Incidence, Clinical Features and Outcome of Patients with Differentiation Syndrome in Acute Promyelocytic Leukemia Treated with All-Trans Retinoic Acid (ATRA) Alone Versus ATRA Plus Idarubicin Versus ATRA Plus Arsenic Trioxide.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1044-1044
Author(s):  
Sameer A Parikh ◽  
Hagop Kantarjian ◽  
Farhad Ravandi ◽  
Gautam Borthakur ◽  
Stefan Faderl ◽  
...  
Keyword(s):  
Heart Failure ◽  
Weight Gain ◽  
Promyelocytic Leukemia ◽  
Newly Diagnosed ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Group 3 ◽  
Frontline Therapy ◽  
Group 2 ◽  
Group 1

Abstract Abstract 1044 Poster Board I-66 Background: Differentiation Syndrome (DS) in patients (pts) with acute promyelocytic leukemia (APL) remains a source of significant morbidity and mortality. DS is reported in 2-27% of pts with newly diagnosed APL treated with all-trans retinoic acid (ATRA) alone or in combination with idarubicin (IDA). More recently, arsenic trioxide (ATO) has been used in combination with ATRA as frontline therapy to improve rates of complete remission (CR) and overall survival (OS). It has been postulated that with the use of ATO, the risk of DS may decrease. Aim To describe the incidence, characteristics and outcome of differentiation syndrome with various modalities of ATRA-based therapy used for APL. Methods: We reviewed the records of 167 pts with newly diagnosed APL treated at our institution from 1992-2009 with three regimens: ATRA + IDA (Group 1), liposomal ATRA (Group 2) and ATRA plus ATO (Group 3). Patients in Group 1 (n=52; 1992-1997) received induction with ATRA 45mg/m2 orally daily in two divided doses until CR and IDA 12mg/m2 IV daily for 4 days. Group 2 (n=34; 1997-2000) received liposomal ATRA at 90mg/m2 IV every other day until CR. Patients in Group3 (n=82; 2002-2009) received 45mg/m2 ATRA orally daily in two divided doses, 9mg/m2 gemtuzumab ozogamicin if the WBC count exceeded 30 ×109/L in the first 4 weeks of therapy, ATO 0.15mg/kg/day IV starting on day 10 in 47 patients and on day 1 in 35 patients, and methylprednisolone (50 mg daily for 5 days) to prevent DS. A diagnosis of DS was made by the presence of: dyspnea, unexplained fever, weight gain, peripheral edema, unexplained hypotension, acute renal failure or congestive heart failure, and particularly by a chest radiograph demonstrating interstitial pulmonary infiltrates, or pleuropericardial effusion [Sanz MA, Blood. 2009;113(9):1875-91].Patients with ≥4 features were classified as having severe DS and those with ≤3 mild DS. No single sign or symptom was considered sufficient for diagnosis of DS. Patients with a final diagnosis of pneumonia, sepsis, diffuse alveolar hemorrhage and decompensated heart failure were not considered to have DS. Patients who developed DS ≤7 days of starting therapy with ATRA were classified as “early DS” and others as having “late DS”. Results: Forty one patients (24%) were diagnosed with DS: 14 (27%) in Group 1, 12 (35%) in Group 2, and 15 (18%) in Group 3. Baseline characteristics of patients with DS in each group are shown in Table. Dyspnea, weight gain and pulmonary infiltrates were the most common features of DS in all groups. The median number of days to develop DS after starting ATRA was 3 (1-15) in Group 1, 5 (2-18) in Group 2 and 10 (1-18) in Group 3. ATRA was held in 8 pts (57%) in Group 1, 9 pts (75%) in Group 2, and 8 pts (53%) in Group 3. Intravenous corticosteroids were used for treatment of all patients with DS. CR was achieved in 7 (50%) pts in group 1, 10 (83%) in Group 2 and 14 (93%) in Group 3. The number of patients who died during induction therapy was 6, 2 and 1 in Groups 1, 2 and 3 respectively. There were no deaths directly attributable to DS in any groups. Three-year survival was 65% for pts with DS and 83% for those without DS (p-value: 0.07). Conclusion: The incidence of DS is higher when ATRA alone is used as frontline therapy for APL. With ATRA + ATO (and prophylaxis with corticosteroids) there is a trend for decreased frequency and more delayed occurrence of DS. The severity of DS appears lower for patients not receiving chemotherapy with ATRA. With adequate management, a diagnosis of DS during induction therapy for APL does not influence outcomes independent of therapy. Disclosures: Ravandi: Cephalon: Consultancy, Honoraria.

