Consolidation with Arsenic Trioxide Significantly Improves Event-free Survival and Overall Survival among Patients with Newly Diagnosed Acute Promyelocytic Leukemia

2007 ◽  
Vol 7 (3) ◽  
pp. 12-12
Author(s):  
W. Alexander ◽  
B. L. Powell
Keyword(s):  
Overall Survival ◽  
Arsenic Trioxide ◽  
Acute Promyelocytic Leukemia ◽  
Promyelocytic Leukemia ◽  
Newly Diagnosed ◽  
Event Free Survival ◽  
Free Survival

Single Agent Arsenic Trioxide Regimen for the Treatment of Newly Diagnosed Acute Promyelocytic Leukemia: Initial Results of a Multicenter Randomized Controlled Study From India to Study the Optimal Duration of Arsenic Trioxide Maintenance Therapy (IAPLSG04).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2082-2082 ◽  
Author(s):  
Vikram Mathews ◽  
Biju George ◽  
Farah Jijina ◽  
Cecil Ross ◽  
Reena Nair ◽  
...  
Keyword(s):  
Maintenance Therapy ◽  
Arsenic Trioxide ◽  
Acute Promyelocytic Leukemia ◽  
Single Agent ◽  
Promyelocytic Leukemia ◽  
Controlled Study ◽  
Newly Diagnosed ◽  
Free Survival ◽  
Short Period

Abstract Abstract 2082 Poster Board II-59 Single agent arsenic trioxide (ATO) has proven efficacy in the management of newly diagnosed cases of acute promyelocytic leukemia (APL). To validate findings of an initial single center experience (Blood 2006:107; 2627) with this low cost, well tolerated, effective regimen, a multicenter study was undertaken in a resource constrained environment. Additionally, in an effort to improve on the earlier experience and study the role of duration of maintenance on reducing late relapses, patients were randomized to 6 vs. 12 months of ATO maintenance (ClinicalTrials.gov Identifier:NCT00517712). From July, 2004 to December, 2008, 182 patients were initially screened and enrolled based on morphological diagnosis of APL from 7 centers in India. Diagnosis was subsequently confirmed by molecular methods. Twenty seven cases were excluded from analysis (6 RT-PCR negative, 4 IC bleed at diagnosis, 5 septic/pneumonia at diagnosis, 9 withdrew consent prior to randomization and some were treated with other protocols, 1 withdrawn by investigator prior to randomization). Patients were treated with single agent ATO at standard doses (10mg/day for adults and 0.15mg/kg/day for pediatric patients) for up to 60 days in induction; this was followed by a 28 day consolidation after a 4 week break. Four weeks after completion of consolidation patients who were in molecular remission were randomized to 6 vs. 12 months of maintenance therapy with ATO administered for 10 days/month. Hydroxyurea was permitted for control of leucocytosis. Anthracyclines were permitted in induction for patients presenting with or WBC count rising >20×109/L in the first week, >50×109/L in the second week and for those who developed a differentiation syndrome. Of the 155 patients who could be evaluated 136 (87.7%) achieved hematological remission (CHR). One patient had primary induction failure and was removed from the study while the other 18 were induction deaths at a median of 17 days (range: 4 – 69). During induction, 52 (33.5%) patients received an anthracycline and 116 (75%) received hydroxyurea. A differentiation syndrome was documented in 25 (16%) cases and was fatal in one. Grade III/IV non hematological toxicity was seen in 26 (16.7%), which resolved in the majority after discontinuing ATO for a short period. One hundred and thirty six patients were randomized, 64 (47%) and 72 (53%) into a 6 and 12 month maintenance regimen respectively. A protocol change after randomization was done in 3 cases for persistent toxicity. Five (3.6%) patients did not complete the scheduled maintenance regimen due to poor compliance or was discontinued by the investigator. At a median follow up of 24 months, the 3-year Kaplan-Meir estimate of overall survival (OS), event free survival (EFS) and disease free survival (DFS) of the entire cohort was 76.87±4.33%, 71.57±4.64% and 80.69±4.77% respectively. Fourteen patients relapsed, the median time to relapse was 19.3 months (range: 9-51). The baseline characteristics of the two groups (6vs12 months) were not significantly different. Post randomization, the two groups were analyzed on an intention to treat basis. The OS, EFS and DFS of the two groups were not statistically significantly different. There was also no evidence that the group that received 12 months of maintenance had any increased incidence of toxicity. Single agent ATO based regimen as reported previously is well tolerated and results in durable remissions. Longer follow up is required to see if 12 months of maintenance therapy reduces risk of late relapses. Disclosures: No relevant conflicts of interest to declare.

