Arsenic Containing Triple-Agent Therapy for Acute Promyelocytic Leukemia-Comparison of Tetra-Arsenic Tetra-Sulfide vs. Arsenic Trioxide in the Long-Term Follow-up at a Single Hospital.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1081-1081
Author(s):  
Shu-Lan Wu ◽  
Dao-Pei Lu ◽  
Yan-Li Zhao ◽  
Lan-Qing Liang ◽  
Jun-Bao He ◽  
...  
Keyword(s):  
Maintenance Therapy ◽  
Arsenic Trioxide ◽  
Acute Promyelocytic Leukemia ◽  
Low Dose ◽  
Promyelocytic Leukemia ◽  
Newly Diagnosed ◽  
Highly Effective ◽  
Low Dose Chemotherapy

Abstract Abstract 1081 Our previous study has demonstrated that oral tetra-arsenic tetra-sulfide (As4S4) alone is highly effective and safe in both induction and maintenance therapy in acute promyelocytic leukemia (APL) (Dao-Pei Lu et al., Blood 2002; 99: 3136). Triple-agent treatment with As4S4, all-trans retinoid acid (ATRA) and low-dose chemotherapy has achieved expeditiously consecutive complete remission (CR) without death during induction, and it has also improved leukemia-free survival (LFS) (Tong Wu et al., ASH abstract 591 2007). To learn the efficacy and safety of As4S4 and arsenic trioxide (ATO), a total of 88 consecutive cases of newly diagnosed APL patients who have been treated with triple-agent regimen with arsenic, either As4S4 (n=42) or ATO (n=46), ATRA and low-dose chemotherapy at Beijing Dao-Pei Hospital were analyzed retrospectively. Major clinical characteristics in two groups were similar. Purified natural oral As4S4 (Dao-Pei Lu's Lab) or commercially available intravenous ATO were used. The regimens for induction, consolidation and maintenance therapy have been reported previously. All 88 patients attained hematological CR (HCR) after induction therapy without early death. A total of 84 cases were monitored for PML/RARA fusion transcript by RQ-PCR. Molecular CR (MCR) reached in all evaluable cases (100%) in As4S4 group and 93.5% of cases in ATO group. In As4S4 group, 3-year and 5-year LFS rates were all 100% with a median follow-up of 57 months (range, 12–103 months). In ATO group, however, 5 cases relapsed and 2 patients died with a median follow-up of 36 months (range, 12–96 months). The 3-year and 5-year LFS rates were both 86.6%. The difference of LFS between As4S4 and ATO groups were remarkable (p=0.028). Three-year and 5-year overall survival (OS) rates were all 100% in As4S4 group, 96.7% and 88.6% in ATO group respectively. Statistically there was no significant difference (p=0.1015). The side effects in As4S4 group were mild and all patients could continue the therapy. However, a total of 15 side events in ATO group including hepatic, cardiac or lung complications led to discontinuation of therapy. Our encouraging clinical results indicate that arsenic, either As4S4 or ATO in combination with ATRA and low-dose chemotherapy is highly effective in the induction of both HCR and MCR in newly diagnosed APL patients. As4S4 containing triple-agent protocol has better results in the prevention of relapse and improvement of LFS, and has less toxicity. Our clinical study has shown for the first time that all consecutive newly diagnosed cases of APL have achieved long-term LFS with As4S4 containing triple-agent regimen, which are significantly better than that of ATO containing one. Disclosures: No relevant conflicts of interest to declare.

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.

Maintenance therapy with arsenic after induction in an alternative and long-term case for the prevention of recurrence of acute promyelocytic leukemia during the period between November 2005 and December 2011.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 6556-6556
Author(s):  
Mozaffar Aznab ◽  
Ghobad Salimi ◽  
Jafar Navabi ◽  
Touraj Jouybari ◽  
Mansour Rezaei ◽  
...  
Keyword(s):  
Maintenance Therapy ◽  
Arsenic Trioxide ◽  
Acute Promyelocytic Leukemia ◽  
Promyelocytic Leukemia ◽  
Remission Induction ◽  
Term Therapy ◽  
First Line ◽  
First Line Therapy

