tretinoin has been researched along with Syndrome* in 140 studies
18 review(s) available for tretinoin and Syndrome
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Differentiation syndrome in acute promyelocytic leukaemia.
Acute promyelocytic leukaemia differentiation syndrome (APL DS) is seen when patients with APL are treated with all-trans retinoic acid (ATRA) and/or arsenic trioxide (ATO). Presenting symptoms are varied but frequently include dyspnoea, unexplained fever, weight gain >5 kg, unexplained hypotension, acute renal failure and a chest radiograph demonstrating pulmonary infiltrates or pleural or pericardial effusion. Immediate treatment with steroids at the first clinical suspicion is recommended and ATRA/ATO should be stopped in severe cases or if there is no response to treatment. The utility of steroid prophylaxis in order to prevent APL DS is less certain. Here we provide a detailed review of the pathogenesis, clinical signs and symptoms as well as management and prophylaxis strategies of APL DS. Topics: Acute Kidney Injury; Arsenic Trioxide; Cell Differentiation; Humans; Hypotension; Leukemia, Promyelocytic, Acute; Pulmonary Edema; Steroids; Syndrome; Tretinoin | 2019 |
Competition between ethanol clearance and retinoic acid biosynthesis in the induction of fetal alcohol syndrome.
Several models have been proposed to explain the neurodevelopmental syndrome induced by exposure of human embryos to alcohol, which is known as fetal alcohol spectrum disorder (FASD). One of the proposed models suggests a competition for the enzymes required for the biosynthesis of retinoic acid. The outcome of such competition is development under conditions of reduced retinoic acid signaling. Retinoic acid is one of the biologically active metabolites of vitamin A (retinol), and regulates numerous embryonic and differentiation processes. The developmental malformations characteristic of FASD resemble those observed in vitamin A deficiency syndrome as well as from inhibition of retinoic acid biosynthesis or signaling in experimental models. There is extensive biochemical and enzymatic overlap between ethanol clearance and retinoic acid biosynthesis. Several lines of evidence suggest that in the embryo, the competition takes place between acetaldehyde and retinaldehyde for the aldehyde dehydrogenase activity available. In adults, this competition also extends to the alcohol dehydrogenase activity. Ethanol-induced developmental defects can be ameliorated by increasing the levels of retinol, retinaldehyde, or retinaldehyde dehydrogenase. Acetaldehyde inhibits the production of retinoic acid by retinaldehyde dehydrogenase, further supporting the competition model. All of the evidence supports the reduction of retinoic acid signaling as the etiological trigger in the induction of FASD. Topics: Animals; Embryo, Mammalian; Ethanol; Fetal Alcohol Spectrum Disorders; Humans; Models, Biological; Syndrome; Tretinoin; Vitamin A Deficiency | 2018 |
How we prevent and treat differentiation syndrome in patients with acute promyelocytic leukemia.
Differentiation syndrome (DS), formerly known as retinoic acid syndrome, is a relatively common and potentially severe complication seen in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and/or arsenic trioxide. The full-blown syndrome consists of unexplained fever, weight gain, dyspnea with pulmonary infiltrates, pleuropericardial effusion, hypotension, and renal failure. Most measures currently used for management of DS have very little evidence-based support, and therefore, many remain controversial. Despite the lack of evidence supporting DS prophylaxis, several groups have adopted a preventive strategy with corticosteroids, especially for patients with leukocyte levels higher than from 5 to 10 × 10(9)/L. DS diagnosis should be suspected in the presence of any of the above-mentioned signs and symptoms, and preemptive treatment with dexamethasone should be started immediately. Other supportive measures can also be crucial for the correct management of DS, especially in those patients with life-threatening complications. Temporary discontinuation of all-trans retinoic acid or arsenic trioxide is indicated only for patients in very poor clinical condition or with severe renal or pulmonary dysfunction, sometimes requiring admission to the intensive care unit. Recognition of specific biomarkers and a better understanding of DS pathogenesis can be helpful for the development of specific therapies to counteract DS in a timely manner. Topics: Adult; Arsenic Trioxide; Arsenicals; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Leukemia, Promyelocytic, Acute; Male; Oxides; Premedication; Syndrome; Tretinoin | 2014 |
Differentiation syndrome in patients with acute promyelocytic leukemia.
To review the pathophysiology, risk factors, and management of differentiation syndrome (DS) associated with acute promyelocytic leukemia (APL).. A MEDLINE search was conducted (1977-November 2010) using the terms APL, DS, all-trans retinoic acid (ATRA), retinoic acid syndrome, and arsenic trioxide (ATO).. English articles identified from the MEDLINE search were evaluated.. With ATRA, ATO, and chemotherapy, a complete remission is achievable for most newly diagnosed APL patients. However, treatment with the differentiating agents, ATRA and ATO, can lead to the development of DS. Signs and symptoms of this syndrome include hyperleukocytosis and cardiorespiratory compromise. Severe complications can develop, if DS is not recognized early and treated promptly with corticosteroids. In addition, patients with a high white blood cell count at diagnosis may benefit from prophylactic steroids.. Early recognition and prompt initiation of corticosteroids are key factors in the management of DS. Healthcare professionals need to be familiar with this complication which can arise from differentiation agents. Topics: Antineoplastic Agents; Arsenic Trioxide; Arsenicals; Glucocorticoids; Humans; Leukemia, Promyelocytic, Acute; Leukocyte Count; Oxides; Risk Factors; Syndrome; Time Factors; Tretinoin | 2012 |
22q11 deletion syndrome: a role for TBX1 in pharyngeal and cardiovascular development.
Tbx1 is a member of the Tbox family of binding domain transcription factors. TBX1 maps within the region of 22q11 deleted in humans with DiGeorge or velocardiofacial syndrome. Mice haploinsufficient for Tbx1 have phenotypes that recapitulate major features of the syndrome, notably abnormal growth and remodelling of the pharyngeal arch arteries. The Tbx1 haploinsufficiency phenotype is modified by genetic background and by mutations in putative downstream targets. Homozygous null mutations of Tbx1 have more severe defects including failure of outflow tract septation, and absence of the caudal pharyngeal arches. Tbx1 is a transcriptional activator, and loss of this activity has been linked to alterations in the expression of various genes involved in cardiovascular morphogenesis. In particular, Fgf and retinoic acid signalling are dysregulated in Tbx1 mutants. This article summarises the tissue specific and temporal requirements for Tbx1, and attempts to synthesis what is know about the developmental pathways under its control. Topics: Animals; Branchial Region; DiGeorge Syndrome; Disease Models, Animal; Gene Deletion; Heart; Heart Defects, Congenital; Mice; Mutation; Phenotype; Signal Transduction; Syndrome; T-Box Domain Proteins; Tretinoin | 2010 |
Retinoic acid syndrome: a review.
The retinoic acid syndrome (RAS) is an unpredictable but frequent complication which may develop after administration of all-trans retinoic acid (ATRA) most commonly in patients with acute promyelocytic leukaemia (APL). In this review, we describe the incidence, predictive factors, clinical course, outcome and treatment of RAS in patients with APL treated with ATRA. The incidence of RAS in patients receiving ATRA is about 14-16%, with an associated mortality of about 2%. Initial high white blood cell (WBC) count, rapidly increasing WBC count and/or the presence of the CD 13 expression on leukaemic cells may help in identifying patients likely to develop RAS. Concurrent chemotherapy will probably decrease the risk of developing RAS but often exacerbates bleeding, leading to leucocytosis, thrombocytopenia, disseminated intravascular coagulation and fibrinolysis. Prophylactic steroids are not recommended but prompt administration of steroids at the first sign of unexplained dyspnea, fever, weight gain or pulmonary infiltrate, is critical. Liposomal ATRA is being investigated to induce haematological cure in APL without chemotherapy and to reduce the incidence of RAS but further validation of its usefulness is necessary. Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; CD13 Antigens; Gene Expression Regulation, Neoplastic; Glucocorticoids; Humans; Incidence; Leukemia, Promyelocytic, Acute; Leukocyte Count; Syndrome; Tretinoin | 2008 |
Acute promyelocytic leukemia: a case-based review.
Retinoid therapy for acute promyelocytic leukemia (APL) is one of the major achievements of leukemia research in the last 15 years. Use of all trans retinoic acid (ATRA) has changed the prognosis of APL from a fatal leukemia to a highly curable disease. This case-based review examines the available clinical and scientific data to form evidence-based decisions in the management of APL. The main aim of this review is to highlight recent progress made in the management of APL and address the role of maintenance therapy, prognostic factors for relapse and treatment of relapsed disease. Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Case Management; Evidence-Based Medicine; Humans; Idarubicin; Leukemia, Promyelocytic, Acute; Male; Methotrexate; Neoplasm Proteins; Oncogene Proteins, Fusion; Prognosis; Recurrence; Remission Induction; Salvage Therapy; Syndrome; Tretinoin | 2003 |
Retinoic acid syndrome: manifestations, pathogenesis, and treatment.
All-trans retinoic acid (ATRA) is a potent differentiation agent that is effective therapy in acute promyelocytic leukaemia. Although ATRA is generally well tolerated, some patients develop retinoic acid syndrome. This syndrome is manifested by unexplained fever, weight gain, respiratory distress, interstitial pulmonary infiltrates, pleural and pericardial effusion, episodic hypotension, and acute renal failure. However, if identified early enough, effective therapy can be administered. This chapter discusses the clinical aspects and pathogenesis of retinoic acid syndrome. Topics: Chemotaxis, Leukocyte; Dexamethasone; Humans; Leukemia, Promyelocytic, Acute; Leukemic Infiltration; Respiration Disorders; Syndrome; Tretinoin | 2003 |
Extensive splenic infarction, deep vein thrombosis and pulmonary emboli complicating induction therapy with all-trans-retinoic acid (ATRA) for acute promyelocytic leukemia.
Bleeding is a common complication during initial induction treatment for acute promyelocytic leukemia (APL). Administration of all-trans-retinoic acid (ATRA), which is in routine use for APL in the past decade improves the bleeding tendency dramatically. Nevertheless, thrombotic events have still been reported in a small proportion of APL patients treated with ATRA. Here we describe a case of splenic infarction and life threatening thrombosis in a young patient with APL treated with ATRA. We review the relevant literature and discuss the pathophysiology, risk factors and treatment of this complication occurring during therapy, for APL. Topics: Adult; Anticoagulants; Humans; Leukemia, Promyelocytic, Acute; Male; Pulmonary Embolism; Remission Induction; Splenic Infarction; Syndrome; Thrombophilia; Tretinoin; Venous Thrombosis | 2003 |
Retinoic acid syndrome. Recognition, prevention and management.
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 | 1998 |
[Retinoic acid syndrome].
Retinoic acid syndrome still remains as the most significant complication of the differentiation treatment of acute promyelocytic leukemia. Of unknown pathogenesis this syndrome is close but not absolutely related to hyperleukocytosis developed during treatment. It shares clinico-biological characteristics with three other known syndromes: adult respiratory distress syndrome, endotoxic shock and capillary leak syndrome. It can be hypothesized that as in these cases, the main target is the endothelial cell. Some observations contribute to support this hypothesis. An interleukin storm is probably triggered by retinoic acid treatment as well as an increase in adhesion molecules, both contributing to an autocatalytic injury in patients developing the retinoic acid syndrome. Topics: Humans; Leukemia, Promyelocytic, Acute; Syndrome; Tretinoin | 1997 |
Treatment of acute promyelocytic leukaemia.
Currently available clinical results show that the combination of ATRA and anthracycline-Ara-C chemotherapy can slightly increase the CR rate in newly diagnosed APL, from about 80% (with chemotherapy alone) to more than 90%, and patients presenting with high leukocyte counts seem to benefit particularly from this combined therapy. ATRA followed by chemotherapy also reduces the incidence of relapse (particularly of early relapse) as compared to chemotherapy alone. However, treatment with ATRA is still complicated by the risk of hyperleukocytosis and potentially fatal ATRA syndrome, whose best preventive approach (addition of chemotherapy and/or dexamethasone) is still debated. Because some patients still relapse after ATRA plus chemotherapy, prognostic factors for relapse need to be precisely determined. They certainly include persistence or re-appearance of PML-RAR transcript during follow-up. Allogeneic BMT should be considered in those patients. Most of the patients who are not cured by the combination of ATRA and chemotherapy or by subsequent allogeneic BMT still die from their disease. This is due to the acquisition by APL cells of progressive resistance to ATRA, that appears to depend on induction of increased ATRA catabolism in APL cells. Current efforts aimed at overcoming this resistance (including intermittent ATRA schedules, synthesis of new retinoid compounds, utilization of inhibitors of cytochrome P450) are being developed. Topics: Antineoplastic Combined Chemotherapy Protocols; Controlled Clinical Trials as Topic; Drug Administration Schedule; Humans; Leukemia, Promyelocytic, Acute; Randomized Controlled Trials as Topic; Remission Induction; Syndrome; Tretinoin | 1996 |
DiGeorge syndrome and related syndromes associated with 22q11.2 deletions. A review.
DiGeorge syndrome (DGS) is a developmental defect which associates hypo- or aplasia of the thymus and parathyroids, facial dysmorphism and conotruncal cardiac malformations. The etiological factor in a great majority of DGS patients is monosomy for the 22q11.2 chromosomal region either through a large interstitial deletion of that region (inherited or de novo) or through an unbalanced translocation involving chromosome 22. In one instance, a balanced translocation of chromosome 22 was associated with a DGS phenotype. Extensive analyses of this region of chromosome 22 has led to the obtention of precise physical maps of the corresponding genomic region, to the cloning of the balanced translocation breakpoint and to the isolation of different genes from the minimal critical deleted region. Topics: Abnormalities, Drug-Induced; Abnormalities, Multiple; Animals; Chromosome Aberrations; Chromosome Deletion; Chromosome Disorders; Chromosome Mapping; Chromosomes, Human, Pair 22; DiGeorge Syndrome; Female; Genes; Humans; Infant, Newborn; Male; Pregnancy; Pregnancy Complications; Rats; Syndrome; Translocation, Genetic; Tretinoin | 1995 |
Molecular genetic approaches to the study of human craniofacial dysmorphologies.
Craniofacial dysmorphologies are common, ranging from simple facial disfigurement to complex malformations involving the whole head. With the advent of gene mapping and cloning techniques, the genetic element of both simple and complex human craniofacial dysmorphologies can be investigated. For many of the dysmorphic syndromes, it is possible to find families that display a particular phenotype in either an autosomal dominant, recessive, or X-linked manner. This article focuses on a subgroup of craniofacial dysmorphologies, covering these three main inheritance patterns, that are being studied using molecular biology techniques: DiGeorge syndrome, Treacher Collins syndrome, Greig cephalopolysyndactyly syndrome, acrocallosal syndrome, amelogenesis imperfecta, and X-linked cleft palate with ankyloglossia. Once the mutated or deleted gene or genes for each syndrome have been cloned, patterns of normal and abnormal craniofacial development should be elucidated. This should enhance both diagnosis and treatment of these common and disfiguring disorders. Topics: Animals; Chromosome Aberrations; Chromosome Disorders; Cleft Palate; Cloning, Molecular; DiGeorge Syndrome; Facial Bones; Fetal Alcohol Spectrum Disorders; Forecasting; Genetic Linkage; Head; Humans; Mandibulofacial Dysostosis; Mice; Skull; Syndrome; Tongue; Tretinoin | 1995 |
The pathophysiology and treatment of hemorrhagic syndrome of acute promyelocytic leukemia.
Acute promyelocytic leukemia (APL) has been historically characterized by a high rate of early hemorrhagic death, particularly from intracranial bleeding. The hemorrhagic complications have been attributed to a combination of intravascular thrombin generation, excessive fibrinolysis and/or proteolytic activities released from blast cells. Before the era of all-trans retinoic acid (ATRA), the incidence of early fatal bleeding in recent series has ranged from 8 to 46%, and no anti-hemorrhagic treatment clearly appeared superior in abating this complication. This uncertainty is due to remain because of the lack of prospective studies. The increasing awareness of the need for prompt diagnosis and treatment of APL and the larger availability of supportive therapy has largely contributed to lessen the incidence of fatal bleeding, which can be reliably estimated around 10% in major centers. Groups pioneering the use of ATRA have reported a rapid improvement of the coagulopathy of APL, usually starting 48 h from the beginning of the treatment. However, the hemostatic changes during ATRA have been monitored only in a few patients and recent results suggest that hyperfibrinolysis/proteolysis is rapidly corrected by ATRA, whereas thrombin generation may persist longer. Moreover, although significantly less frequent, fatal bleeding may occur during ATRA and thrombotic events have also been reported so that hemostatic death rate is also approximately 10% in patients treated with ATRA. The combination of chemotherapy plus ATRA administration during induction has been suggested as a useful means of controlling hyperleukocytosis, and this could contribute in abating this unacceptably high rate of early death. On the other side, chemotherapy can dramatically exacerbate clotting abnormalities leading to catastrophic clinical outcomes. Thus, more detailed studies of the coagulopathy of APL and its changes during treatment with ATRA, or ATRA combined with chemotherapy, are required in order to offer the most appropriate treatment to these patients still at risk of severe bleeding and thrombotic complications. Topics: Antineoplastic Combined Chemotherapy Protocols; Blood Coagulation; Hemorrhage; Humans; Leukemia, Promyelocytic, Acute; Syndrome; Thrombosis; Tretinoin | 1994 |
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.
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 Topics: Adrenal Cortex Hormones; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Cause of Death; CD13 Antigens; Cerebral Hemorrhage; Combined Modality Therapy; Gene Expression Regulation, Leukemic; Humans; Leukapheresis; Leukemia, Promyelocytic, Acute; Leukocytosis; Neoplasm Proteins; Pulmonary Edema; Receptors, Retinoic Acid; Remission Induction; Retinoic Acid Receptor alpha; Retrospective Studies; Survival Analysis; Syndrome; Treatment Outcome; Tretinoin | 1994 |
The present status in all-trans retinoic acid (ATRA) treatment for acute promyelocytic leukemia patients: further understanding and comprehensive strategy are required in the future.
All-trans retinoic acid (ATRA) has recently been recognized as the first line therapeutic agent in the treatment of patients with acute promyelocytic leukemia (APL). The extraordinary high remission rate achieved by ATRA in comparison with other chemotherapeutic agents suggested that ATRA differentiation induction therapy seemed superior to conventional chemotherapy for APL patients. However, after the great excitement aroused after the initial successes, we have to take stock and examine in detail several problems which have emerged preventing us from improving the clinical outcome in APL. Maintenance in order to prolong remission and prevention of or retreatment for the relapse are the major subjects of concern at present. Efforts should be made either to keep ATRA effective for APL patients or to resensitize the relapsing patients for repeated ATRA therapy. The administration of ATRA should be carefully adapted in accordance with the individual patient's condition. From both conceptual and practical points of view, ATRA differentiation therapy should be combined with chemotherapy, bone marrow transplantation and biomodifier treatment. Thus, a more comprehensive strategy must be planned and developed in the near future. Using molecular biological techniques, the diagnosis of APL can be more precisely made and the course of the disease more closely monitored. The central dogma, still to be revealed, is the relationship between APL pathogenesis, the chromosome translocation present with the relevant molecular alterations and the response to ATRA treatment. Current studies in all these above fields have provided us with a deeper understanding of the pathogenesis of APL and the physiological function and curative action of ATRA.(ABSTRACT TRUNCATED AT 250 WORDS) Topics: Antineoplastic Combined Chemotherapy Protocols; Drug Evaluation; Edema; Fever; Humans; Leukemia, Promyelocytic, Acute; Leukocytosis; Lung Diseases; Remission Induction; Syndrome; Treatment Outcome; Tretinoin | 1992 |
Experimental models of anterior segment dysgenesis.
