All-trans Retinoic Acid Syndrome Research Articles

Differentiation Syndrome Presenting as Acute Kidney Injury in a Patient of Acute Promyelocytic Leukemia on All-trans Retinoic Acid and Arsenic Trioxide Regimen: A Case Report

Introduction: Acute promyelocytic leukemia (APL), classified as Subtype M3 of acute myeloid leukemia, is known for its relatively favorable prognosis, primarily due to the high effectiveness of all-trans retinoic acid (ATRA) in treating the maturation block. However, it is essential to be aware of potential complications such as ATRA syndrome, which can affect 5%–25% of patients and manifest with symptoms such as fever, interstitial pulmonary infiltration, pleural/pericardial effusion, and acute renal failure. Methods: We present the case of a 47-year-old female with a history of hypertension, who experienced rash, fever, and reduced urine output during the induction phase with ATRA. Her serum creatinine levels exhibited a rapid increase from 2.63 mg/dL on October 07, 2022, to 7 mg/dL on October 18, 2022, despite having normal-sized kidneys and normal corticomedullary differentiation. A renal biopsy conducted on October 20, 2022, revealed features consistent with active tubulointerstitial nephritis, with direct immunofluorescence showing no significant glomerular immune deposits. A total of 17 hemodialysis sessions were performed. Results: A subsequent bone marrow examination conducted on October 26, 2022, demonstrated a hypercellular aspirate with normal morphology. However, due to the persistence of renal failure, a repeat biopsy was performed, revealing severe acute tubular injury. Pulse steroids were initiated, and ATRA was discontinued, resulting in an improvement in renal function. Conclusion: This case highlights an instance of acute, early, and severe differentiation syndrome (DS) occurring after induction therapy in a patient with APL. The DS in this case was particularly severe, leading to renal failure necessitating hemodialysis. The prompt initiation of pulse steroids and discontinuation of ATRA proved to be effective in managing this complication. Clinicians should remain vigilant for DS and its potential complications, including acute kidney injury and acute tubulointerstitial nephritis, when treating patients with APL.

Responding well to corticosteroid in an acitretin treatmentRelated acute lung injury patient with psoriasis

Acitretin is retinoic acid derivative that is approved for treatment of severe psoriasis. The side effect of retinoic therapy is all-trans retinoic acid syndrome. Here, we report a case of acitretin treatment associated acute lung injury in a psoriasis patient. Exhibited as a diffuse lung parenchymal injury, the differential diagnosis of infection, heart failure, and alveolar hemorrhage should be ruled out. A definite medication history is prerequisite for diagnosis of the disease. After correct diagnosis, the patient responded well to corticosteroid and the symptom and radiological changes of acitretin-induced acute lung injury alleviated soon.

Differentiation Syndrome Mimicking COVID-19 Pneumonia

Introduction: SARS-CoV-2 infection is spreading worldwide, and due to multi-organ involvement, it could mimic other well-known diseases. Case Presentation: Herein, we describe the case of a pediatric patient with acute promyelocytic leukemia (APL), who developed severe respiratory illness with diffuse pulmonary involvement after consuming all-transretinoic acid during the COVID-19 pandemic. Conclusions: All-transretinoic acid syndrome is a very similar condition to COVID-19 both in clinical presentations and radiologic findings; thus, the treatment of such patients may be challenging.

Treatment Outcome of Newly Diagnosed Acute Promyelocytic Leukaemia by All-Trans Retinoic Acid followed by Arsenic Tri-Oxide