6556 Background: Arsenic trioxide has been used in the first line treatment of acute promyelocytic leukemia and also for recurrence after ATRA and chemotherapy. In this study, it we used it in induction of remission and maintenance therapy Methods: Between November 2005 to December 2011, 42 patients admitted in our department with APL diagnosis. There were 27 male and 15 women with a median age of 28 years. Arsenic trioxide started at 0.15 mg/kg intravenous infusion till patient’s bone marrows achieve to complete remission. Then, after 28 days rest, we did consolidation with Arsenic trioxide with the same dosage for 28 more days. We continued treatment with 14 days courses of Arsenic trioxide every 3-4 months for 2 years, as maintenance therapy Results: Four patients died during the first 20 days of treatment. Thirty-eight patients achieved to remission. Two patients refused to continue treatment after achieving to remission and excluded from this study. Thirty-six patients finished whole treatment. After a median follow-up of 54 months, 4 patients died due to disease relapse and one patient relapsed and initiated treatment with Arsenic and ATRA. Five patients faced leukocytosis over 100,000/ml. In these cases we were obligated to discontinue Arsenic for 3-4 days and did chemotherapy by Danourobicin for 2 days. Totally 8 patients died during remission induction and long-term follow up. One year, 3 and 5 years RFS were 97%, 87.1% and 79.4 respectively and we didn’t observe any relapse for patients who remained in remission after 5 years. Finally, 31 patients are alive and free of disease. The overall survival was 79.5% for our cohort. Conclusions: Arsenic trioxide is an effective treatment as the first line therapy for new cases of APL and long term therapy with will reduce the risk of diseases recurrence without any major toxicity in long time.

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.

Final Analysis of a Multi-Center Randomized Controlled Trial (IAPLSG04) to Study the Optimal Duration of Arsenic Trioxide Maintenance Therapy in the Treatment of Newly Diagnosed Acute Promyelocytic Leukemia

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 426-426 ◽  
Author(s):  
Vikram Mathews ◽  
Biju George ◽  
Farah Jijina ◽  
Cecil Ross ◽  
Reena Nair ◽  
...  
Keyword(s):  
Maintenance Therapy ◽  
Arsenic Trioxide ◽  
Acute Promyelocytic Leukemia ◽  
Low Cost ◽  
Single Agent ◽  
Promyelocytic Leukemia ◽  
Newly Diagnosed ◽  
Molecular Remission ◽  
Short Period

Abstract Abstract 426 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 who achieved molecular remission were randomized to 6 vs. 12 months of ATO maintenance. From July, 2004 to December, 2008, 186 patients were initially screened and enrolled based on morphological diagnosis of APL from 7 centers in India. Twenty seven cases were excluded from analysis (6 RT-PCR negative, 4 IC bleed at diagnosis, 5 septicemia/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 for up to 60 days in induction; this was followed by 28 day consolidation after a 4 week break following induction. 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. 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. Hydroxyurea was permitted for control of leucocytosis. Of the 159 patients who could be evaluated 138 (86.8%) achieved hematological remission (CHR), one patient had primary induction failure and was removed from the study the rest were induction deaths at a median of 17 days (range: 4 – 69). 52 (32.7%) received an anthracycline in induction while 116 (73%) received hydroxyurea in induction. A differentiation syndrome was documented in 25 (16%) cases and was fatal in one. Grade III/IV non hematological toxicity was seen in 26 (16.3%), in the majority they resolved after discontinuing ATO for a short period. 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 48 months the 5 year Kaplan-Meir estimate of overall survival (OS), event free survival (EFS) and disease free surivival (DFS) was 75.7±3.9%, 68±4% and 76.9±4.2% respectively. Twenty five patients relapsed, the median time to relapse was 19.2 months (range: 8.2–51). There were no relapses beyond 4 years of follow up. 136 patients who achieved molecular remission after consolidation were randomized in to 6 months (n=63) or 12 months (n=73) of maintenance therapy. The baseline characteristics of the two groups were not significantly different. Post randomization, the two groups were analyzed on an intention to treat basis. The OS, EFS (Figure 1) and DFS of the two groups were not statistically different. There was no evidence that the group that received 12 months of maintenance had any increased incidence of toxicity. This study confirms that this low cost, low intensity single agent ATO based regimen, as reported previously, is well tolerated and results in durable remissions. However, there is no apparent clinical benefit from increasing the duration of maintenance from 6 to 12 months. Disclosures: No relevant conflicts of interest to declare.

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.