scholarly journals How is juvenile rheumatic heart disease different: baseline results from a prospective north Indian registry

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
K Mahajan ◽  
D.R Prakash Chand Negi
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Pulmonary Hypertension ◽  
Heart Disease ◽  
Funding Source ◽  
Thromboembolic Events ◽  
Group 3 ◽  
Group 2 ◽  
Rheumatic Heart ◽  
Group 1

Abstract Introduction Juvenile rheumatic heart disease (RHD) refers to RHD in patients <20 years of age. There are no contemporary data highlighting the differences between juvenile and older RHD patients. Purpose We aim to report the age related differences in the pattern, and consequencies of valvular dysfunction in patients of RHD. Methods The 2475 consecutive patients of RHD diagnosed using clinical and echocardiographic criteria were registered prospectively from 2011 till December 2019. Patients were divided into 3 groups according to their age: Group 1 (Juvenile RHD), Group 2 (21–50 years), and Group 2 (>51 years).The data concerning the socio-demographic and clinical profile were recorded systematically, and the nature and severity of valvular dysfunction was assessed by echocardiography. The data were analyzed using the Epi-InfoTM Software. Results Out of 2475 RHD patients, Juvenile RHD comprised of 211 (8.5%) patients. Group 2 and 3 comprised of 1691 (68.3%) and 573 (23.2%) patients respectively. Overall, 1767 (71.4%) patients were females, however this female predilection was less pronounced in juvenile RHD (55.5% females vs 44.5% males) as compared to older groups. Past history of acute rheumatic fever was more commonly recorded in Juvenile RHD group (37.9% vs 18.8% in group 2 and 10% in group 3, p=0.0001). At the time of registration, the presence of advanced heart failure symptoms (dyspnea class III and IV) (11.4% group 1 vs 13.9% group 2 vs 20.6% group 3, p<0.0001), right heart failure symptoms (0.9% group 1 vs 2.5% group 2 vs 7.3% group 3, p<0.01), thromboembolic events (0% group 1 vs 4.1% group 2 vs 3.3% group 3, p<0.01), atrial fibrillation (2.8% group 1 vs 24.5% group 2 vs 45.9% group 3, p<0.0001), and pulmonary hypertension (27.1% group 1 vs 40.3% group 2 vs 51.9% group 3, p<0.01), were all more commonly recorded in non-juvenile older RHD groups. Multivalvular involvement was also less common in juvenile RHD (34.6% vs 42.4% and 44.5%, p=0.04). Mitral regurgitation was the most common lesion in Juvenile RHD followed by aortic regurgitation (68.7% and 40.2% respectively). Stenotic lesions (both mitral and aortic) were present more commonly in older age groups. Conclusion RHD is predominantly a disease of females, however the predilection is less common in juvenile patients. Juvenile RHD predominantly affects the mitral valve and mainly leads to regurgitant lesions. As the age advances, the complications of RHD, mainly heart failure symptoms, thromboembolic events, pulmonary hypertension, and atrial fibrillation, become more common. Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): Self sponsored registry

The Relation Between Epicardial Fat Tissue Thickness and TSH Receptor Antibody in Hyperthyroidism