Background: Acute promyelocytic leukaemia (APL) is curable with carefully selected treatment protocol. Reduction of early fatal haemorrhage in initial phase of induction with cost effective combination of chemotherapeutic agents is considered to be the main challenge for successful outcome in APL. Objective: The study was conducted to see the effectiveness of the use of all-trans retinoic acid (ATRA) followed by single agent Arsenic tri oxide (ATO) in the induction phase of the management of APL. Methodology: This is an observational study and was conducted from October 2012 to September 2013, in department of Haematology and BMT of Dhaka Medical College Hospital, Dhaka, Bangladesh. Total 17 patients with PML/RARA positive APL were enrolled and all patients were treated with sequential use of ATRA in a dose of 45mg/m2 for initial 2-3 weeks up to differentiation and then ATO in a dose of 0.15mg/kg daily was used in induction up to 60 days after taking informed written consent. Outcome was drawn after consolidation of therapy. Results: The morphologic complete remission rate was 88.2%. Remission failure was in observed in 2 cases (11.8%) that died at day 12 and day 51 due to differentiation syndrome and arrhythmia respectively. No death observed within first 10 days of treatment initiation. Complications observed during management were weight gain (11, 64.7%), hyper leucocytosis (10, 58.8%), ATRA syndrome (9, 52.9%), headache (6, 35.3%), tachycardia (5, 29.4%), hypomagnesaemia (3, 17.7%) and supra ventricular tachycardia (1, 5.8%). Conclusion: Initial use of ATRA up to differentiation of promyelocytes before use of single agent ATO induction and consolidation can be a cost-effective alternative against newly diagnosed APL in reduction of early haemorrhagic death.

Retinoic acid syndrome followed by scrotal ulcer during treatment of acute promyelocytic leukemia with all-trans retinoic acid

All-trans-retinoic acid (ATRA) has shown a significant improvement in the outcome of patients of acute promyelocytic leukemia and is associated with certain unique adverse effects. We report one such case of APL, who developed ATRA syndrome on day 7 of ATRA, which was relieved after ATRA withdrawal and dexamethasone therapy. Subsequently, with the reintroduction of ATRA, patient developed an unexplained fever which was followed by multiple painless ulcers over the scrotum on day 28 of ATRA. ATRA was withdrawn so as not to induce Fournier’s gangrene, and ulcers were closely monitored without the administration of systemic or local corticosteroids. Eventually, ulcers improved and completely healed by 4 weeks. This is a rare case report, wherein the same patient develops ATRA syndrome followed by scrotal ulcers, suggesting that the scrotal ulcer is a rare specific adverse effect of ATRA and its monitoring is required especially in patients having unexplained fever and leucocytosis.

Acute Promyelocytic Leukemia: Clinical Outcomes, Induction Deaths and Challenges

IntroductionAcute promyelocytic leukemia (APL) was an oncologic emergency but the introduction of All-trans retinoic acid (ATRA) and arsenic trioxide (ATO) ameliorated the treatment outcomes. A translocation of chromosomes which was once considered most fatal and patients bled till death in the course; is highly curable now, thanks to the dramatic advancement happened in the development of single/combined use of regimens.It is reported way back in 2008 that APL cases in India have a varied genetic setup. There is a significant dearth of published articles on APL cases from India. In a developing country, especially like India; where the patient pays for the cancer care ‘out of pocket’ and also where the GDP spent on health care is less than 5 percent, the management of APL is certainly challenging as the average cost of treatment runs to $2183 (Median per capita income in India is $616). In addition, clinical outcomes are highly influenced by multidrug resistant microbes and several environmental factors. They have critically increased the infection and early death rate.MethodsTo discern the clinical outcomes of APL at our center we performed a retrospective record-based study of APL patients. We went through 156 Acute myelocytic leukemia patients over the past 16 years from July 2002 to January 2018 and out of which 19 patients were diagnosed with APL in our tertiary care hospital. Our aim was to determine the clinical outcome, cause of induction death and the current challenges in APL management. We included all the fresh cases diagnosed at our center and we set exclusion criteria as those who denied the treatment due to social/financial constraints and those whom we have lost follow-up.ResultsThe patients were from the age of 10 years to 67 years (Mean age: 38.5). 31.5 percent of the patients were male and 68.4 percent were female. 47.3 percent of the patients were in the high-risk APL group and 15.7 percent of the patients belonged to the low risk group. The remaining 36.8 percent patients comprised the intermediate risk group. Promyelocytic retinoid acid receptor alpha (PML/RARX) was standard for all patients. For 18 patients we gave ATRA for 45 days and one patient expired during induction due to bleeding (ATRA syndrome). Arsenic was given for 20 days. At the end of induction, we did a bone marrow aspiration and PML/RARA. All 18 patients had complete remission. PML/RARX shows Zero for all 18 patients. 11.1 percent of the patientsexpired and16.66 percent of the patients are alive with disease. 72.2 percent of the patients are alive without disease and until the most recent follow-up; they showed no sign of recurrence.ConclusionsDespite certain noteworthy challenges which must be taken into consideration, our center presents more than 70 percent relapse free survival. In conclusion, if infection control, social support and health security improves, the survival rate can go even higher as a lot of AML patients diagnosed in our hospital and other various centers across India had denied the treatment because of the financial and social constraints. Our finding reveals a good survival rate and must open novel prospects for cost-effective targeted therapies of a much shorter duration in developing countries. DisclosuresNo relevant conflicts of interest to declare.