Phase II Study of Single-Agent Arsenic Trioxide for the Front-Line Therapy of Acute Promyelocytic Leukemia

2011 ◽  
Vol 29 (20) ◽  
pp. 2753-2757 ◽  
Author(s):  
Ardeshir Ghavamzadeh ◽  
Kamran Alimoghaddam ◽  
Shahrbano Rostami ◽  
Seyed Hamidolah Ghaffari ◽  
Mohamad Jahani ◽  
...  
Keyword(s):  
Arsenic Trioxide ◽  
Acute Promyelocytic Leukemia ◽  
Residual Disease ◽  
Single Agent ◽  
Disease Free Survival ◽  
Promyelocytic Leukemia ◽  
Newly Diagnosed ◽  
Long Term Follow Up

Purpose The long-term follow-up results of patients with acute promyelocytic leukemia (APL) treated with all-trans retinoic acid and chemotherapy show high cure rates. Several studies have shown high efficacy of single-agent arsenic trioxide in newly diagnosed APL. However, long-term follow-up results are needed. Patients and Methods One hundred ninety-seven patients with newly diagnosed APL were treated with arsenic trioxide 0.15 mg/kg daily intravenous infusion until complete remission (CR). After achieving CR, the patients received one to four more courses of therapy with arsenic trioxide as consolidation and were observed with reverse-transcriptase polymerase chain reaction studies from peripheral blood (to detect of minimal residual disease) every 3 months or until relapse or death. Results The morphologic CR rate was 85.8%. The most common cause of remission failure was early death owing to APL differentiation syndrome (13.2%). The most important prognostic factor for early mortality was a high WBC count at presentation. The 5-year disease-free survival (DFS) rate was 66.7% ± 4% (SE). Relapse after 5 years in CR was rare. The 5-year overall survival (OS) rate by intention-to-treat analysis was 64.4% ± 4%. In patients who achieved CR, OS and DFS were identical. Conclusion The long-term follow-up of newly diagnosed patients with APL treated with single-agent arsenic trioxide shows high rates of DFS and OS.

Studies on Treatment of Acute Promyelocytic Leukemia With Arsenic Trioxide: Remission Induction, Follow-Up, and Molecular Monitoring in 11 Newly Diagnosed and 47 Relapsed Acute Promyelocytic Leukemia Patients

Blood ◽  
1999 ◽  
Vol 94 (10) ◽  
pp. 3315-3324 ◽  
Author(s):  
Chao Niu ◽  
Hua Yan ◽  
Ting Yu ◽  
Hui-Ping Sun ◽  
Jian-Xiang Liu ◽  
...  
Keyword(s):  
Arsenic Trioxide ◽  
Acute Promyelocytic Leukemia ◽  
Disease Free Survival ◽  
Promyelocytic Leukemia ◽  
Pcr Analysis ◽  
Remission Induction ◽  
Newly Diagnosed ◽  
First Choice ◽  
Wbc Count

Fifty-eight acute promyelocytic leukemia (APL) patients (11 newly diagnosed and 47 relapsed) were studied for arsenic trioxide (As2O3) treatment. Clinical complete remission (CR) was obtained in 8 of 11 (72.7%) newly diagnosed cases. However, As2O3 treatment resulted in hepatic toxicity in 7 cases including 2 deaths, in contrast to the mild liver dysfunction in one third of the relapsed patients. Forty of forty-seven (85.1%) relapsed patients achieved CR. Two of three nonresponders showed clonal evolution at relapse, with disappearance of t(15;17) and PML-RAR fusion gene in 1 and shift to a dominant AML-1-ETO population in another, suggesting a correlation between PML-RAR expression and therapeutic response. In a follow-up of 33 relapsed cases over 7 to 48 months, the estimated disease-free survival (DFS) rates for 1 and 2 years were 63.6% and 41.6%, respectively, and the actual median DFS was 17 months. Patients with white blood cell (WBC) count below 10 × 109/L at relapse had better survival than those with WBC count over 10 × 109/L (P = .038). The duration of As2O3-induced CR was related to postremission therapy, because there was only 2 of 11 relapses in patients treated with As2O3 combined with chemotherapy, compared with 12 of 18 relapses with As2O3 alone (P = .01). Reverse transcription polymerase chain reaction (RT-PCR) analysis in both newly diagnosed and relapsed groups showed long-term use of As2O3 could lead to a molecular remission in some patients. We thus recommend that ATRA be used as first choice for remission induction in newly diagnosed APL cases, whereas As2O3 can be either used as a rescue for relapsed cases or included into multidrug consolidation/maintenance clinical trials.