2018 ◽  
Vol 6 (01) ◽  
pp. 37-40
Author(s):  
Rıza Altunbaş ◽  
Mehmet Eren ◽  
İbrahim Altıparmak ◽  
Hüseyin Karaaslan ◽  
Tevfik Sabuncu
Keyword(s):  
Tsh Receptor ◽  
Newly Diagnosed ◽  
Fat Tissue ◽  
Tissue Thickness ◽  
Receptor Antibody ◽  
Tsh Receptor Antibody ◽  
Epicardial Fat Tissue ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Abstract Background Although hyperthyroidism may be associated with atherosclerosis, its pathogenesis is not well known. TSH receptor antibody (TRAb) has been shown to be responsible for increased orbital fat tissue in Graves ophthalmopathy. Epicardial fat tissue thickness (EFT) has been found to be increased in case of overt hyperthyroidism. In our study, we aimed to investigate if TRAb is associated with the increased EFT in newly diagnosed hyperthyroidism. Methods Twenty six TRAb positive (group 1) and 26 TRAb negative (group 2) newly diagnosed patients with hyperthyroidism, and 26 healthy control subjects (group 3) were enrolled. EFT was measured by the same cardiologist using an echocardiography device. Serum TRAb levels were measured by the radio-receptor assay and levels above 1.75 IU/L were considered as positive. Results There was no difference among groups in terms of age, gender and body mass index. Although there was no significant difference between group 1 and 2, both group 1 (0.38±0.15 cm) and group 2 (0.4±0.17 cm) had significantly higher EFT levels when compared to group 3 (0.25±0.06 cm) (p=0.004 and p=0.001, respectively). However we did not find any correlation between TRAb and EFT levels. Conclusion The results of our study suggested that EFT was increased in hyperthyroidism and this increasing was not dependent of TRAb level. EFT elevation might be depending directly to the cardiovascular effects of hyperthyroidism.

Abstract 13073: ECG, Clinical, and Imaging Characteristics of Arrhythmogenic Right Ventricular Cardiomyopathy With Fat and Fibrotic Invasion Into the Left Ventricular Myocardium Revealed by Four-dimensional (4D) Cardiac CT

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Nobusada FUNABASHI ◽  
Yoshio Kobayashi
Keyword(s):  
Heart Failure ◽  
Right Ventricular ◽  
Cardiac Ct ◽  
4D Ct ◽  
Imaging Characteristics ◽  
Group 3 ◽  
Clinical Heart Failure ◽  
Group 2 ◽  
Group 1 ◽  
T Waves

Introduction: 4D cardiac CT can reveal characteristics of arrhythmogenic right ventricular (RV) cardiomyopathy (ARVC) such as fat and fibrotic invasion into the RV and LV myocardium (RVM, LVM), an enlarged RV, reduced RV motion and bulging. Hypothesis: We could differentiate ARVC patients with fat and fibrotic invasion into the LVM from those without, using ECG, clinical, and other imaging characteristics. Methods: Retrospective analysis of 17 patients (11 males, 57±17 years) with suspected ARVC who underwent 4D cardiac CT. Results: 9 patients met the 2010 ARVC task force criteria. 4 had fat and fibrotic invasion into the LVM (group 1) but 5 did not (group 2). The remaining 8 did not fulfill the ARVC criteria (group 3). The proportion of males and age did not differ between groups. In groups 1, 2 and 3, respectively, 3 (75%), 4 (80%), and 1 (13%) patients had epsilon waves in V1-3 (group 1>3, P=0.033, group 2>3, P=0.005). 2 (50%), one (20%) and 4 (50%) had complete right bundle branch block (CRBBB) (all P=NS). Three (75%), 3 (60%), and 1 (13%) had inverted T waves in V1-3 or beyond (group 1>3, P=0.033). One (50%), 3 (75%), and 2 (50%) had terminal activation duration of QRS ≥55 ms measured from the nadir of the S wave to the end of the QRS, including R’, in V1, V2, or V3, in the absence of CRBBB (all P=NS). One (25%), 4 (80%) and 1 (13%) had sustained ventricular tachycardia (SVT; group 2>3, P=0.005). Two (50%), 1 (20%), and 3 (38%) had non-SVT (all P=NS). 4 (100%), 2 (40%), and 2 (25%) had clinical heart failure (group 1>2, P=0.019, group 1>3, P<0.001). Finally, 4 (100% and 80%) and 6 (75%) had RV enlargement on TTE (all P=NS). On 4D CT, 4 (100%), 5 (100%), and 5 (63%) of patients in groups 1, 2 and 3, showed RV enlargement (all P=NS); 4 (100%), 2 (40%), and 1 (13%) showed reduced RV motion (group 1>2, P=0.019, group 1>3, P<0.001); 75, 100, and 0%, had RV fat invasion (group 1>3, P=0.002, group 2>3, P<0.001); and 25, 0, and 0% showed bulging (all P=NS). Conclusions: Most patients had RV enlargement on TTE and/or 4D CT. Presence of epsilon waves, reduced RV motion, and RV fat invasion on 4D CT may differentiate groups 1 and 2 from group 3, inverted T waves in V1-3 leads or beyond may differentiate group 1 from group 3, SVT may differentiate group 2 from group 3 but only clinical heart failure may differentiate groups 1 and 2.