Normal anterior segment embryogenesis is summarized followed by a review of syndromes of spontaneous and inherited conditions of abnormal development in humans and animals. The study of teratogen-induced malformations in animal models has provided valuable information about critical periods during gestation for the initiation of anterior segment dysgenesis. Although the major developmental events leading to iridocorneal angle formation occur during the third trimester, it appears that embryonic insult much earlier in human gestation (during the first three to five weeks post fertilization) can induce an abnormal sequence of events leading to anterior segment dysgenesis. Topics: Abnormalities, Drug-Induced; Animals; Anterior Eye Segment; Cataract; Disease Models, Animal; Ethanol; Female; Glaucoma; Humans; Mice; Mice, Inbred C57BL; Microscopy, Electron, Scanning; Ochratoxins; Pregnancy; Syndrome; Teratogens; Trabecular Meshwork; Tretinoin | 1989 |
9 trial(s) available for tretinoin and Syndrome
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High body mass index is an independent predictor of differentiation syndrome in patients with acute promyelocytic leukemia.
Increased BMI has been correlated to an increased incidence of APL, but not to the occurrence of differentiation syndrome (DS) in APL. We consecutively treated 39 APL patients with ATRA and idarubicin (according to PETHEMA regimen). Median age was 26 years. Forty-one percent patients were classified as intermediate risk, and 59% as high risk according to Sanz's score. Thirty-three patients (85%) reached CR. Eleven of the 36 patients evaluable for DS (30.5%) developed this syndrome (severe in 7 cases, moderate in 4, and fatal in 3 cases) within a median of 12 days (range 3-23) of ATRA onset. Six of the 9 (66.6%) patients with BMI>or=30 developed DS vs. 5 of 27 (18.5%) with BMI<30 (p=0.012). Other predictors of DS in univariate analysis were: age>or=40 year (p=0.033), baseline WBC>or=20 x 10(9)/l (p=0.003), and creatinine>1.4 mg/dl (p=0.009). In multivariate analysis, BMI>or=30 remained an independent predictor of DS in addition to baseline WBC>or=20 x 10(9)/l. Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Body Mass Index; Child; Child, Preschool; Disease Progression; Female; Humans; Idarubicin; Leukemia, Promyelocytic, Acute; Leukocyte Count; Male; Middle Aged; Prognosis; Survival Analysis; Syndrome; Tretinoin; Young Adult | 2010 |
Differentiation syndrome in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and anthracycline chemotherapy: characteristics, outcome, and prognostic factors.
Differentiation syndrome (DS) can be a life-threatening complication in patients with acute promyelocytic leukemia (APL) undergoing induction therapy with all-trans retinoic acid (ATRA). Detailed knowledge about DS has remained limited. We present an analysis of the incidence, characteristics, prognostic factors, and outcome of 739 APL patients treated with ATRA plus idarubicin in 2 consecutive trials (Programa Español de Tratamientos en Hematología [PETHEMA] LPA96 and LPA99). Overall, 183 patients (24.8%) experienced DS, 93 with a severe form (12.6%) and 90 with a moderate form (12.2%). Severe but not moderate DS was associated with an increase in mortality. A bimodal incidence of DS was observed, with peaks occurring in the first and third weeks after the start of ATRA therapy. A multivariate analysis indicated that a WBC count greater than 5 x 10(9)/L and an abnormal serum creatinine level correlated with an increased risk of developing severe DS. Patients receiving systematic prednisone prophylaxis (LPA99 trial) in contrast to those receiving selective prophylaxis with dexamethasone (LPA96 trial) had a lower incidence of severe DS. Patients developing severe DS showed a reduced 7-year relapse-free survival in the LPA96 trial (60% vs 85%, P = .003), but this difference was not apparent in the LPA99 trial (86% vs 88%). Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anthracyclines; Child; Child, Preschool; Disease-Free Survival; Drug Therapy, Combination; Female; Humans; Leukemia, Promyelocytic, Acute; Male; Middle Aged; Prognosis; Recurrence; Risk Factors; Syndrome; Time Factors; Tretinoin | 2009 |
Causes and prognostic factors of remission induction failure in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and idarubicin.
An understanding of the prognostic factors associated with the various forms of induction mortality in patients with acute promyelocytic leukemia (APL) has remained remarkably limited. This study reports the incidence, time of occurrence, and prognostic factors of the major categories of induction failure in a series of 732 patients of all ages (range, 2-83 years) with newly diagnosed APL who received all-trans retinoic acid (ATRA) plus idarubicin as induction therapy in 2 consecutive studies of the Programa de Estudio y Tratamiento de las Hemopatias Malignas (PETHEMA) Group. Complete remission was attained in 666 patients (91%). All the 66 induction failures were due to induction death. Hemorrhage was the most common cause of induction death (5%), followed by infection (2.3%) and differentiation syndrome (1.4%). Multivariate analysis identified specific and distinct pretreatment characteristics to correlate with an increased risk of death caused by hemorrhage (abnormal creatinine level, increased peripheral blast counts, and presence of coagulopathy), infection (age>60 years, male sex, and fever at presentation), and differentiation syndrome (Eastern Cooperative Oncology Group [ECOG] score>1 and low albumin levels), respectively. These data furnish clinically relevant information that might be useful for designing more appropriately risk-adapted treatment protocols aimed at reducing the considerable problem of induction mortality in APL. Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Blast Crisis; Child; Child, Preschool; Creatinine; Disease-Free Survival; Female; Hemorrhage; Humans; Idarubicin; Infections; Leukemia, Promyelocytic, Acute; Male; Middle Aged; Remission Induction; Risk Factors; Sex Factors; Survival Rate; Syndrome; Treatment Failure; Tretinoin | 2008 |
Early onset of chemotherapy can reduce the incidence of ATRA syndrome in newly diagnosed acute promyelocytic leukemia (APL) with low white blood cell counts: results from APL 93 trial.
Treatment combining ATRA and chemotherapy (CT) has improved the outcome of APL patients, by comparison with CT alone. ATRA syndrome is a life-threatening complication of ATRA treatment whose prophylaxis remains somewhat controversial. In APL93 trial, newly diagnosed APL patients =65 years and with initial WBC counts below 5000/mm(3) were randomized between ATRA until CR achievement followed by CT (ATRA --> CT) and ATRA with early addition of CT, on day 3 of ATRA treatment (ATRA + CT). The incidence of ATRA syndrome in the ATRA --> CT arm was 18% (22/122) as compared to 9.2% (17/184) in the ATRA + CT arm (P = 0.035). In the ATRA --> CT arm, three (2.5%) patients died from ATRA syndrome, as compared to one (0.5%) in the ATRA + CT group. Early addition of chemotherapy to ATRA in newly diagnosed APL with low WBC counts significantly reduced the incidence of ATRA syndrome. Topics: Adult; Age of Onset; Antineoplastic Agents; Female; Humans; Leukemia, Promyelocytic, Acute; Leukocyte Count; Leukopenia; Male; Middle Aged; Retrospective Studies; Syndrome; Treatment Outcome; Tretinoin | 2003 |
Clinical description of 44 patients with acute promyelocytic leukemia who developed the retinoic acid syndrome.
We examined the incidence, clinical course, and outcome of patients with newly diagnosed acute promyelocytic leukemia (APL) who developed the retinoic acid syndrome (RAS) treated on the Intergroup Protocol 0129, which prospectively evaluated the role of alltrans retinoic acid (ATRA) alone during induction and as maintenance therapy. Forty-four of 167 (26%) patients receiving ATRA for induction developed the syndrome at a median of 11 days of ATRA (range, 2-47). The median white blood cell (WBC) count was 1,450/microL at diagnosis and was 31,000/microL (range, 6,800-72,000/microL) at the time the syndrome developed. ATRA was discontinued in 36 of the 44 patients (82%) and continued in 8 patients (18%), with subsequent resolution of the syndrome in 7 of the 8. ATRA was resumed in 19 of the 36 patients (53%) in whom ATRA was stopped and not in 17 (47%). The syndrome recurred in 3 of those 19 patients, with 1 death attributable to resumption of the drug. Ten of these 36 patients received chemotherapy without further ATRA, and 8 achieved complete remission (CR). Among 7 patients in whom ATRA was not restarted and were not treated with chemotherapy, 5 achieved CR and 2 died. Two deaths were definitely attributable to the syndrome. No patient receiving ATRA as maintenance developed the syndrome. (Blood. 2000;95:90-95) Topics: Adolescent; Adult; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Cytarabine; Daunorubicin; Dexamethasone; Female; Fever; Glucocorticoids; Humans; Incidence; Infant; Leukemia, Promyelocytic, Acute; Lung; Male; Middle Aged; Pericardial Effusion; Pleural Effusion; Remission Induction; Respiratory Distress Syndrome; Syndrome; Tretinoin; Weight Gain | 2000 |
Incidence, clinical features, and outcome of all trans-retinoic acid syndrome in 413 cases of newly diagnosed acute promyelocytic leukemia. The European APL Group.
All trans-retinoic acid (ATRA) syndrome is a life-threatening complication of uncertain pathogenesis that can occur during the treatment of acute promyelocytic leukemia (APL) by ATRA. Since its initial description, however, no large series of ATRA syndrome has been reported in detail. We analyzed cases of ATRA syndrome observed in an ongoing European trial of treatment of newly diagnosed APL. In this trial, patients 65 years of age or less with an initial white blood cell count (WBC) less than 5,000/microL were initially randomized between ATRA followed by chemotherapy (CT) (ATRA-->CT group) or ATRA with CT started on day 3; patients with WBC greater than 5,000/microL received ATRA and CT from day 1; patients aged 66 to 75 received ATRA-->CT. In patients with initial WBC less than 5, 000/microL and allocated to ATRA-->CT, CT was rapidly added if WBC was greater than 6,000, 10,000, 15,000/microL by days 5, 10, and 15 of ATRA treatment. A total of 64 (15%) of the 413 patients included in this trial experienced ATRA syndrome during induction treatment. Clinical signs developed after a median of 7 days (range, 0 to 35 days). In two of them, they were in fact present before the onset of ATRA. In 11 patients, they occurred upon recovery from the phase of aplasia due to the addition of CT. Respiratory distress (89% of the patients), fever (81%), pulmonary infiltrates (81%), weight gain (50%), pleural effusion (47%), renal failure (39%), pericardial effusion (19%), cardiac failure (17%), and hypotension (12%) were the main clinical signs, and 63 of the 64 patients had at least three of them. Thirteen patients required mechanical ventilation and two dialysis. A total of 60 patients received CT in addition to ATRA as per protocol or based on increasing WBC; 58 also received high dose dexamethasone (DXM); ATRA was stopped when clinical signs developed in 30 patients. A total of 55 patients (86%) who experienced ATRA syndrome achieved complete remission (CR), as compared with 94% of patients who had no ATRA syndrome (P = .07) and nine (14%) died of ATRA syndrome (5 cases), sepsis (2 cases), leukemic resistance (1 patient), and central nervous system (CNS) bleeding (1 patient). None of the patients who achieved CR and received ATRA for maintenance had ATRA syndrome recurrence. No significant predictive factors of ATRA syndrome, including pretreatment WBC, could be found. Kaplan Meier estimates of relapse, event-free survival (EFS), and survival at 2 years were 32% +/- Topics: Acute Kidney Injury; Adult; Aged; Antibiotics, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cardiovascular Diseases; Cytarabine; Dexamethasone; Disease-Free Survival; Female; Humans; Incidence; Leukemia, Promyelocytic, Acute; Leukocyte Count; Life Tables; Male; Middle Aged; Pericardial Effusion; Pleural Effusion; Proportional Hazards Models; Remission Induction; Respiration Disorders; Survival Rate; Syndrome; Treatment Outcome; Tretinoin | 1998 |
Molecular remission in PML/RAR alpha-positive acute promyelocytic leukemia by combined all-trans retinoic acid and idarubicin (AIDA) therapy. Gruppo Italiano-Malattie Ematologiche Maligne dell'Adulto and Associazione Italiana di Ematologia ed Oncologia Pe
Two hundred fifty-three patients with newly diagnosed acute promyelocytic leukemia (APL) were eligible to enter the multicentric GIMEMA-AIEOP "AIDA" trial during the period July 1993 to February 1996. As a mandatory prerequisite for eligibility, all patients had genetic evidence of the specific t(15;17) lesion in their leukemic cells confirmed by karyotyping or by reverse transcription-polymerase chain reaction (RT-PCR) of the PML/RAR alpha fusion gene (the latter available in 247 cases). Median age was 37.8 years (range, 2.2 to 73.9). Induction treatment consisted of oral all-trans retinoic acid (ATRA), 45 mg/m2/d until complete remission (CR), given with intravenous Idarubicin, 12 mg/m2/d on days 2, 4, 6, and 8. Three polychemotherapy cycles were given as consolidation. Hematologic and molecular response by RT-PCR was assessed after induction and after consolidation. At the time of analysis, 240 of the 253 eligible patients were evaluable for induction. Of these, 11 (5%) died of early complications and 229 (95%) achieved hematologic remission. No cases of resistant leukemia were observed. Of 139 cases studied by RT-PCR after induction, 84 (60.5%) were PCR-negative and 55 (39.5%) PCR-positive. One hundred sixty-two patients were evaluable by RT-PCR at the end of consolidation. Of these, 159 (98%) tested PCR-negative and 3 (2%), PCR-positive. After a median follow up of 12 months (range, 0 to 33), the estimated actuarial event-free survival for the whole series of 253 eligible patients was 83% +/- 2.6% and 79% +/- 3.2% at 1 and 2 years, respectively. This study indicates that the AIDA protocol is a well-tolerated regimen that induces molecular remission in almost all patients with PML/RAR alpha-positive APL. Preliminary survival data suggest that a remarkable cure rate can be obtained with this treatment. Topics: Adolescent; Adult; Aged; Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Bone Marrow; Child; Child, Preschool; Chromosomes, Human, Pair 15; Chromosomes, Human, Pair 17; Disease-Free Survival; Female; Humans; Idarubicin; Leukemia, Promyelocytic, Acute; Leukocytosis; Male; Middle Aged; Neoplasm Proteins; Neoplasm, Residual; Oncogene Proteins, Fusion; Polymerase Chain Reaction; Prospective Studies; Remission Induction; Syndrome; Translocation, Genetic; Treatment Outcome; Tretinoin | 1997 |
All-trans retinoic acid in adult chronic myelomonocytic leukemia: results of a pilot study.
Retinoids can inhibit the spontaneous in vitro growth of CFU-GM observed in juvenile chronic myeloid leukemia (JCML) and, when administered in vivo, have shown some clinical benefit in this disease. Because adult chronic myelomonocytic leukemia (CMML) has many features in common with JCML, we treated 10 cases of advanced adult CMML with ATRA (45 mg/m2/day). Five of them were also tested in vitro. After two patients had a rapid increase in WBC counts and clinical signs reminiscent of the 'ATRA syndrome' seen in acute promyelocytic leukemia, with fatal outcome in one of them, it was decided to add hydroxyurea (HY) to ATRA to patients with high WBC at inclusion or during ATRA treatment, and no more cases of ATRA syndrome were seen. Overall, six patients received ATRA + HY and four ATRA alone. Four patients had a minor but significant response with reduction of transfusion requirement (two cases) or increase in platelet counts (two cases). Apart from the ATRA syndrome, no other side-effect of ATRA was seen. Bone marrow mononuclear cells showed spontaneous growth of CFU-C in methylcellulose in the five patients tested in vitro, with a predominance of CFU-M. ATRA (10(-7) M) inhibited CFU-M growth in all cases, but increased CFU-G growth in one patient who developed the ATRA syndrome. No differentiation of bone marrow myeloid cells after short-term liquid culture with ATRA was observed. A decrease of CFU-C growth was observed in the four patients reevaluated during follow-up. In some cases of CMML, ATRA can improve anemia or thrombocytopenia but not other parameters. Furthermore, it can also induce hyperleukocytosis and ATRA syndrome in some patients, requiring the rapid addition of cytoreductive agents such as HY. Topics: Aged; Antineoplastic Agents; Bone Marrow; Colony-Forming Units Assay; Female; Hematopoietic Stem Cells; Humans; Hydroxyurea; Leukemia, Myelomonocytic, Chronic; Leukocytosis; Male; Middle Aged; Pilot Projects; Platelet Count; Syndrome; Tretinoin; Tumor Cells, Cultured | 1996 |
All-trans retinoic acid for the treatment of newly diagnosed acute promyelocytic leukemia. Japan Adult Leukemia Study Group.
We conducted a multicenter trial of treatment with all-trans retinoic acid (ATRA) for newly diagnosed acute promyelocytic leukemia (APL) in the AML-92 study and compared it with our previous study with standard intensive chemotherapy, the AML-89 study, in the view of complete remission (CR) rate, incidence of early death, and event-free survival (EFS). Patients were scheduled to receive oral ATRA 45 mg/m2 daily until CR. If patients had leukocyte counts above 3 x 10(9)/L at the start of therapy, they received daunorubicine (DNR) 40 mg/m2 for 3 days and behenoyl cytosine arabinoside (BHAC) 200 mg/m2 for 5 days in addition to ATRA. During the ATRA therapy, if patients showed myeloblast plus promyelocyte counts higher than 1 x 10(9)/L in the peripheral blood, they received additional DNR and BHAC in the same schedule, as well. A total of 110 patients were entered into the study. Median age was 43 years (range, 16 to 74). Twenty-eight (26%) of 109 patients (one died before the start of therapy) received ATRA alone. Ninety-seven patients (89%) achieved CR; 48 of 49 (98%) aged less than 40 years, 44 of 52 (84%) aged between 40 and 69, and 5 of 8 (63%) aged above 70 achieved CR, respectively; 25 of 28 (89%) with ATRA alone, 46 of 51 (90%) with ATRA plus initial chemotherapy and 26 of 30 (87%) with ATRA plus later chemotherapy attained CR, respectively. Nine (8%) patients died within 28 days after the start of therapy. In contrast, 44 of 62 patients (71%) attained CR, and 13 (21%) died within 28 days in the AML-89 study with the combination of DNR, BHAC, 6-mercaptopurine and prednisolone. Seven developed retinoic acid syndrome and one died of it in the present study. Other toxicities associated with this drug included cheilitis, desquamation, muscle pain, and hypertriglyceridemia. Predicted 23 months EFS for all ATRA-treated patients and disease-free survival (DFS) in the CR cases were 75% and 81%, respectively, in a median follow-up period of 21 months. Compared to the AML-89 study, there was a highly significant difference in remission rate (P = .004), EFS (P = .0007), and also early mortality rate (P = .02). Present results demonstrated that ATRA with or without chemotherapy gives a statistical improvement in CR rate and early mortality rate, as well as superior survival in newly diagnosed APL. Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Cytarabine; Daunorubicin; Female; Humans; Immunologic Factors; Japan; Leukemia, Promyelocytic, Acute; Leukocytosis; Life Tables; Male; Mercaptopurine; Middle Aged; Prednisolone; Prospective Studies; Remission Induction; Syndrome; Treatment Outcome; Tretinoin | 1995 |
113 other study(ies) available for tretinoin and Syndrome
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Effects of peripheral blood leukocyte count and tumor necrosis factor-alpha on early death in acute promyelocytic leukemia.
