The Experts below are selected from a list of 1671 Experts worldwide ranked by ideXlab platform
Raymond P Warrell - One of the best experts on this subject based on the ideXlab platform.
-
leukocytosis and the Retinoic Acid Syndrome in patients with acute promyelocytic leukemia treated with arsenic trioxide
Journal of Clinical Oncology, 2000Co-Authors: Luis H Camacho, D A Scheinberg, Steven L Soignet, S Chanel, Glen Heller, Ralph Ellison, Raymond P WarrellAbstract:PURPOSE: 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. PATIENTS AND METHODS: 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. RESULTS: 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/μL (range, 1,200 to 72,300 cells/μL), which was higher than that for patients who did not develop leukocytosis (2,100 cells/μL; range, 500 to 5,400 cells/μL; P = .01). No other cytotoxic therapy was administered, and the leukocytosis resolved in...
-
leukocytosis and the Retinoic Acid Syndrome in patients with acute promyelocytic leukemia treated with arsenic trioxide
Annual Meeting of American Society of Hematology, 2000Co-Authors: Luis H Camacho, D A Scheinberg, Steven L Soignet, S Chanel, Glen Heller, Ralph Ellison, Raymond P WarrellAbstract:Purpose: 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. Patients and Methods: 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. Results: 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/μL (range, 1,200 to 72,300 cells/μL), which was higher than that for patients who did not develop leukocytosis (2,100 cells/μL; range, 500 to 5,400 cells/μL; 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/μL 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). Conclusion: 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.
-
acute renal failure associated with the Retinoic Acid Syndrome in acute promyelocytic leukemia
American Journal of Kidney Diseases, 1996Co-Authors: Carlos D Flombaum, Marian Isaacs, L Reich, Ellin Berman, Raymond P WarrellAbstract: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.
-
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
Blood, 1994Co-Authors: Linda T Vahdat, Anna Eardley, P Maslak, Wilson H Miller, Glenn Heller, D A Scheinberg, Raymond P WarrellAbstract: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 “short”) was associated with a significantly shorter duration of relapse-free and overall survival (P = .005).(ABSTRACT TRUNCATED AT 400 WORDS)
-
the Retinoic Acid Syndrome in acute promyelocytic leukemia
Annals of Internal Medicine, 1992Co-Authors: Stanley R Frankel, Anna Eardley, Gregory Y Lauwers, Mark Weiss, Raymond P WarrellAbstract:Abstract ▪Objective:To describe a novel complication of therapy with all-trans Retinoic Acid in patients with acute promyelocytic leukemia. ▪Design:Case series. ▪Setting:Comprehensive cancer center...
Luis H Camacho - One of the best experts on this subject based on the ideXlab platform.
-
Retinoic Acid induced cd38 antigen promotes leukemia cells attachment and interferon γ interleukin 1β dependent apoptosis of endothelial cells implications in the etiology of Retinoic Acid Syndrome
Leukemia Research, 2007Co-Authors: Yin Gao, Kapil Mehta, Luis H CamachoAbstract:Abstract 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-γ (IFN-γ) and interleukin-1β (IL-1β) in peripheral blast cells from APL patients. IFN-γ and IL-1β 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-γ alone or low concentration of IL-1β and IFN-γ (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.
-
leukocytosis and the Retinoic Acid Syndrome in patients with acute promyelocytic leukemia treated with arsenic trioxide
Journal of Clinical Oncology, 2000Co-Authors: Luis H Camacho, D A Scheinberg, Steven L Soignet, S Chanel, Glen Heller, Ralph Ellison, Raymond P WarrellAbstract:PURPOSE: 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. PATIENTS AND METHODS: 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. RESULTS: 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/μL (range, 1,200 to 72,300 cells/μL), which was higher than that for patients who did not develop leukocytosis (2,100 cells/μL; range, 500 to 5,400 cells/μL; P = .01). No other cytotoxic therapy was administered, and the leukocytosis resolved in...
-
leukocytosis and the Retinoic Acid Syndrome in patients with acute promyelocytic leukemia treated with arsenic trioxide
Annual Meeting of American Society of Hematology, 2000Co-Authors: Luis H Camacho, D A Scheinberg, Steven L Soignet, S Chanel, Glen Heller, Ralph Ellison, Raymond P WarrellAbstract:Purpose: 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. Patients and Methods: 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. Results: 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/μL (range, 1,200 to 72,300 cells/μL), which was higher than that for patients who did not develop leukocytosis (2,100 cells/μL; range, 500 to 5,400 cells/μL; 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/μL 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). Conclusion: 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.
