scholarly journals ACUTE PROMYELOCYTIC LEUKEMIA (APL): COMPARISON BETWEEN CHILDREN AND ADULTS

2014 ◽  
Vol 6 (1) ◽  
pp. e2014032 ◽  
Author(s):  
Anna Maria Testi ◽  
Francesco Lococo
Keyword(s):  
Acute Promyelocytic Leukemia ◽  
Low Dose ◽  
Adult Population ◽  
Promyelocytic Leukemia ◽  
Multicenter Trials ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Adults And Children ◽  
Cure Rates ◽  
Low Dose Chemotherapy

The outcome of adults and children with Acute Promyelocytic Leukemia (APL) has dramatically changed since the introduction of all trans retinoic acid (ATRA) therapy. Based on the results of several multicenter trials, the current recommendations for the treatment of patients with APL include ATRA and anthracycline-based chemotherapy for the induction of remission and for consolidation, and ATRA combined with low-dose chemotherapy for maintenance. This has improved the prognosis of APL by increasing the complete remission (CR) rate, actually > 90%, decreasing the induction deaths and by reducing the relapse rate, leading to cure rates nowadays exceeding  80% considering both adults and children1-9. More recently the combination of ATRA and arsenic trioxide (ATO) as induction and consolidation therapy has been shown to be at least not inferior and possibly superior to ATRA plus chemotherapy in adult patients with APL conventionally defined as non-high risk (Sanz score)10. Childhood APL has customarily been treated on adult protocols. Data from several trials have shown that the overall outcome in pediatric APL appears similar to that reported for the adult population, however some clinical and therapeutic aspects differ in the two cohorts which require some important considerations and treatment adjustments.

Modern Approaches to Treating Acute Promyelocytic Leukemia

2011 ◽  
Vol 29 (5) ◽  
pp. 495-503 ◽  
Author(s):  
Miguel A. Sanz ◽  
Francesco Lo-Coco
Keyword(s):  
Acute Promyelocytic Leukemia ◽  
Promyelocytic Leukemia ◽  
Virtual Absence ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Improved Outcomes ◽  
Experimental Trials ◽  
Cure Rates ◽  
Standard Risk

The advent of all-trans-retinoic acid (ATRA) and its combination with anthracycline-containing chemotherapy have contributed in the past 2 decades to optimize the antileukemic efficacy in acute promyelocytic leukemia (APL), leading to complete remission rates greater than 90%, virtual absence of resistance, and cure rates of nearly 80%. Recently reported studies from large cooperative trials have also shown that more rational delivery of treatment and improved outcomes may derive from the use of risk-adapted protocols. In particular, patients at higher risk of relapse (ie, those presenting with WBC > 10 × 109/L) seem to benefit from treatments that include cytarabine in the ATRA-plus-chemotherapy scheme, whereas patients with standard-risk disease can be successfully managed with less-intensive regimens that contain ATRA and anthracycline-based chemotherapy. After the outstanding results with arsenic trioxide (ATO) in the treatment of APL relapse, several experimental trials have been designed to explore the role of ATO in front-line therapy with the aim not only of minimizing the use of chemotherapy but also to reinforce standard ATRA-plus-chemotherapy regimens and additionally improve therapeutic efficacy. In this review article, we discuss most recent advances in the treatment of patients with newly diagnosed and relapsed APL.

Risk-adapted treatment of acute promyelocytic leukemia with all-trans retinoic acid and anthracycline monochemotherapy: long-term outcome of the LPA 99 multicenter study by the PETHEMA Group

Blood ◽  
2008 ◽  
Vol 112 (8) ◽  
pp. 3130-3134 ◽  
Author(s):  
Miguel A. Sanz ◽  
Pau Montesinos ◽  
Edo Vellenga ◽  
Consuelo Rayón ◽  
Javier de la Serna ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Acute Promyelocytic Leukemia ◽  
Disease Free Survival ◽  
Promyelocytic Leukemia ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Low Dose Chemotherapy ◽  
High Degree

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.

Pharmacokinetics of all-trans retinoic acid in adults and children with acute promyelocytic leukemia

2006 ◽  
Vol 81 (9) ◽  
pp. 720-721 ◽  
Author(s):  
Kimitaka Takitani ◽  
Maki Koh ◽  
Akiko Inoue ◽  
Chihiro Kawakami ◽  
Tomoko Kuno ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Acute Promyelocytic Leukemia ◽  
Promyelocytic Leukemia ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Adults And Children

How I treat acute promyelocytic leukemia

Blood ◽  
2009 ◽  
Vol 114 (25) ◽  
pp. 5126-5135 ◽  
Author(s):  
Martin S. Tallman ◽  
Jessica K. Altman
Keyword(s):  
Acute Promyelocytic Leukemia ◽  
Myeloid Leukemia ◽  
Malignant Disease ◽  
Standard Of Care ◽  
Promyelocytic Leukemia ◽  
Newly Diagnosed ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Low Dose Chemotherapy ◽  
Near Future