Early death remains a major factor in survival in APL. We aimed to analyze the risk factors for differentiation syndrome and early death in acute promyelocytic leukemia (APL).. The clinical data of APL patients who were newly diagnosed at Mianyang Central Hospital from January 2013 to January 2022 were retrospectively analyzed.. Eighty-six newly diagnosed APL patients (37 males and 49 females) were included in this study. The median age was 46 (17-75) years. Sixty-one patients (70.9%) had low/intermediate-risk APL, and 25 patients (29.1%) had high-risk APL. The incidence of differentiation syndrome (DS) was 62.4%. The multivariate analysis showed that a peak white blood cell (WBC) count ≥16 × 10^9/L was an independent risk factor (OR = 11.000, 95% CI: 2.830-42.756, P = 0.001) for DS in all APL patients, while a WBC count ≥10 × 10^9/L on Day 5 was an independent risk factor for DS in low-intermediate risk APL patients (OR = 9.114, 95% CI: 2.384-34.849, P = 0.001). There were 31 patients (36.5%) with mild DS and 22 patients (25.9%) with severe DS. The multivariate analysis showed that WBC count ≥23 × 10^9/L at chemotherapy was an independent risk factor for severe DS (OR = 10.500, 95% CI: 2.344-47.034, P = 0.002). The rate of early death (ED) was 24.4% (21/86). The multivariate analysis showed that male gender (OR = 7.578,95% CI:1.136-50.551, P = 0.036), HGB < 65 g/L (OR = 16.271,95% CI:2.012-131.594, P = 0.009) and WBC count ≥7 × 10^9/L on Day 3(OR = 23.359,95% CI:1.825-298.959, P = 0.015) were independent risk factors for ED. The WBC count at diagnosis, WBC count on Day 3 and WBC count on Day 5 had moderate positive correlations with tumor necrosis factor-α (TNF-α) at diagnosis, and the correlation coefficients were 0.648 (P = 0.012), 0.615 (P = 0.033), and 0.609 (P = 0.035), respectively. The WBC count had no correlation with IL-6.. During induction treatment, cytotoxic chemotherapy may need to be initiated to reduce the risk of DS for APL patients with a low-intermediate risk WBC count ≥10 × 10^9/L on Day 5 or for all patients with a peak WBC count ≥16 × 10^9/L. Patients with WBC > 7 × 10^9/L on Day 3 have a higher risk of ED. Leukocyte proliferation is associated with TNF-α rather than IL-6, and TNF-α may be a potential biomarker for predicting ED. Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Female; Humans; Interleukin-6; Leukemia, Myeloid, Acute; Leukemia, Promyelocytic, Acute; Leukocyte Count; Leukocytes; Leukopenia; Male; Middle Aged; Retrospective Studies; Syndrome; Thrombocytopenia; Tretinoin; Tumor Necrosis Factor-alpha; Young Adult | 2023 |
Detailed short-term follow-up high-resolution CT series of differentiation syndrome.
A 57-year-old man with acute promyelocytic leukaemia (APML) received induction therapy including all-trans-retinoic acid (ATRA). At day 15, he developed dyspnoea, haemoptysis and hypoxia. Thorax CT demonstrated diffuse ground-glass opacity and consolidation predominantly in dorsal regions, which may reflect increased vascular permeability. He was diagnosed with differentiation syndrome. After dexamethasone was administered and chemotherapy suspended, his symptoms improved and abnormal lesions mostly disappeared on follow-up CT examinations. We report a short-term high-resolution CT series of differentiation syndrome. Topics: Antineoplastic Combined Chemotherapy Protocols; Follow-Up Studies; Humans; Leukemia, Promyelocytic, Acute; Male; Middle Aged; Syndrome; Tomography, X-Ray Computed; Tretinoin | 2022 |
Do high-mobility group box 1 gene polymorphisms affect the incidence of differentiation syndrome in acute promyelocytic leukemia?
Differentiation syndrome (DS) is an inflammatory complication seen in some patients with acute promyelocytic leukemia (APL) undergoing differentiation therapy with all-trans retinoic acid (ATRA) and/or arsenic trioxide (ATO). It is unknown how DS occurs, but it is believed that it is caused by inflammatory cytokines release from differentiating leukemic cells. High mobility group box-1 (HMGB1) is a DNA-binding protein that acts as a cytokine outside of cells and may play a role in inflammation. This study was conducted to determine whether HMGB1 polymorphisms (rs1360485, rs2249825 and rs1060348) are associated with the incidence of differentiation syndrome in acute promyelocytic leukemia patients treated with all-trans retinoic acid and arsenic trioxide.. One hundred and thirty APL patients and 100 healthy controls were included. Seventeen patients with differentiation syndrome were selected according to the PETHEMA criteria. Tetra-primer ARMS polymerase chain reaction (tetra-ARMS PCR) was used to determine the genotype distribution of polymorphisms. DNA sequencing was done to validate the results.. In both healthy and APL patients, AA was the most frequent genotype in rs1360485 followed by AG and GG. CC, CG, and GG were the most frequent genotypes in rs2249825 polymorphism in the order mentioned. CC was more frequent than CT, and CT was more frequent than TT in rs1060348. There was no correlation between HMGB1 polymorphisms and the incidence of differentiation syndrome based on genetic models (p-value > 0.05).. HMGB1 polymorphisms are not probably associated with DS development in APL patients treated with ATRA and ATO. Topics: Arsenic Trioxide; Cytokines; HMGB1 Protein; Humans; Incidence; Leukemia, Promyelocytic, Acute; Polymorphism, Genetic; Syndrome; Tretinoin | 2022 |
Shifting gears to differentiation agents in acute promyelocytic leukemia with resource constraints-a cohort study.
Treatment of acute promyelocytic leukaemia has emerged as a major success in hemato-oncology. While literature from the developed world boasts of outstanding outcomes, there is a paucity of data from the developing world. This study aimed to assess complications and outcomes of acute promyelocytic leukaemia in a resource-constrained setting.. We retrospectively collected data from patients diagnosed with APL from January 2016 to December 2020.. Sixty-four patients were treated-32 in both the Sanz high and low-risk groups. In the Sanz low-risk group, 12.5% of patients received ATRA with daunorubicin and 81.25% received ATRA with ATO. In the Sanz high-risk group, 18.8% of patients received ATRA with daunorubicin, 34.3% received ATRA with daunorubicin and ATO while 40.6% received ATRA with ATO. 56.25% of patients developed differentiation syndrome. The incidence was higher in Sanz high-risk group as compared to Sanz low-risk group. 57.4% of patients had an infection at the time of presentation. 62.5% of patients developed neutropenic fever during treatment. 17.2% of patients developed pseudotumor cerebri. The 4-year EFS and OS were 71.25 and 73.13%, respectively. Sanz low-risk group had a better 4-year EFS and OS as compared to the Sanz high-risk group. Haemoglobin at presentation and Sanz high-risk group were associated with poorer outcomes with a hazard ratio of 0.8 and 3.1, respectively. Outcomes in high-risk patients were better with the use of ATRA + ATO + daunorubicin.. In the Indian population, APL patients have a high incidence of differentiation syndrome, pseudotumor cerebri, and infections during induction. CR, EFS, and OS compared to the developed world can be achieved with optimal therapy. Low haemoglobin at presentation and Sanz high-risk group were associated with poorer outcomes. ATRA, ATO, and daunorubicin combination is the preferred protocol for treating high-risk patients. Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cohort Studies; Daunorubicin; Humans; Leukemia, Promyelocytic, Acute; Pseudotumor Cerebri; Retrospective Studies; Syndrome; Treatment Outcome; Tretinoin | 2022 |
The impact of ICAM-1, CCL2 and TGM2 gene polymorphisms on differentiation syndrome in acute promyelocytic leukemia.
Although arsenic trioxide (ATO) and all-trans retinoic acid (ATRA) are well-tolerated and effective treatments for Acute Promyelocytic Leukemia (APL), Differentiation Syndrome (DS) is a lethal side effect in some patients. The pathogenesis of DS is complex and not well understood; however, it is considered as an inflammatory response due to cytokines release of differentiated cells. Moreover, adhesion molecules that are widely expressed on the surface of differentiated cells and gene expression changes of transglutaminase2 (TGM2) are mechanisms involved in the development of DS. The purpose of this study was to assess the association of single nucleotide polymorphisms (SNP) of Intercellular Adhesion Molecule-1 (ICAM-1), chemokine (C-C motif) ligand 2 (CCL2) and TGM2 as inflammatory factors with differentiation syndrome susceptibility.. DNA was extracted from 133 APL patients and 100 normal controls. Assessment according to the PETHEMA criteria revealed that 13.5% of these patients experienced differentiation syndrome. Tetra-ARMS PCR and PCR-RFLP were done to amplify DNA fragments in APL patients with and without DS. Then DNA sequencing was done to validate the results. SNPStats, SPSS and Finch TV were used to analyze the results.. A significant correlation was found between rs4811528 in the TGM2 gene and differentiation syndrome susceptibility (P = 0.002, 95% CI = 1.74-18.81, OR = 5.72) while rs5498 in ICAM-1, rs1024611 in CCL2, and rs7270785 in TGM2 genes showed no correlation with differentiation syndrome. The G allele of rs7270785 and rs4811528 showed a haplotypic association with differentiation syndrome (P = 0.03, 95% CI = 1.13-13.86, OR = 3.96).. AA genotype of the TGM2 SNP (rs4811528) may be a risk factor for development of DS in patients with APL following the use of ATRA/ATO. Topics: Acute Kidney Injury; Adult; Antineoplastic Agents; Biomarkers, Tumor; Case-Control Studies; Cell Differentiation; Chemokine CCL2; Female; Follow-Up Studies; GTP-Binding Proteins; Humans; Intercellular Adhesion Molecule-1; Leukemia, Promyelocytic, Acute; Lung Diseases; Male; Polymorphism, Genetic; Prognosis; Protein Glutamine gamma Glutamyltransferase 2; Survival Rate; Syndrome; Systemic Inflammatory Response Syndrome; Transglutaminases; Tretinoin | 2021 |
Biallelic hypomorphic variants in ALDH1A2 cause a novel lethal human multiple congenital anomaly syndrome encompassing diaphragmatic, pulmonary, and cardiovascular defects.
This study shows a causal association between ALDH1A2 variants and a novel, severe multiple congenital anomaly syndrome in humans that is neonatally lethal due to associated pulmonary hypoplasia and respiratory failure. In two families, exome sequencing identified compound heterozygous missense variants in ALDH1A2. ALDH1A2 is involved in the conversion of retinol (vitamin A) into retinoic acid (RA), which is an essential regulator of diaphragm and cardiovascular formation during embryogenesis. Reduced RA causes cardiovascular, diaphragmatic, and associated pulmonary defects in several animal models, matching the phenotype observed in our patients. In silico protein modeling showed probable impairment of ALDH1A2 for three of the four substitutions. In vitro studies show a reduction of RA. Few pathogenic variants in genes encoding components of the retinoic signaling pathway have been described to date, likely due to embryonic lethality. Thus, this study contributes significantly to knowledge of the role of this pathway in human diaphragm and cardiovascular development and disease. Some clinical features in our patients are also observed in Fryns syndrome (MIM# 229850), syndromic microphthalmia 9 (MIM# 601186), and DiGeorge syndrome (MIM# 188400). Patients with similar clinical features who are genetically undiagnosed should be tested for recessive ALDH1A2-deficient malformation syndrome. Topics: Abnormalities, Multiple; Aldehyde Dehydrogenase 1 Family; Animals; Cardiovascular Diseases; Diaphragm; Humans; Lung Diseases; Retinal Dehydrogenase; Syndrome; Tretinoin | 2021 |
Multidisciplinary corroboration in differentiation syndrome: a case report.
Differentiation syndrome (DS) is a life-threatening complication that may be seen in patients with acute promyelocytic leukaemia undergoing induction therapy with all-trans retinoic acid or arsenic trioxide. It can lead to severe inflammatory response syndrome and shock if adequate measures are not taken immediately. The radiological features of lung nodules with changes in ground-glass opacity can represent DS. The principal unique feature of the case reported here is that the diagnosis of DS was based on imaging results in the absence of a low total leukocyte count.. A 14-year-old Indian girl diagnosed with acute promyelocytic leukaemia currently undergoing a chemotherapy regimen that included all-trans retinoic acid/arsenic trioxide was sent to the radiology department for investigation of respiratory distress which she had developed soon after the initiation of chemotherapy. Her chest radiograph showed bilateral lower zone lung infiltrates. Computed tomography (CT) revealed changes in ground-glass opacity in the lower lobes with multiple lung nodules. Differential diagnosis included bacterial, viral or fungal infections, leukemic infiltrates, drug toxicity, pulmonary haemorrhage or leukostasis. She was started on dexamethasone immediately after stopping the chemotherapy with all-trans retinoic acid/arsenic trioxide and given ventilatory support. Her condition subsequently improved and her follow-up chest radiograph and CT scan showed a significant reduction of abnormal lung findings. Based on the clinical improvement and the resolution of findings on imaging following the withdrawal of all-trans retinoic acid/arsenic trioxide, we made the diagnosis of DS.. Though a rather unusual possibility, the treatment history of the patient enabled a rather crucial diagnosis in the nick of time and imaging played a pivotal role. This case further iterates the importance of keeping DS in mind when dealing with similar patients in the future. Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Arsenic Trioxide; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Leukemia, Promyelocytic, Acute; Syndrome; Tretinoin | 2021 |
Differentiation Syndrome in a Patient With Acute Promyelocytic Leukemia: Importance of Chest CT.
Topics: Humans; Leukemia, Promyelocytic, Acute; Neoplasms; Syndrome; Tomography, X-Ray Computed; Tretinoin | 2020 |
Interleukin-8 is not a predictive biomarker for the development of the acute promyelocytic leukemia differentiation syndrome.
Differentiation syndrome (DS) is the main life-threatening adverse event that occurs in acute promyelocytic leukemia (APL) patients treated with all-trans retinoic acid (ATRA). Cytokine imbalances have been reported to play role during the developing of acute promyelocytic leukemia differentiation syndrome (APL-DS). However, the relationship between the plasma cytokine levels and their prognostic value for the prediction of DS developing in patients with APL during the treatment with ATRA and anthracyclines has not been previously reported.. In this study, we followed an APL cohort (n = 17) over 7 days of ATRA therapy in DS (n = 6) and non-DS groups (n = 11). Interleukin (IL)-1β, IL-6, IL-8, IL-10, IL-12p70 and TNF-α were measured in the peripheral blood plasma from 17 patients with APL and 11 healthy adult controls by using the cytometric bead array method.. In non-DS patients, IL-8 plasma levels were significantly reduced in the seventh day of ATRA treatment (34.16; 6.99 to 147.11 pg mL. We demonstrated that the modulation of IL-8 following ATRA treatment may occur regardless of the development of DS and, therefore, does not appear to be a predictive biomarker to monitor the APL-DS. Topics: Adult; Aged; Antineoplastic Agents; Biomarkers, Tumor; Cell Differentiation; Female; Humans; Interleukin-6; Interleukin-8; Leukemia, Promyelocytic, Acute; Male; Middle Aged; Retrospective Studies; Syndrome; Treatment Outcome; Tretinoin; Young Adult | 2020 |
COVID-19: Endogenous Retinoic Acid Theory and Retinoic Acid Depletion Syndrome.
This study presents two new concepts and definitions to the medical literature. One of those is "endogenous retinoic acid theory" and the other "retinoic acid depletion syndrome". A new classification will be provided for the immune system: "retinoic acid-dependent component" and "retinoic acid non-dependent component". If this theory is verified, all the diseases where the retinoic acid metabolism is defective and retinoic acid levels are low will be identified and new approaches will be developed fortreating such diseases. When the need for retinoic acids increases, such as acute infection, high fever, severe catabolic process, or chronic antigenic stimulation, cytochrome oxidase enzymes are inhibited by drugs or internal mechanisms. Metabolism and excretion of retinoic acids stored in the liver are prevented. In this way, retinoic acid levels in the blood are raised to therapeutic levels. This is called "Endogenous Retinoic Acid Theory". Retinoic acids also manage their metabolism through feedback mechanisms. Despite compensatory mechanisms, causes such as high fever, serious catabolic process and excessively large viral genome (SARS-CoV-2), excessive use of RIG-I and Type I interferon synthesis pathway using retinoic acid causes emptying of retinoic acid stores. As a result, the RIG-I pathway becomes ineffective, Type I IFN synthesis stops, and the congenital immune system collapses. Then the immune mechanism passes to TLR3, TLR7, TLR8, TLR9, MDA5 and UPS pathways in the monocyte, macrophage, neutrophil and dendritic cells of the adaptive immune defense system that do not require retinoic acid. This leads to excessive TNFα and cytokine discharge from the pathway. With the depletion of retinoic acid stores as a result of this overuse, the immune defense mechanism switches from the congenital immune system to the adaptive immune system, where retinoic acids cannot be used. As a result of this depletion of retinoic acids, the shift of the immune system to the NFκB arm, which causes excessive cytokine release, is called "retinoic acid depletion syndrome". COVID-19 and previously defined sepsis, SIRS and ARDS are each retinoic acid depletion syndrome. We claim that retinoic acid metabolism is defective in most inflammatory diseases, particularly COVID-19 (cytokine storm) sepsis, SIRS and ARDS. Finding a solution to this mechanism will bring a new perspective and treatment approach to such diseases. Topics: Autoimmunity; Carotenoids; COVID-19; DEAD Box Protein 58; Humans; Immune System; Interferon Type I; Interferons; Liver; Models, Theoretical; Nervous System; Receptors, Immunologic; Syndrome; Tretinoin; Viral Load; Vitamin A; Vitamin A Deficiency; Zinc | 2020 |
Early detection of differentiation syndrome by chest ultrasound in acute promyelocytic leukaemia.
Topics: Antineoplastic Combined Chemotherapy Protocols; Arsenic Trioxide; Female; Humans; Leukemia, Promyelocytic, Acute; Male; Point-of-Care Systems; Prospective Studies; Syndrome; Tretinoin; Ultrasonography | 2019 |
[Acute kidney failure in differentiation syndrome: a possible complication during therapy with differentiating agents for acute promyelocytic leukemia. A case report].
Differentiation syndrome (DS), previously known as retinoic acid syndrome or ATRA (all-trans retinoic acid) or ATO (arsenic trioxide) syndrome, is a life-threatening complication of the therapy with differentiating agents in patients with acute promyelocytic leukemia (APL). The latter is a rare subtype of acute myeloid leukemia and represents a hematological emergency. The clinical manifestations of DS, after induction therapy with differentiating agents, include unexplained fever, acute respiratory distress with interstitial pulmonary infiltrates, unexplained hypotension, peripheral edema, congestive heart failure and acute renal failure. The therapy is based on early intravenous administration of high-dose dexamethasone, in order to counteract the cytokine storm responsible for the DS. Among the supportive measures for the management of DS, furosemide (in 87% of patients) and dialysis (12% of patients) are used to manage acute renal failure, peripheral and pulmonary edema. We describe a case of acute renal failure, treated with haemodialysis, in a young patient with APL and an early and severe DS after induction therapy. This is a rare condition, not well known among nephrologists, where early recognition and treatment are crucial for the prognosis. Topics: Acute Kidney Injury; Adult; Antineoplastic Agents; Arsenic Trioxide; Dexamethasone; Edema; Fever of Unknown Origin; Humans; Hypotension; Induction Chemotherapy; Leukemia, Promyelocytic, Acute; Male; Renal Dialysis; Respiratory Distress Syndrome; Syndrome; Tretinoin | 2019 |
[Very Severe Differentiation Syndrome in Low Risk Acute Promyelocytic Leukemia - A Peril of Differentiating Therapy].
Topics: Adult; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Arsenic Trioxide; Arsenicals; Diagnosis, Differential; Dyspnea; Female; Fever; Humans; Hypotension; Leukemia, Promyelocytic, Acute; Leukocytosis; Lung Diseases; Oxides; Risk Factors; Severity of Illness Index; Syndrome; Treatment Outcome; Tretinoin | 2017 |
Lingual ulceration associated with retinoic acid syndrome during treatment of acute promyelocytic leukemia.
