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Conference Paper: Oral Arsenic Trioxide, ATRA and Ascorbic Acid (AAA) Maintenance Following First Complete Remission in Acute Promyelocytic Leukemia - Long-Term Data and Unique Prognostic Indicators

TitleOral Arsenic Trioxide, ATRA and Ascorbic Acid (AAA) Maintenance Following First Complete Remission in Acute Promyelocytic Leukemia - Long-Term Data and Unique Prognostic Indicators
Authors
Issue Date2019
PublisherAmerican Society of Hematology. The Journal's web site is located at http://bloodjournal.hematologylibrary.org/
Citation
61st American Society of Hematology Annual Meeting, Orlando, Florida, 7-10 December 2019, v. 134 n. S1, p. 3853-3853 How to Cite?
AbstractBackground Oral arsenic trioxide (oral-As2O3)-based regimens are highly effective in the treatment of newly-diagnosed or relapsed acute promyelocytic leukemia (APL)1,2. Data on the long-term outcome of patients who received prolonged maintenance with oral-As2O3-based regimens in first complete remission (CR1) following non-arsenic-based induction is lacking. Methods Patients aged ≥ 18 years with APL in first complete remission (CR1) were recruited for maintenance treatment with oral-As2O3 (10mg/day), all-trans-retinoic acid (ATRA) (45mg/m2/day in 2 divided doses), ascorbic acid (1g/day) (AAA). AAA was administered for 2 weeks every 2 months for a total of 2 years. Prior induction treatment comprised ATRA (45mg/m2/day in 2 divided doses for 42 days) and daunorubicin (50mg/m2/day for 3 days). Consolidation comprised 2 monthly cycles of daunorubicin (50 mg/m2/day for 2 days) and cytarabine (100 mg/m2/day for 5 days). Daunorubicin induction and consolidation chemotherapy were omitted in patients aged ≥ 70 years or those with cardiac co-morbidities. Results Between 1 August 2002 and 31 July 2019, 129 patients (63 men and 66 women) with a median age of 46 (18-82) years underwent maintenance with AAA. After a median follow-up of 100 (8-215) months, 117 (90.1%) patients completed 2 years of AAA maintenance. Seventeen (13.2%) patients relapsed after a median of 19 (7-96) months from CR1 (morphologic relapse, N=14; molecular relapse; N=3). Two patients had central nervous system (CNS) involvement at first relapse (R1). There were 13 (10.1%) deaths. Five patients died from refractory APL. Eight patients died in remission (pneumonia, N=4; acute myocardial infarction, N=2; second malignancy, N=2). The 5-year and 10-year relapse-free survival (RFS) were 88.8% and 85.1% respectively. The 5-year and 10-year overall survival (OS) were 94.2% and 87.4%. On univariate analysis, PML-RARA bcr3 (short) isoform (P=0.02), FLT3-ITD (P=0.005) and CNS involvement at diagnosis (P=0.002) were associated with worse RFS. On multivariate analysis, FLT3-ITD (P=0.005) and central nervous system (CNS) involvement at diagnosis (P=0.004) were associated with worse RFS. On univariate analysis, PML-RARA bcr3 isoform (P=0.03), FLT3-ITD (P=0.01) and relapsed APL (P=0.002) were associated with worse OS. On multivariate analysis, therapy-related APL (P=0.03), FLT3-ITD (P=0.03) and relapsed APL (P=0.03) were associated with worse OS. Grade 1 leucopenia occurred in 7 (5.4%). The commonest non-hematological toxicity was headache and occurred in 38 (29.5%) (Grade 1/2, N=38; Grade 3/4, N=0). Grade 1 hepatoxicity occurred in 7 (5.4%) patients during AAA maintenance. Cutaneous herpes zoster infection occurred in 6 (4.7%) patients. Conclusion Maintenance therapy with oral-As2O3, ATRA and ascorbic acid in CR1 was safe and resulted in excellent long-term survivals in APL. References: 1. Gill H, Yim R, Lee HKK, Mak V, Lin SY, Kho B et al. Long-term outcome of relapsed acute promyelocytic leukemia treated with oral arsenic trioxide-based reinduction and maintenance regimens: A 15-year prospective study. Cancer 2018; 124(11): 2316-2326. 2. Gill H, Kumana CR, Yim R, Hwang YY, Chan TSY, Yip SF et al. Oral arsenic trioxide incorporation into frontline treatment with all-trans retinoic acid and chemotherapy in newly diagnosed acute promyelocytic leukemia: A 5-year prospective study. Cancer 2019 [Epub].