AbstractAcute promyelocytic leukemia is the first malignant disease highly curable with targeted therapy directed at a unique molecular abnormality. The characteristic bleeding diathesis is the most notorious manifestation of the disease, which historically has accounted for a high mortality rate during induction. Acute promyelocytic leukemia is one of the few hematologic diseases that must be recognized under the microscope by the practicing hematologist because early institution of all-trans retinoic acid (ATRA) at the first suspicion of the disease before confirmation of the diagnosis and aggressive blood product support are critical to reduce early mortality. ATRA plus anthracycline-based chemotherapy for induction and consolidation followed by maintenance ATRA with low-dose chemotherapy is currently the standard of care. However, the combination of ATRA and arsenic trioxide, with minimal chemotherapy to control leukocytosis, is very effective therapy for newly diagnosed patients. This combination may replace conventional approaches for most, if not all, patients in the very near future. Acute promyelocytic leukemia should be considered in any patient with newly diagnosed acute myeloid leukemia because the treatment is urgent and different from all other subtypes.

scholarly journals Early mortality and the retinoic acid syndrome in acute promyelocytic leukemia: impact of leukocytosis, low-dose chemotherapy, PMN/RAR-alpha isoform, and CD13 expression in patients treated with all-trans retinoic acid

Blood ◽  
1994 ◽  
Vol 84 (11) ◽  
pp. 3843-3849 ◽  
Author(s):  
L Vahdat ◽  
P Maslak ◽  
WH Jr Miller ◽  
A Eardley ◽  
G Heller ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Low Dose ◽  
Leukocyte Count ◽  
Promyelocytic Leukemia ◽  
Early Mortality ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Leukocyte Counts ◽  
Low Dose Chemotherapy ◽  
Retinoic Acid Syndrome

All-trans retinoic acid (RA) has proven a major advance in the treatment of acute promyelocytic leukemia (APL). However, the proper management of patients who present with or develop leukocytosis during remission induction with all-trans RA is not established, nor is there a clear relation between leukocytosis and the development of the retinoic acid syndrome. We reviewed the course of our patients who underwent induction with all-trans RA to identify potential factors that might predict for the development of this syndrome and to identify which patients, if any, might specifically benefit from additional treatment with cytotoxic chemotherapy. Seventy-eight courses of all- trans RA therapy were administered to patients with a molecular diagnosis of APL. Initial and peak leukocyte counts, their rate of rise, leukocyte count criteria developed in Europe, and cell surface marker expression were all analyzed relative to subsequent development of both the RA syndrome as well as all causes of early mortality. The outcome of patients who received specific treatment for retinoid- induced leukocytosis was also examined. No factor was found to consistently predict for the development of the RA syndrome. Although the occurrence of the syndrome was positively associated with the peak value of the peripheral blood leukocyte count (P = .001), neither the initial leukocyte count nor the rate of rise in leukocyte counts on days preceding onset of the syndrome were sufficiently well-correlated to be clinically useful (P = .21). The leukocyte count criteria developed in Europe had a sensitivity of 62%, a specificity of 69%, and a positive predictive value that ranged from only 44% to 72%. However, we unexpectedly found that basal expression of CD13 (aminopeptidase N), a cell surface enzyme previously linked to tumor cell invasion and an inferior outcome in patients with acute myeloid leukemia, was highly associated with both development of the syndrome (P < .05) as well as an elevated leukocyte count (P = .006). Neither low-dose chemotherapy nor leukapheresis prevented development of the syndrome nor ameliorated its effects. In fact, 9 of 11 patients who received these interventions sustained fatal or near-fatal events, most of which were due to hemorrhage. However, early treatment with a short-course of high-dose corticosteroids halted progression of the syndrome in most cases. Finally, we found that expression of the type “A” isoform of PML/RAR- alpha (also known as bcr3 or “short”) was associated with a significantly shorter duration of relapse-free and overall survival (P = .005).(ABSTRACT TRUNCATED AT 400 WORDS)

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.

Hypercalcemia associated with the interaction between all trans retinoic acid and posaconazole in an acute promyelocytic leukemia case

2021 ◽  
pp. 107815522110078
Author(s):  
Hacer Berna Afacan Ozturk ◽  
Murat Albayrak ◽  
Senem Maral ◽  
Merih Reis Aras ◽  
Fatma Yilmaz ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Acute Promyelocytic Leukemia ◽  
Serum Calcium ◽  
Promyelocytic Leukemia ◽  
Cytochrome P450 Enzymes ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Normal Ranges ◽  
Rare Side Effect ◽  
High Level

Introduction All-trans retinoic acid (ATRA) is a physiological metabolite of vitamin A and it is used for the treatment of acute promyelocytic leukemia (APL). Hypercalcemia is a rare side effect of ATRA and it may be potentiated after interaction of ATRA with azole group antifungals. Herein, we have reported an APL case with hypercalcemia that is caused by the interaction of ATRA and posaconazole. Case Report A 49-year-old female patient was diagnosed as APL after the examinations performed upon the detection of pancytopenia when she had presented with the complaints of widespread bruising and fever. After the initiation of posaconazole and ATRA, her serum calcium levels begin to increase (10.3 to 11.1mg/dl). Her vitamin D level was 21.9 ng/ml and PTH 17.8 pg/ml, both were in the normal ranges. The Drug Interaction Probability Scale score of our case was calculated as 6, indicating that the probable adverse drug reaction. Therefore, the high level of serum calcium was attributed to the interaction between ATRA and posaconazole. Management & Outcome Although hypercalcemia with ATRA and other antifungal agents have been previously reported in the literature, this is the first report of hypercalcemia with the concomitant use of ATRA and posaconazole. Discussion This case highlights the importance of monitoring ATRA’s side effects when it is used in combination with drugs inhibiting the cytochrome P450 enzymes. In conclusion, the concomitant use of posaconazole and ATRA may lead to hypercalcemia and serum calcium levels return to normal ranges with the discontinuation of these drugs.

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