Effective Management of Acute Promyelocytic Leukemia with High Risk of Fatal Intracranial Hemorrhage

Although the prognosis of acute promyelocytic leukemia (APL) are favorable because of disease-specific drugs, such as all-trans retinoic acid (ATRA) and arsenic trioxide (ATO), early death due to fatal intracranial hemorrhage has been observed in many cases. The aim of this study is to examine the relationship between the treatment and intracranial hemorrhage complication in APL patients.46 patients diagnosed of APL during a period from 2000 to 2014 in our hospital were examined. The distribution of fatal intracranial hemorrhage (FICH) risk score in the 46 APL patients showed 23.9%, 58.6% and 17.3% for low, intermediate, and high categories, respectively. Among the 46 patients, 5 patients developed intracranial hemorrhage before remission, including 4 patients who developed such hemorrhage after chemotherapy and ATRA administration, and 1 patient who developed intracranial hemorrhage before treatment. All of the 5 patients were included in the high risk group of FICH score, including 1 patient who died and 3 patients who had serious paralysis. These hemorrhage tended to expand for several days because of progression of disseminated intravascular coagulation (DIC) accompanied by tumor lysis syndrome after chemotherapy. Based on this experience, we firstly provided single administration of ATRA for 5 days to a patient with intracranial hemorrhage and then added chemotherapy after improvement of DIC. As a result, we could lead remission with no expansion of intracranial hemorrhage. In most of induction therapy protocols for APL, patients with high white blood cell counts are recommended to receive combination of chemotherapy and ATRA with a focus on ATRA syndrome, but the risk of fatal intracranial hemorrhage is not reflected in the treatment regimen. Such a complication may be prevented using initial single administration of ATRA followed by concomitant chemotherapy after treatment for DIC in patients with a high-risk FICH score.

Clinico-hematological profile and outcome of acute promyelocytic leukemia patients at a tertiary care center in North India.

Acute promyelocytic leukemia (APL) is the only acute leukemia amenable to targeted therapy. However, there is limited Indian data on APL. We aimed to analyze data of APL patients treated with all trans retinoic acid (ATRA) and anthracycline based chemotherapy. A total of 34 cases of APL were treated at our center over 4 years. Induction chemotherapy consisted of a combination of ATRA and daunorubicin. Most of our patients were intermediate risk (50%) followed by high risk (41.17%). Induction mortality was 14.7%. We observed a high incidence of febrile neutropenia (91%) and 50% of our patients developed ATRA syndrome. Four patients (11.76%) relapsed during follow-up (median - 15 months, range: 13-33 months). There was no correlation between risk status and death or relapse or ATRA syndrome. Median event free survival (EFS) duration was not reached however mean duration was 38.45 ± 3.84 months. Median overall survival (OS) duration was also not reached at 53 months of follow-up. The 4 year OS and EFS were 75.45% and 64.5% respectively. On multivariate analysis, only disseminated intravascular coagulation (DIC) significantly correlated with a poor OS and EFS. Our data reflects that APL remains a highly curable malignancy with good response to ATRA plus anthracycline based chemotherapy even with a greater number of high and intermediate risk patients. Only DIC during induction chemotherapy bore an impact on survival in our patients.

