Long-term outcome of 31 cases of refractory acute promyelocytic leukemia treated with compound realgar natural indigo tablets administered alternately with chemotherapy

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.

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Single-agent arsenic trioxide in the treatment of newly diagnosed acute promyelocytic leukemia: durable remissions with minimal toxicity

Blood ◽

10.1182/blood-2005-08-3532 ◽

2006 ◽

Vol 107 (7) ◽

pp. 2627-2632 ◽

Cited By ~ 226

Author(s):

Vikram Mathews ◽

Biju George ◽

Kavitha M. Lakshmi ◽

Auro Viswabandya ◽

Ashish Bajel ◽

...

Keyword(s):

Arsenic Trioxide ◽

Acute Promyelocytic Leukemia ◽

Single Agent ◽

Promyelocytic Leukemia ◽

Remission Induction ◽

Outpatient Basis ◽

Newly Diagnosed ◽

Term Outcome ◽

Long Term Outcome ◽

Minimal Toxicity

AbstractArsenic trioxide, as a single agent, has proven efficacy in inducing molecular remission in patients with acute promyelocytic leukemia (APL). There is limited long-term outcome data with single-agent As2O3 in the management of newly diagnosed cases of APL. Between January 1998 to December 2004, 72 newly diagnosed cases of APL were treated with a regimen of single-agent As2O3 at our center. Complete hematologic remission was achieved in 86.1%. At a median follow-up of 25 months (range: 8-92 months), the 3-year Kaplan-Meier estimate of EFS, DFS, and OS was 74.87% ± 5.6%, 87.21% ± 4.93%, and 86.11% ± 4.08%, respectively. Patients presenting with a white blood cell (WBC) count lower than 5 × 109/L and a platelet count higher than 20 × 109/L at diagnosis (n = 22 [30.6%]) have an excellent prognosis with this regimen (EFS, OS, and DFS of 100%). The toxicity profile, in the majority, was mild and reversible. After remission induction, this regimen was administered on an outpatient basis. Single-agent As2O3, as used in this series, in the management of newly diagnosed cases of APL, is associated with responses comparable with conventional chemotherapy regimens. Additionally, this regimen has minimal toxicity and can be administered on an outpatient basis after remission induction.

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All-trans retinoic acid in acute promyelocytic leukemia: long-term outcome and prognostic factor analysis from the North American Intergroup protocol

Blood ◽

10.1182/blood-2002-02-0632 ◽

2002 ◽

Vol 100 (13) ◽

pp. 4298-4302 ◽

Cited By ~ 298

Author(s):

M. S. Tallman

Keyword(s):

Factor Analysis ◽

Retinoic Acid ◽

Prognostic Factor ◽

Promyelocytic Leukemia ◽

Term Outcome ◽

Long Term Outcome ◽

The North ◽

Trans Retinoic Acid ◽

All Trans Retinoic Acid

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

Blood ◽

10.1182/blood-2016-09-736686 ◽

2017 ◽

Vol 129 (10) ◽

pp. 1275-1283 ◽

Cited By ~ 87

Author(s):

Yasmin Abaza ◽

Hagop Kantarjian ◽

Guillermo Garcia-Manero ◽

Elihu Estey ◽

Gautam Borthakur ◽

...

Keyword(s):

Promyelocytic Leukemia ◽

Newly Diagnosed ◽

Term Outcome ◽

Long Term Outcome ◽

Trans Retinoic Acid ◽

All Trans Retinoic Acid ◽

Key Points ◽

Long Term Follow Up

Key Points The combination of ATRA and ATO, with or without GO, is effective and safe for newly diagnosed APL patients, including the high-risk subset. Long-term follow-up suggests the responses are durable, with very rare relapses.

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Very long-term outcome of acute promyelocytic leukemia after treatment with all-trans retinoic acid and chemotherapy: the European APL Group experience

Blood ◽

10.1182/blood-2009-07-233387 ◽

2010 ◽

Vol 115 (9) ◽

pp. 1690-1696 ◽

Cited By ~ 146

Author(s):

Lionel Adès ◽

Agnes Guerci ◽

Emmanuel Raffoux ◽

Miguel Sanz ◽

Patrice Chevallier ◽

...

Keyword(s):

Retinoic Acid ◽

Acute Promyelocytic Leukemia ◽

Cumulative Incidence ◽

Maintenance Treatment ◽

Promyelocytic Leukemia ◽

Long Term Results ◽

Long Term Outcome ◽

Trans Retinoic Acid ◽

All Trans Retinoic Acid

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

Blood ◽

10.1182/blood-2019-125185 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 3853-3853

Author(s):

Harinder Gill ◽

Rita Yim ◽

Cyrus R Kumana ◽

Yok-Lam Kwong

Keyword(s):

Ascorbic Acid ◽

Complete Remission ◽

Arsenic Trioxide ◽

Acute Promyelocytic Leukemia ◽

Univariate Analysis ◽

Promyelocytic Leukemia ◽

Cns Involvement ◽

Long Term Outcome ◽

First Complete Remission

Background 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 (17-96) 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]. Figure Disclosures No relevant conflicts of interest to declare.

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