Leukocytosis and the Retinoic Acid Syndrome in Patients With Acute Promyelocytic Leukemia Treated With Arsenic Trioxide

Camacho, L. H.; Soignet, Steven L.; Chanel, Suzanne; Ho, Raymond; Heller, Glenn; Scheinberg, David A.; Ellison, Ralph; Warrell, Raymond P.

doi:10.1200/jco.2000.18.13.2620

Cited by 158 publications

(98 citation statements)

References 36 publications

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“…1 Although the pathogenesis of the syndrome is unclear, laboratory investigations indicate that ATRA promotes inflammatory cytokine generation by APL cells and activates homotypic and heterotypic adhesion, thereby enhancing endovascular permeability and promoting leukemia cell adhesion and transmembrane migration. 2,3 Initially termed the retinoic acid syndrome, subsequent studies revealed that the analogous syndrome may occur in APL patients treated with arsenic trioxide, 4 and rarely in patients with non-promyelocytic subtypes of acute myeloid leukemia treated with ATRA. 5 Lonafarnib (SCH66336 or Sarasart; Schering-Plough Research Institute, Kenilworth, NJ, USA) is a member of a novel class of therapeutics under investigation in hematologic malignancies, termed the farnesyl transferase inhibitors (FTIs).…”

Section: To the Editormentioning

confidence: 99%

Hyperleukocytosis complicating lonafarnib treatment in patients with chronic myelomonocytic leukemia

et al. 2004

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Section: To the Editormentioning

confidence: 99%

Hyperleukocytosis complicating lonafarnib treatment in patients with chronic myelomonocytic leukemia

et al. 2004

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“…Currently used in the treatment of acute promyelocytic leukemia [80,81], these agents have both been associated with the development of NCPE/ARDS in the context of ATRA syndrome. This is a life-threatening complication that occurs in a quarter of patients with acute promyelocytic leukemia who undergo remission induction treatment with ATRA or As 2 0 3 , with or without chemotherapy [82,83]. The ATRA syndrome characterizes a loosely defined constellation of signs and symptoms that primarily consist of fever and respiratory distress, but also of weight gain, peripheral edema, pleural or pericardial effusions, and hypotension [84].…”

Section: Atra Syndromementioning

confidence: 99%

Noncardiogenic Pulmonary Edema: An Unusual and Serious Complication of Anticancer Therapy

Briasoulis

Pavlidis

2001

The Oncologist

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Noncardiogenic pulmonary edema (NCPE) is a rare and less well-recognizable pulmonotoxic syndrome of anticancer therapy than pneumonitis/fibrosis. NCPE is a clinical syndrome characterized by simultaneous presence of severe hypoxemia, bilateral alveolar infiltrates on chest radiograph, and no evidence of left atrial hypertension/congestive heart failure. The diagnosis of drug-related NCPE relies upon documented exclusion of any infectious, metabolic, or cancer-related causes. The Oncologist 2001;6:153-161 www.TheOncologist.com Correspondence: Evangelos Briasoulis, M.D., Medical Oncology Department, Ioannina University, Ioannina, 45110, Greece. Telephone and Fax: 30-651-99394; e-mail: ebriasou@otenet.gr. Received August 15, 2000; accepted for publication November 30, 2000. ©AlphaMed Press 1083-7159/2001 INTRODUCTIONSeveral cancer therapeutic drugs are known to induce pulmonary damage, which may result in a variety of clinicopathologic syndromes with minor to severe clinical consequences [1]. Clinical syndromes associated with drug-induced pulmonary toxicity include pneumonitis/fibrosis, hypersensitivity lung disease, and noncardiogenic pulmonary edema (NCPE)/acute respiratory distress syndrome (ARDS). These syndromes share a similar symptomatology but differ in regard to the time-relation to cancer treatment, the radiographic findings, the duration of pulmonary damage, and the long-term outcome [2]. Non-specific symptomatology of cough, progressive dyspnea, and often a low-grade fever alert clinicians confronted with the diagnostic challenge to recognize subclinical syndromes and differentiate fully developed drug-induced pulmonary reactions from lung injuries caused by infectious, cardiac, and neoplastic causes.

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“…6,7 RAS is not observed in APL patients with consolidation/maintenance therapy using ATRA, but sometimes observed during arsenic trioxide therapy for APL. 8 In both cases, hyperleukocytosis of differentiated APL cells during therapy is likely associated with RAS. 7 In addition, administration of G-CSF or hyperleukocytosis in myeloid leukemia is associated with adult acute respiratory distress syndrome, which has an indistinguishable clinical presentation from RAS.…”

Section: Introductionmentioning

confidence: 99%

Retinoic acid syndrome in NOD/scid mice induced by injecting an acute promyelocytic leukemia cell line

et al. 2004

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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 Â 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.

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Leukocytosis and the Retinoic Acid Syndrome in Patients With Acute Promyelocytic Leukemia Treated With Arsenic Trioxide

Abstract: 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.

Cited by 158 publications

References 36 publications

Hyperleukocytosis complicating lonafarnib treatment in patients with chronic myelomonocytic leukemia

Hyperleukocytosis complicating lonafarnib treatment in patients with chronic myelomonocytic leukemia

Noncardiogenic Pulmonary Edema: An Unusual and Serious Complication of Anticancer Therapy

Retinoic acid syndrome in NOD/scid mice induced by injecting an acute promyelocytic leukemia cell line

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