Abstract 9411: Urine Aquaporin-2 Level is a Novel Marker for the Better Prognosis After Long-Term Tolvaptan Treatment in Patients With Advanced Heart Failure

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Teruhiko Imamura ◽  
Koichiro Kinugawa ◽  
Takeo Fujino ◽  
Toshiro Inaba ◽  
Hisataka Maki ◽  
...  
Keyword(s):  
Heart Failure ◽  
De Novo ◽  
Collecting Duct ◽  
Initial Response ◽  
Aquaporin 2 ◽  
Long Term Treatment ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Introduction: Preserved function of collecting duct is essential for the response to tolvaptan (TLV), and urinary level of aquaporin 2 (U-AQP2) can be a marker for vasopressin-dependent activity of collecting duct. Hypothesis: Higher levels of U-AQP2 in proportion to plasma levels of vasopressin (P-AVP) may be associated with better initial responses to TLV and eventually result in the improved prognosis after long-term treatment of TLV. Methods: Consecutive 60 in-hospital patients with stage D heart failure (HF) who received TLV on a de novo basis were enrolled during 2011-2013. We also selected 60 HF patients by propensity score matching who were hospitalized during the same period but never treated with TLV. Events were defined as death and/or HF re-hospitalization. Results: TLV (3.75-15 mg/day) was continuously administered except death or ventricular assist device implantation occurred. There were 41 patients (group 1) who had increases in UV over the first 24 h after TLV initiation, and all of them had U-AQP2/P-AVP ≥0.5 х103 with higher U-AQP2 levels (5.42 ± 3.54 ng/mL) before TLV treatment. On the other hand, UV rather decreased even after TLV initiation in 19 patients over the first 24 h (group 2). Those in the group 2 universally had U-AQP2/P-AVP <0.5 х103, extremely low U-AQP2 levels (0.76 ± 0.59 ng/mL, p<0.001 vs. group 1), and similar P-AVP with the group 1 at baseline. The 41 and 19 patients without TLV treatment (group 3 and 4) were respectively matched to the group 1 and 2 by propensity scores. Interestingly, every patient in the group 3 had U-AQP2/P-AVP ≥0.5 х103, and vice versa in the group 4. Among the four groups, congestion-related symptoms were only improved in the group 1 after 1 month of enrollment. The patients in the group 1 had significantly better event-free survival over 2-year by TLV treatment compared with the group 3 (76% vs. 43%, p<0.014). In contrast, the patients in the group 2 and 4 had very poor prognoses regardless of TLV treatment (7% vs. 11%, p=0.823). Conclusions: U-AQP2/P-AVP is a novel predictor for the initial response to TLV in HF patients. Patients with higher U-AQP2/P-AVP may enjoy a better prognosis by long-term TLV treatment probably due to efficient resolution of congestion.

scholarly journals M86. CAN WEIGHT GAIN CAUSE METABOLIC SYNDROME A DECADE LATER IN PATIENTS WITH SCHIZOPHRENIA SPECTRUM DISORDER?

