scholarly journals Acute Promyelocytic Leukemia in Children: A Model of Precision Medicine and Chemotherapy-Free Therapy

2021 ◽  
Vol 22 (2) ◽  
pp. 642
Author(s):  
Carmelo Gurnari ◽  
Maria Teresa Voso ◽  
Katia Girardi ◽  
Angela Mastronuzzi ◽  
Luisa Strocchio
Keyword(s):  
Precision Medicine ◽  
Acute Promyelocytic Leukemia ◽  
Survival Rates ◽  
Early Death ◽  
Pseudotumor Cerebri ◽  
Promyelocytic Leukemia ◽  
All Trans Retinoic Acid ◽  
Free Treatment ◽  
Leukemia In Children

Acute promyelocytic leukemia (APL) represents a paradigm of precision medicine. Indeed, in the last decades, the introduction of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) completely revolutionized the therapeutic approach to this previously highly fatal disorder. This entirely chemotherapy-free treatment, which provided excellent survival rates, has been initially validated in adults and, recently, translated in the pediatric setting. This review summarizes currently available data on the use of ATRA and ATO combination in pediatric APL, providing a particular focus on peculiar issues and challenges, such as the occurrence of pseudotumor cerebri and death during induction (early death), as well as the advantage offered by the ATO/ATRA combination in sparing long-term sequelae.

Outcome of Childhood Acute Promyelocytic Leukemia With All-Trans-Retinoic Acid and Chemotherapy

2004 ◽  
Vol 22 (8) ◽  
pp. 1404-1412 ◽  
Author(s):  
S. de Botton ◽  
V. Coiteux ◽  
S. Chevret ◽  
C. Rayon ◽  
E. Vilmer ◽  
...  
Keyword(s):  
Overall Survival ◽  
Retinoic Acid ◽  
Acute Promyelocytic Leukemia ◽  
Survival Rates ◽  
Age Groups ◽  
Pseudotumor Cerebri ◽  
Promyelocytic Leukemia ◽  
Results Of Treatment ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid

Purpose To determine the results of treatment combining all-trans-retinoic acid (ATRA) and chemotherapy (CT) in childhood acute promyelocytic leukemia (APL). Patients and Methods Children (< 18 years) with newly diagnosed APL were included in the APL93 trial, treated by ATRA followed or combined with daunorubicin-cytarabine, and then randomly assigned between no maintenance, intermittent ATRA, continuous CT, or both. Results Of the 576 patients included in APL93 trial, 31 (5%) were children, including 22 girls (71%) and nine boys (29%). Thirty of the children (97%) obtained complete remission (CR). ATRA syndrome occurred in four children (13%), who all achieved CR, and headaches occurred in 12 children (39%), with signs of pseudotumor cerebri in five children (16%). Seven patients (23%) relapsed. None of the eight patients who received both ATRA and CT for maintenance relapsed. All relapsing patients achieved a second CR. Twenty-two patients remained in first CR after 43+ to 96+ months, six remained in second CR after 17+ to 66+ months, and three patients had died. The 5-year event-free survival (EFS), relapse, and overall survival rates were 71%, 27%, and 90%, respectively. No difference between adults and children included in the APL93 trial was seen for CR rate, 5-year relapse rate, EFS, and overall survival, but significantly better survival was seen in children after adjustment on WBC counts (P = .02) and incidence of microgranular M3 variant (P = .04). Conclusion ATRA combined with CT for induction and also probably for maintenance provides as favorable results in children with APL as in adults and currently constitutes the reference first-line treatment in both age groups.

scholarly journals ACUTE PROMYELOCYTIC LEUKEMIA IN CHILDREN: A SINGLE CENTRE EXPERIENCE FROM TURKEY

2018 ◽  
Vol 10 (1) ◽  
pp. e2018045 ◽  
Author(s):  
Tekin Aksu
Keyword(s):  
Acute Promyelocytic Leukemia ◽  
Death Rate ◽  
Clinical Symptoms ◽  
Early Death ◽  
Pseudotumor Cerebri ◽  
Promyelocytic Leukemia ◽  
Severe Bleeding ◽  
Pediatric Hematology ◽  
All Trans Retinoic Acid ◽  
Problem Awareness

