Meta-analysis of all-trans retinoic acid-linked arsenic trioxide treatment for acute promyelocytic leukemia
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To explore the combination therapy of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO, As2O3) on acute promyelocytic leukemia (APL).A meta-analysis of six studies was performed. Among 415 included cases, 165 cases were in the ATRA + ATO group, 129 cases in the ATRA-alone group, and 121 cases in the ATO-alone group. The complete remission (CR) rate and incidences of three groups were compared, respectively, between the therapies of ATRA + ATO with ATRA-alone, ATRA + ATO with ATO-alone, and ATRA with ATO.The assessment results showed that ATRA + ATO therapy significantly improved the CR rate and decreased the incidences of cutaneous reaction compared with ATRA-alone (P < 0.05). However, incidence of liver injury was higher in the ATRA + ATO and ATO-alone groups than that in ATRA-alone group (P < 0.05). Difference in the complications between ATRA + ATO therapy and ATO-alone was not significant (P > 0.05).In conclusion, we suggest low-dose ATRA and ATO combination therapy may be more effective for the treatment of APL.Keywords:
Arsenic Trioxide
Tretinoin
Abstract The use of arsenic trioxide (As 2 O 3 , ATO) combined with all‐trans retinoic acid (ATRA) has recently been reported to induce remission in patients with acute promyelocytic leukemia (APL). However, its efficiency remains inconclusive mainly due to the small number of the available cases. In this study, therefore, we present a clinical study using a combination of ATO with low‐dose ATRA (LD‐ATRA) to treat 108 APL patients (80 newly diagnosed patients, 28 relapsed patients). Therapeutic outcomes using the ATO/LD‐ATRA approach were compared with those of APL patients treated either with ATO alone (65 patients) or ATRA alone (51 patients). The results showed that the ATO/LD‐ATRA approach provided significantly better therapeutic outcomes as compared to either ATO or ATRA alone, as evidenced by lower mortality, a higher CR rate and a reduced period to CR. In addition, the toxic side‐effects have been no worse with the combined ATO/LD‐ATRA treatment than with either ATO or ATRO alone and in some cases have been reduced. These data suggest that the ATO/LD‐ATRA regimen is superior to either regimen given alone to patients with APL. Copyright © 2004 John Wiley & Sons, Ltd.
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Objective To observe the eficacy and side efect of the all-trans retinoic acid (ATRA)and arsenic trioxide(As2O3)combination in acute promyeloeytic leukemia (APL). Methods Thirty-eight APL pa tients were treated with the ATRA and As2O3 combination. ATRA was given 25 mg/m2 every day and As2O3 was given 0. 16 mg/(kg · d). Doses were adjusted according to adverse effects. Results Thirty-four patients a chieved complete remission(CR) ,the CR rate was 89.5％. The time to achieve CR was(24. 4 ± 5.2)d. Two patients died due to intracranial hemorrhage. Conclusion The ATRA and As2O3 in the treatment of APL can obtain a higher CR rate and a shorter duration for achieving CR.
Key words:
Retinoic acid; Arsenic trioxide; Leukemia; Promyelocytic; Acute
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Objective the clinical effects of arsenic trioxide in previously untreated patients of acute promyelocytic leukemia. Methods As2O3 was given to twenty-two previously untreated patients, and DA regimens were used as maintenance treatment. Continual complete remission and adverse effects were followed. Results complete remission rate was 81.8%. The longest survival time was five years. Conclusions arsenic trioxide is effective in the treatment of APL.