2020 ◽  
Vol 46 (Supplement_1) ◽  
pp. S167-S167
Author(s):  
Moradi Hawar ◽  
Lars Helldin ◽  
Anna-Karin Olsson ◽  
Pontén Anna
Keyword(s):  
Metabolic Syndrome ◽  
Weight Gain ◽  
Life Time ◽  
Spectrum Disorder ◽  
Schizophrenia Spectrum Disorder ◽  
Group 4 ◽  
Schizophrenia Spectrum ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Abstract Background Patients with schizophrenia spectrum disorder have a reduced life time expectancy with up to 20 years. Obesity and metabolic syndrome is highly prevalent and cardio vascular disease, CVD, remain the most common cause of the excess mortality. Despite studies showing the reduced life time expectancy and its causes the patients with schizophrenia spectrum disorder yet remain to benefit of the development of the healthcare. In this study we aim to focus on how the weight changes in different age groups and when do the cluster of conditions of metabolic syndrome start to occur. Methods In this naturalistic study we follow 71 patients, 47 man and 24 women diagnosed with schizophrenia spectrum disorder. We divided the patients into 5 different groups based on age. Group 1 aged 20–30 years, Group 2 aged 31–40 years, Group 3 aged 41–50 years, group 4 aged 51–60 years and Group 5 aged 61 years and elder. The longest time of observation was 18 years. Data on weight (kg) and disorders such as diabetes, hypertension and dyslipidemia were collected at baseline and then yearly thereafter. Data from baseline and the last yearly follow up were included in this study. Weight and the presence of the cluster of conditions that make up metabolic syndrome in the above-mentioned groups were analyzed. Results Patients in group 1 make the highest gain of weight with 0, 9 kg per year and group 2 with the least gain of weight only 0, 01 kg per year. Patients in group 3 have a weight loss of 0, 2 kg per year. At endpoint 9 out 19 patients in group 3 and 11 out of 21 patients in group 4 were treated for one, two or three conditions of the metabolic syndrome. Discussion In our study we show that weight gain appears at least 10 years before the development of metabolic syndrome. Despite the loss of weight that appear in group 3 the negative effects of the weight gained a decade earlier may be a factor that make patients aged 41 years and older to be at risk of developing metabolic syndrome.

scholarly journals Different Pathophysiology and Outcomes of Heart Failure With Preserved Ejection Fraction Stratified by K-Means Clustering

2020 ◽  
Vol 7 ◽  
Author(s):  
Daisuke Harada ◽  
Hidetsugu Asanoi ◽  
Takahisa Noto ◽  
Junya Takagawa
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Right Ventricle ◽  
Preserved Ejection Fraction ◽  
Stratified Medicine ◽  
Cardiac Events ◽  
Group 4 ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Background: Stratified medicine may enable the development of effective treatments for particular groups of patients with heart failure with preserved ejection fraction (HFpEF); however, the heterogeneity of this syndrome makes it difficult to group patients together by common disease features. The aim of the present study was to find new subgroups of HFpEF using machine learning.Methods: K-means clustering was used to stratify patients with HFpEF. We retrospectively enrolled 350 outpatients with HFpEF. Their clinical characteristics, blood sample test results and hemodynamic parameters assessed by echocardiography, electrocardiography and jugular venous pulse, and clinical outcomes were applied to k-means clustering. The optimal k was detected using Hartigan's rule.Results: HFpEF was stratified into four groups. The characteristic feature in group 1 was left ventricular relaxation abnormality. Compared with group 1, patients in groups 2, 3, and 4 had a high mean mitral E/e′ ratio. The estimated glomerular filtration rate was lower in group 2 than in group 3 (median 51 ml/min/1.73 m2 vs. 63 ml/min/1.73 m2p &lt; 0.05). The prevalence of less-distensible right ventricle and atrial fibrillation was higher, and the deceleration time of mitral inflow was shorter in group 3 than in group 2 (93 vs. 22% p &lt; 0.05, 95 vs. 1% p &lt; 0.05, and median 167 vs. 223 ms p &lt; 0.05, respectively). Group 4 was characterized by older age (median 85 years) and had a high systolic pulmonary arterial pressure (median 37 mmHg), less-distensible right ventricle (89%) and renal dysfunction (median 54 ml/min/1.73 m2). Compared with group 1, group 4 exhibited the highest risk of the cardiac events (hazard ratio [HR]: 19; 95% confidence interval [CI] 8.9–41); group 2 and 3 demonstrated similar rates of cardiac events (group 2 HR: 5.1; 95% CI 2.2–12; group 3 HR: 3.7; 95%CI, 1.3–10). The event-free rates were the lowest in group 4 (p for trend &lt; 0.001).Conclusions: K-means clustering divided HFpEF into 4 groups. Older patients with HFpEF may suffer from complication of RV afterload mismatch and renal dysfunction. Our study may be useful for stratified medicine for HFpEF.

