tretinoin and Renal-Insufficiency

With the introduction of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) acute promyelocytic leukemia (APL) has become from a detrimental to one of the most curable malignant diseases in humans. In particular, the chemotherapy-free regimen with ATO/ATRA has been proven to be highly effective in de novo APL and has become standard first-line therapy in younger adult, non-high-risk patients. Nevertheless, early death is still a major issue in APL, particularly in older patients, emphasizing the need of rapid diagnostics and supportive care together with immediate access to ATRA-based therapy. Despite the dramatic progress achieved in therapy of APL challenging situations occur, particularly in patients excluded from controlled studies with clinical knowledge mainly based on case reports and registries. Rapid identification and treatment of newly diagnosed patients as well as the management of toxicities and complications remain challenging. We offer up-to-date information and guidance regarding treatment of APL. Based on a literature review of existing scientific evidence we also discuss the approach to high-risk, elderly, pregnant and pediatric patients, treatment in patients with renal failure as well as of therapy-related or relapsed/refractory APL.

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Arsenic Trioxide; Electrocardiography; Female; Fetus; Humans; Induction Chemotherapy; Leukemia, Promyelocytic, Acute; Leukocytosis; Neoplasms, Second Primary; Pregnancy; Recurrence; Renal Dialysis; Renal Insufficiency; Tretinoin

The introduction of treatment with tretinoin (all-trans retinoic acid) and its combination with antineoplastic therapy has improved the outcome of acute promyelocytic leukaemia (APL). Retinoic acid syndrome is the major adverse effect of tretinoin and it occurs in about 25% of treated APL patients in the absence of prophylactic measures and is often fatal. Generally, the retinoic acid syndrome is associated with increasing leucocyte counts and is probably caused by the release of several cytokines by maturing blast cells. The retinoic acid syndrome gives a clinical picture of bodyweight gain, respiratory distress, serous effusions and cardiac and renal failure. Adequate prophylaxis, based on the addition to tretinoin of dexamethasone and also, according to most authors, antineoplastic therapy (in case of rapidly increasing leucocyte counts) has decreased the incidence of retinoic acid syndrome to about 15%. Most importantly, these measures have reduced its mortality to about 1% of all treated patients.

Topics: Anti-Inflammatory Agents; Antineoplastic Agents; Clinical Trials as Topic; Cytokines; Dexamethasone; Heart Failure; Humans; Infant, Newborn; Leukemia, Promyelocytic, Acute; Leukocyte Count; Renal Insufficiency; Respiratory Distress Syndrome, Newborn; Syndrome; Tretinoin; Weight Gain

Topics: Adult; Cholestasis, Intrahepatic; Disseminated Intravascular Coagulation; Humans; Leukemia, Promyelocytic, Acute; Male; Renal Insufficiency; Tretinoin

1. Prenatal alcohol exposure impairs kidney development, resulting in a reduced nephron number. However, the mechanism through which alcohol acts to disrupt renal development is largely unknown. Retinoic acid (RA) is critically involved in kidney development and it has been proposed that a diminished concentration of RA is a contributing factor to fetal alcohol syndrome. 2. In the present study we proposed that the ethanol-induced inhibition of ureteric branching morphogenesis and glomerular development in the cultured rat kidney would be ameliorated by coculture with exogenous RA and that examining the expression profile of key genes involved in the development of the kidney would provide insights into the potential molecular pathways involved. 3. Whole rat metanephroi cultured in the presence of exogenous RA (10-20 nmol/L) without ethanol appeared larger and had significantly more ureteric branch points, tips and glomeruli than metanephroi cultured in control media. Those cultured in the presence of ethanol alone (0.2%) had 20% fewer ureteric branch points, tips and glomeruli, which was ameliorated by coculture with retinoic acid. 4. Gene expression analysis identified changes in the expression of enzymes involved in the metabolism of alcohol in conjunction with changes in key regulators of kidney development, including cRET. 5. These results demonstrate that the teratogenic effects of alcohol in vitro on kidney development resulting in reduced ureteric branching morphogenesis and glomerular development can be ameliorated through coculture with RA. These results provide the foundation for future research into the mechanism through which alcohol acts to disrupt kidney development.

Topics: Animals; Ethanol; Female; Fetal Alcohol Spectrum Disorders; Gene Expression Profiling; Gene Expression Regulation, Developmental; Glial Cell Line-Derived Neurotrophic Factor; Kidney; Kidney Glomerulus; Organ Culture Techniques; Organogenesis; Osmolar Concentration; Pregnancy; Protective Agents; Proto-Oncogene Proteins c-ret; Random Allocation; Rats; Rats, Sprague-Dawley; Renal Insufficiency; Retinoid X Receptor alpha; Teratogens; Tretinoin

All trans retinoic acid (ATRA) combined with chemotherapy has become the mainstay of treatment for patients with acute promyelocytic leukemia (APL). Renal dysfunction (RD) is commonly seen in patients with APL. We describe a patient with APL and multi-organ failure, who was on chronic veno-venous hemofiltration followed by hemodialysis (HD) and later peritoneal dialysis (PD), who received ATRA. ATRA levels were assessed as the body clearance of ATRA in children on HD and/or PD was unknown. Neither HD nor PD significantly affected ATRA levels, suggesting that dose modifications of ATRA may not be necessary for children with these forms of renal replacement therapy.

Topics: Administration, Oral; Antineoplastic Combined Chemotherapy Protocols; Child, Preschool; Dose-Response Relationship, Drug; Drug Administration Schedule; Follow-Up Studies; Humans; Leukemia, Promyelocytic, Acute; Male; Multiple Organ Failure; Renal Dialysis; Renal Insufficiency; Treatment Outcome; Tretinoin

Topics: Acute Disease; Adult; Bilirubin; Hepatomegaly; Humans; Leukemia, Promyelocytic, Acute; Male; Renal Insufficiency; Transaminases; Tretinoin