Reversible cardiac dysfunction without myocytolysis related to all-trans retinoic acid administration during induction therapy of acute promyelocytic leukemia

Manna, Annunziata; Cadenotti, Luigi; Motto, Andrea; Ballo, Piercarlo

doi:10.1007/s00277-008-0552-2

Cited by 10 publications

(9 citation statements)

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“…How these animal studies relate to heart disease in humans remains largely untested. Unfortunately, in the context of acute promyelocytic leukemia, retinoic acid treatment has been associated with cardiac dysfunction in at least one case report [183]. Continuing research aimed at verifying the therapeutic potential of retinoic acid treatment in heart disease is warranted.…”

Section: Uptake Of Retinoids By Extrahepatic Tissuesmentioning

confidence: 99%

Vitamin A Metabolism: An Update

2011

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Retinoids are required for maintaining many essential physiological processes in the body, including normal growth and development, normal vision, a healthy immune system, normal reproduction, and healthy skin and barrier functions. In excess of 500 genes are thought to be regulated by retinoic acid. 11-cis-retinal serves as the visual chromophore in vision. The body must acquire retinoid from the diet in order to maintain these essential physiological processes. Retinoid metabolism is complex and involves many different retinoid forms, including retinyl esters, retinol, retinal, retinoic acid and oxidized and conjugated metabolites of both retinol and retinoic acid. In addition, retinoid metabolism involves many carrier proteins and enzymes that are specific to retinoid metabolism, as well as other proteins which may be involved in mediating also triglyceride and/or cholesterol metabolism. This review will focus on recent advances for understanding retinoid metabolism that have taken place in the last ten to fifteen years.

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Section: Uptake Of Retinoids By Extrahepatic Tissuesmentioning

confidence: 99%

Vitamin A Metabolism: An Update

2011

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“…The prevalence of retinoic syndrome while using ATRA has been reported 6% to 31%, and there are also some long‐term complications. These include myeloid sarcoma at the time of relapse , cardiac dysfunction , myelodysplastic syndromes , and secondary malignancies. New strategies using arsenic trioxide (ATO) in the treatment of new patients with APL may possibly eliminate early and late complications.…”

Section: Introductionmentioning

confidence: 99%

Induction, consolidation, and maintenance therapies with arsenic as a single agent for acute promyelocytic leukaemia in a 11‐year follow‐up

Aznab

Rezaei

2015

Hematological Oncology

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The aim of this study was to evaluate the effect of arsenic trioxide as a single agent in acute promyelocytic leukaemia cases for induction, consolidation, and maintenance therapy in a long-term, 11-year follow-up. We studied 60 patients with acute promyelocytic leukaemia. Sixty percent of the patients were aged between 12 and 24 years. Arsenic trioxide was infused at a 0.15 mg/kg daily dose until complete remission was achieved. After 2 weeks of rest, arsenic trioxide was infused daily for 28 days as a consolidation therapy. Then, arsenic infusions were given every 3-4 months for 14 days for 2 years, and the patients were followed until relapse or death. The rates of complete remission, disease-free survival, overall survival, and drug toxicity were evaluated. The morphologic complete remission was observed in 55 out of the 60 patients. The most common causes of a remission failure were early mortality because of the APL differentiation syndrome and the lack of response to arsenic treatment. The mean follow-up was 90 months. The primary outcomes for males and females were a mean disease-free survival of 101 and 97 months, respectively, and a mean overall survival of 103 and 101 months, respectively. From the 55 cases with remission, three patients died (late mortality). Of the 60 patients, 85% are still alive. Arsenic trioxide was generally well tolerated. The long-term follow-up of patients with APL, treated with arsenic alone as induction, consolidation, and maintenance therapy, shows high cure rates and excellent outcomes.

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confidence: 99%

“…59 Interestingly, reversible cardiac dysfunction related to ATRA has been reported. 60 New strategies that incorporate ATO early in the treatment of the disease possibly may obviate such complications.ATO is the single most active agent in APL. Its mechanisms include direct degradation of the PML-RAR-␣ fusion transcript, with resulting transcription of RAR-␣ target genes leading to apparent differentiation as well as growth arrest of leukemiainitiating cells by apoptosis or loss of self-renewal.…”

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How I treat acute promyelocytic leukemia

Tallman

Altman

2009

Blood

240

229

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Acute 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. (Blood. 2009; 114:5126-5135) IntroductionAcute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia (AML) with distinctive biologic and clinical features that is now highly curable. Most patients are young, present with leukopenia, and exhibit a life-threatening coagulopathy, which is the most notorious manifestation of the disease. The cells from almost all patients have a balanced reciprocal translocation between chromosomes 15 and 17, 1 which generates a fusion transcript joining the PML (promyelocyte) and RAR-␣ (retinoic acid receptor-␣) genes. 2 Leukemic promyelocytes have the unique ability to undergo differentiation with exposure to retinoic acid and both differentiation and apoptosis with exposure to arsenic trioxide (ATO). The disease is relatively rare in adults, accounting for only 10% to 15% of the approximately 13 400 adults diagnosed with AML in the United States each year. Although the incidence of APL among children with AML is similar in some series, a higher overall percentage of APL in children with AML compared with adults has been reported in others. 3 In children, the disease is often associated with a high white blood cell count (WBC Ͼ 10 000/ L), the microgranular variant (M3V), and more all-trans retinoic acid (ATRA)-related toxicities, particularly pseudotumor cerebri. 4 Intensive studies of the biology and treatment of the disease have resulted in a remarkably thorough understanding of its pathogenesis. 5 Furthermore, a cure rate of approximately 80% to 90% of patients who survive induction and achieve complete remission (CR) can be expected. 6 Yet there are nuances in the approach to patients with APL that are often overlooked, and complicated issues in treatment that remain to be studied. Here, the initial approa...

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Reversible cardiac dysfunction without myocytolysis related to all-trans retinoic acid administration during induction therapy of acute promyelocytic leukemia

Abstract: . Reversible cardiac dysfunction without myocytolysis related to all-trans retinoic acid administration during induction therapy of acute promyelocytic leukemia.

Cited by 10 publications

References 3 publications

Vitamin A Metabolism: An Update

Vitamin A Metabolism: An Update

Induction, consolidation, and maintenance therapies with arsenic as a single agent for acute promyelocytic leukaemia in a 11‐year follow‐up

How I treat acute promyelocytic leukemia

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