1409Use of phenomapping to determine response of treatment by sacubitril/valsartan in patients with heart failure with reduced ejection fraction

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M Godet ◽  
O Raitiere ◽  
H Chopra ◽  
P Guignant ◽  
C Fauvel ◽  
...  
Keyword(s):  
Heart Failure ◽  
Pulmonary Hypertension ◽  
Ejection Fraction ◽  
Left Ventricular ◽  
Heat Map ◽  
Reduced Ejection Fraction ◽  
Patients With Heart Failure ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Abstract Background Treatment by sacubitril/valsartan decreases mortality, improves KCCQ score and ejection fraction in patients with heart failure with reduced ejection fraction (HF REF), but there is currently no data to predict response to treatment. Purpose The purpose of our work was to assess whether unbiased clustering analysis, using dense phenotypic data, could identify phenotypically distinct HF-REF subtypes with good or no response after 6 months of sacubitril/valsartan administration. Methods A total of 78 patients in NYHA functional class 2–3 and treated by ACE inhibitor or AAR2, were prospectively assigned to equimolar sacubitril/valsartan replacement. We collected demographic, clinical, biological and imaging continuous variables. Phenotypic domains were imputed with 5 eigenvectors for missing value, then filtered if the Pearson correlation coefficient was >0.6 and standardized to mean±SD of 0±1. Thereafter, we used agglomerative hierarchical clustering for grouping phenotypic variables and patients, then generate a heat map (figure 1). Subsequently, participants were categorized using Penalized Model-Based Clustering. P<0,05 was considered significant. Results Mean age was 60.4±13.4 yo and 79.0% patients were males. Mean ejection fraction was 29.3±7.0%. Overall, 16 phenotypic domains were isolated (figure 1) and 3 phenogroups were identified (Table 1). Phenogroup 1 was remarkable by isolated left ventricular involvement (LVTDD 64.3±5.9mm vs 73.9±8.7 in group 2 and 63.8±5.7 in group3, p<0.001) with moderate diastolic dysfunction (DD), no mitral regurgitation (MR) and no pulmonary hypertension (PH). Phenogroups 2 and 3 corresponded to patients with severe PH (TRMV: 2.93±0.47m/s in group 2 and 3.15±0.61m/s in groupe 3 vs 2.16±0.32m/s in group 1), related to severe DD (phenogroup 2) or MR (phenogroup 3). In both phenogroups, the left atrium was significantly enlarged and the right ventricle was remodeled, compared with phenogroup 1. Despite more severe remodeling and more compromised hemodynamic in phenogroups 2 and 3, the echocardiographic response to sacubitril/valsartan was comparable in all groups with similar improvement of EF and reduction of cardiac chambers dimensions (response of treatment, defined by improvement of FE +15% and/or decreased of indexed left ventricule diastolic volume −15% = group 2: 22 (76%); group 3: 18 (60%); group 1: 9 (50%); p=0.17; OR group 2 vs 1: OR=3.14; IC95% [0.9–11.03]; p=0.074; OR group 3 vs 1: OR=1.5; IC95% [0.46–4.87]; p=0.5)). The clinical response was even better in phenogroups 2 and 3 (Group 2: 19 (66%); group 3: 21 (78%) vs group 1: 9 (50%); p=0.05). Heat map Conclusion HF-REF patients with severe diastolic dysfunction, significant mitral regurgitation and elevated pulmonary hypertension by echocardiographic had similar reverse remodeling but better clinical improvement than patients with isolated left ventricular systolic dysfunction.