Lethal small bowel necrosis due to aspergillosis during acute promyelocytic leukemia induction

Lethal small bowel necrosis due to aspergillosis during acute promyelocytic leukemia induction

Abstract LB-519: Chemotaxis of acute promyelocytic leukemia cells toward CXCL12 is involved in ATRA syndrome and the requirement of chemotherapy during Induction therapy with ATRA

Abstract We previously reported that treatment of acute promyelocytic leukemia (APL) cells with all-trans retinoic acid (ATRA) in vitro increases the directed migration towards CXCL12. Here we report the clinical significance of this phenomenon. Bone marrow cells were corrected from 13 de-novo APL patients after obtaining informed consent. Flow-cytometric analysis revealed that all cases expressed CXCR4, the receptor of CXCL12. The CXCR4 expression was enhanced after 24 hour treatment with ATRA in vitro. Chemotaxis analysis using Boyden chamber demonstrated that the directed migration towards CXCL12 increased 1.03 to 4.16 (median 1.65) times in ATRA-treated APL cells as compared to non-treated cells. Four out of 13 APL patients developed ATRA syndrome during induction therapy with ATRA. The chemotaxis towards CXCL12 was enhanced in these four patients (p<0.01). Six cases required chemotherapy with IDR and Ara-C during induction therapy with ATRA. The significant increase in chemotaxis toward CXCL12 was also observed in these patients as compared with those who achieved CR by the induction therapy with ATRA alone (p<0.01). Interestingly, the ability of chemotaxis of APL cells appeared to be more well correlated with the occurrence of ATRA syndrome and the requirement of additional chemotherapy during ATRA treatment as compared with other well known predictable factors such as the APL cell number or white blood cell number in the peripheral blood, and the expression level of CXCR4. To investigate the possible mechanism of the chemotaxis, we used APL cell lines such as ATRA-sensitive NB4 cells and ATRA-resistant UF-1 cells as well as primary APL cells. An inhibitory antibody against CXCR4 and pertussis toxin effectively suppressed chemotaxis of APL cells toward CXCL12. Chemotaxis assay using selective signaling inhibitors demonstrated that activation of phospholipase C but not MAP kinase was strongly involved in the directed migration towards CXCL12 in APL cells. Additionally, the Akt-PI3-kinse pathway was partly participated in this chemotaxis. These results suggest that chemotaxis ability of APL cells toward CXCL12 is involved in the pathogenesis of ATRA syndrome and the requirement of chemotherapy during induction therapy with ATRA. Furthermore, specific signal targeted-therapy might contribute to prevent ATRA syndrome and/or avid administration of excessive chemotherapeutic agents. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-519. doi:1538-7445.AM2012-LB-519

Insuficiência renal aguda em paciente tratada com ATRA e anfotericina B: relato de caso

This is a report of the case of a patient with acute promyelocytic leukemia treated with all trans-retinoic acid (ATRA), who had suspected all-trans retinoic acid syndrome (ATRA syndrome). The nonspecific febrile leukopenia observed justified the association with antimicrobial and antifungal therapy. Signs and symptoms contributed to the suspicion of ATRA syndrome, and renal function was impaired by the combination with antifungal agents. The decrease in renal function observed initially contributed to the suspicion of ATRA syndrome and was aggravated by antifungals. Thus, the use of ATRA was discontinued. Eight days after the pneumonia characterization, the possibility of ATRA syndrome was dismissed. In this context, ATR's nephrotoxicity and the synergic adverse effect by the use of nephrotoxic antifungal agents were discussed, particularly amphotericin B, as well as the importance of differential diagnosis between ATRA syndrome and infectious diseases.

Risk Factors and Clinical Outcome of Central Nervous System (CNS) Leukemia In Patients with Acute Promyelocytic Leukemia (APL) on Long-Term Oral Arsenic Trioxide Maintenance.