Single-Agent Arsenic Trioxide in the Treatment of Newly Diagnosed Acute Promyelocytic Leukemia: Long-Term Follow-Up Data

2010 ◽  
Vol 28 (24) ◽  
pp. 3866-3871 ◽  
Author(s):  
Vikram Mathews ◽  
Biju George ◽  
Ezhilarasi Chendamarai ◽  
Kavitha M. Lakshmi ◽  
Salamun Desire ◽  
...  
Keyword(s):  
Arsenic Trioxide ◽  
Acute Promyelocytic Leukemia ◽  
Risk Group ◽  
Single Agent ◽  
Promyelocytic Leukemia ◽  
Newly Diagnosed ◽  
Free Survival ◽  
Long Term Follow Up

Purpose We previously reported our results with a single-agent arsenic trioxide (ATO) –based regimen in newly diagnosed cases of acute promyelocytic leukemia (APL). The concern remained about the long-term outcome of this well-tolerated regimen. We report our long-term follow-up data on the same cohort. Patients and Methods From January 1998 to December 2004, 72 patients with PML/RARα+ APL were enrolled. All patients were treated with a single-agent ATO regimen. Results Overall 62 (86.1%) achieved a hematologic remission (complete remission). After the initial report, an additional seven patients have relapsed for a total of 13 relapses. There were no additional toxicities to report on follow-up. At a median follow-up 60 months, the 5-year Kaplan-Meier estimate (± SE) of event-free survival, disease-free survival, and overall survival (OS) was 69% ± 5.5%, 80% ± 5.2%, and 74.2% ± 5.2%, respectively. The OS in the good risk group as defined by us remains 100% over this period. Conclusion Single-agent ATO as used in this study in the management of newly diagnosed cases of APL is safe and is associated with durable responses. Results in the low-risk group are comparable to that reported with conventional therapy while additional interventions would probably be required in high-risk cases.

scholarly journals Oral arsenic trioxide–based maintenance regimens for first complete remission of acute promyelocytic leukemia: a 10-year follow-up study

Blood ◽  
2011 ◽  
Vol 118 (25) ◽  
pp. 6535-6543 ◽  
Author(s):  
Wing-Yan Au ◽  
Cyrus R. Kumana ◽  
Harold K. K. Lee ◽  
Shek-Ying Lin ◽  
Herman Liu ◽  
...  
Keyword(s):  
Overall Survival ◽  
Complete Remission ◽  
Arsenic Trioxide ◽  
Acute Promyelocytic Leukemia ◽  
Chemotherapeutic Agents ◽  
Promyelocytic Leukemia ◽  
Free Survival ◽  
Wbc Count ◽  
First Complete Remission

Abstract Seventy-six patients with acute promyelocytic leukemia (APL) in first complete remission after induction and consolidation by daunorubicin and cytosine arabinoside received oral arsenic trioxide (As2O3)-based maintenance. Three regimens were used: oral As2O3 (10 mg/day, regimen A, n = 20), oral As2O3 plus all-trans retinoic acid (ATRA, 45 mg/m2 per day, regimen AA, n = 19), and oral As2O3 plus ATRA plus ascorbic acid (1000 mg/day, regimen AAA, n = 37), each given for 2 weeks every 2 months for 2 years. Patients receiving A, AA, and AAA maintenance did not differ significantly in clinicopathologic features and risk factors. Headache, dyspepsia, reversible liver function derangement, and herpes zoster reactivation were adverse effects observed during maintenance. QTc prolongation and arrhythmias were not encountered. At a median follow-up of 24 months (range, 1-115 months), there were 8 relapses. The 3-year leukemia-free-survival, event-free-survival, and overall-survival were 87.7%, 83.7%, and 90.6%, respectively. Adverse prognostic factors included male gender for leukemia-free-survival, and unrelated cancers for overall survival. Age, presentation WBC count and platelet count, and the type of oral As2O3 maintenance regimens had no impact on survivals. Prolonged oral As2O3 maintenance was feasible and safe and resulted in favorable outcomes when used with a simple induction and consolidation regimen compared with other protocols composed of multiple chemotherapeutic agents.