All-trans retinoic acid (ATRA) is routinely associated with chemotherapy for the treatment of acute promyelocytic leukemia (APL). Several reports of scrotal ulceration induced by this agent have been made in the recent years.. The aim of this article was to report the first case of a lingual ulceration associated with retinoic acid syndrome (RAS).. We presented a 32-year-old man with a diagnosis of acute promyelocytic leukemia who received treatment with ATRA. He presented with febrile neutropenia and a lingual ulcer that did not respond to antibiotic and antifungal regimens. He developed weight gain, lower limb edema, polyserositis, and acute renal failure. Retinoic acid syndrome syndrome was diagnosed.. An exhaustive attempt to exclude infectious causes was made performing repeated cultures, histologic examinations, and direct immunofluorescence for HSV. No causative agent was identified. Re-epithelialization of the ulcer was achieved with ATRA cessation and treatment with systemic steroids.. As far as we are concerned, we report the first case of a lingual ulceration associated with RAS.. It is important for dermatologists to recognize this cutaneous complication of ATRA as it poses many differential diagnoses in neutropenic patients. Topics: Acute Kidney Injury; Adult; Antineoplastic Combined Chemotherapy Protocols; Febrile Neutropenia; Humans; Idarubicin; Leukemia, Promyelocytic, Acute; Male; Oral Ulcer; Syndrome; Tongue Diseases; Tretinoin | 2014 |
Celastrol inhibits lung infiltration in differential syndrome animal models by reducing TNF-α and ICAM-1 levels while preserving differentiation in ATRA-induced acute promyelocytic leukemia cells.
All-trans retinoic acid (ATRA) is a revolutionary agent for acute promyelocytic leukemia (APL) treatment via differentiation induction. However, ATRA treatment also increases cytokine, chemokine, and adhesive molecule (mainly ICAM-1) expression, which can cause clinical complications, including a severe situation known as differentiation syndrome (DS) which can cause death. Therefore, it is of clinical significance to find a strategy to specifically blunt inflammatory effects while preserving differentiation. Here we report that the natural compound, celastrol, could effectively block lung infiltrations in DS animal models created by loading ATRA-induced APL cell line NB4. In ATRA-treated NB4 cells, celastrol could potently inhibit ICAM-1 elevation and partially reduce TNF-α and IL-1β secretion, though treatment showed no effects on IL-8 and MCP-1 levels. Celastrol's effect on ICAM-1 in ATRA-treated NB4 was related to reducing MEK1/ERK1 activation. Strikingly and encouragingly, celastrol showed no obvious effects on ATRA-induced NB4 differentiation, as determined by morphology, enzymes, and surface markers. Our results show that celastrol is a promising and unique agent for managing the side effects of ATRA application on APL, and suggest that hyper-inflammatory ability is accompanied by, but not necessary for, APL differentiation. Thus we offered an encouraging novel strategy to further improve differentiation therapy. Topics: Animals; Cell Differentiation; Cell Line, Tumor; Humans; Intercellular Adhesion Molecule-1; Leukemia, Promyelocytic, Acute; Lung; Male; MAP Kinase Signaling System; Mice; Mice, Inbred NOD; Mice, SCID; Pentacyclic Triterpenes; RNA, Messenger; RNA, Neoplasm; Syndrome; Tretinoin; Triterpenes; Tumor Necrosis Factor-alpha | 2014 |
Oroxylin A inhibits ATRA-induced IL-6 expression involved in retinoic acid syndrome by down-regulating CHOP.
Production of IL-6 constituted the major cause of death in the ATRA trial called retinoic acid syndrome (RAS). LAP and LIP are active and inactive isoforms of C/EBPβ, respectively. Inactive LIP dimerized with LAP to eliminate its activity. Following treatment with ATRA, CHOP expression was increased and dimerized with LIP more preferentially than LAP to rescue function of LAP. Oroxylin A has been reported to activate CHOP, a key mediator of unfolded protein response (UPR) pathway, and resulted in apoptosis. Interestingly, we found that low concentration of oroxylin A (≦ 40 μM) showed no apoptosis effect on NB4 and HL-60 cells and decreased the CHOP protein level via promoting its degradation. MG132 was utilized to conform the effect of oroxylin A on degrading CHOP. Our results showed that oroxylin A decreased the level of IL-6 secretion of NB4 cells with or without ATRA treatment while the effect was eliminated by C/EBPβ siRNA. We conclude that oroxylin A possessed abilities of inhibiting the ATRA-induced IL-6 production via modulation of LAP/LIP/CHOP in leukemia cell lines, which could providing a therapeutic strategy for RAS. Topics: Antineoplastic Agents; Apoptosis; Blotting, Western; CCAAT-Enhancer-Binding Protein-beta; Cell Line, Tumor; Dose-Response Relationship, Drug; Down-Regulation; Flavonoids; Gene Expression; HL-60 Cells; Humans; Interleukin-6; K562 Cells; Leupeptins; RNA Interference; Syndrome; Transcription Factor CHOP; Tretinoin; U937 Cells | 2014 |
High cutoff membrane to reduce systemic inflammation due to differentiation syndrome: a case report.
Differentiation syndrome is a life-threatening complication of therapy that is carried out with agents used for acute promyelocytic leukemia. Its physiopathology comprehends the production of inflammatory mediators by differentiating granulocytes, endothelial and alveolar cells due to stimulation by all-trans retinoic acid and leading to sustained systemic inflammation.. Treatment with high cut-off continuous veno-venous hemodialysis (HCO-CVVHD) was performed to reduce the circulating mediators of systemic inflammation.. After 52 h of treatment, an important reduction was observed in inflammatory mediators (IL-1β: from 10 to 2 pg/ml; IL-8: from 57 to 40 pg/ml; TNF-α: from 200 to 105 pg/ml; IL-6: from 263 to 91 pg/ml), as well as in anti-inflammatory mediators (IL-10: from 349 to 216 pg/ml).. HCO-CVVHD should be explored as a part of treatment in systemic inflammation states other than sepsis (e.g., differentiation syndrome). Furthermore, its immunomodulatory effects could be particularly useful in immunocompromised patient treated with corticosteroids. Topics: Acute Kidney Injury; Adult; Anticoagulants; Antineoplastic Combined Chemotherapy Protocols; Calcium Citrate; Capillary Leak Syndrome; Cell Differentiation; Disseminated Intravascular Coagulation; Fatal Outcome; Hemofiltration; Humans; Idarubicin; Immunomodulation; Inflammation; Inflammation Mediators; Leukemia, Promyelocytic, Acute; Male; Membranes, Artificial; Molecular Weight; Permeability; Prednisolone; Respiratory Insufficiency; Serum Albumin; Syndrome; Tretinoin | 2014 |
Acute promyelocytic leukemia, study of predictive factors for Differentiation Syndrome, single center experience.
Reports about patients with acute promyelocytic leukemia from the Middle East are few; in this study we are reporting our single center experience of treating 29 patients over 6years. Acute promyelocytic leukemia treatment response is markedly improved after the introduction of ATRA. Treatment related complication is still an important issue particularly Differentiation Syndrome. Prediction to its occurrence has been tried by other groups. We aimed to study all the possible predictive factors of acute promyelocytic leukemia. Our chemotherapy induction protocol is AIDA protocol which includes ATRA 45mg/m(2)/d in divided doses every12h, and Idarubicin 12mg/m(2)/d IV on days 3, 5, 7, and 9. Differentiation Syndrome occurred in 48.3% of patients and was mainly presented by pulmonary symptoms in 55.2%, 6 cases died during induction. None of the predictive factors studied showed a statistically significant difference between patients who developed Differentiation Syndrome and those who did not. Differentiation Syndrome did not affect overall survival. Cox regression showed an inverse yet a non significant association between PETHEMA and overall survival probability (P=0.168). In conclusion, Differentiation Syndrome has no clear predictive factor to date. The best approach is to hold ATRA and give dexamethasone which is quite effective as reported in the literature. PETHEMA risk model has a moderately significant prognostic value. Topics: Adolescent; Adult; Aged; Aged, 80 and over; Female; Fever; Hemorrhage; Humans; Kaplan-Meier Estimate; Leukemia, Promyelocytic, Acute; Lung Diseases; Male; Middle Aged; Proportional Hazards Models; Risk Factors; Syndrome; Tretinoin; Young Adult | 2013 |
Predictive factors for all-trans retinoic acid-related differentiation syndrome in patients with acute promyelocytic leukemia.
All-trans retinoic acid (ATRA) used for the treatment of APL can lead to the development of differentiation syndrome (DS), a potentially life threatening complication. Since ATRA is metabolized by cytochrome P450 (CYP) enzymes, we sought to identify drug interactions that might be associated with a higher risk for the development of DS in addition to other predictive factors related to the incidence of DS. We identified 60 consecutive patients with APL treated at our institution with ATRA from May 2004 until January 2010. Of the 60 patients identified, 29 (48%) developed DS within a median of 5 days (range 1-31) of ATRA initiation. We did not find any difference in overall incidence of DS whether patients were on concurrent CYP 2C8, 2C9 or 3A4 inhibitors, inducers or substrates. In multivariable analysis, higher peripheral blood blast counts on admission (p=0.04) as well as higher body mass index (p=0.003) were associated with developing DS. Out of the 29 patients with DS, there were 4 early deaths of which 2 were attributed to DS compared to no early deaths in the patients who did not develop DS (p=0.05). Regarding disease-related outcomes, only CR rate was different between patients developing DS versus those who did not develop DS. Topics: Adolescent; Adult; Aged; Antineoplastic Agents; Body Mass Index; Cell Differentiation; Female; Follow-Up Studies; Humans; Leukemia, Promyelocytic, Acute; Male; Middle Aged; Neoplasm Recurrence, Local; Prognosis; Retrospective Studies; Survival Rate; Syndrome; Tretinoin; Young Adult | 2013 |
Retinoic acid syndrome--cardiac complication.
Retinoic acid syndrome is a novel complication of therapy with all-trans retinoic acid (ATRA) in patients with acute promyelocytic leukemia (APML). Primarily the syndrome consists of fever and respiratory distress. Additional features include weight gain, oedema over lower extremities, pleural or pericardial effusion and hypotension. We report electrophysiological changes in a 16 year old patient with acute promyelocytic leukemia following treatment with ATRA. Such an unusual complication is a rarity and to the best of our knowledge has not been previously reported. Topics: Adolescent; Antineoplastic Agents; Arrhythmias, Cardiac; Dexamethasone; Dyspnea; Female; Glucocorticoids; Humans; Leukemia, Promyelocytic, Acute; Pericardial Effusion; Syndrome; Tretinoin | 2012 |
Cardiac stunning as a manifestation of ATRA differentiation syndrome in acute promyelocytic leukemia.
Topics: Aged; Antineoplastic Agents; Coronary Angiography; Echocardiography; Female; Humans; Leukemia, Promyelocytic, Acute; Myocardial Stunning; Syndrome; Tretinoin | 2012 |
Increased BMI correlates with higher risk of disease relapse and differentiation syndrome in patients with acute promyelocytic leukemia treated with the AIDA protocols.
We investigated whether body mass index (BMI) correlates with distinct outcomes in newly diagnosed acute promyelocytic leukemia (APL). The study population included 144 patients with newly diagnosed and genetically confirmed APL consecutively treated at a single institution. All patients received All-trans retinoic acid and idarubicin according to the GIMEMA protocols AIDA-0493 and AIDA-2000. Outcome estimates according to the BMI were carried out together with multivariable analysis for the risk of relapse and differentiation syndrome. Fifty-four (37.5%) were under/normal weight (BMI < 25), whereas 90 (62.5%) patients were overweight/obese (BMI ≥ 25). An increased BMI was associated with older age (P < .0001) and male sex (P = .02). BMI was the most powerful predictor of differentiation syndrome in multivariable analysis (odds ratio = 7.24; 95% CI, 1.50-34; P = .014). After a median follow-up of 6 years, the estimated cumulative incidence of relapse at 5 years was 31.6% (95% CI, 22.7%-43.8%) in overweight/obese and 11.2% (95% CI, 5.3%-23.8%) in underweight/normal weight patients (P = .029). Multivariable analysis showed that BMI was an independent predictor of relapse (hazard ratio = 2.45, 95% CI, 1.00-5.99, in overweight/obese vs under/normal weight patients, P = .049). An increased BMI at diagnosis is associated with a higher risk of developing differentiation syndrome and disease relapse in APL patients treated with AIDA protocols. Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Body Mass Index; Child; Child, Preschool; Female; Follow-Up Studies; Humans; Idarubicin; Infant; Infant, Newborn; Leukemia, Promyelocytic, Acute; Male; Middle Aged; Neoplasm Recurrence, Local; Obesity; Overweight; Prognosis; Risk Factors; Survival Rate; Syndrome; Tretinoin; Young Adult | 2012 |
Perioperative retinoic acid syndrome in a patient with acute promyelocytic leukemia.
All-trans retinoic acid (ATRA), a vitamin A derivative, is prescribed for induction of chemotherapy in patients with acute promyelocytic leukemia. Like other chemotherapy agents, ATRA has an adverse effect known as retinoic acid syndrome. The case of a 22 year old woman with acute promyelocytic leukemia, who received ATRA and subsequently developed retinoic acid syndrome, is presented. The patient's symptoms resolved after administration of dexamethasone, allowing the completion of chemotherapy without further complications. Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Dexamethasone; Female; Glucocorticoids; Humans; Hypotension; Intraoperative Complications; Leukemia, Promyelocytic, Acute; Lung Diseases; Postoperative Complications; Syndrome; Tooth Extraction; Tretinoin; Young Adult | 2012 |
Bradycardia following retinoic acid differentiation syndrome in a patient with acute promyelocytic leukaemia.
The authors describe a 28-year-old woman with newly diagnosed acute promyelocytic leukaemia (APL), who developed junctional bradycardia after receiving the molecular-targeted therapy all-trans retinoic acid (ATRA) and the anthracycline-based chemotherapeutic agent idarubicin following sepsis and the APL differentiation syndrome. The patient was asymptomatic of the bradycardia. Electrolytes and cardiac imaging were unremarkable. No other cases have been reported in this context and the mechanisms of the sinus node dysfunction are unclear. The patient achieved normal sinus rhythm after ATRA was withheld. The patient recovered and went on to achieve complete remission after re-starting ATRA and idarubicin. Topics: Antineoplastic Agents; Bradycardia; Cell Differentiation; Electrocardiography; Female; Follow-Up Studies; Granulocyte Precursor Cells; Humans; Leukemia, Promyelocytic, Acute; Remission Induction; Syndrome; Tretinoin | 2012 |
Recurrent differentiation syndrome or septic shock? Unresolved dilemma in a patient with acute promyelocytic leukemia.
Differentiation syndrome (DS) is a life-threatening complication observed in patients with acute promyelocytic leukemia (APL) receiving induction therapy with all-trans-retinoic acid (ATRA). A bimodal incidence of DS has been observed, with a majority of cases occurring during the first week of ATRA treatment ("early" DS), but a substantial number of cases occurring during the third or even fourth week of ATRA treatment ("late" DS). However, to our knowledge occurrence of both early and late DS in the same patient has not been reported. We report an APL patient treated with the AIDA regimen, who experienced both early and late DS, a situation where differential diagnosis was difficult. Topics: Adult; Antineoplastic Agents; Cell Differentiation; Diagnosis, Differential; Humans; Leukemia, Promyelocytic, Acute; Male; Prognosis; Recurrence; Shock, Septic; Syndrome; Tretinoin | 2011 |
A new malformation syndrome with congenital arthrogryposis and severe hyperkeratosis.
Topics: Abnormalities, Multiple; Adult; Arthrogryposis; Facial Asymmetry; Female; Humans; Keratoderma, Palmoplantar; Neck; Scoliosis; Syndrome; Tretinoin | 2011 |
Hemophagocytic lymphohistiocytosis following differentiation syndrome in acute promyelocytic leukemia.
Topics: Aged; Antineoplastic Agents; Humans; Leukemia, Promyelocytic, Acute; Lung Diseases; Lymphohistiocytosis, Hemophagocytic; Male; Syndrome; Tretinoin; Weight Gain | 2011 |
Late-onset differentiation syndrome in a child with acute promyelocytic leukemia.
Topics: Cell Differentiation; Child; Humans; Leukemia, Promyelocytic, Acute; Male; Syndrome; Tretinoin | 2010 |
Noninvasive ventilation in a pregnant patient with respiratory failure from all-trans-retinoic-acid (ATRA) syndrome.
We saw a 34-year-old pregnant woman with acute promyelocytic leukemia, who developed acute respiratory failure from all-trans-retinoic acid (ATRA) syndrome. We applied noninvasive ventilation (NIV, continuous positive airway pressure plus pressure-support ventilation) to try to improve gas exchange, reduce the work of breathing, and prevent intubation. Initially we applied NIV continuously (24 hours a day), then gradually reduced the daily amount of time on NIV as her condition improved. She was discharged from the intensive care unit after 12 days. Three months after hospital discharge she gave vaginal birth to a healthy female baby. NIV was effective and safe for the mother and fetus, and NIV should be considered for respiratory failure in pregnant patients, especially if immunosuppressed. Topics: Antineoplastic Agents; Female; Humans; Leukemia, Myeloid, Acute; Pregnancy; Pregnancy Complications, Neoplastic; Respiration, Artificial; Respiratory Insufficiency; Syndrome; Tretinoin | 2009 |
Chemokine induction by all-trans retinoic acid and arsenic trioxide in acute promyelocytic leukemia: triggering the differentiation syndrome.
In acute promyelocytic leukemia (APL), differentiation therapy with all-trans retinoic acid (ATRA) and/or arsenic trioxide can induce a differentiation syndrome (DS) with massive pulmonary infiltration of differentiating leukemic cells. Because chemokines are implicated in migration and extravasation of leukemic cells, chemokines might play a role in DS. ATRA stimulation of the APL cell line NB4 induced expression of multiple CC-chemokines (CCLs) and their receptors (> 19-fold), resulting in increased chemokine levels and chemotaxis. Induction of CCL2 and CCL24 was directly mediated by ligand-activated retinoic acid receptors. In primary leukemia cells derived from APL patients at diagnosis, ATRA induced chemokine production as well. Furthermore, in plasma of an APL patient with DS, we observed chemokine induction, suggesting that chemokines might be important in DS. Dexamethasone, which efficiently reduces pulmonary chemokine production, did not inhibit chemokine induction in APL cells. Finally, chemokine production was also induced by arsenic trioxide as single agent or in combination with ATRA. We propose that differentiation therapy may induce chemokine production in the lung and in APL cells, which both trigger migration of leukemic cells. Because dexamethasone does not efficiently reduce leukemic chemokine production, pulmonary infiltration of leukemic cells may induce an uncontrollable hyperinflammatory reaction in the lung. Topics: Anti-Inflammatory Agents; Apoptosis; Arsenic Trioxide; Arsenicals; Cell Differentiation; Cell Line, Tumor; Chemokine CCL2; Chemokine CCL24; Chemokine CCL7; Chemokines; Dexamethasone; Enzyme-Linked Immunosorbent Assay; Gene Expression Profiling; Gene Expression Regulation, Leukemic; Humans; Leukemia, Promyelocytic, Acute; Oligonucleotide Array Sequence Analysis; Oxides; Receptors, Retinoic Acid; Reverse Transcriptase Polymerase Chain Reaction; Syndrome; Tretinoin; Tumor Cells, Cultured | 2009 |
Inhibiting the platelet derived growth factor receptor increases signs of retinoic acid syndrome in myeloid differentiated HL-60 cells.
