tretinoin and Hypotension

Differentiation Syndrome (DS) has been identified in a subset of patients undergoing treatment with novel classes of differentiating therapies for acute myeloid leukemia (AML) such as IDH and FLT3 inhibitors. While DS is a well-known treatment-related complication in acute promyelocytic leukemia (APL), efforts are still ongoing to standardize diagnostic and treatment parameters for DS in AML. Though the rates of incidence vary, many of the signs and symptoms of DS are common between APL and AML. So, DS can lead to fatal complications in AML, but prompt management is usually effective and rarely necessitates interruption or discontinuation of AML therapy.

Topics: Acute Kidney Injury; Adrenal Cortex Hormones; Antineoplastic Agents; Arsenic Trioxide; Cell Differentiation; Clinical Trials as Topic; Cytokine Release Syndrome; Edema; Enzyme Inhibitors; Epigenesis, Genetic; Fever; fms-Like Tyrosine Kinase 3; Humans; Hypotension; Isocitrate Dehydrogenase; Leukemia, Myeloid, Acute; Molecular Targeted Therapy; Myelopoiesis; Neoplasm Proteins; Pleural Effusion; Respiration Disorders; Tretinoin

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

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

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

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

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Fever; Humans; Hypotension; Idarubicin; Leukemia, Promyelocytic, Acute; Leukocytosis; Lung; Male; Respiratory Distress Syndrome; Syndrome; Tretinoin

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

Topics: Adolescent; Antineoplastic Agents; Cytokines; Hemofiltration; Humans; Hypotension; Leukemia, Promyelocytic, Acute; Male; Oliguria; Syndrome; Tretinoin

Topics: Adult; Dyspnea; Female; Fever; Humans; Hypotension; Leukemia, Promyelocytic, Acute; Middle Aged; Syndrome; Tretinoin

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