Retrospective Study on 46 Chinese Children with Acute Promyelocytic Leukemia: A Single Center Experience in China.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4567-4567
Author(s):  
Yongmin Tang ◽  
Xiaojun Xu ◽  
Chan Liao ◽  
Limin Zou ◽  
Hua Song ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Promyelocytic Leukemia ◽  
Fusion Gene ◽  
Promyelocytic Leukemia ◽  
Induction Treatment ◽  
Event Free Survival ◽  
Term Survival ◽  
Free Survival ◽  
Wbc Count

Abstract Acute promyelocytic leukemia (APL) is a specific type of hematopoietic malignancy, accounting for ~ 10% of the de novo acute myeloid leukemia (AML). During the old days, severe complications as disseminated intravascular coagulation (DIC) and intracranial hemorrhage were the most common causes of treatment failure after conventional chemotherapy without all-trans retinoic acid (RA). Owing to the application of RA for the induction treatment, the overall survival (OS), the disease free survival (DFS) and the event free survival (EFS) rates have been dramatically improved in adult patients with APL. However, data on long-term outcome of APL in children, especially in Chinese children, have been very limited. Objective The aim of this study was to investigate the clinical biological features, diagnosis, prognosis and long-term survival in childhood APL. Methods 46 children (26 boys and 20 girls, aged 1.5 ~13.8 yrs with a median of 9.3 yrs) with APL from April 1998 to October 2005 were enrolled into this study. Immunophenotyping analysis was carried out in 43 patients using multi-parameter flow cytometry. 32 patients went through PML/RARα fusion gene detection using RT-PCR. Induction treatment consisted of ATRA and daunorubicin(DNR) or pirarubicin (THP) followed by 6 courses of multi-drug chemotherapy consolidation and a long-term maintenance therapy including ATRA, high dose Ara-C (HD-Ara-C), DNR+Ara-C (DA), homoharringtonine+Ara-C (HA) and etoposide+Ara-C (EA). Results Pale, hemorrhage and fever were the most common symptoms in APL patients at the time of presentation. 19 patients (41.3%) were found to have WBC count more than 10.0×109/L at diagnosis. Immunophenotyping analysis showed that CD13, CD33, CD117 and MPO were the most commonly expressed antigens while HLA-DR, CD14 and CD34 were mostly the negative markers on APL cells. 71.9%(23/32) of the patients analyzed were PML/RARα fusion gene positive. Of the 39 patients receiving treatment, 36 children (92.3%) achieved complete remission. 7 children replased during therapy, and 3 relapsed after finishing the entire courses. The 5-year cumulative incidence of relapse (CIR) was 28.6%. The estimated overall survival (OS) rates at one, three and five years were 86.1%, 76.1%and 70.2%, respectively while the event free survival (EFS) rates were 78.4%, 63.6%and 53.1%, respectively. The probability of remaining alive after 5 years for patients with WBC≤10.0×109/L group was 81.4%, significantly higher than those with WBC>10.0×109/L group (51.6%, P=0.026). 5 children with positive PML/RARα S (short) subtype died eventually although all of them achieved CR, which was significantly different from the group with the L (long) subtype (13/13, P=0.001). Conclusion Induction with ATRA + DNR or THP is an effective and safe therapy for newly diagnosed childhood APL with very high long-term survival rates after 2.5 years of alternative multi-drug chemotherapy and maintenance. High WBC count and S subtype of PML-RARα are the two poor prognostic factors for children with APL.