PDGFR inhibitors are successfully used in a number of cancer treatments. The standard treatment for acute promyelocytic leukemia (APL) involves differentiation therapy with retinoic acid (RA). However, the relapse rates are significant. In the present work we evaluated the effects of RA therapy in the presence of PDGFR inhibitor, AG1296. Adding AG1296 with RA increased secretion of TNF-alpha, IL-8, and MMP-9 expression. This treatment induced higher levels of ICAM-1 endothelial cell expression, and increased cellular mobility. Inhibiting PDGFR enhanced RA-induced expression of integrin. Integrin ligand increased differentiation markers CD11b, inducible oxidative metabolism and PDGFR-beta phosphorylation. While the neutrophil-endothelial cell interactions are strengthened by the combined treatment, the endothelium-substratum interactions are weakened, a situation common in RAS. Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; CD18 Antigens; Cell Differentiation; Cell Movement; Contraindications; Drug Resistance, Neoplasm; Endothelial Cells; HL-60 Cells; Humans; Intercellular Adhesion Molecule-1; Interleukin-8; Leukemia, Promyelocytic, Acute; Ligands; Macrophage-1 Antigen; Matrix Metalloproteinase 9; Protein Kinase Inhibitors; Receptor, Platelet-Derived Growth Factor beta; Receptors, Platelet-Derived Growth Factor; Syndrome; Tretinoin; Tumor Necrosis Factor-alpha; Tyrphostins | 2008 |
Clinical and biological features of acute promyelocytic leukemia patients developing retinoic acid syndrome during induction treatment with all-trans retinoic acid and idarubicin.
Topics: Humans; Idarubicin; Leukemia, Promyelocytic, Acute; Syndrome; Treatment Outcome; Tretinoin | 2008 |
Hypothesis: Possible role of retinoic acid therapy in patients with biallelic mismatch repair gene defects.
A boy showing symptoms of a Turcot-like childhood cancer syndrome together with stigmata of neurofibromatosis type I is reported. His brother suffers from an infantile myofibromatosis, and a sister died of glioblastoma at age 7. Another 7-year-old brother is so far clinically unaffected. The parents are consanguineous. Molecular diagnosis in the index patient revealed a constitutional homozygous mutation of the mismatch repair gene PMS2. The patient was in remission of his glioblastoma (WHO grade IV) after multimodal treatment followed by retinoic acid chemoprevention for 7 years. After discontinuation of retinoic acid medication, he developed a relapse of his brain tumour together with the simultaneous occurrence of three other different HNPCC-related carcinomas. We think that retinoic acid might have provided an effective chemoprevention in this patient with homozygous mismatch repair gene defect. We propose to take a retinoic acid chemoprevention into account in children with proven biallelic PMS2 mismatch repair mutations being at highest risk concerning the development of a malignancy. Topics: Adenomatous Polyps; Adenosine Triphosphatases; Alleles; Base Pair Mismatch; Brain Neoplasms; Child; Colorectal Neoplasms; DNA Repair Enzymes; DNA-Binding Proteins; Female; Germ-Line Mutation; Glioblastoma; Homozygote; Humans; Magnetic Resonance Imaging; Male; Microsatellite Instability; Microsatellite Repeats; Mismatch Repair Endonuclease PMS2; Mutation; Neoplasm Recurrence, Local; Syndrome; Tretinoin | 2008 |
Retinoic acid syndrome after first dose of ATRA and ileal perforation secondary to promyelocytes infiltration.
Topics: Adult; Antineoplastic Agents; Fatal Outcome; Humans; Ileum; Intestinal Perforation; Leukemia, Promyelocytic, Acute; Leukemic Infiltration; Male; Syndrome; Tretinoin | 2008 |
RBP4 disrupts vitamin A uptake homeostasis in a STRA6-deficient animal model for Matthew-Wood syndrome.
The cellular uptake of vitamin A from its RBP4-bound circulating form (holo-RBP4) is a homeostatic process that evidently depends on the multidomain membrane protein STRA6. In humans, mutations in STRA6 are associated with Matthew-Wood syndrome, manifested by multisystem developmental malformations. Here we addressed the metabolic basis of this inherited disease. STRA6-dependent transfer of retinol from RBP4 into cultured NIH 3T3 fibroblasts was enhanced by lecithin:retinol acyltransferase (LRAT). The retinol transfer was bidirectional, strongly suggesting that STRA6 acts as a retinol channel/transporter. Loss-of-function analysis in zebrafish embryos revealed that Stra6 deficiency caused vitamin A deprivation of the developing eyes. We provide evidence that, in the absence of Stra6, holo-Rbp4 provokes nonspecific vitamin A excess in several embryonic tissues, impairing retinoic acid receptor signaling and gene regulation. These fatal consequences of Stra6 deficiency, including craniofacial and cardiac defects and microphthalmia, were largely alleviated by reducing embryonic Rbp4 levels by morpholino oligonucleotide or pharmacological treatments. Topics: Abnormalities, Multiple; Acyltransferases; Animals; Cardiovascular Abnormalities; Craniofacial Abnormalities; Disease Models, Animal; Eye; Gene Deletion; Gene Expression Regulation, Developmental; Homeostasis; Humans; Membrane Proteins; Membrane Transport Proteins; Mice; Morpholines; NIH 3T3 Cells; Oligonucleotides, Antisense; Retinol-Binding Proteins, Plasma; Syndrome; Time Factors; Transduction, Genetic; Tretinoin; Vitamin A; Zebrafish; Zebrafish Proteins | 2008 |
Retinoic acid-induced CD38 antigen promotes leukemia cells attachment and interferon-gamma/interleukin-1beta-dependent apoptosis of endothelial cells: implications in the etiology of retinoic acid syndrome.
All-trans retinoic acid (RA) treatment of patients with acute promyelocytic leukemia (APL) induces complete remission in more than 90% of the cases. Although RA therapy is well tolerated, about 25% of APL patients develop a potentially fatal condition called retinoic acid syndrome (RAS). Molecular mechanisms underlying the development of RAS pathogenesis, especially those that result in the damage of endothelial cells remain elusive. In the present study, we found that RA treatment induces the expression of interferon-gamma (IFN-gamma) and interleukin-1beta (IL-1beta) in peripheral blast cells from APL patients. IFN-gamma and IL-1beta also exerted synergistic effect in driving human umbilical cord endothelial cells (HUVECs) and human lung microvascular endothelial cells (HLMVECs) into apoptosis. RA also upregulated the expression of CD38, an ectoenzyme responsible for the generation of the calcium messenger cyclic ADP-ribose. Importantly, RA-induced CD38 expression promoted strong attachment of leukemia cells to endothelial cells, and incubation of endothelial cells with either high concentration (100 ng/ml) of IFN-gamma alone or low concentration of IL-1beta and IFN-gamma (10 ng/ml, each) induced strong apoptotic responses as revealed by caspase-8 activation and DNA fragmentation. Our results suggest that these RA-induced events could contribute to the development of RAS pathogenesis in patients with APL. Topics: ADP-ribosyl Cyclase 1; Antineoplastic Agents; Apoptosis; Blast Crisis; Blotting, Western; Cell Adhesion; Cell Differentiation; Cells, Cultured; Endothelium, Vascular; Humans; Interferon-gamma; Interleukin-1beta; Leukemia, Promyelocytic, Acute; Lung; Nitric Oxide; Receptors, Retinoic Acid; Respiration Disorders; Syndrome; Tretinoin; Umbilical Veins | 2007 |
Understanding another acute respiratory distress syndrome.
Topics: Antineoplastic Agents; Cell Line, Tumor; Cell Movement; Chemokine CXCL1; Chemokines, CXC; Chemotaxis, Leukocyte; Epithelial Cells; Flow Cytometry; Humans; In Vitro Techniques; Interleukin-8; Leukemia, Promyelocytic, Acute; Pulmonary Alveoli; Respiratory Distress Syndrome; Syndrome; Tretinoin | 2007 |
Haemolytic uremic syndrome during induction therapy in an acute promyelocytic leukemia patient with aberrant phenotype: a possible manifestation of retinoic acid syndrome.
Topics: Diagnosis, Differential; Electrolytes; Female; Hemolytic-Uremic Syndrome; Humans; Leukemia, Promyelocytic, Acute; Middle Aged; Phenotype; Remission Induction; Syndrome; Thrombocytopenia; Treatment Outcome; Tretinoin | 2007 |
Stephen L. Gans Distinguished Overseas Lecture. The neural crest in pediatric surgery.
This review highlights the relevance of the neural crest (NC) as a developmental control mechanism involved in several pediatric surgical conditions and the investigative interest of following some of its known signaling pathways.. The participation of the NC in facial clefts, ear defects, branchial fistulae and cysts, heart outflow tract and aortic arch anomalies, pigmentary disorders, abnormal enteric innervation, neural tumors, hemangiomas, and vascular anomalies is briefly reviewed. Then, the literature on clinical and experimental esophageal atresia-tracheoesophageal fistula (EA-TEF) and congenital diaphragmatic hernia (CDH) is reviewed for the presence of associated NC defects. Finally, some of the molecular signaling pathways involved in both conditions (sonic hedgehog, Hox genes, and retinoids) are summarized.. The association of facial, cardiovascular, thymic, parathyroid, and C-cell defects together with anomalies of extrinsic and intrinsic esophageal innervation in babies and/or animals with both EA-TEF and CDH strongly supports the hypothesis that NC is involved in the pathogenesis of these malformative clusters. On the other hand, both EA-TEF and CDH are observed in mice mutant for genes involved in the previously mentioned signaling pathways.. The investigation of NC-related molecular pathogenic pathways involved in malformative associations like EA-TEF and CDH that are induced by chromosomal anomalies, chemical teratogens, and engineered mutations is a promising way of clarifying why and how some pediatric surgical conditions occur. Pediatric surgeons should be actively involved in these investigations. Topics: Abnormalities, Multiple; Blood Vessels; Branchial Region; Cardiovascular Abnormalities; Cell Lineage; Cell Movement; Child; Child, Preschool; Enteric Nervous System; Esophageal Atresia; Face; Genes, Homeobox; Hedgehog Proteins; Hernia, Diaphragmatic; Hernias, Diaphragmatic, Congenital; Homeodomain Proteins; Humans; Infant; Infant, Newborn; Neoplasms; Neural Crest; Patched Receptors; Pigmentation Disorders; Receptors, Cell Surface; Receptors, G-Protein-Coupled; Receptors, Retinoic Acid; Signal Transduction; Smoothened Receptor; Syndrome; Transcription Factors; Tretinoin; Zinc Finger Protein GLI1 | 2007 |
[Acute renal failure in the transretinoic syndrome].
The all-trans retinoic acid (ATRA) is the treatment of first line of acute promyelocytic leukemia (APL). ATRA is usually well tolerated, but a few major side effects can be observed, ATRA syndrome (RAS) being the most important of them, potentially fatal. The manifestations of this Syndrome are fever, weight gain, pulmonary infiltrates, pleural or pericardial effusions, hypotension, liver dysfunction and renal failure.. We studied to the 29 patients diagnosed in (January of 2002 - December of 2004) of acute promyelocytic leukemia (APL), which were treated with ATRA, all received the 45 dose of mg/m(2)/d . The diagnosis of the leukemia was made by citomorphologist analysis. The criterion of renal insufficiency, it was an increase of the creatinina superior to 20% of the basal level. The definition of the transretinoico acid Syndrome was based on the clinical criteria of Frankel.. Fourteen patients presented the Transretinoico Syndrome (48.3%), 11 of which (37.9%) died. The fundamental differences between the patients with or without ATRA were: fever (14 vs. 9, p=0,017), gain of weight (14 vs 0, p=0,000), pleural effusion (14 vs 2, p=0.000), pulmonary infiltrates (13 vs 1, p=0,000), cardiac failure (12 versus 2, p=0,000), respiratory distress (12 versus 4, p=0,003), presence of renal failure (10 vs 4, p=0,02), necessity of substitute renal treatment (6 vs 0, p=0,006) and arterial hypotension (12 vs. 3, p=0,001). The acute renal failure appeared in 10 of the 14 patients with SAR (71.4%), to 12+/-5 (1-25) days of the beginning of the treatment and their duration it was of 14+/-5 (1-46) days. Six (60%) needed substitute renal treatment and 5 (50%) died. Of the patients who survived, only a patient continues in dialysis. In both patient in that renal biopsy was made, the study showed signs of cortical necrosis.. The appearance of acute renal failure in the course of the SAR is frequent, being observed deterioration of the renal function that needs substitute renal treatment in more than half the cases. The association of RAS with renal failure entails the high mortality (50%). The diagnosis and the precocious restoration of suitable the preventive measures and therapeutic are very important to avoid in possible the this serious complication of the treatment with ATRA. Topics: Acute Kidney Injury; Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Child; Female; Humans; Male; Middle Aged; Prevalence; Syndrome; Tretinoin | 2007 |
The association of ICAM-1 Exon 6 (E469K) but not of ICAM-1 Exon 4 (G241R) and PECAM-1 Exon 3 (L125V) polymorphisms with the development of differentiation syndrome in acute promyelocytic leukemia.
The use of all trans-retinoic acid (ATRA) is the basis of treatment of acute promyelocytic leukemia (APL) and represents the paradigm of differentiation therapy. In general, ATRA is well-tolerated but may be associated with a potentially lethal side-effect, referred to as retinoic acid or differentiation syndrome (DS). The cellular and molecular mechanisms of DS are poorly understood and involve changes in the adhesive qualities and cytokine secretion of leukemic cells during ATRA-induced differentiation. As leukocyte extravasation is a key event in DS pathogenesis, we analyzed the association between the polymorphisms at Exon 4 (G241R) and Exon 6 (E469K) of ICAM-1 and Exon 3 (L125V) of PECAM-1 genes with DS development in APL patients treated with ATRA and anthracyclines. DS was diagnosed in 23/127 (18.1%) APL patients at an average of 11.5 days after the start of ATRA. All patients presented respiratory distress associated with increased ground-glass opacity in chest radiographies. Other accompanying symptoms were: fever not attributable to infection (65.2%), generalized edema (37.5%), weight gain (37.5%), and impairment of renal function (8.6%). We detected an association between development of DS and the AA genotype at Codon 469 of ICAM-1 (odds ratio of 3.5; 95% confidence interval: 1.2-10.2). Conversely, no significant association was detected between G241R or L125V polymorphisms at Exon 4 of ICAM-1 and Exon 3 of PECAM-1, respectively. Our results suggest that susceptibility to DS in APL patients may be influenced by genetic variation in adhesion molecule loci. Topics: Adult; Antineoplastic Agents; Cell Differentiation; Diagnosis, Differential; Exons; Female; Humans; Intercellular Adhesion Molecule-1; Leukemia, Promyelocytic, Acute; Male; Platelet Endothelial Cell Adhesion Molecule-1; Polymorphism, Genetic; Syndrome; Tretinoin | 2007 |
Atypical presentation of retinoic acid syndrome that mimics septic arthritis in a patient with acute promyelocytic leukemia.
Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Arthritis, Infectious; Diagnosis, Differential; Female; Humans; Joint Diseases; Leukemia, Promyelocytic, Acute; Syndrome; Tretinoin | 2007 |
Adhesion molecules and Differentiation Syndrome: phenotypic and functional analysis of the effect of ATRA, As2O3, phenylbutyrate, and G-CSF in acute promyelocytic leukemia.
Differentiation Syndrome (DS) is a treatment complication which can occur in patients treated with acute promyelocytic leukemia (APL) with all transretinoic acid (ATRA) or As(2)O(3), and is characterized by enhanced leukocyte transmigration. As(2)O(3), Phenylbutyrate (PB) and G-CSF are known to potentiate ATRA effects. Our aim was to analyze the changes in expression and function of adhesion molecules induced by ATRA, As(2)O(3), G-CSF and PB, and their association.. APL blasts and NB4 cells were treated with ATRA, As(2)O(3), PB, G-CSF or their association and the expression of adhesion molecules was determined by flow cytometry. Cell adhesion was evaluated in vitro using Matrigel and for the in vivo analysis, Balb-c mice were injected with NB4 cells pre-treated with ATRA, As(2)O(3), ATRA+G-CSF or ATRA+As(2)O(3). In addition, CD54 and CD18 knock-out mice were injected with NB4 cells and concomitantly treated with ATRA. In both models, the MPO activity in the lungs was determined 6 hours after the injection of the cells.. In NB4 and APL blasts, ATRA and As(2)O(3) increased CD54 expression, but no synergism was detected. CD11b and CD18 were also up-regulated by ATRA in primary cells. PB and G-CSF had no effect, but the latter potentiated ATRA-induced CD18 up-regulation. These changes were accompanied by increased adhesion to Matrigel and to lung microvasculature, and reversed by anti-CD54, anti-CD18 antibodies. In CD54 and CD18 knock-out mice the ATRA effect was canceled.. The use of As(2)O(3), PB and G-CSF in association with ATRA should not aggravate DS in APL. Topics: Animals; Antigens, CD; Antineoplastic Agents; Arsenic Trioxide; Arsenicals; Cell Adhesion; Cell Adhesion Molecules; Cell Differentiation; Gene Expression Regulation, Leukemic; Granulocyte Colony-Stimulating Factor; Humans; Leukemia, Promyelocytic, Acute; Mice; Mice, Inbred BALB C; Mice, Knockout; Neoplasm Proteins; Oxides; Phenylbutyrates; Syndrome; Tretinoin; Tumor Cells, Cultured | 2007 |
[All-trans retinoic acid syndrome [corrected] and renal cortical necrosis].
We described a patient with acute promyelocytic leukemia (APL) who developed all-trans retinoic acid syndrome (ATRAS). ATRAS presents in patients with APL treated with all-trans retinoic acid (ATRA). It has an incidence from 5-27% with mortality of 29%. ATRAS clinical manifestations are fever, hypotension, respiratory, renal and hepatic insufficiency, lung infiltrates, pleural and pericardic effusion, and generalized edema. It is secondary to ATRA effect on promyelocyte differentiation, which causes systemic inflammatory response syndrome, endothelium damage with increase in capillary permeability, microcirculation obstruction, and tissue infiltration. Treatment is based on ATRA suspension, steroids and support measures. Topics: Adult; Antineoplastic Agents; Female; Humans; Kidney Cortex Necrosis; Leukemia, Promyelocytic, Acute; Syndrome; Tretinoin | 2007 |
Implication of Wt1 in the pathogenesis of nephrogenic failure in a mouse model of retinoic acid-induced caudal regression syndrome.
Renal malformations are common human birth defects that sometimes occur in the context of the caudal regression syndrome. Here, we found that exposure of pregnant mice to all-trans retinoic acid, at a time when the metanephros has yet to form, causes a failure of kidney development along with caudal regression. Maternal treatment with Am580 (retinoic acid receptor alpha agonist) also induced similar patterns of kidney maldevelopment in the fetus. In metanephroi from retinoic acid-treated pregnancies, renal mesenchyme condensed around the ureteric bud but then failed to differentiate into nephrons, instead undergoing involution by fulminant apoptosis to produce a renal agenesis phenotype. Results of whole organ cultures in serum-free medium, and also tissue recombination experiments, showed that the nephrogenic defect was intrinsic to the kidney and that it resided in the metanephric mesenchyme and not the ureteric bud. Renal mesenchyme from control embryos expressed Wilms' tumor 1 (Wt1), but this transcription factor, which is indispensable for kidney development, failed to express in metanephroi of retinoic acid-exposed embryos. Wt1 expression and organogenesis were both restored, however, when metanephroi from retinoic acid-treated pregnancies were grown in serum-containing media. Our data illuminate the pathobiology of a severe, teratogen-induced kidney malformation. Topics: Abnormalities, Multiple; Anal Canal; Animals; Coculture Techniques; Congenital Abnormalities; Embryonic Development; Female; Gene Expression; Genes, Wilms Tumor; Kidney; Lumbar Vertebrae; Mesoderm; Mice; Mice, Inbred ICR; Spinal Cord; Syndrome; Tissue Culture Techniques; Tretinoin | 2005 |
Nevus comedonicus syndrome: a case associated with multiple basal cell carcinomas and a rudimentary toe.