Prognostic significance of minimal residual disease detection and PML/RAR-α isoform type: long-term follow-up in acute promyelocytic leukemia

Blood ◽  
2001 ◽  
Vol 98 (9) ◽  
pp. 2651-2656 ◽  
Author(s):  
Joseph G. Jurcic ◽  
Stephen D. Nimer ◽  
David A. Scheinberg ◽  
Tony DeBlasio ◽  
Raymond P. Warrell ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Promyelocytic Leukemia ◽  
Residual Disease ◽  
Prognostic Significance ◽  
Promyelocytic Leukemia ◽  
Newly Diagnosed ◽  
Rt Pcr ◽  
Pcr Assays

Abstract The t(15;17) translocation in acute promyelocytic leukemia (APL) yields a PML/RAR-α fusion messenger RNA species that can be detected by reverse transcription–polymerase chain reaction (RT-PCR) amplification. Breakpoints within intron 3 of PML produce a short PML/RAR-α isoform, whereas breakpoints within intron 6 result in a longer form. Using RT-PCR, serial evaluations were performed on the bone marrow of 82 patients with APL (median follow-up, > 63 months) who received retinoic acid (RA) induction followed by postremission treatment with chemotherapy, RA, and biologic agents. Sixty-four patients attained a clinical complete remission and had at least 2 RT-PCR assays performed after completing therapy. Forty of 47 patients (85%) with newly diagnosed APL who were induced using RA had residual disease detectable by RT-PCR before additional therapy. After 3 cycles of consolidation therapy, residual disease was found in only 4 of 40 evaluable patients (10%). Among newly diagnosed patients who had 2 or more negative RT-PCR assays, only 3 of 41 (7%) had a relapse, whereas all 4 patients (100%) who had 2 or more positive results had a relapse. Among 63 newly diagnosed patients, those who expressed the short isoform appeared to have shorter disease-free and overall survival durations than patients who expressed the long isoform. These data indicate that 2 or more negative RT-PCR assays on bone marrow, performed at least 1 month apart after completing therapy, are strongly associated with long-term remissions. Conversely, a confirmed positive test is highly predictive of relapse.

Quantitative analysis of PML-RARα in newly diagnosed acute promyelocytic leukemia patients treated with arsenic trioxide as a front-line therapy

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 6571-6571
Author(s):  
S. H. Ghaffari ◽  
S. Rostami ◽  
D. Bashash ◽  
K. Alimoghaddam ◽  
A. Ghavamzadeh
Keyword(s):  
Arsenic Trioxide ◽  
Acute Promyelocytic Leukemia ◽  
Transcript Level ◽  
Threshold Level ◽  
Promyelocytic Leukemia ◽  
Newly Diagnosed ◽  
Rt Pcr ◽  
Front Line ◽  
Line Therapy

6571 Background: Recently, patients with acute promyelocytic leukemia (APL) have experienced significant clinical gains after treatment with arsenic trioxide (As2O3). However, the potential role for use of this agent as a front-line therapy for newly diagnosed patients is unclear. Methods: From 95 patients with APL, 85 patients who achieved complete remission (CR) were sequentially evaluated during 4–60 months period of follow-up by conventional RT-PCR. A total of 30 patients (6 relapsed and 24 in continued long remission) were selected and monitored by quantitative real-time PCR (RQ-PCR) assay. Using ‘Hybridization Probes‘ technology, the expression of PML-RARα/G6PDH transcript ratio was analyzed in serial PB samples taken at different courses of disease and the results were compared with the clinical outcome. Results: More than 90% of patients obtained molecular remission, as determined by conventional RT-PCR in 1–3 months after start of arsenic therapy. RQ-PCR analyses showed a rapid rate of clearance of PML-RARα/G6PDH transcript level during the courses of arsenic therapy. In majority of the patients in CR the level of PML-RARα/ G6PDH ratio was always below 5×102 in PB samples. In all the relapsed cases with follow-up intervals of 1–6 months (median 3) clinical relapse was predictable by increasing transcript level above this threshold. Conclusions: Using a sensitive and quantitative method provided valuable information about effectiveness of arsenic as a front-line therapy in the management of newly diagnosed APL. Our study highlights the usefulness of PB and the definition of threshold level for early prediction of relapse. The threshold level correlates well with relapse risk; therefore, transcript ratio below the level should be regarded as a goal in the clinical management of this disease. No significant financial relationships to disclose.

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