Retinoic Acid Syndrome in Patients with Acute Promyelocytic Leukemia Treated with All-Trans Retinoic Acid and Anthracycline Monochemotherapy.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2010-2010
Author(s):  
Pau Montesinos ◽  
Juan Bergua ◽  
Guillermo Martin ◽  
Javier de la Serna ◽  
Edo Vellenga ◽  
...  
Keyword(s):  
Renal Failure ◽  
Prognostic Factors ◽  
Retinoic Acid ◽  
Weight Gain ◽  
High Risk ◽  
Pleural Effusion ◽  
Promyelocytic Leukemia ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Retinoic Acid Syndrome

Abstract Retinoic acid syndrome (RAS) can be a life-threatening complication in patients with acute promyelocytic leukemia (APL) undergoing induction therapy with all-trans retinoic acid (ATRA). Incidence of RAS has been reported ranging from 2% to 30%. It has been suggested that patients with leukocytes >5 x109/L at presentation are at high risk for the development of RAS. The impact of RAS on long term outcome is still a matter of controversy. We analyze the incidence, prognostic factors and outcome of RAS in 733 patients with newly diagnosed APL enrolled in the PETHEMA LPA96 and LPA99 trials (175 and 558 patients, respectively). Induction therapy consisted of ATRA and idarubicin, followed by three consolidation courses of anthracycline monochemotherapy. In the LPA99 trial, ATRA was added in each cycle of consolidation, except for low-risk patients. In the LPA99 trial, all patients received RAS prophylaxis with oral prednisone (0.5 mg/kg). Temporary discontinuation of ATRA and treatment with intravenous dexamethasone were recommended at the first signs of suspected RAS, in both trials. Definite RAS was defined as the presence of at least four of the following criteria: unexplained fever, respiratory distress, radiological pulmonary infiltrates, pericardial/pleural effusion, hypotension, renal failure, and weight gain over 5 kg. Overall, 87 patients (12%) experienced RAS, after a median of 6 days of ATRA (range, 0 to 46). Forty-seven cases (54%) occurred from days 0 to 7, 4 (5%) from days 8 to 14, 32 (36%) from days 15 to 30, and 4 (5%) from days 31 to 46. The main clinical signs were pulmonary infiltrates (83%), fever (80%), weight gain (74%), pleural effusion (63%) and renal failure (49%). ATRA was discontinued in 63% of patients. RAS was associated with age >50 years (41% vs 29%, p=0.02), serum level of creatinine >1.4 mg/dl (9% vs 3%, p<0.01) and leukocytes at presentation >5x109/L (46% vs 32%, p=0.01). Leukocytes >5x109/L and creatinine >1.4 mg/dl remained as independent prognostic factors in multivariate analysis. The incidence of RAS was not statistically different between the LPA96 (without prednisone prophylaxis) and LPA99 trials (15% vs 11%, p=0.16). RAS was associated with induction death (26% vs 7%, p<0.01) and was the main cause of death in 10 patients (1.4%). Age >60 years, leukocytes >10x109/L, RAS, male gender and serum creatinine level >1.4 mg/dl at presentation were independent prognostic factors for induction death. Patients developing RAS had a higher cumulative incidence of relapse (CIR) in the LPA96 trial (40% vs 15%, p<0.01), but there were no significant differences in the LPA99 trial (12% vs 13%). In conclusion, we have observed a bimodal peak incidence of RAS during the induction phase, with the first peak from days 0 to 7 and the second peak from days 15 to 30. Patients with leukocytes >5x109/L and serum creatinine level >1.4 mg/dl are at high risk for development of RAS, which is an adverse prognostic factor for induction death. The negative impact of RAS on CIR among patients treated with the LPA96 trial was not observed in the LPA99, in which patients received additional doses of ATRA for consolidation therapy.

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