Long-term follow-up of homoharringtonine plus all-trans retinoic acid-based induction and consolidation therapy in newly diagnosed acute promyelocytic leukemia

All-trans retinoic acid administered orally (oral ATRA) may not regularly lead to either molecular complete remissions (CRs) or prolonged hematologic CRs (HCR) unless combined with chemotherapy. Because serum tretinoin concentrations are higher, and maintained longer, after use of liposomal-encapsulated ATRA (lipoATRA) rather than oral ATRA, we investigated lipoATRA monotherapy in newly diagnosed acute promyelocytic leukemia (APL). Patients received lipoATRA 90 mg/m2 every other day for remission induction. The same dose was given 3 times a week until 9 months had elapsed from HCR date. Treatment then stopped. Chemotherapy (idarubicin 12 mg/m2daily days 1-2 for 2 courses) was to be added only if 2 polymerase chain reaction (PCR) tests, performed 2 weeks apart, were positive at 3, 6, or 9 months from HCR date. The sensitivity level of the PCR was 10−4. We treated 18 patients (median age, 54 years; median white blood cell [WBC] count 4,500/μL). The HCR rate was 12/18 (67%, 95% confidence interval [CI], 41% to 87%). This rate was similar to that we observed in a previous study using oral ATRA + idarubicin. Nine of 10 patients studied at HCR date were PCR-positive. Subsequently, however, overall (+/− idarubicin) rates of PCR positivity were 0/12 at 3 months, 1/10 at 6 months, 1/7 at 9 and 12 months, and 0/4 at 15 to 17 months. Idarubicin has been added in 3 patients, with this addition occurring at 6 months in 2 patients and at 9 months in 1 patient. Among patients who had not received idarubicin when the PCR was evaluated, 0 of 12 were PCR-positive at 3 months, 1 of 10 was positive at 6 months, 1 of 6 was positive at 9 months, 0 of 4 were positive at 12 months, and 0 of 3 were positive at 15 to 17 months. Morphologic APL has recurred in 1 patient, with a median follow-up time of 13 months in the 11 patients remaining in first CR. The median follow-up time is 9½ months (range, 3 to 17) in the 9 patients who have received only lipoATRA and who remain PCR-negative and in first CR. Our data suggest that lipoATRA is an effective means of producing molecular CR in newly diagnosed APL.

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A single course of all-trans retinoic acid plus arsenic trioxide reached a long-term survival in a patient with newly diagnosed acute promyelocytic leukemia: a suggestion for reduction of treatment courses?

European Journal Of Haematology ◽

10.1111/ejh.12177 ◽

2013 ◽

Vol 91 (5) ◽

pp. 470-471 ◽

Cited By ~ 16

Author(s):

Jinsong Yan ◽

Xueyu Chen ◽

Jing Shao

Keyword(s):

Retinoic Acid ◽

Arsenic Trioxide ◽

Acute Promyelocytic Leukemia ◽

Promyelocytic Leukemia ◽

Newly Diagnosed ◽

Term Survival ◽

Long Term Survival ◽

Trans Retinoic Acid ◽

All Trans Retinoic Acid

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Prolonged follow-up confirms that all-trans retinoic acid followed by chemotherapy reduces the risk of relapse in newly diagnosed acute promyelocytic leukemia. The French APL Group [letter]

Blood ◽

10.1182/blood.v84.2.666.666 ◽

1994 ◽

Vol 84 (2) ◽

pp. 666-667 ◽

Cited By ~ 30

Author(s):

P Fenaux ◽

E Wattel ◽

E Archimbaud ◽

M Sanz ◽

B Hecquet ◽

...

Keyword(s):

Retinoic Acid ◽

Acute Promyelocytic Leukemia ◽

Promyelocytic Leukemia ◽

Newly Diagnosed ◽

Trans Retinoic Acid ◽

All Trans Retinoic Acid ◽

Risk Of Relapse

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Front-Line Therapy with Arsenic Trioxide/All-Trans-Retinoic Acid Combination and Chemotherapy Improves Cure Rates in Newly Diagnosed Patients with Acute Promyelocytic Leukemia

Blood ◽

10.1182/blood.v112.11.2970.2970 ◽

2008 ◽

Vol 112 (11) ◽

pp. 2970-2970

Author(s):

Jiong Hu ◽

Yuan-fang Liu ◽

Chuan-feng Wu ◽

Guang-biao Zhou ◽

Zhi-Xiang Shen ◽

...

Keyword(s):

Retinoic Acid ◽

Arsenic Trioxide ◽

Acute Promyelocytic Leukemia ◽

Promyelocytic Leukemia ◽

Newly Diagnosed ◽

Trans Retinoic Acid ◽

All Trans Retinoic Acid ◽

Healthy Donors

Abstract BACKGROUND: In this study, we analyzed the clinical benefit and safety of upfront use of all-trans-retinoic acid (ATRA), arsenic trioxide (ATO) and chemotherapy in patients with newly-diagnosed acute promyelocytic leukemia (APL) during Apr 2001 and Dec 2005. METHODS: A total of 85 patients were treated with ATRA and ATO as induction therapy, followed by consolidation/maintenance therapy composed of ATRA, ATO and chemotherapy. All patients were followed-up to evaluate the long-term efficacy and safety. RESULTS: A total of 81 (95.3%) patients entered complete remission (CR) with a median of 27 days. Among these 81 patients, 4 patients relapsed and 2 patients died from the disease with a median follow-up of 70 months (15–87). The 5-year leukemia-free survival (5-yr-LFS) and overall survival (5-yr-OS) for all patients were 89.2±3.4% and 91.7±3.0% while for patients who achieved CR (n=81), the 5-yr-LFS and 5-yr-OS were 96.2±2.1% and 96.2±2.1% respectively. With careful monitoring of in vivo arsenic levels in 33 evaluable long-term survivors, we demonstrated that the serum and urine arsenic concentrations were within safety limits, although a slight but significantly increase in arsenic levels was observed as compared to healthy donors. Overall, no obvious arsenic associated long-term toxicity was documented in these patients. CONCLUSIONS: Use of up-front ATRA/ATO/chemotherapy combination treatment in newly-diagnosed APL has proven relatively safe and has lead to a significant improvement in long-term LFS/OS.

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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 ◽

10.1182/blood.v120.21.1480.1480 ◽

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.

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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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