Background and objectives: Acute promyelocytic leukemia (APL), characterized by tendency to hemorrhage and excellent response to all-trans retinoic acid (ATRA), is a distinct subtype of acute myeloid leukemia (AML). In this retrospective study, we aimed to determine the incidence, clinical symptoms, toxicities and outcome of children with APL in our center. Methods: We retrospectively reviewed the medical records of children (age < 18 years) diagnosed with APL at our pediatric hematology department between January 2006-December 2016.Results: Pediatric APL represents 20.5% of AML cases in this cohort. Most of the cases presented as classical M3, albeit hypogranular variant was described in 12% of the cohort. Patients with hypogranular variant APL were differed from classical APL by co-expression of CD2 and CD34. About ¾ of APL patients had hemorrhagic findings at admission or at initial phase of the treatment. Severe bleeding manifested as intracranial hemorrhage was present in three patients and intracranial arterial thrombosis was present in one. Five patients showed side effects of ATRA such as pseudotumor cerebri, dilated cardiomyopathy, and pulmonary infiltrates. Six year overall survival (OS) and early death rate was found to be 82.5% and 12% respectively.Conclusions: A high frequency (20.5%) of APL was noted among children with AML in this single center study. The overall mortality rate was 17.5%. Since the induction death rate was 12% and life threatening bleeding was the major problem, awareness and urgent treatment are critical factors to reduce early losses.

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.

scholarly journals Real-life outcomes of unselected acute promyelocytic leukemia patients: a single-center 14-year experience

2020 ◽  
Vol 58 (3) ◽  
pp. 138-145
Author(s):  
Omer Faruk Akcay ◽  
Haci Hasan Yeter ◽  
Yahya Buyukasik
Keyword(s):  
Acute Promyelocytic Leukemia ◽  
Survival Rates ◽  
Real Life ◽  
Disease Free Survival ◽  
Early Death ◽  
Population Based ◽  
Promyelocytic Leukemia ◽  
Term Survival ◽  
Probability Of Survival ◽  
All Trans Retinoic Acid

AbstractBackground. After the inclusion of all-trans retinoic acid (ATRA) into the treatment of Acute Promyelocytic leukemia (APL), a notable improvement concerning the survival rates of patients with APL has been observed. However, the population-based studies demonstrated that there was no marked improvement in the survival of patients after the 2000s. We aim to describe the clinical response and prognosis of adult patients diagnosed with APL and examine the change in these outcomes by the time period of diagnosis.Methods. We retrospectively reviewed thirty-six unselected APL patients who were diagnosed between September 2003 and February 2016.Results. The probability of survival at two years was 58%, while disease-free survival (DFS) was 87%. The overall early death (ED) rate was 33% and remain stable over time [42% in 2003–2009 vs. 24% in 2010–2016 (p=.20)]. In addition, the 2-year overall survival (OS) rates were 47% in 2003–2009 and 70% in 2010–2016 (p=.29), and no differences were noted. Univariate analyses showed possible predictors of poor OS were defined as leukocytosis (≥10x109/L), high Sanz score, hemorrhage, infection, disseminated intravascular coagulopathy (DIC) at presentation and microgranular morphologic subtype.Conclusions. This study shows that long-term survival remains low in APL patients, particularly related to a high ED rate. Initiatives to reduce ED are exceedingly substantial for improving the survival in APL.

scholarly journals Acute promyelocytic leukemia: preventing early complications and late toxicities

Hematology ◽  
2016 ◽  
Vol 2016 (1) ◽  
pp. 10-15 ◽  
Author(s):  
Sameem Abedin ◽  
Jessica K. Altman
Keyword(s):  
Acute Myeloid Leukemia ◽  
Acute Promyelocytic Leukemia ◽  
Myeloid Leukemia ◽  
Early Death ◽  
Promyelocytic Leukemia ◽  
Early Complications ◽  
Younger Patients ◽  
Success Stories ◽  
Acute Myeloid

Abstract Acute promyelocytic leukemia (APL) is a unique subtype of acute myeloid leukemia (AML), which presents with a distinct coagulopathy. Therapeutic advances have made APL one of the true success stories in oncology, transforming this once lethal disease into the most curable form of AML. For many patients, cure will now be achieved without the use of chemotherapy. It is hoped that limiting chemotherapy will reduce mortality even further, particularly among more vulnerable older adults whose survival lagged behind that of younger patients. It should be noted that early death persists in patients with APL and continues to negatively affect survival. Further, among survivors treated with chemotherapy or even arsenic trioxide (ATO), there remains the potential for long-term toxicities that must be monitored. Understanding the management of these issues is an important complement to ensure maximal survival for patients with APL.

scholarly journals All-trans-retinoic acid–induced pseudotumor cerebri in acute promyelocytic leukemia

2014 ◽  
Vol 05 (03) ◽  
pp. 273-275
Author(s):  
T. M. Anoop ◽  
Nidhi Jain ◽  
Sreejith G. Nair ◽  
Geetha Narayanan
Keyword(s):  
Retinoic Acid ◽  
Acute Promyelocytic Leukemia ◽  
Induction Therapy ◽  
Treatment Strategy ◽  
Pseudotumor Cerebri ◽  
Promyelocytic Leukemia ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid

ABSTRACTAll-trans-retinoic acid is an integral part in the treatment strategy of acute promyelocytic leukemia (APL). Here we describe a case of pseudotumor cerebri associated with all-trans-retinoic acid (ATRA) during the induction therapy in an adult with acute promyelocytic leukemia (APL).

