tretinoin and Pleural-Effusion

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

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

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

We report a rare case of hypercalcemia and acute pancreatitis in a subject with acute promyelocytic leukemia (APL) and pulmonary tuberculosis, during all-trans-retinoic acid (ATRA) treatment. Both associated complications were potentially due to several causes. A careful monitoring and exclusion of all causative factors must be addressed. Further research is necessary to improve our understanding of risk factors for these complications in patients with (APL). Studying these patterns may help us to improve outcomes for all children and young adults with hematologic malignancies.

Topics: Acute Disease; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Causality; Febrile Neutropenia; Humans; Hypercalcemia; Leukemia, Promyelocytic, Acute; Male; Mercaptopurine; Methotrexate; Middle Aged; Models, Biological; Pancreatitis; Pleural Effusion; Prednisone; Pulmonary Aspergillosis; Risk Factors; Tretinoin; Tuberculosis, Pulmonary; Vincristine

Topics: Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Daunorubicin; Diagnosis, Differential; Dyspnea; Female; Follow-Up Studies; Humans; Induction Chemotherapy; Leukemia, Promyelocytic, Acute; Middle Aged; Mitoxantrone; Pleural Effusion; Pulmonary Edema; Thioguanine; Tomography, X-Ray Computed; Tretinoin

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

Topics: Aged; Antineoplastic Agents; Humans; Lung; Male; Pleural Effusion; Radiography, Thoracic; Tomography, X-Ray Computed; Tretinoin

It has been shown that arsenic trioxide (As2O3) may induce hematologic remissions in patients with acute promyelocytic leukemia (APL) refractory to all-trans retinoic acid (ATRA). We reported on a patient with ATRA and drug-resistant APL that was successfully treated with As2O3. The patient had been given a diagnosis of typical APL and was treated with ATRA and chemotherapy for 12 months. He achieved complete remission (CR), but leukemia relapsed with 43% APL cells in the bone marrow in the 16th month of treatment. ATRA and cytarabine plus daunorubicin were administered; however, the APL cells in the bone marrow increased to 97.2%. As2O3 was initiated intravenously, and bone marrow showed a decrease of APL cells (6.7%) and a partial differentiation after 9 days. The patient received idarubicin (IDA) and steroid pulse because of the development of ATRA-like syndrome, and achieved CR 37 days after the initiation of As2O3. He received an additional 2 courses of As2O3 with IDA, and is in CR. These results demonstrated the therapeutic efficacy of As2O3 in treating ATRA and drug-resistant APL.

Topics: Adult; Antineoplastic Agents; Arsenic Trioxide; Arsenicals; Drug Resistance, Neoplasm; Humans; Idarubicin; Leukemia, Promyelocytic, Acute; Male; Neoplasm Recurrence, Local; Oxides; Pleural Effusion; Remission Induction; Treatment Outcome; Tretinoin

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

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: Adult; Female; Humans; Hypoxia; Leukemia, Promyelocytic, Acute; Pleural Effusion; Radiography; Syndrome; Tretinoin

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

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

Topics: Acute Disease; Adult; Fever; Humans; Leukemia, Promyelocytic, Acute; Male; Pleural Effusion; Respiratory Insufficiency; Syndrome; Tretinoin