AbstractAbstract 1082 Background:The prognosis of patients with APL has improved with all trans-retinoic acid (ATRA) and arsenic trioxide (As2O3) therapy. An increasing frequency of isolated CNS relapse is reported in APL survivors and intrathecal prophylaxis has been proposed. We have used oral As2O3 as prolonged maintenance therapy for APL patients in first remission (CR1) and beyond. During oral As2O3 therapy, elemental arsenic penetrates the CNS at meaningful levels. The risk factors for CNS APL in this setting are unknown. Material and methods:From 2001 to 2009, consecutive APL patients in ATRA +/− chemotherapy-induced CR1, or As2O3 +/− chemotherapy-induced CR2 and beyond, were given As2O3 maintenance therapy, comprising oral As2O3 therapy (10mg daily) and ATRA (30mg twice daily), given two weeks every two months for two years. CNS leukemia was diagnosed by the presence of typical APL cells in the cerebrospinal fluid (CSF). Patients with CNS leukemia were treated with intrathecal methotrexate (12 mg twice weekly until clearing of CSF) and oral-As2O3, ATRA and ascorbic acid. Results:A total of 102 APL patients (46 men, 56 women) at a median age of 43 (13–43) years received oral As2O3 maintenance during CR1 (n=63) and CR2 or beyond (n=39). The median follow-up period was 55 (8–143) months. At initial presentation, the hematological parameters were hemoglobin: 8.5 (3–14.6) g/dL, white cell count: 10.1 (0.3–121) × 109/L (with 21 cases >10 × 109/L) and platelet count: 35 (3–162) × 109/L (with 67 cases <40 × 109/L). A total of 25 patients had a history of steroid treatment for APL differentiation syndrome. Leucocytosis (> 15 × 109/L) developing either during ATRA or As2O3 treatment occurred in 62 patients. For the whole cohort, the median peak leucocyte count at any time point in the clinical course was 29.3 (0.8–243) × 109/L. Eight patients (7 men, 1 woman, median age 49 years) developed CNS leukemia, at a median of 42 (1–56) months from commencement of As2O3 maintenance. All had a history of elevated peak WCC, at a median of 69.5 (26–123) × 109/L. Symptoms included headache (n=3), dizziness (n=2), confusion, blurred vision and leg weakness. The median CSF cell count was 35 (7–2500) × 106/L. Concurrent marrow morphologic relapse was found in 4 cases (first relapse, R1, n=1; R2, n=3). Four patients had normal blood counts and marrow morphology (still in CR1, n=1; CR2, n=3), although their peripheral blood cells were positive for PML-RARA by polymerase chain reaction. All patients responded completely to treatment initially, but recurrent CNS leukemia still occurred in 4 cases after 12–16 months. Additional treatment including cranial radiotherapy (n=6), systemic high dose cytarabine (n=2) and autologous hematopoietic stem cell transplantation (n=1). Three patients ultimately died of refractory APL at a median of 13 months after CNS relapse. On univariate analysis, risk factors for CNS relapse were male gender (RR 6.8, p=0.001), and leucocytosis at any time point (for WCC > 15×109/L, RR 8.4, p=0.004; for WCC > 20×109/L, RR 12.1, p<0.001). There was no significant relation to age, ATRA syndrome, hematologic parameters on presentation and disease status at commencement of oral As2O3 maintenance. Conclusions:With prolonged survival of APL patients, CNS leukemia is emerging as an important problem that curtails survival. Based on the use of oral As2O3 maintenance, patients who at any time point in the clinical course developing a leucocytosis of > 15–20 × 109/L are at high risk of CNS relapse and should be considered suitable candidates for CNS prophylaxis. Disclosures:Off Label Use: Oral arsenic trioxide for maintenance of APL in remission. Kwong:HKU: YL Kwong is an employee of the University of Hong Kong that holds a patent for oral arsenic trioxide.

