promyelocytic Leukemia ◽  
Promyelocytic Leukemia ◽  
Newly Diagnosed ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid
Sign in / Sign up

Export Citation Format

Share Document