In vitro all-trans retinoic acid sensitivity of acute promyelocytic leukemia blasts: a novel indicator of poor patient outcome

Blood ◽  
2001 ◽  
Vol 98 (9) ◽  
pp. 2862-2864 ◽  
Author(s):  
Bruno Cassinat ◽  
Sylvie Chevret ◽  
Fabien Zassadowski ◽  
Nicole Balitrand ◽  
Isabelle Guillemot ◽  
...  
Keyword(s):  
Acute Promyelocytic Leukemia ◽  
Promyelocytic Leukemia ◽  
Leukemic Cells ◽  
Event Free Survival ◽  
Free Survival ◽  
Acid Sensitivity ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid

Abstract Acute promyelocytic leukemia (APL) blasts possess a unique sensitivity to the differentiating effects of all-transretinoic acid (ATRA). Multicenter trials confirm that the combination of differentiation and cytotoxic therapy prolongs survival in APL patients. However relapses still occur, and exquisite adaptation of therapy to prognostic factors is essential to aim at a possible cure of the disease. A heterogeneity was previously reported in the differentiation rate of patients' APL blasts, and it was postulated that this may reflect the in vivo heterogeneous outcome. In this study, it is demonstrated that patients of the APL93 trial whose leukemic cells achieved optimal differentiation with ATRA in vitro at diagnosis had a significantly improved event-free survival (P = .01) and lower relapse rate (P = .04). This analysis highlights the importance of the differentiation step in APL therapy and justifies ongoing studies aimed at identifying novel RA-differentiation enhancers.

scholarly journals Remission in Patients with Acute Promyelocytic Leukemia Treated with Arsenic Trioxide (varitrinox) As the First Line in Colombia

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 3-3
Author(s):  
Gustavo Milone ◽  
Samuel Sarmiento Doncel ◽  
Carol Agudelo Rico ◽  
Fabiola Vizcarra Reyes ◽  
Gina Alejandra Diaz Mosquera ◽  
...  
Keyword(s):  
High Risk ◽  
Arsenic Trioxide ◽  
Acute Promyelocytic Leukemia ◽  
Conflicts Of Interest ◽  
Promyelocytic Leukemia ◽  
Remission Induction ◽  
Intermediate Risk ◽  
Newly Diagnosed ◽  
First Line ◽  
Risk Patients

Acute promyelocytic leukemia (APL) is a subtype of Acute Myeloid Leukemia (AML) in which a chromosomal translocation t (15; 17) (q22; q12) is generated by fusing produces a hybrid PML / RARα gene, generating an altered signal . The combination of transretinoic acid (ATRA) plus arsenic trioxide (ATO) has been shown to be superior to ATRA plus chemotherapy in the treatment of newly diagnosed standard risk patients with acute promyelocytic leukemia (APL) in several countries. The objective of the present study is to describe the frequency of remission in patients with acute promyelocytic leukemia who were administered as a first line Arsenic Trioxide (varitrinox) during the period from November 2017 to June 2020 in Colombian patients. Methods: Retrospective observational and descriptive study of 12 patients diagnosed with acute promyelocytic leukemia treated with ATO Arsenic trioxide (Varitrinox) as first line, the source of information was provided by the treating hematologists (medical records) by filling out the technical concept format. Active pharmacovigilance scientist in Colombia, this format keeps the identification information of the patient anonymized and the confidentiality of the data is guaranteed as well as compliance with the rules of good clinical practice. Results: Twelve patients with age range between 22 and 69 years with a median age of 34.0 were analyzed. It was found in the analysis that 100% had induction hematologic remission with a median of 45 days. 75% of patients received ATO + ATRA and were at low and intermediate risk, the remaining 25% received ATRA + ATO + Chemotherapy and were at high risk, and intermediate risk. 91.7% of molecular remission in consolidation was obtained and it was measured in cycle 3 by means of PCR (undetectable), 8.3% (n = 1) was positive 3% and is finishing consolidation. Regarding the most frequent adverse events, intravascular coagulation (n = 9), neutropenia (n = 6) and thrombocytopenia (n = 6) were observed. 75% of patients are disease-free, 16.7% are on maintenance (they received ATO + ATRA + Induction chemotherapy) and 8.3% are on consolidation. So far, none of the patients under study have died. Conclusions: Our results support the use of ATO (Varitrinox) in newly diagnosed APL patients (as first line), as a care strategy for low, intermediate and high risk patients. The role of ATRA-ATO is guaranteed in other studies where they manage patients of different risks. Key words: Arsenic trioxide, leukemia promyelocytic acute, leukemia myeloid acute, remission induction, tretinoin. Disclosures No relevant conflicts of interest to declare.

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