Qian Sixua - One of the best experts on this subject based on the ideXlab platform.
-
clinical features of Retinoic Acid Syndrome in acute promyelocytic leukemia treated with all trans Retinoic Acid
Chinese clinical oncology, 2005Co-Authors: Qian SixuaAbstract:Objective:To further explore the clinical features of all-trans Retinoic Acid(ATRA) caused Retinoic Acid Syndrome(RAS).Methods:The clinical manifestations,treatment and prognosis of 9 acute promyelocytic leukemia(APL) patients with RAS were retrospectively studied.Results:Patients receiving ATRA for induction developed RAS at a median time of 11 days of ATRA (range 3-28).Fever (all of the 9 patients),respiratory distress(7/9),pulmonary infiltrates(4/9),pleural effusion(4/9),pericardial effusion(2/9),celiac effusion(5/9),crura edema(5/9),and urine decrease(3/9)were the main clinical signs.With treatment of dexamethasone,ATRA decreasing or withdraw,with or without chemotherapy,most clinic sings resolved.Seven patients got complete remission,one died of intracranial bleeding.Conclusion:RAS is a servere Syndrome which need active therapy.
Melissa L Fishel - One of the best experts on this subject based on the ideXlab platform.
-
apx3330 inhibition of the redox function of ape 1 ref 1 ref 1 in promyelocytic leukemia cells enhances Retinoic Acid atra induced myeloid differentiation and limits cell proliferation as an approach to the prevention of the Retinoic Acid Syndrome ras
Journal of Clinical Oncology, 2009Co-Authors: Kent A Robertson, E S Colvin, Mark R Kelley, Melissa L FishelAbstract:e14613 Background: ATRA + chemotherapy has improved the treatment of promyelocytic leukemia(APL). However, 25% of ATRA treated APL patients experience toxicities that comprise the RAS (life-threate...
Martin S Tallman - One of the best experts on this subject based on the ideXlab platform.
-
a phase 2 study of atra arsenic trioxide and gemtuzumab ozogamicin in patients with high risk apl swog 0535
Blood Advances, 2020Co-Authors: Jeffrey E Lancet, Martin S Tallman, Anna Moseley, Steven Coutre, Daniel J Deangelo, Megan Othus, Mark R Litzow, Rami S Komrokji, Harry P Erba, Frederick R AppelbaumAbstract:High-risk acute promyelocytic leukemia (APL) remains a therapeutic challenge, with higher associated rates of early mortality and relapse than standard-risk APL. All-trans Retinoic Acid (ATRA) plus arsenic trioxide (ATO) is a well-established treatment for patients with standard-risk APL, but it is not well defined for those with high-risk APL. In a prior study of patients with high-risk APL, the addition of gemtuzumab ozogamicin (GO) to ATO plus ATRA suggested benefit. The SWOG Cancer Research Network conducted a phase 2 study to confirm the efficacy and safety of the combination of ATRA plus ATO plus GO in treating high-risk APL patients. The primary end points were 3-year event-free survival (EFS) and early (6-week) death rates associated with this combination. Seventy patients were treated. With a median follow-up of 3.4 years, the 3-year EFS and overall survival estimates were 78% (95% confidence interval [CI], 67%-86%) and 86% (95% CI, 75%-92%), respectively. Overall, 86% of patients achieved complete response. The 6-week mortality rate was 11%. The most common treatment-emergent toxicities during the induction phase included febrile neutropenia, aspartate aminotransferase/alanine aminotransferase elevation, hyperglycemia, hypoxia, headache, and prolonged QT interval corrected for heart rate. Retinoic Acid Syndrome occurred in 9% of patients. Approximately 37% of patients did not complete all planned courses of postremission therapy. The combination of ATRA plus ATO plus GO in high-risk APL patients was effective and generally well tolerated, suggesting an opportunity to offer a chemotherapy-free induction platform for patients with this disease. This trial was registered at www.clinicaltrials.gov as #NCT00551460.
-
Retinoic Acid Syndrome manifestations pathogenesis and treatment
Best Practice & Research Clinical Haematology, 2003Co-Authors: Richard S Larson, Martin S TallmanAbstract: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.
-
clinical description of 44 patients with acute promyelocytic leukemia who developed the Retinoic Acid Syndrome
Blood, 2000Co-Authors: Martin S Tallman, Janet Andersen, Charles A Schiffer, Frederick R Appelbaum, James Feusner, Angela Ogden, Lois E Shepherd, Jacob M Rowe, Christopher J Francois, Richard S LarsonAbstract: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 1450/μL at diagnosis and was 31 000/μL (range, 6800-72 000/μL) 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)