All-transretinoic Acid (ATRA) Treatment-related Pancarditis and Severe Pulmonary Edema in a Child With Acute Promyelocytic Leukemia

Use of all-transretinoic acid (ATRA) with other chemotherapeutic agents in the treatment of acute promyelocytic leukemia (APL) has been shown to cause the differentiation of abnormally granulated specific blast cells into mature granulocytes by acting on the t(15; 17) fusion gene product. The complete remission rate is increased and survival time is prolonged in APL patients who receive chemotherapy plus ATRA, whereas ATRA syndrome and other ATRA-related adverse effects including pseudo tumor cerebri, headache, severe bone pain, mucosal and skin dryness, hypercholesterolemia, and cheilitis may be observed especially during induction phase of the treatment. In this paper, we report a 9-year-old girl with APL who developed pancarditis while receiving the APL-93 treatment protocol. In our patient, endocarditis and myocarditis were initially determined after ATRA treatment during the induction part of the protocol. All findings disappeared after ATRA was discontinued. When ATRA was readministered in the maintenance part of the treatment protocol, she developed pancarditis and severe pulmonary edema. As her symptoms decreased dramatically with the discontinuation of ATRA and the initiation of steroid treatment, the clinical picture strongly suggested the ATRA treatment as the causative factor. To the best of our knowledge, this clinical picture of pancarditis secondary to ATRA treatment has not been reported earlier in the English literature.

Outcome of childhood acute promyelocytic leukemia treated using a modified AIDA protocol

BackgroundCombination treatment with all-trans-retinoic acid (ATRA) and anthracycline-based chemotherapy has led to major advances in the treatment of acute promyelocytic leukemia (APL).MethodsIn this study, we reviewed the outcome of pediatric APL patients treated using a modified AIDA protocol at our institution.ResultsBetween May 1999 and December 2007, 23 patients were diagnosed with APL at the Department of Pediatrics, Saint Mary's Hospital, The Catholic University of Korea. Eleven patients were male (48%) (median age at diagnosis, 11 (range, 2-14) years). The treatment protocol consisted of remission induction (achieved by coadministration of ATRA and idarubicin), 3 courses of consolidation treatment, and 2 years of maintenance treatment during which ATRA was also administered. Three patients died early during remission induction due to CNS hemorrhage. The remaining 20 patients achieved complete remission (CR), with an overall CR rate of 87%. Two patients relapsed and died, and another patient died of pneumonia unrelated to APL. Four patients (17%) were diagnosed with ATRA syndrome, and all patients showed resolution of symptoms. The event-free survival (EFS) and overall survival (OS) of the cohort were 78.3±8.6% and 76.3±9.5%, respectively. Initial WBC count at diagnosis was the only significant prognostic factor for the rate of CR (P=0.039) and OS (P=0.039).ConclusionA modified AIDA protocol for the treatment of childhood APL leads to improved EFS and OS, with limited ATRA syndrome-associated toxicity. Active monitoring and treatment of patients with high initial WBC counts may help in reducing mortality.

ACUTE PROMYELOCYTIC LEUKEMIA (APL) IN PATIENTS AGED > 70 Years.

Abstract 4160Acute Promyelocytic Leukemia (APL) is a rare subtype of Acute Myeloid Leukemia (AML) more common in younger adults, with a median age of 45 – 50 years at onset. The use of All-trans Retinoic Acid (ATRA) as tailored treatment has made APL a very curable disease also in patients aged > 60 years; however, there are only few case reports in very elderly APL patients. To address this issue, we revised clinical data and treatment results in 12 patients aged > 70 years with newly diagnosed APL followed at our Institution from 1/91 to 12/2008. Clinical characteristics at onset were as follows: M/F 7/5, median age 74.7 years (range 70.0 – 80.8), M3/M3v 11/1, median WBC 1.3 × 109/l (range 1.0 – 7.4), median PLTS 53 × 109/l (range 12 – 302), BCR1/BCR3 6/6. According to Sanz risk score, 7 patients were at low-risk and 5 at intermediate-risk; 6/12 patients had arterial hypertension, 4/12 a concomitant cardiologic disease, 3/12 a cerebro-vascular disease and 2/12 a previous neoplasia. Induction therapy consisted of ATRA + Idarubicin in 8 patients (2/8 with reduced Idarubicin dosage) and ATRA alone in 4 patients; in this latter group, however, 2/4 needed to add chemotherapy (CHT) based on Mitoxantrone + AraC due to hyperleukocytosis during ATRA treatment. All patients achieved both morphological and molecular Complete Remission (CR) after a median time of 50 (range 29 – 65) and 105 (range 51 – 239) days, respectively. Infective complications were observed in 10/12 patients (4 episodes of FUO, 6 sepsis, 2 cystitis and 1 oral abscess) while ATRA syndrome occurred in 2/12 patients; in addition, there were 3 episodes of cardiac ischemia and 3 episodes of paroxystic atrial fibrillation. All but one patient received consolidation therapy (based on CHT alone in 7 patients, CHT + ATRA in 3 patients and ATRA alone in 1 patient), followed by maintenance treatment in 8 patients. Four patients had a relapse (hematological in 3 cases and molecular in 1 case) after 8, 11, 35 and 56 months respectively. At present, 6 patients are still alive, 4 died due to disease progression (3) or senectus while in CR (1) and 2 were lost to follow-up while in CR: mean event-free survival and overall survival were 89.2 months (95%CI 52.6 – 125.8) and 99.9 months (95%CI 65.0 – 134.7), respectively. In conclusion, ATRA-based treatment of APL is safe and effective also in very elderly patients, with long-lasting disease-free and overall survival. Disclosures:No relevant conflicts of interest to declare.