Topics: Adult; Amoxicillin-Potassium Clavulanate Combination; Benzoyl Peroxide; Carcinoma, Basal Cell; Cryosurgery; Dermatologic Agents; Drug Therapy, Combination; Humans; Male; Nevus, Pigmented; Skin Neoplasms; Syndrome; Toes; Tretinoin | 2005 |
Successful treatment of retinoic acid syndrome with dexamethasone: a case report.
Retinoic acid syndrome (RAS) is the clinical syndrome that occurs after treatment of acute promyelocytic leukemia with all-trans-retinoic acid (ATRA). The patients experience fever, dyspnea, hypotension, respiratory distress, edema and weight gain. Chest x-ray will show pulmonary infiltrates and pleuropericardial effusion. The onset of this syndrome is usually 5-21 days after ATRA treatment when white blood cell counts are rising more than 10,000/cu.mm. The authors have reported a case of RAS. The patient was a 29-year-old man who had been working in a battery manufacturing factory for 7 years. He presented with easily bruising for one month. The initial blood test showed hematocrit of 36.2%, white blood cells count of 3,200/cu.mm with 28% neutrophils, 20% lymphocytes, 2% eosinophils and 50% promyelocytes and platelet of 20,000/cu.mm. Peripheral blood smear revealed numerous fragmented red blood cells. Bone marrow examination showed hypercellularity with abnormal promyelocytes of 95% and bone marrow cytogenetics was translocation of chromosome 15 and 17 [t (15;17)(q22;q12)]. The diagnosis was acute promyelocytic leukemia and the patient was treated with ATRA 45 mg/m2/day per oral starting on day 1 and intravenous idarubicin 10 mg/n2 on day 4, 5 and 6. On day 13, he had a body temperature of 39 degrees C and a dry cough. The white blood cells were rising to 7,400/cu.mm with 16% neutrophils. On day 18, he had oliguria, high grade fever, hypotension, cough with chest pain and white blood cells rose to 21,300/cu.mm with 65% neutrophils and rising of blood urea nitrogen and creatinine. Chest x-ray showed enlarged cardiac shadow with pleural effusion. Echocardiogram revealed moderate amount of pericardial effusion. The diagnosis of RAS was made and ATRA was withdrawn. Intravenous dexamethasone 4 mg every 6 hours and hemodialysis was started. The patient's symptoms improved dramatically and bone marrow examination was in complete remission. He was subsequently given cytarabine and idarubicin as consolidation. This patient had clinical manifestation consistent with RAS, which improved after prompt treatment. Topics: Acute Kidney Injury; Adult; Dexamethasone; Glucocorticoids; Humans; Leukemia, Promyelocytic, Acute; Male; Respiration Disorders; Syndrome; Tretinoin | 2005 |
Retinoic acid syndrome in NOD/scid mice induced by injecting an acute promyelocytic leukemia cell line.
All-trans retinoic acid (ATRA) induces complete remission in patients with acute promyelocytic leukemia (APL). However, ATRA sometimes causes retinoic acid syndrome (RAS) characterized by respiratory distress, pleural effusions, fever and weight gain. To investigate the pathophysiology of RAS, we generated an animal model by injecting an APL cell line, NB4, into immunodeficient mice. When NOD/scid mice were injected intravenously with fully differentiated NB4 cells (1 x 10(7)) and then given a daily administration of ATRA, three of 12 mice died of pulmonary edema within 14 days. Pathologically, dilated lung capillary vessels and alveolar effusions were observed. After the injection, NB4 cells were detected in the lung within 2 days and in the pleural effusion later on. The gene expression levels of CXC chemokines (MIP-2 and KC) and ICAM-1 were increased in the lung and heart by the ATRA administration. In immunohistochemical analyses, MIP-2 was clearly detected in alveolar macrophages of the lung in mice with RAS. Dexamethasone treatment prevented the development of RAS and decreased the CXC chemokine mRNA expression in the lung. These findings suggested that the activation of adhesion molecules for leukocytes and expression of CXC chemokines in the lung are closely involved in triggering RAS. Topics: Animals; Antineoplastic Agents; Cell Differentiation; Chemokines, CXC; Doxorubicin; Heart; Humans; Injections, Intravenous; Leukemia, Promyelocytic, Acute; Lung; Mice; Mice, Inbred C57BL; Mice, Inbred NOD; Mice, SCID; Neoplastic Stem Cells; Pulmonary Edema; Remission Induction; Syndrome; Tretinoin; Tumor Cells, Cultured | 2004 |
Hemophagocytic syndrome associated with retinoic acid syndrome in acute promyelocytic leukemia.
A 56-year-old woman with an acute promyelocytic leukemia (APL) developed a severe all-trans-retinoic (ATRA) syndrome on day 17 of treatment. Shortly after, she presented a picture of pancytopenia, hepatosplenomegaly, increased triglycerides, ferritin, and liver enzymes. A bone marrow biopsy showed abundant macrophages and no evidence of leukemia. Tests for secondary hemophagocytic syndrome (HPS) were negative. A diagnosis of HPS was made. Treatment with dexamethasone and high-dose immunoglobulins was unsuccessful. Consolidation chemotherapy with idarubicin and ATRA rapidly reversed the HPS. The HPS in this patient could be related to the release of macrophage-stimulating cytokines by APL cells during ATRA syndrome. Topics: Antineoplastic Agents; Female; Histiocytosis; Humans; Leukemia, Promyelocytic, Acute; Middle Aged; Syndrome; Treatment Outcome; Tretinoin | 2004 |
Retinoic acid and steroid in acute promyelocytic leukemia.
Topics: Dexamethasone; Drug Therapy, Combination; Humans; Leukemia, Promyelocytic, Acute; Risk Factors; Syndrome; Tretinoin | 2003 |
[Clinical analysis of retinoic acid syndrome developed in 11 patients with acute promyelocytic leukemia].
To explore the clinical features, risk factors an d treatment of retinoic acid syndrome (RAS) in patients with acute promyelocytic leukemia (APL) treated with retinoic acid, the clinical and laboratory data of 11 APL patients with RAS were retrospectively analysed. The results showed that earlier and more common symptoms of RAS were successively dyspnea (11/11), fever (10/11) and hydrothorax (6/11). Higher WBC count (> or = 15.0 x 10(9)/L) in the course of treatment of all-trans retinoic acid susceptible to develop RAS (9/11). The RAS patients were treated with dexamethasone without discontinuing the treatment of retinoic acid, complete remission was achieved in 10 cases and one patient died from disseminated intravascular coagulation. It is concluded that the identification and dexamethasone treatment of RAS in earlier period are extremely important for obtaining better clinical curative effect, and it does not influence therapeutic effect of continuing application of retinoic acid. Topics: Adolescent; Adult; Child; Dyspnea; Female; Fever; Humans; Hydrothorax; Leukemia, Promyelocytic, Acute; Male; Middle Aged; Syndrome; Tretinoin | 2003 |
Retinoic acid syndrome.
Vitamin A derivative all-transretinoic acid (ATRA) has been reported to improve the outcome in patients with acute promyelocytic leukemia (APL). Retinoic Acid Syndrome (RAS) is a complication that has been noted to occur during the treatment of APL with ATRA. It is a clinical syndrome consisting of a constellation of signs and symptoms. In a patient with APL on ATRA, the diagnosis of RAS can be made based upon the presence of three of the following features: Fever, dyspnea, weight gain, hypotension, renal failure, pulmonary infiltrates, pleural effusion, and pericardial effusion. Pulmonary manifestations, especially pulmonary edema, are the most common presentation. Incidence of this adverse effect ranges from 6% to 27%. The pathogenesis of this complication is not completely understood. It can be potentially life threatening if not promptly recognized and treated. We report a case of retinoic acid syndrome in a young male with APL being treated with ATRA. Topics: Adult; Humans; Leukemia, Promyelocytic, Acute; Male; Syndrome; Tretinoin | 2003 |
ATRA syndrome with extensive organ infiltration.
Topics: Antineoplastic Agents; Digestive System; Endothelium, Vascular; Fatal Outcome; Humans; Kidney; Leukemia, Promyelocytic, Acute; Leukocytosis; Male; Myocardium; Neoplastic Stem Cells; Respiratory System; Syndrome; Testis; Tretinoin | 2002 |
Radiologic features of all-trans-retinoic acid syndrome.
The treatment of acute promyelocytic leukemia with all-trans-retinoic acid (ATRA) sometimes results in a syndrome characterized by fever, respiratory distress, weight gain, pleural and pericardial effusion, and pulmonary infiltrates. We report the radiologic features of ATRA syndrome.. During the past 5 years, 69 patients with acute promyelocytic leukemia were treated with ATRA. Of this group, 15 patients developed ATRA syndrome. Serial chest radiographs of the 15 patients with ATRA syndrome were evaluated retrospectively for the presence of pleural effusion, pulmonary nodules, consolidation, ground-glass opacity, septal lines, increased pulmonary blood volume, peribronchial cuffing, and air bronchogram. Also, we measured the cardiothoracic ratio and the vascular pedicle width.. Chest radiographs showed increased cardiothoracic ratio in 13 of the 15 patients, increased vascular pedicle width in 13, increased pulmonary blood volume in 13, septal lines in nine, peribronchial cuffing in nine, ground-glass opacity in nine, consolidation in seven, and nodules in seven. Pleural effusion was noted in 11 of the 15 patients, and air bronchogram was noted in five of the 15 patients. Pulmonary hemorrhage developed in three patients who were being treated with ATRA; they showed bilateral, diffuse, poorly defined nodules and ground-glass opacity on radiography.. Most patients with ATRA syndrome have abnormal findings on chest radiographs, and the abnormalities are similar to those of pulmonary edema. Topics: Adult; Antineoplastic Agents; Female; Fever; Humans; Lung Diseases; Male; Middle Aged; Pericardial Effusion; Pleural Effusion; Radiography; Syndrome; Tretinoin; Weight Gain | 2002 |
Retinoic acid syndrome: a case of massive lung consolidation.
Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Fever; Humans; Hypotension; Idarubicin; Leukemia, Promyelocytic, Acute; Leukocytosis; Lung; Male; Respiratory Distress Syndrome; Syndrome; Tretinoin | 2002 |
Retinoic acid syndrome: a problem of the past?
Topics: Acute Kidney Injury; Antineoplastic Agents; Dexamethasone; Humans; Hypertension; Incidence; Leukemia, Promyelocytic, Acute; Leukocyte Count; Leukocytosis; Leukostasis; Mortality; Premedication; Respiratory Distress Syndrome; Risk Factors; Syndrome; Tretinoin | 2002 |
Sweet's syndrome associated with retinoic acid syndrome in a patient with promyelocytic leukemia.
We report a case of Sweet's syndrome associated with retinoic acid syndrome in a patient with acute promyelocytic leukemia treated with all- trans retinoic acid (ATRA). Sweet's syndrome appeared on day 6 of ATRA therapy for promyelocytic leukemia. It was associated with a mild retinoic acid syndrome, an inflammatory syndrome occurring in 25% of patients treated with ATRA and characterized by features of capillary leakage with systemic inflammatory signs. The ATRA therapy was discontinued for 11 days and treatment with corticosteroids improved the systemic and cutaneous signs. Only 11 cases of Sweet's syndrome associated with ATRA have been previously reported in the literature, involving only the skin in eight cases, the skin and muscles in two cases, and the lung, kidney, fascia, and muscles in one case. Sweet's syndrome was followed by retinoic acid syndrome in one of these cases. The previously reported cases are reviewed, and the mechanisms of Sweet's and retinoic acid syndromes and the link between them are discussed. Topics: Antineoplastic Agents; Fever; Humans; Leukemia, Promyelocytic, Acute; Male; Middle Aged; Sweet Syndrome; Syndrome; Tretinoin; Weight Gain | 2002 |
[The retinoic acid syndrome, a complication of acute promyelocytic leukemia therapy].
To describe the retinoic acid syndrome, a complication of therapy with all-trans retinoic acid (ATRA) in acute promyelocitic leukemia (APL).. Retrospective study of five patients with a morphologic diagnosis of APL by the French-American-British (FAB) classification that were treated for remission induction with ATRA and developed the ATRA syndrome.. Three patients in newly diagnosed APL and two in leukemia relapse were analyzed. All patients received with ATRA 45 mgrs/m2/day, and three of them also received chemotherapy. Patients developed fever, respiratory distress, pulmonary infiltrates, weight gain and edemas. The onset of this symptom complex occurred from 1 to 11 days after starting treatment and was preceded by an increased in peripheral blood leukocytes. Infections or congestive heart failure were ruled out. The clinical course progressed while patients being treated with wide spectrum antibiotics. Four patients were treated with high doses corticosteroid therapy (dexametasone 10 mgrs intravenously every 12 hours), in three of them full recovery was attained and one died. One patient that did not received steroids died.. The use of all-trans retinoic acid to induce hematologic remission in APL patients is associated in same patients with the development of ATRA syndrome, a life threatening complication. Symptoms begin in the first days of treatment. If this syndrome is suspected, early treatment with high dose steroids should be initiated. Topics: Adolescent; Antineoplastic Agents; Female; Humans; Leukemia, Myeloid, Acute; Lung Diseases, Interstitial; Male; Middle Aged; Pulmonary Edema; Respiratory Insufficiency; Retrospective Studies; Syndrome; Tretinoin | 2001 |
Embryonic gut anomalies in a mouse model of retinoic Acid-induced caudal regression syndrome: delayed gut looping, rudimentary cecum, and anorectal anomalies.
Vitamin A and its derivatives such as retinoic acid (RA) are important signaling molecules for morphogenesis of vertebrate embryos. Little is known, however, about morphogenetic factors controlling the development of the gastrointestinal tract and RA is likely to be involved. In the mouse, teratogenic doses of RA cause truncation of the embryonic caudal body axis that parallel the caudal regression syndrome as described in humans. These changes are often associated with anomalies of the lower digestive tract. Overlapping spatiotemporal expression of retinoic acid receptor-beta (RAR beta) and cellular retinol-binding protein I, CRBPI, with Hoxb5 and c-ret in the gut mesoderm imply possible cooperation required for proper neuromuscular development. To determine susceptibility and responsiveness of the developing gut and its neuromusculature to exogenous retinoids we used a mouse model of RA-induced caudal regression syndrome. The results showed that stage-specific RA treatment both in vivo and in vitro affected gut looping/rotation morphogenesis and growth of asymmetrical structures such as the cecum together with delayed differentiation of the gut mesoderm and colonization of the postcecal gut by neural crest-derived enteric neuronal precursors. These observations demonstrate that RA has a direct effect on gut morphogenesis and innervation. Topics: Animals; Disease Models, Animal; Embryo, Mammalian; Female; Intestines; Lumbar Vertebrae; Mice; Muscles; Nervous System; Organ Culture Techniques; Pregnancy; Sacrum; Syndrome; Time Factors; Tretinoin | 2001 |
A case for steroids in acute lung injury associated with the retinoic acid syndrome.
A 62-year-old woman with acute promyelocytic leukaemia was treated with all-trans retinoic acid. On day 2 she suffered with dyspnoea and general fatigue. Marked hypoxia suggested the occurrence of retinoic acid syndrome. She underwent endotracheal intubation and mechanical ventilation with the administration of dexamethasone. Her symptoms promptly abated. She was subsequently treated with conventional chemotherapy and achieved complete remission. Topics: Antineoplastic Agents; Dyspnea; Female; Fever; Humans; Leukemia, Promyelocytic, Acute; Middle Aged; Radiography; Respiration, Artificial; Respiratory Distress Syndrome; Syndrome; Tretinoin | 2000 |
Leukocytosis and the retinoic acid syndrome in patients with acute promyelocytic leukemia treated with arsenic trioxide.
Arsenic trioxide, like all-trans-retinoic acid (RA), induces differentiation of acute promyelocytic leukemia (APL) cells in vivo. Treatment of APL patients with all-trans RA is commonly associated with leukocytosis, and approximately 50% of patients develop the RA syndrome. We reviewed our clinical experience with arsenic trioxide to determine the incidence of these two phenomena.. Twenty-six patients with relapsed or refractory APL were treated with arsenic trioxide for remission induction at daily doses that ranged from 0.06 to 0.17 mg/kg.. Twenty-three patients (88%) achieved complete remission. Leukocytosis was observed in 15 patients (58%). The median baseline leukocyte count for patients with leukocytosis was 3,900 cells/microL (range, 1,200 to 72,300 cells/microL), which was higher than that for patients who did not develop leukocytosis (2,100 cells/microL; range, 500 to 5,400 cells/microL; P =.01). No other cytotoxic therapy was administered, and the leukocytosis resolved in all cases. The RA syndrome was observed in eight patients (31%). Patients who developed leukocytosis were significantly more likely to develop the RA syndrome (P <.001), and no patient without a peak leukocyte count greater than 10,000 cells/microL developed the syndrome. Among the patients with leukocytosis, there was no observed relation between the leukocyte peak and the probability of developing the syndrome (P =.37).. Induction therapy of APL with all-trans RA and arsenic trioxide is associated with leukocytosis and the RA syndrome. These clinical effects seem to be intrinsically related to the biologic responsiveness and the differentiation process induced by these new agents. Topics: Antineoplastic Agents; Arsenic Trioxide; Arsenicals; Dyspnea; Fever; Humans; Leukemia, Promyelocytic, Acute; Leukocytosis; Oxides; Pleural Effusion; Syndrome; Tretinoin | 2000 |
Diffuse alveolar hemorrhage in acute promyelocytic leukemia patients treated with ATRA--a manifestation of the basic disease or the treatment.
All-trans-retinoic acid (ATRA) is considered the recommended induction treatment for acute promyelocytic leukemia. In the pre-ATRA era pulmonary bleeding was a common cause of death in these patients, mostly due to disseminated intravascular coagulation which was further exacerbated by the administration of chemotherapy. Although ATRA syndrome, the most serious adverse effect of ATRA treatment, involves the lungs, pulmonary hemorrhage has only rarely been reported as a manifestation of ATRA syndrome. Here we describe 2 patients who developed diffuse alveolar hemorrhage during treatment with ATRA. The possible mechanisms of pulmonary bleeding in these cases are discussed. Topics: Adult; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Blood Coagulation Tests; Cytarabine; Daunorubicin; Dyspnea; Fatal Outcome; Fever; Hemorrhage; Humans; Leukemia, Promyelocytic, Acute; Lung Diseases; Male; Middle Aged; Pulmonary Alveoli; Remission Induction; Syndrome; Tretinoin | 2000 |
The influence of the genetic background on the interaction of retinoic acid with Lx mutation of the rat.
The teratogenic effect of RA was found to be significantly influenced both by genetic background and by the genotype of malformation mutation Lx. The presence of the Lx mutation and BN genetic background strongly increases the teratogenic effect of RA. On the contrary, the SHR genetic background was shown to protect foetuses from RA teratogenic affliction. Recombinant inbred strain BXH2 is endowed with a specific combination of BN and SHR genes, and following RA administration it exhibits the same embryolethal effect as the BN genetic background alone. Without the Lx mutation there was no effect of RA on hind limbs in SHR/SHR or SHR/BN progeny whilst there was a significantly higher occurence of oligodactyly in SHR/BN on forelimbs as compared to SHR/SHR (92.2% vs 11.5%). In +/Lx progeny, forelimbs were significantly more afflicted with oligodactyly in SHR/BN +/Lx in comparison with both SHR/SHR and SHR/BXH2 foetuses, which indicates that BN modifiers responsible for oligodactyly were not passed to the BXH2 strain. On the contrary, hind limbs of SHR/BXH2, +/Lx progeny exhibited the highest affliction (62% of polydactyly and/or oligodactyly). In homozygous Lx/Lx progeny, polydactyly prevailed in forelimbs of SHR/BXH2 following RA administration, whilst in BN/BN progeny oligodactyly was the most frequent affliction. On the hind limbs, the highest reduction of toe number after RA treatment was connected with BN modifiers. The polymorphism of normal morphogenetic factors was shown to be responsible not only for Lx. phenotypic manifestation, but also for the variability in the response to RA teratogenic action. Topics: Abnormalities, Drug-Induced; Abnormalities, Multiple; Alleles; Animals; Animals, Congenic; Crosses, Genetic; Embryonic and Fetal Development; Face; Female; Forelimb; Genetic Predisposition to Disease; Genotype; Gestational Age; Hindlimb; Male; Morphogenesis; Polydactyly; Rats; Rats, Inbred BN; Rats, Inbred SHR; Rats, Mutant Strains; Syndrome; Tail; Teratogens; Toes; Tretinoin | 2000 |
Extramedullary relapse after all-trans retinoic acid treatment in acute promyelocytic leukemia--the occurrence of retinoic acid syndrome is a risk factor.