Pseudotumor Cerebri Associated with All-Trans Retinoic Acid Treatment During Induction Therapy for Acute Promyelocytic Leukemia: A Case Report and Literature Review

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4264-4264
Author(s):  
Dylan Holmes ◽  
David M. Aboulafia
Keyword(s):  
Retinoic Acid ◽  
Intracranial Pressure ◽  
Literature Review ◽  
Acute Promyelocytic Leukemia ◽  
Pseudotumor Cerebri ◽  
Promyelocytic Leukemia ◽  
Induction Treatment ◽  
Fluid Composition ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid

Abstract Abstract 4264 Pseudotumor cerebri (PC) is a rare disorder characterized by elevated intracranial pressure with normal cerebrospinal fluid composition, normal cranial imaging findings, and symptoms and signs of increased intracranial pressure. A number of medications have been linked to PC including vitamin A and its derivative all-trans-retinoic acid (ATRA). Herein, we describe the case of a 38-year-old woman who was diagnosed with PC during standard induction treatment for acute promyelocytic leukemia (APL). Her neurologic complaints of severe headache and diplopia improved slightly after ATRA was discontinued and she was treated with acetazolamide, but symptoms did not abate until fluconazole was held five days later. Through a literature review, we identified 41 case reports of APL patients with ATRA-associated PC, 23 of which provided details of clinical presentation and follow-up. The median age at diagnosis of PC was 27 for females and 16 for males; the female-to-male ratio was 1.3:1. All 23 patients complained of headache; papilledema was present in all 21 instances (100%) where a retinal exam was described. ATRA was held due to PC in 20 cases (87%), and neurologic symptoms resolved without further intervention in 7 of 20 (35%). The remaining 13 patients were treated with diuretics (11 of 13 cases, 85%), high-volume lumbar punctures (5, 38%), corticosteroids (4, 31%), and/or analgesics (3, 23%). Including our index patient, eight patients were rechallenged with ATRA after neurologic improvement, and 5 (63%) required further interventions to resolve recrudescent symptoms. We identified one other patient whose neurologic complaints persisted despite dose reductions in ATRA. This patient improved only after fluconazole was discontinued. Because both ATRA and fluconazole are metabolized by the cytochrome P-450 system, we suggest that if taken concurrently, they may exacerbate the risk of PC. Physicians should be aware of this interaction between ATRA and fluconazole and consider discontinuing both fluconazole and ATRA in APL patients who develop PC. Disclosures: No relevant conflicts of interest to declare.

scholarly journals 4-Oxo Retinoic Acid for Refractory Acute Promyelocytic Leukemia in Children with All-Trans Retinoic Acid Therapy.

1995 ◽  
Vol 41 (4) ◽  
pp. 493-498 ◽  
Author(s):  
Kimitaka TAKITANI ◽  
Hiroshi TAMAI ◽  
Takao MORINOBU ◽  
Naohisa KAWAMURA ◽  
Munenori MIYAKE ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Acute Promyelocytic Leukemia ◽  
Promyelocytic Leukemia ◽  
Acid Therapy ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Leukemia In Children

scholarly journals EPIDEMIOLOGY, DIAGNOSIS AND TREATMENT OF ACUTE PROMYELOCYTIC LEUKEMIA IN CHILDREN: THE EXPERIENCE IN CHINA

2012 ◽  
Vol 4 (1) ◽  
pp. e2012012 ◽  
Author(s):  
Li Zhang ◽  
Xiaofan Zhu
Keyword(s):  
Developing Countries ◽  
Treatment Failure ◽  
Acute Promyelocytic Leukemia ◽  
Promyelocytic Leukemia ◽  
Early Mortality ◽  
Term Survival ◽  
The Status ◽  
Treatment Abandonment ◽  
Leukemia In Children

The limited available data suggest that the rate of early mortality is high and that long-term survival is poor in many developing countries. Death from bleeding and infection during chemotherapy, relapse and treatment abandonment are among the main cause of treatment failure in APL children. The status of children APL treatment in China is not described in general.

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