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To summarize limitations involved in arsenic trioxide therapeutic effects in acute promyelocytic leukemia, because current studies show that some individuals of acute promyelocytic leukemia have relatively poor outcomes during treatment with arsenic trioxide.Most relevant articles were included in the PubMed database between 2000 and 2013 with the keywords "acute promyelocytic leukemia," "arsenic trioxide," "thiol" or "methylation." In addition, a few older articles were also reviewed.Data and articles related to arsenic trioxide effect in acute promyelocytic leukemia treatment were selected and reviewed. We developed an overview of limitations associated with arsenic trioxide therapeutic effect.This review focuses on the researches about the arsenic trioxide therapeutic effect in acute promyelocytic leukemia and summarizes three mainly limitations which can influence the arsenic trioxide therapeutic effect to different degrees. First, with the combination of arsenic and glutathione the therapeutic effect and cytotoxicity decrease when glutathione concentration increases; second, arsenic methylation, stable arsenic methylation products weaken the apoptosis effect of arsenic trioxide in leukemia cells; third, gene mutations affect the sensitivity of tumor cells to arsenic trioxide and increase the resistance of leukemia cells to arsenic trioxide.The chief limitations are listed in the review. If we can exclude all of them, we can obtain a better therapeutic effect of arsenic trioxide in patients with acute promyelocytic leukemia.
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Objective:To observe the arsenic trioxide (As2O3) combined with alltransretinoic acid (ATRA) treatment of acute promyelocytic leukemia (APL) of the efficacy and toxicity.Methods: 21 patients with acute promyelocytic leukemia (APL) patients with doubleAs2O3 combined ATRA induction therapy,patients with high white blood cell with a single chemotherapy drug third year plus tipshirt ester base (H) or daunorubicin (DNR).Results:In 21 patients,19 cases of complete remission,complete remission (CR) rate of 90.47%;1 patient died of intracranial hemorrhage.Conclusion:arsenic trioxide combined with alltrans retinoic acid treatment of acute promyelocytic leukemia precise and well tolerated in patients.
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Objective To study the effect of all-trans retinoic acid(ATRA)combined with arsenic trioxide for acute promyelocytic leukemia.Methods 24 cases were selected who had been diagnosed with acute promyelocytic leukemia,by the way of clinical diagnosis,blood,bone marrow,cell immunity,cellular genetics and other tests.One group was treated with ATRA combined with arsenic trioxide,another group was treated with arsenic trioxide.Clinical effective was compared between two groups.Results Laboratory parameters and complete remission rate of combined group were better than monotherapy group,there was significant difference between two groups(P0.05).Conclusion ATRA pluses arsenic trioxide for acute promyelocytic leukemia,can increase complete remission rate and survival rate,which is an effective treatment method.
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Chinese clinical investigators in 1986 demonstrated the therapeutic potential of tretinoin and in 1992 that of arsenic trioxide in the treatment of acute promyelocytic leukaemia. These observations have been confirmed in European and American centres. In acute promyelocytic leukaemia there is an abnormal receptor for retinoids, designated PML/RAR-alpha. This receptor binds retinoids inadequately so that extra retinoids (in the form of tretinoin) are required to restart the normal cellular maturation, after which the promyelocytes can mature into granulocytes. Arsenic trioxide has a different mode of action, possibly related to its effects on sulfhydryl-rich proteins, resulting in dysplastic leukaemic promyelocytes, ending up in apoptotic cell death. Since 1990 tretinoin has been included worldwide in the treatment of acute promyelocytic leukaemia. The use of arsenic trioxide has not yet been included in treatment protocols for promyelocytic leukaemia in western medicine.
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Objective: To observe the clinical efficacy of the chemotherapy regimen with all-trans retinoic acid(ATRA) combined with arsenic trioxide in adult patients with acute promyelocytic leukemia.Methods: The clinical data of 32 newly diagnosed patients with acute promyelocytic leukemia were retrospectively analyzed,and the remission rate,early mortality rate,and complications were compared between the cases treated with ATRA(ATRA group) and the patients treated with ATRA combined with srsenic trioxide(combination group).Results: The difference in remission rate was not significant between two groups,but the time required for complete remission in combination group was significantly shorter than in ATRA group.Conclusion: For the patients with acute promyelocytic leukemia,the clinical efficacy of ATRA combined with arsenic trioxide is better than that of ATRA.ATRA combined with arsenic trioxide chemotherapy regimen is worthy of promotion.
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