급성전골수구성백혈병 환자에서 all-trans retinoic acid (ATRA)의 분화증후군 발생과 위험인자 분석
Incidence and Risk Factors for All-Trans Retinoic Acid-Induced Differentiation Syndrome in Acute Promyelocytic Leukemia
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Background : Acute promyelocytic leukemia (APL) is a unique subtype of acute myeloid leukemia (AML). All-trans retinoic acid (ATRA) triggers APL cells to differentiate into mature granulocytes. Differentiation syndrome (DS) otherwise known as retinoic acid syndrome is a complication associated with the treatment of APL with ATRA. DS is characterized by unexplained fever, weight gain, peripheral edema, dyspnea, pleuropericardial effusion, hypotension, and acute renal failure. Incidence of DS ranges from 2-27%, and detailed knowledge about DS is limited. The purpose of this study is to investigate the prevalence and risk factors of DS in APL patients. Methods : This study was retrospectively conducted on patients diagnosed with APL that received initial oral administration of ATRA January 2012-June 2015. This study analyzed incidence, onset, clinical signs and symptoms, management, and risk factors of DS. Results : Among 95 patients, 29 patients (30.5%) experienced DS, 12 with moderate form (12.6%) and 17 with severe form (17.9%). The first peak occurred during the first week of ATRA treatment. The most frequent clinical manifestations of DS were edema (82.8%), pleuropericardial effusion (75.9%), dyspnea (65.5%), and fever (62.1%). Intravenous dexamethasone was administered in 82.8% of patients with DS. ATRA was discontinued in 93.1% of patients with DS. The univariate analysis of prognostic factors identified the following characteristics as significantly associated with DS: blood urea nitrogen (BUN) ≥20 mg/dL and lactate dehyrogenase (LDH) ≥900 U/L. Upon multivariate analysis, abnormal levels of BUN remained independent prognostic factors for DS (OR 4.06; 95% CI 1.19-13.79; p=0.03). Conclusion : In this study, high level of BUN is one of the risk factors that can predict the potential side effects of DS. We recommend the use of steroid to prevent DS for people taking ATRA with abnormal level of BUN.
Abstract
Background : Acute promyelocytic leukemia (APL) is a unique subtype of acute myeloid leukemia (AML). All-trans retinoic acid (ATRA) triggers APL cells to differentiate into mature granulocytes. Differentiation syndrome (DS) otherwise known as retinoic acid syndrome is a complication associated with the treatment of APL with ATRA. DS is characterized by unexplained fever, weight gain, peripheral edema, dyspnea, pleuropericardial effusion, hypotension, and acute renal failure. Incidence of DS ranges from 2-27%, and detailed knowledge about DS is limited. The purpose of this study is to investigate the prevalence and risk factors of DS in APL patients. Methods : This study was retrospectively conducted on patients diagnosed with APL that received initial oral administration of ATRA January 2012-June 2015. This study analyzed incidence, onset, clinical signs and symptoms, management, and risk factors of DS. Results : Among 95 patients, 29 patients (30.5%) experienced DS, 12 with moderate form (12.6%) and 17 with severe form (17.9%). The first peak occurred during the first week of ATRA treatment. The most frequent clinical manifestations of DS were edema (82.8%), pleuropericardial effusion (75.9%), dyspnea (65.5%), and fever (62.1%). Intravenous dexamethasone was administered in 82.8% of patients with DS. ATRA was discontinued in 93.1% of patients with DS. The univariate analysis of prognostic factors identified the following characteristics as significantly associated with DS: blood urea nitrogen (BUN) ≥20 mg/dL and lactate dehyrogenase (LDH) ≥900 U/L. Upon multivariate analysis, abnormal levels of BUN remained independent prognostic factors for DS (OR 4.06; 95% CI 1.19-13.79; p=0.03). Conclusion : In this study, high level of BUN is one of the risk factors that can predict the potential side effects of DS. We recommend the use of steroid to prevent DS for people taking ATRA with abnormal level of BUN.
참고문헌 (19)
- Watts JM, "Acute promyelocytic leukemia: what is the new standard of care", Blood Rev, 28(5), pp.205~212 (2014)[DOI]
- Coombs CC, "Acute promyelocytic leukemia: where did we start, where are we now, and the future", Blood Cancer J, 5, pp.e304~ (2015)[DOI]
- Avvisati G, "All-trans retinoic acid in acute promyelocytic leukaemia", Best Pract Res Clin Haematol, 16(3), pp.419~432 (2003)[DOI]
- Cabral R, "Late differentiation syndrome in acute promyelocytic leukemia: a challenging diagnosis", Hematol Rep, 6(4), pp.5654~ (2014)
- Tallman MS, "Clinical description of 44 patients with acute promyelocytic leukemia who developed the retinoic acid syndrome", Blood, 95(1), pp.90~95 (2000)
- De Botton S, "Incidence, clinical features, and outcome of all trans-retinoic acid syndrome in 413 cases of newly diagnosed acute promyelocytic leukemia", Blood, 92(8), pp.2712~2718 (1998)
- Montesinos P, "Differ-entiation syndrome in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and anthracycline chemotherapy: characteristics, outcome, and prognostic factors", Blood, 113(4), pp.775~783 (2009)[DOI]
- Fenaux P, "A randomized comparison of all transretinoic acid (ATRA) followed by chemotherapy and ATRA plus chemotherapy and the role of maintenance therapy in newly diagnosed acute promyelocytic leukemia. The European APL Group", Blood, 94(4), pp.1192~1200 (1999)
- Patatanian E, "Retinoic acid syndrome: a review", J Clin Pharm Ther, 33(4), pp.331~338 (2008)[DOI]
- Rogers JE, "Differentiation syndrome in patients with acute promyelocytic leukemia", J Oncol Pharm Pract, 18(1), pp.109~114 (2012)[DOI]
- Rego EM, "Differentiation syndrome in promyelocytic leukemia: clinical presentation, pathogenesis and treatment", Mediterr J Hematol Infect Dis, 3(1), pp.e2011048~ (2011)[DOI]
- De Botton S, "Early onset of chemotherapy can reduce the incidence of ATRA syndrome in newly diagnosed acute promyelocytic leukemia (APL) with low white blood cell counts: results from APL 93 trial", Leukemia, 17(2), pp.339~342 (2003)[DOI]
- Breccia M, "Increased BMI correlates with higher risk of disease relapse and differentiation syndrome in patients with acute promyelocytic leukemia treated with the AIDA protocols", Blood, 119(1), pp.49~54 (2012)[DOI]
- Leblebjian H, "Predictive factors for all-trans retinoic acid-related differentiation syndrome in patients with acute promyelocytic leukemia", Leuk Res, 37(7), pp.747~751 (2013)[DOI]
- Jeddi R, "High body mass index is an independent predictor of differentiation syndrome in patients with acute promyelocytic leukemia", Leuk Res, 34(4), pp.545~547 (2010)[DOI]
- Jeddi R, "Predictive factors of all-trans-retinoic acid related complications during induction therapy for acute promyelocytic leukemia", Hematology, 13(3), pp.142~146 (2008)[DOI]
- De la Serna J, "Causes and prognostic factors of remission induction failure in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and idarubicin", Blood, 111(7), pp.3395~3402 (2008)[DOI]
- Sanz MA, "How we prevent and treat differentiation syndrome in patients with acute promyelocytic leukemia", Blood, 123(18), pp.2777~2782 (2014)[DOI]
- "National Comprehensive Cancer Network clinical practice guidelines in oncology, Acute myeloid leukemia Version 3.2017-June 6,2017", ~ (2017)