All-Trans Retinoic Acid-Induced Focal Myositis, Synovitis, and Mononeuritis

All-trans retinoic acid has revolutionized the treatment of acute promyelocytic leukemia, but this therapy is often complicated by the all-trans retinoic acid syndrome. Here we report a patient with newly diagnosed acute promyelocytic leukemia who developed acute focal myositis, synovitis, and possible vasculitis, after receiving all-trans retinoic acid therapy. We review the existing literature on this rare clinical entity, all-trans retinoic acid-induced myositis. This condition can manifest as fever, myalgia, arthralgia, and Sweet syndrome, accompanied by distinct magnetic resonance findings involving the lower extremity musculature. Treatment consists of discontinuation of the offending drug and often high dose corticosteroids.

Pediatric Acute Promyelocytic Leukemia: All-transretinoic Acid Therapy in a Brazilian Pediatric Hospital

Acute promyelocytic leukemia (APL) is an uncommon form of pediatric acute nonlymphocytic leukemia. It is characterized by clinical (refractory coagulopathy), morphologic (promyelocytic differentiation arrest), and cytogenetic t(15;17) hallmarks. The introduction of all-transretinoic acid (ATRA) or tretinoin, a biologic response modifier, in its therapy was followed by dramatic improvement in its outcome. To show the results of APL treatment in our hospital, we reviewed the information about 15 patients less than 18 years old, newly diagnosed with APL between November 2002 and November 2006. The diagnosis was made upon examination of bone marrow aspirates. The clinical charts were searched for data regarding clinical presentation, diagnosis, initial response with induction therapy, toxicity of ATRA, and antracyclic drug (daunorubicin). The median age was 10 years; the male-to-female ratio was 2:1. Fourteen patients received induction chemotherapy. Thirteen achieved complete remission. Six patients showed signs of coagulopathy. Only 1 patient was diagnosed with ATRA syndrome. There was a death owing to sepsis before the beginning of the therapy and 2 relapses with death associated with the therapy discontinuation. Preliminary results are encouraging and confirm that ATRA is safe and efficacious as first choice therapy for APL.

Síndrome del ácido transretinoico y necrosis cortical renal

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.

All-trans Retinoic Acid Syndrome: Another Cause of Drug-induced Respiratory Failure

It is now possible to achieve complete remission in the majority of patients with acute promyelocytic leukemia (APL) if all-trans retinoic acid (ATRA) is administered as a single agent or in combination with cytotoxic chemotherapy. Despite its positive influence on recovery, ATRA is not without the potential for toxicity. It is important for clinicians participating in the care of patients undergoing treatment with this drug to be aware of ATRA syndrome and institute the appropriate therapy to reduce the likelihood of an adverse outcome.

Two cases of isolated symptomatic myocarditis induced by all-trans retinoic acid (ATRA)

Two cases of isolated symptomatic myocarditis induced by all-trans retinoic acid (ATRA)