All-trans retinoic acid (ATRA) is now a standard agent for remission induction of acute promyelocytic leukemia (APL). Recently, extramedullary relapse, which was a rare condition in APL patients after chemotherapy alone, was reported with an increased frequency after ATRA treatment. However, it is not yet clear whether ATRA truly increases the risk of extramedullary recurrence and what are the risk factors. In this study, three of 13 patients with recurrent APL after prior treatment of ATRA were found to have extramedullary involvement, compared with none in 11 recurrent patients previously treated with chemotherapy alone (estimated relative risk 2.100, 95% confidence interval 1.341-3.289). Furthermore, in the former group of patients, the development of retinoic acid (RA) syndrome during prior induction treatment was significantly associated with extramedullary involvement at relapse (three in five patients with RA syndrome vs none in eight without the syndrome, estimated relative risk 5.000, 95% confidence interval 1.448-17.271). In conclusion, ATRA may predispose APL patients to extramedullary involvement at relapse and the occurrence of RA syndrome is a risk factor for it. Further studies are needed to confirm these findings. It also remains to be clarified whether treatment modification is necessary in patients who develop RA syndrome during ATRA treatment. Topics: Adolescent; Adult; Aged; Female; Hematopoiesis, Extramedullary; Humans; Leukemia, Promyelocytic, Acute; Male; Recurrence; Remission Induction; Retrospective Studies; Risk Factors; Syndrome; Tretinoin | 1999 |
Retinoic acid syndrome during the treatment of acute myelomonocytic leukaemia with all-trans-retinoic acid and low-dose cytosine arabinoside.
Topics: Cytarabine; Humans; Leukemia, Myelomonocytic, Acute; Leukocyte Count; Leukocytosis; Male; Middle Aged; Syndrome; Tretinoin | 1998 |
Diffuse alveolar hemorrhage with underlying pulmonary capillaritis in the retinoic acid syndrome.
All-trans-retinoic acid (ATRA) can induce a clinical remission in patients with acute promyelocytic leukemia. An adverse condition called "retinoic acid syndrome" limits this therapy. It is characterized by fever and respiratory distress, along with weight gain, pleural or pericardial effusions, peripheral edema, thromboembolic events, and intermittent hypotension. The lung disease has been previously ascribed to an infiltration of leukemic or maturing myeloid cells into lung parenchyma, which is sometimes associated with pleural effusions and diffuse alveolar hemorrhage. We report a case of retinoic acid syndrome in an 18-yr-old woman who developed diffuse alveolar hemorrhage while being treated with ATRA for acute promyelocytic leukemia. An open lung biopsy revealed pulmonary capillaritis. Topics: Adolescent; Antineoplastic Agents; Capillaries; Edema; Female; Fever; Hemoptysis; Humans; Hypotension; Leukemia, Promyelocytic, Acute; Lung; Pericardial Effusion; Pleural Effusion; Pulmonary Alveoli; Respiratory Insufficiency; Syndrome; Thromboembolism; Tretinoin; Vasculitis; Weight Gain | 1998 |
Retinoic acid syndrome--radiological features.
Topics: Adult; Female; Humans; Hypoxia; Leukemia, Promyelocytic, Acute; Pleural Effusion; Radiography; Syndrome; Tretinoin | 1997 |
Retinoic acid syndrome in acute promyelocytic leukemia.
All-trans retinoic acid (ATRA) has been used successfully in inducing remission in patients with acute promyelocytic leukemia (APL). Its overall toxicity is considerably less compared to standard induction chemotherapy; however, it is associated with a high incidence of a potentially fatal symptom complex referred to as "retinoic acid syndrome." This report describes a patient with APL who developed the syndrome a few weeks after initiating induction therapy with ATRA despite being treated for hyperleukocytosis. The case illustrates the classic features of the syndrome and its dramatic response to corticosteroid treatment. Topics: Antineoplastic Agents; Dexamethasone; Dyspnea; Glucocorticoids; Humans; Leukemia, Promyelocytic, Acute; Leukocytosis; Male; Middle Aged; Pulmonary Edema; Syndrome; Tretinoin | 1997 |
Retinoic acid teratogenicity in rat congenic and recombinant inbred strains with malformation syndrome.
Topics: Abnormalities, Drug-Induced; Abnormalities, Multiple; Animals; Crosses, Genetic; Genetic Carrier Screening; Hindlimb; Inbreeding; Polydactyly; Rats; Rats, Inbred BN; Rats, Inbred Lew; Rats, Mutant Strains; Recombination, Genetic; Syndrome; Teratogens; Tretinoin | 1997 |
Continuous hemofiltration in the management of 'retinoic acid syndrome'.
Topics: Adolescent; Antineoplastic Agents; Cytokines; Hemofiltration; Humans; Hypotension; Leukemia, Promyelocytic, Acute; Male; Oliguria; Syndrome; Tretinoin | 1997 |
Retinoic acid syndrome: a case report.
All-trans-retinoic acid (ATRA) is a differentiation agent which can induce complete remission in a majority of patients with acute promyelocytic leukemia (APL). Unfortunately, about one-fourth of patients thus treated may develop potentially fatal complications, including respiratory distress, fever, pericardial and pleural effusion, renal failure and hypotension which constitute the retinoic acid syndrome (RA syndrome). We report one APL patient, who presented with leukocytosis and subacute disseminated intravascular coagulopathy, and developed RA syndrome during treatment with ATRA. Topics: Adult; Female; Humans; Leukemia, Promyelocytic, Acute; Syndrome; Tretinoin | 1997 |
Acute renal failure associated with the retinoic acid syndrome in acute promyelocytic leukemia.
All-trans-retinoic acid is an effective agent to induce remission in patients with acute promyelocytic leukemia (APL). Unlike conventional chemotherapy, this drug exerts its effect by inducing differentiation of immature leukemic cells. A distinctive clinical syndrome characterized by fever, dyspnea, effusions, weight gain, and organ failure (the "retinoic acid syndrome") can occur during treatment with this drug. Postmortem studies have shown extensive organ infiltration by leukemic cells, and the early administration of corticosteroids can result in prompt resolution of symptoms. We describe a patient with APL in whom acute renal failure developed during treatment with all-trans-retinoic acid. Transient renal enlargement during a period of leukocytosis and a beneficial response to treatment with dexamethasone suggest that renal failure in this patient was probably related to the retinoic acid syndrome. Topics: Acute Kidney Injury; Dyspnea; Fever; Humans; Leukemia, Promyelocytic, Acute; Male; Middle Aged; Pericardial Effusion; Pleural Effusion; Syndrome; Tretinoin | 1996 |
All-trans retinoic acid and short-time, high-dose cytarabine in two children with acute promyelocytic leukemia.
We report on two girls, 3 and 13 years old, with acute promyelocytic leukemia (APL) who were successfully treated with all-trans retinoic acid (ATRA) 45 mg/m2/day. "Retinoic acid syndrome" was prevented with short-time treatment of high dose (4 x 1.5 g/m2) cytarabine. This regimen was well tolerated, although both children were critically ill. They achieved a complete remission confirmed by light microscopy, but reverse transcriptase polymerase chain reaction remained positive after ATRA, underlining the need of further chemotherapy. Topics: Adolescent; Antimetabolites, Antineoplastic; Antineoplastic Agents; Child, Preschool; Critical Illness; Cytarabine; Female; Humans; Leukemia, Promyelocytic, Acute; Leukocytosis; Remission Induction; Syndrome; Tretinoin | 1996 |
Cytologic examination of broncho-alveolar fluid during the retinoic acid syndrome.
Topics: Adrenal Cortex Hormones; Adult; Antineoplastic Combined Chemotherapy Protocols; Bronchoalveolar Lavage Fluid; Dyspnea; Fever; Humans; Leukemia, Promyelocytic, Acute; Male; Syndrome; Tretinoin; Weight Gain | 1996 |
Retinoic acid syndrome: a report of two cases.
Topics: Adult; Dyspnea; Female; Fever; Humans; Hypotension; Leukemia, Promyelocytic, Acute; Middle Aged; Syndrome; Tretinoin | 1996 |
Bilateral osteonecrosis of the head of the femur complicating acute promyelocytic leukemia: a sequel to treatment of retinoic acid syndrome with dexamethasone.
The complication of 'retinoic acid syndrome' occurs in 25-30% of patients with acute promyelocytic leukemia (APL) treated with all-transretinoic acid (ATRA). Early dexamethasone therapy has reduced mortality from this complication. No long-term sequel of the syndrome or its treatment with dexamethasone has been described. We report a patient with APL treated with ATRA who developed avascular necrosis of both femoral heads following treatment of retinoic acid syndrome with short-duration, high-dose dexamethasone. Topics: Adult; Dexamethasone; Female; Femur Head Necrosis; Humans; Kuwait; Leukemia, Promyelocytic, Acute; Radionuclide Imaging; Syndrome; Tomography, X-Ray Computed; Tretinoin | 1996 |
Retinoic acid syndrome: pulmonary computed tomography (CT) findings.
We report the pulmonary computed tomography (CT) findings in three patients with acute promyelocytic leukaemia who developed the retinoic acid syndrome following all-trans retinoic acid (ATRA) therapy. The most consistent CT findings were small, irregular peripheral nodules in the lung fields and pleural effusions. Two of the patients also showed evidence of reticular and ground glass shadowing as well as abnormal anterior mediastinal soft tissue. We report for the first time an association between ATRA and pneumothorax. We conclude that routine CT scanning may provide a sensitive means of early detection or monitoring of the syndrome and thereby may facilitate its management. Topics: Adult; Antineoplastic Agents; Child; Female; Humans; Leukemia, Promyelocytic, Acute; Lung; Male; Pleural Effusion; Pneumothorax; Syndrome; Tomography, X-Ray Computed; Tretinoin | 1996 |
More on acute promyelocytic leukemia pneumonitis.
Topics: Humans; Leukemia, Promyelocytic, Acute; Lung Diseases; Male; Middle Aged; Syndrome; Tretinoin | 1995 |
Successful treatment of retinoic acid syndrome with high-dose dexamethasone pulse therapy in a child with acute promyelocytic leukemia treated with ATRA.
A 5 year old female developed femoral pain, fever, and hemorrhagic tendency. She was diagnosed as having acute promyelocytic leukemia (APL). Approximately 2 weeks after the administration of all-trans retinoic acid (ATRA), she developed a high fever, edema, and respiratory distress which met the criteria for retinoic acid syndrome. At first, we tried to treat the patient with oral corticosteroid, however, this approach was unsuccessful. Considering the worsening of her condition, we then chose to administer a large dose of intravenous dexamethasone therapy for 3 days. Immediately after this therapy, she became afebrile, respiratory distress and edema disappeared, and there was a general improvement of the symptoms. All-trans retinoic acid at the reduced dose of 25 mg/m2, was continued for an additional 6 weeks and then discontinued. Since the cessation of dexamethasone and ATRA, there has been no relapse of APL in this patient. Although based on only one case, we recommend the intravenous high-dose dexamethasone pulse therapy (13 mg/m2 per day, for 3 days) for treating retinoic acid syndrome which develops in pediatric APL patients treated with ATRA. Topics: Child, Preschool; Dexamethasone; Female; Humans; Infusions, Intravenous; Leukemia, Promyelocytic, Acute; Respiratory Insufficiency; Syndrome; Tretinoin | 1995 |
Clinical and molecular characterization of a rare syndrome of acute promyelocytic leukemia associated with translocation (11;17).
Analysis of a variant translocation t(11;17) in a case of acute promyelocytic leukemia (APL) led to discovery of a novel zinc finger gene, PLZF, fused to the retinoic acid receptor-alpha (RAR alpha) gene. We reviewed the clinical and molecular features of five additional patients with t(11;17)-associated APL. The clinical course of three patients was characterized by early death and three experienced disseminated intravascular coagulation. Morphologically all of the patients fell in a unusual morphologic spectrum of APL, with features intermediate between M2 and M3 AML. All six patients had PLZF-RAR alpha gene fusion as detected by reverse transcription/polymerase chain reaction assay, Southern blotting, or pulsed-field gel electrophoresis. Five of the six patients failed to achieve complete remission after initial chemotherapy or differentiation therapy with all-trans retinoic acid (ATRA). A sixth patient responded to initial chemotherapy, but on relapse failed to respond to ATRA. When tested in vitro, cultured cells from three of the patients failed to differentiate in response to ATRA. APL associated with t(11;17) and fusion of the PLZF and RAR alpha genes is a discrete clinico-pathologic syndrome with a distinctly worse prognosis than t(15;17) APL. Topics: Adult; Aged; Aged, 80 and over; Amino Acid Sequence; Antineoplastic Combined Chemotherapy Protocols; Base Sequence; Chromosome Mapping; Chromosomes, Human, Pair 11; Chromosomes, Human, Pair 17; Cloning, Molecular; DNA Primers; DNA-Binding Proteins; Female; Humans; Kruppel-Like Transcription Factors; Leukemia, Promyelocytic, Acute; Male; Middle Aged; Molecular Sequence Data; Polymerase Chain Reaction; Promyelocytic Leukemia Zinc Finger Protein; Receptors, Retinoic Acid; Retinoic Acid Receptor alpha; RNA, Messenger; Syndrome; Transcription Factors; Translocation, Genetic; Tretinoin; Zinc Fingers | 1995 |
Visceral heterotaxy syndrome induced by retinoids in mouse embryo.
Visceral heterotaxy syndrome causes abnormal arrangement of thoracoabdominal organs and severe complex cardiac anomalies by abnormal laterality. The purpose of the present study is to analyze the incidence and pattern of heterotaxy syndrome in etretinate and all-tran retinoic acid treated pregnant DDY mice. Pregnant DDY mice were intragastrically given a single dose of 15 mg/kg of etretinate at day 6, 7 of gestation, 30 mg/kg of etretinate at day 7 of gestation and 20 mg/kg of all-trans retinoic acid at day 7 of gestation. The incidence of visceral heterotaxy was highest in the etretinate 15 mg/kg treated group on day 7 of gestation (38.5%). The major cardiovascular anomalies in heterotaxy syndrome were common atrium, common atrioventricular valve, atrioventricular septal defect, transposition of great arteries, pulmonary atresia, pulmonary artery hypoplasia and aortic arch anomalies. Atrial situs of heterotaxy syndrome were right isomerism, solitus-like, inversus-like and left atrial aplasia, but right isomerism was observed most frequently. The results suggest that retinoic acid exerts a significant effect on the determination of atrial situs during the development of mouse embryo. Topics: Abnormalities, Drug-Induced; Animals; Blood Vessels; Female; Heart Defects, Congenital; Mice; Pregnancy; Syndrome; Tretinoin | 1995 |
Rapid progression of 'retinoic acid syndrome' in the hypogranular variant of acute promyelocytic leukaemia, despite treatment with dexamethasone and conventional chemotherapy.
Topics: Acute Kidney Injury; Adult; Antineoplastic Combined Chemotherapy Protocols; Cerebral Hemorrhage; Combined Modality Therapy; Cytarabine; Daunorubicin; Dexamethasone; Disease Progression; Fatal Outcome; Female; Humans; Leukemia, Promyelocytic, Acute; Leukocytosis; Renal Dialysis; Respiration, Artificial; Respiratory Insufficiency; Syndrome; Tretinoin | 1994 |
Acute promyelocytic leukemia.
Topics: Acute Disease; Adult; Fever; Humans; Leukemia, Promyelocytic, Acute; Male; Pleural Effusion; Respiratory Insufficiency; Syndrome; Tretinoin | 1994 |
Tretinoin toxicity in children with acute promyelocytic leukaemia.
Tretinoin is effective in acute promyelocytic leukaemia in adults. Data about its efficacy and safety in children are limited. We have treated 9 children with tretinoin at 45 mg/m2 per day. Pseudotumour cerebri or hyperleucocytosis occurred in 5 patients. Retinoic acid syndrome was seen in 3 cases. 1 of 2 children who developed hyperleucocytosis, pseudotumour cerebri, and retinoic acid syndrome died despite steroids and mechanical ventilation. Complete remissions with tretinoin alone were achieved in 15 patients. All 8 surviving children received consolidation chemotherapy. Our experience with tretinoin therapy suggests that toxicity is frequent in children. Topics: Adolescent; Child; Child, Preschool; Female; Humans; Infant; Leukemia, Promyelocytic, Acute; Leukocyte Count; Leukocytes; Male; Pseudotumor Cerebri; Syndrome; Tretinoin | 1993 |
Retinoic acid syndrome.
Topics: Adult; Dyspnea; Female; Humans; Leukemia, Promyelocytic, Acute; Leukocytosis; Male; Syndrome; Tretinoin | 1993 |
Terson's syndrome in a patient with acute promyelocytic leukemia on all-trans retinoic acid treatment.
The syndrome of vitreous hemorrhage in association with any form of intracranial bleeding is known as Terson's syndrome. Acute promyelocytic leukemia (APL) constitutes 5% to 15% of cases of acute nonlymphocytic leukemias, in which hemorrhagic diathesis often occurs and results in a rapid fatal outcome. In this report we describe a patient with APL who developed cerebral bleeding in association with bilateral subhyaloid and vitreous hemorrhages consistent with Terson's syndrome while she was on all-trans retinoic acid induction therapy. Topics: Adult; Cerebral Hemorrhage; Female; Fundus Oculi; Humans; Leukemia, Promyelocytic, Acute; Syndrome; Tomography, X-Ray Computed; Tretinoin; Vitreous Hemorrhage | 1993 |
[Effective methyl prednisolone pulse therapy for a patient with retinoic acid syndrome in acute promyelocytic leukemia].
A 46-year-old woman with acute promyelocytic leukemia (APL) was treated with all-trans retinoic acid (ATRA) and chemotherapy according to the AML-92, M3 regimen of the Japan Adult Leukemia Study Group (JALSG). Between days 7 and 18 of therapy, she suffered chest discomfort, fever, cough, dyspnea and general fatigue. A chest roentogenogram showed bilateral interstitial infiltrates. Her leukocyte count began to increase rapidly to 6,400/microliters on day 14. Marked hypoxia (PO2 35.9 mmHg) suggested occurrence of retinoic acid (RA) syndrome. She underwent endotracheal intubation and mechanical ventilation with administration of methyl-prednisolone (m-PSL) pulse therapy. Her symptoms promptly abated. Therapy with ATRA was continued and her leukocyte count reached 44,800/microliters on day 19 of therapy. She achieved complete remission on day 48. Topics: Dyspnea; Female; Fever; Humans; Leukemia, Promyelocytic, Acute; Methylprednisolone; Middle Aged; Remission Induction; Syndrome; Tretinoin | 1993 |
[A "retinoic acid syndrome" observed in two cases of acute promyelocytic leukemia].