Description613. Acute myeloid leukemia: clinical studies
Persistent Identifierhttp://hdl.handle.net/10722/280103
ISSN
2019 Impact Factor: 17.543
2015 SCImago Journal Rankings: 6.395
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorSingh, GHH-
dc.contributor.authorYim, RLH-
dc.contributor.authorKumana, CR-
dc.contributor.authorKwong, YL-
dc.date.accessioned2020-01-06T02:01:00Z-
dc.date.available2020-01-06T02:01:00Z-
dc.date.issued2019-
dc.identifier.citation61st American Society of Hematology Annual Meeting, Orlando, Florida, 7-10 December 2019, v. 134 n. S1, p. 3853-3853-
dc.identifier.issn0006-4971-
dc.identifier.urihttp://hdl.handle.net/10722/280103-
dc.description613. Acute myeloid leukemia: clinical studies-
dc.description.abstractBackground Oral arsenic trioxide (oral-As2O3)-based regimens are highly effective in the treatment of newly-diagnosed or relapsed acute promyelocytic leukemia (APL)1,2. Data on the long-term outcome of patients who received prolonged maintenance with oral-As2O3-based regimens in first complete remission (CR1) following non-arsenic-based induction is lacking. Methods Patients aged ≥ 18 years with APL in first complete remission (CR1) were recruited for maintenance treatment with oral-As2O3 (10mg/day), all-trans-retinoic acid (ATRA) (45mg/m2/day in 2 divided doses), ascorbic acid (1g/day) (AAA). AAA was administered for 2 weeks every 2 months for a total of 2 years. Prior induction treatment comprised ATRA (45mg/m2/day in 2 divided doses for 42 days) and daunorubicin (50mg/m2/day for 3 days). Consolidation comprised 2 monthly cycles of daunorubicin (50 mg/m2/day for 2 days) and cytarabine (100 mg/m2/day for 5 days). Daunorubicin induction and consolidation chemotherapy were omitted in patients aged ≥ 70 years or those with cardiac co-morbidities. Results Between 1 August 2002 and 31 July 2019, 129 patients (63 men and 66 women) with a median age of 46 (18-82) years underwent maintenance with AAA. After a median follow-up of 100 (8-215) months, 117 (90.1%) patients completed 2 years of AAA maintenance. Seventeen (13.2%) patients relapsed after a median of 19 (7-96) months from CR1 (morphologic relapse, N=14; molecular relapse; N=3). Two patients had central nervous system (CNS) involvement at first relapse (R1). There were 13 (10.1%) deaths. Five patients died from refractory APL. Eight patients died in remission (pneumonia, N=4; acute myocardial infarction, N=2; second malignancy, N=2). The 5-year and 10-year relapse-free survival (RFS) were 88.8% and 85.1% respectively. The 5-year and 10-year overall survival (OS) were 94.2% and 87.4%. On univariate analysis, PML-RARA bcr3 (short) isoform (P=0.02), FLT3-ITD (P=0.005) and CNS involvement at diagnosis (P=0.002) were associated with worse RFS. On multivariate analysis, FLT3-ITD (P=0.005) and central nervous system (CNS) involvement at diagnosis (P=0.004) were associated with worse RFS. On univariate analysis, PML-RARA bcr3 isoform (P=0.03), FLT3-ITD (P=0.01) and relapsed APL (P=0.002) were associated with worse OS. On multivariate analysis, therapy-related APL (P=0.03), FLT3-ITD (P=0.03) and relapsed APL (P=0.03) were associated with worse OS. Grade 1 leucopenia occurred in 7 (5.4%). The commonest non-hematological toxicity was headache and occurred in 38 (29.5%) (Grade 1/2, N=38; Grade 3/4, N=0). Grade 1 hepatoxicity occurred in 7 (5.4%) patients during AAA maintenance. Cutaneous herpes zoster infection occurred in 6 (4.7%) patients. Conclusion Maintenance therapy with oral-As2O3, ATRA and ascorbic acid in CR1 was safe and resulted in excellent long-term survivals in APL. References: 1. Gill H, Yim R, Lee HKK, Mak V, Lin SY, Kho B et al. Long-term outcome of relapsed acute promyelocytic leukemia treated with oral arsenic trioxide-based reinduction and maintenance regimens: A 15-year prospective study. Cancer 2018; 124(11): 2316-2326. 2. Gill H, Kumana CR, Yim R, Hwang YY, Chan TSY, Yip SF et al. Oral arsenic trioxide incorporation into frontline treatment with all-trans retinoic acid and chemotherapy in newly diagnosed acute promyelocytic leukemia: A 5-year prospective study. Cancer 2019 [Epub].-
dc.languageeng-
dc.publisherAmerican Society of Hematology. The Journal's web site is located at http://bloodjournal.hematologylibrary.org/-
dc.relation.ispartofBlood-
dc.rightsThis research was originally published in [Journal Title]. Author(s). Title. [Journal Title]. Year;Vol,Issue:pp-pp. © the American Society of Hematology.-
dc.titleOral Arsenic Trioxide, ATRA and Ascorbic Acid (AAA) Maintenance Following First Complete Remission in Acute Promyelocytic Leukemia - Long-Term Data and Unique Prognostic Indicators-
dc.typeConference_Paper-
dc.identifier.emailSingh, GHH: gillhsh@hku.hk-
dc.identifier.emailYim, RLH: ritayim@hku.hk-
dc.identifier.emailKwong, YL: ylkwong@hkucc.hku.hk-
dc.identifier.authoritySingh, GHH=rp01914-
dc.identifier.authorityKwong, YL=rp00358-
dc.identifier.doi10.1182/blood-2019-125185-
dc.identifier.hkuros308876-
dc.identifier.volume134-
dc.identifier.issueS1-
dc.identifier.spage3853-
dc.identifier.epage3853-
dc.identifier.isiWOS:000577164601146-
dc.publisher.placeUnited States-
dc.identifier.issnl0006-4971-

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