Two cases of acute promyelocytic leukemia (APL) treated with all-trans retinoic acid (ATRA) developed fever, dyspnea and chest pain. A chest roentgenogram showed bilateral pleural effusion (case 1) and bilateral interstitial infiltration (case 2). The first case was a 50-year-old female in her first relapse, who was initially diagnosed as having pleuritis tuberculosa and was treated with anti-tuberculotic agents. Her symptoms continued for 44 days and complete remission was achieved 53 days after commencing ATRA therapy. The second case was a previously untreated 46-year-old male. His case had been diagnosed as adult respiratory distress syndrome and he had been treated with prednisolone. His symptoms rapidly improved and complete remission was achieved 38 days after the ATRA therapy. This was the first report of patients in Japan considered to have developed "retinoic acid syndrome (RAS)". In our five APL cases treated with ATRA, the syndrome was not always accompanied by peripheral blood leukocytosis even though the two cases with RAS showed higher leukocyte counts than the other two cases without RAS and also had DIC. We should pay attention to the severe respiratory symptoms that develop in APL patients after ATRA treatment and immediate steroid therapy is required for such patients. Topics: Adult; Chest Pain; Dyspnea; Female; Fever; Humans; Leukemia, Promyelocytic, Acute; Male; Middle Aged; Syndrome; Tretinoin | 1993 |
[Treatment of acute leukemia by differentiation: effects of all trans retinoic acid in acute promyelocytic leukemia].
All trans retinoic acid (ATRA) in the treatment of acute promyelocytic leukemia is the first model of differentiation therapy in malignancies, and represents the first strict correlation between a genetic defect and a specific treatment. In this disease the association of differentiating agents and chemotherapy gives much better results than each type of treatment (differentiating agent or chemotherapy). Topics: Blood Coagulation Disorders; Cell Differentiation; Drug Resistance; Humans; Leukemia, Promyelocytic, Acute; Syndrome; Tretinoin | 1993 |
Treatment of acute promyelocytic leukemia with all-trans retinoic acid: successful control of hyperleukocytosis and leukostasis syndrome with leukaphereses and hydroxyurea.
Topics: Administration, Oral; Adult; Female; Humans; Hydroxyurea; Leukapheresis; Leukemia, Promyelocytic, Acute; Leukocytosis; Stereoisomerism; Syndrome; Tretinoin | 1993 |
Fatal all-trans retinoic acid pneumonitis.
Topics: Child, Preschool; Female; Humans; Pneumonia; Syndrome; Tretinoin | 1993 |
The "retinoic acid syndrome" in acute promyelocytic leukemia.
To describe a novel complication of therapy with all-trans retinoic acid in patients with acute promyelocytic leukemia.. Case series.. Comprehensive cancer center.. Consecutive patients with a morphologic diagnosis of acute promyelocytic leukemia who underwent remission induction treatment with all-trans retinoic acid, 45 mg/m2 body surface area per day.. Nine of 35 patients (26%; 95% CI, 9% to 52%) with acute promyelocytic leukemia who were treated with all-trans retinoic acid developed a syndrome consisting primarily of fever and respiratory distress. Additional prominent signs and symptoms included weight gain, lower-extremity edema, pleural or pericardial effusions, and episodic hypotension. The onset of this symptom complex occurred from 2 to 21 days after starting treatment. Three deaths occurred; post-mortem examinations in two patients showed pulmonary interstitial infiltration with maturing myeloid cells. Six other patients survived, each achieving complete remission (five patients with all-trans retinoic acid only; 1 patient with chemotherapy). In six of the nine cases, the onset of the syndrome was preceded by an increase in peripheral blood leukocytes to a level of at least 20 x 10(9) cells/L. Certain therapeutic interventions, including leukapheresis, temporary cessation of therapy with all-trans retinoic acid, and cytotoxic chemotherapy in moderate doses were not useful after respiratory distress was established. However, the administration of high-dose corticosteroid therapy (dexamethasone, 10 mg IV intravenously every 12 hours for 3 or more days) early in the course of the syndrome resulted in prompt symptomatic improvement and full recovery in three of four patients.. The use of all-trans retinoic acid to induce hematologic remission in patients with acute promyelocytic leukemia is associated in some patients with the development of a potentially lethal syndrome that is not uniformly accompanied by peripheral blood leukocytosis. Early recognition of the symptom complex of fever and dyspnea, combined with prompt corticosteroid treatment, may decrease morbidity and mortality associated with this syndrome. Topics: Adult; Aged; Autopsy; Dyspnea; Edema; Female; Fever; Humans; Hypotension; Leukemia, Promyelocytic, Acute; Leukocytosis; Male; Middle Aged; Remission Induction; Syndrome; Tretinoin | 1992 |
Long-time survival of a patient with glioblastoma and Turcot's syndrome. Case report.
A rare case of Turcot's syndrome is reported in a long-time survivor of glioblastoma multiforme. The patient was treated for his tumor in 1976 with macroscopically complete surgical resection and radiotherapy consisting of 60 Gy to the tumor bed and 40 Gy to the whole brain. Five years later, in 1981, he developed adenocarcinoma of the colon Dukes Stage B which was successfully treated at another hospital by surgery alone. In 1990, he presented with multiple colon polyps and adenocarcinoma Dukes Stage A. For more than 15 years, the patient has been afflicted with cystic and conglobate acne. Possible mechanisms and treatment with 13-cis retinoic acid are discussed. Topics: Acne Vulgaris; Adenocarcinoma; Adenomatous Polyposis Coli; Adult; Brain Neoplasms; Glioblastoma; Humans; Male; Neoplasms, Multiple Primary; Syndrome; Time Factors; Tretinoin | 1991 |
Experimental craniofacial malformations induced by retinoids and resembling branchial arch syndromes.
A syndrome which showed similarities to human branchial arch syndromes could be induced in Sprague-Dawley rat embryos by exposing them to retinoids prenatally. Treatment of pregnant rats with 40 mg/kg retinoic acid or 10 mg/kg etretinate on pregnancy day 8.5-9 resulted in craniofacial defects in 100% of the embryos. A scanning electron microscopic investigation of the early stages in the development of these malformations showed abnormal skull form, disorganised surface epithelium with "cell blebbing", lateral facial clefts, facial fistulas, narrowed skull-base and reduced size of the nasal and maxillary complexes. Histological examination confirmed these findings and supported the hypothesis that a main reason for this syndrome is hindrance of migration of the cranial neural crest cells to the facial processes during early craniofacial formation. Topics: Abnormalities, Drug-Induced; Animals; Branchial Region; Facial Bones; Female; Maternal-Fetal Exchange; Models, Biological; Pregnancy; Prevalence; Rats; Skull; Syndrome; Teratogens; Tretinoin | 1990 |
[Successful retinoid therapy of Netherton syndrome].
A young patient with Netherton's syndrome characterized by the classic triad of ichthyosis linearis circumflexa, trichorhexis invaginata and atopy was treated with Acitretin, a new retinoid preparation: 35 mg Acitretin/day resulted in a severe, erosive dermatitis which necessitated interruption of therapy. Even with 10 mg/day the patient had intolerable irritation of the integument. After a further dosage reduction to 5 mg/day there were no obvious side effects and a long-term treatment was possible, resulting in an obvious reduction of the ichthyotic lesions and improved hair growth. Electron microscopy in the active part of the skin lesions from untreated skin revealed granular, membrane-enclosed material intracellularly and in the intercellular spaces of the granular layer. Keratinization was almost completely suppressed. Therapy with Acitretin drastically reduced the deposition of intra- and extracellular material and normalized keratinization. Our results underline the importance of starting retinoid therapy in Netherton's syndrome at a low dosage and adjusting it carefully in each case with reference to the skin manifestations and the side effects. Topics: Acitretin; Adolescent; Biopsy; Chromosome Aberrations; Chromosome Disorders; Dermatologic Agents; Female; Genes, Recessive; Humans; Ichthyosis; Skin; Syndrome; Tretinoin | 1989 |
Netherton's syndrome: ultrastructure of the active lesion under retinoid therapy.
A young female patient, expressing the symptom triad of Netherton's syndrome, i.e., ichthyosis linearis circumflexa Comèl, trichorrhexis invaginata and other hair shaft defects, and atopic diathesis, has been treated successfully with the new retinoid preparation Etretin. Our electron microscopical study especially focused on the ultrastructural effect on the characteristic, active part of the skin lesions, which is only found within a narrow borderline just preceding the lesion's margin. In untreated skin, this part is characterized by dermal inflammation, immigrating inflammatory cells, and specific keratinization disturbances: synthesis of keratinization proteins is suppressed, serum exudates invade the epidermis, either filling the intercellular spaces of the upper spinous and the granular layer as finely granular, amorphous material, or they are partly phagocytosed and lie within intracellular, round-oval inclusions. The portions of the lesions lying towards the center are unspecific and represent recovery stages, ultrastructurally resembling stages of normal wound repair. Oral therapy with Etretin did not heal the basic defect, but drastically reduced exoserosis and the deposition of intra- and extracellular material. Keratinization seemed to normalize. The condition of the hair was also improved. Topics: Acitretin; Adolescent; Cell Differentiation; Female; Humans; Ichthyosis; Microscopy, Electron; Skin; Syndrome; Tretinoin | 1989 |
A phenocopy of the isotretinoin syndrome?
Topics: Abnormalities, Multiple; Humans; Infant; Isotretinoin; Phenotype; Syndrome; Tretinoin | 1988 |
Structure-toxicity relationships of the tetramethylated tetralin and indane analogs of retinoic acid.
The teratogenicity of retinoids containing either tetramethylated tetralin (Ro 13-6307 or Ro 13-2389) or tetramethylated indane (Ro 13-4306) ring system substitutions was compared to the teratogenic potency of all-trans-retinoic acid. Single oral doses, administered to Syrian Golden hamsters at 10:00 A.M. on day 8 of gestation, induced a syndrome of malformations identical to that induced by treatment with all-trans-retinoic acid. These retinoids failed to induce signs of maternal hypervitaminosis A at doses associated with a significant teratogenic response. The tetramethylated tetralin retinoids and indane retinoid were 18 and 2.4 times as embryotoxic on a molar basis, respectively, as all-trans-retinoic acid. Introduction of a supplementary ring in the side-chain restricted polyene chain flexibility and maintained the hydrophobic plane of the chain. The present results are consistent with previous studies showing that the presence of or biotransformation to a free acid congener was necessary for retinoid teratogenic activity in hamsters and that increasing conformational restriction of acidic retinoids increased teratogenic potency. Topics: Abnormalities, Drug-Induced; Animals; Cricetinae; Female; Indans; Indenes; Mesocricetus; Naphthalenes; Pregnancy; Structure-Activity Relationship; Syndrome; Teratogens; Tetrahydronaphthalenes; Tretinoin | 1987 |
Developmental aspects of lissencephaly and the lissencephaly syndromes.
Topics: Abnormalities, Multiple; Brain; Brain Diseases; Humans; Isotretinoin; Syndrome; Tomography, X-Ray Computed; Tretinoin | 1987 |
Corneal effect of isotretinoin: possible exacerbation of corneal neovascularization in a patient with the keratitis, ichthyosis, deafness ("KID") syndrome.
Topics: Adult; Cornea; Female; Hearing Loss, Sensorineural; Humans; Ichthyosis; Isotretinoin; Keratitis; Neovascularization, Pathologic; Syndrome; Tretinoin | 1986 |
Oral isotretinoin therapy for familial Muir-Torre syndrome.
Two representative cases of familial Muir-Torre syndrome are presented. Multiple benign sebaceous neoplasms in both cases and a solitary keratoacanthoma in one were successfully treated with oral isotretinoin. Low-dose maintenance therapy has stabilized the cutaneous manifestations in the two patients, and no new epithelial neoplasms have appeared. This report emphasizes (1) the rationale for the use of isotretinoin in the Muir-Torre syndrome and (2) the potential for a familial pattern of inheritance and a possible association with the cancer family syndrome. It speculates on the prevention of future internal malignancies in Muir-Torre syndrome patients by maintenance oral isotretinoin treatment. Topics: Administration, Oral; Female; Humans; Isotretinoin; Keratoacanthoma; Middle Aged; Neoplasms, Multiple Primary; Sebaceous Gland Neoplasms; Syndrome; Tretinoin | 1985 |
Increased plasma chemoattractant in Sweet's syndrome.
The neutrophil function and plasma leukotactic activity of a patient with Sweet's syndrome and cystonodular acne were evaluated during a 2 1/2-year period. These studies demonstrated that chemotaxis was frequently slightly increased, especially during an exacerbation of Sweet's syndrome, but showed some decrease during isotretinoin therapy. Other functions, such as phagocytosis, metabolic activation, and bacterial killing, also were slightly increased. In addition, the patient's serum contained a heat-stable, nonlipid chemoattractant that was present at all times except during a course of isotretinoin. Although his symptoms responded to aspirin, the plasma continued to show this chemoattractant. These findings are consistent with the hypothesis that excess chemoattractant in Sweet's syndrome attracts neutrophils, which then mediate an inflammatory response. In addition, aspirin may be used to control Sweet's syndrome symptoms, although it does not suppress the plasma chemoattractant. Topics: Adult; Aspirin; Chemotaxis, Leukocyte; Dialysis; Hot Temperature; Humans; Isotretinoin; Leukocytosis; Male; N-Formylmethionine Leucyl-Phenylalanine; Neutrophils; Pentose Phosphate Pathway; Phagocytosis; Plasma; Skin Diseases; Syndrome; Tretinoin; Zymosan | 1985 |
[Accutane--a new human teratogen as a cause of a new syndrome].
Topics: Abnormalities, Drug-Induced; Brain; Ear; Heart Defects, Congenital; Humans; Isotretinoin; Syndrome; Teratogens; Tretinoin | 1985 |
Peeling skin syndrome.
Topics: Child; Humans; Isotretinoin; Male; Skin Diseases; Syndrome; Tretinoin | 1985 |
Synergistic interaction between differentiation inducers and DNA synthesis inhibitors: a new approach to differentiation induction in myelodysplasia and acute myeloid leukaemia.
Numerous agents induce differentiation and maturation of neoplastic and dysplastic myeloid cells in vitro and some of these agents have been used with limited success in the treatment of patients with myelodysplastic syndromes (MDS) and myeloid leukaemias. We recently proposed that physiological and pharmacological agents which enhance differentiation and maturation in vitro act by two fundamentally different routes: (1) by hastening the progression through various differentiation/maturation steps; (2) by slowing proliferation (usually by inhibition of DNA synthesis). In order to test this thesis we looked for synergistic effects on differentiation using pairs of agents from the two groups in cultures of cells from myelodysplastic and acute myeloid leukaemia (AML) patients and from normal marrow donors. The results with three MDS, two AML and three normal samples show that combinations of differentiation inducing agents (retinoic acid, N-methylformamide) with DNA synthesis inhibitors (6-mercaptopurine, cytosine arabinoside and aphidicolin) produce a differentiation inducing effect equivalent to that of 10-100, or even 1000 fold higher concentrations of single agents. Myelotoxic effects in vitro were not synergistic. The use of these synergistic combinations should greatly enhance the usefulness of differentiation inducers in the therapy of MDS and myeloid leukaemia. Topics: Antineoplastic Combined Chemotherapy Protocols; Aphidicolin; Bone Marrow; Bone Marrow Diseases; Cell Differentiation; Cells, Cultured; Cytarabine; Diterpenes; DNA; Drug Synergism; Formamides; Humans; Leukemia, Myeloid, Acute; Mercaptopurine; Preleukemia; Syndrome; Tretinoin | 1985 |
Confluent and reticulated papillomatosis.
Topics: Adolescent; Female; Humans; Keratolytic Agents; Middle Aged; Papilloma; Skin; Skin Neoplasms; Syndrome; Tretinoin | 1982 |
[The Netherton syndrome--a case report. Treatment with the aromatic retinoid RO-9359].
Topics: Adolescent; Dermatitis, Atopic; Etretinate; Female; Hair Diseases; Humans; Ichthyosis; Syndrome; Tretinoin | 1982 |
Successful treatment of keratoderma hereditaria mutilans with an aromatic retinoid.
Clinical features and treatment of keratoderma hereditaria mutilans (Vohwinkel's syndrome) are described in an 11-year-old boy. The disease, in particular the mutilating complications (pseudo-ainhum), responded satisfactorily to the oral administration of etretinate, an aromatic retinoid. Topics: Administration, Oral; Ainhum; Child; Constriction, Pathologic; Edema; Etretinate; Humans; Keratoderma, Palmoplantar; Male; Pigmentation Disorders; Syndrome; Tretinoin | 1981 |
[Retinoic acid and 5-FU mixture in the topical treatment of several skin diseases (author's transl)].
The need for safe and effective topical treatments is underlined by several clinical trials over the years treating miscellaneous dermatosis with many and heterologous drugs, sometimes on a simple empirical basis. In a recent study Robinson and Kligman claimed to have obtained satisfactory results treating several cases of actinic keratosis with an alternate regimen of retinoic acid and 5-FU. We wish to report an open-label pilot study using a simple and readily accessible combination of commercially formulated and available agents as 0,05% retinoic acid cream and 5% 5-FU cream over two groups of patients. Treatment consisted of bid application of sparing amounts of an equal parts combination of retinoic acid and 5-FU. The first group consisted of 7 patients affected by skin diseases associated with an altered epidermal keratinization (actinic keratosis, Darier's disease, seborrheic keratosis, phrynoderma and epidermodysplasia verruciformis). The patients were followed up for a period of 15 to 60 days and, as it might be expected, the results were quite good. The second group, on the contrary, consisted of 6 patients affected mainly by dermatosis involving the corium (LED, milium, colloid pseudomilium). The patients were followed up for the same period of time as the first group was, but the results were much less rewarding. Only a partial resolution of the process, which was followed soon after by a relapse, was noted. Finally we believe that this modified regimen of equal parts of retinoic acid and 5-FU has to be recommended in the topical treatment of the above mentioned dermatosis associated with an altered keratinization. Topics: Drug Combinations; Fluorouracil; Humans; Keratosis; Ointments; Radiation Injuries; Skin Diseases; Syndrome; Tretinoin | 1980 |
Treatment with an oral aromatic retinoid in linear porokeratosis.
Linear porokeratosis is a rare variant of porokeratosis of Mibelli and usually occurs in childhood. A 15-year-old boy is presented with typical clinical lesions of linear porokeratosis on the extensor surface of the right arm exhibiting the classical histopathologic criteria of the disease. Treatment with an oral aromatic retinoid resulted in a remission of the lesion. Topics: Administration, Oral; Adolescent; Etretinate; Foot Dermatoses; Hand Dermatoses; Humans; Keratosis; Male; Syndrome; Tretinoin | 1980 |
Disseminated porokeratosis Mibelli treated with RO 10-9359. A study of two cases with ultrastructural remarks.
2 patients with widespread porokeratosis Mibelli (PM) were treated orally with RO 10-9359. The dose was 75 mg/day for 10 days, then 50 mg/day for 3 weeks. The drug produced a good improvement of condition with no serious side effect. Ultrastructural examination of a healed lesion showed the presence of a fine granular substance in the intercellular space of the spinous layer, most likely produced by keratinocytes; ultrastructural cellular alterations of PM were still evident and the lesion recurred after suspension of treatment. Topics: Aged; Etretinate; Foot Dermatoses; Hand Dermatoses; Humans; Keratosis; Male; Middle Aged; Skin; Syndrome; Tretinoin | 1980 |
[Treatment of Mibelli's porokeratosis with vitamin A acid].
Topics: Administration, Topical; Adult; Drug Evaluation; Female; Foot Dermatoses; Hand Dermatoses; Humans; Keratosis; Syndrome; Tretinoin; Vitamin A | 1977 |
Retinoyl complexes in Batten disease.
Topics: Cholesterol; Humans; Lipidoses; Neurons; Syndrome; Tretinoin; Vitamin A | 1977 |