Hypertension crisis significantly precede the occurrence of differentiation

by Jeddi
(Tunisia)

Original Text: Hypertension crisis significantly precede the occurrence of differentiation

Cardiovascular manifestations observed during DS a life threatening side effect of ATRA include hypotension, weight gain and pericardial effusion. The observation that several APL patients develop hypertension crisis before the occurrence of DS led us to investigate its predictive value for such complication.

Fifty one pts (31 female, 20 male) with genetically confirmed APL either by t(15,17) or PML/RARA were treated with the Spanish PETHEMA LPA99 trial between 2004 and 2010. Median age was 40 years (range,7-71).According to Sanz score ,2 pts (4%) ,33pts (61%) and 18 pts (35%) were considered respectively as low, intermediate and high risk. Additional cytogenetic abnormalities were observed in 39%. Median body mass index was 24 kg/m2 (range; 14-40). 43 pts achieved CR (86%). DS prophylaxis included prednisone 0.5mg/kg from d1 to d15 in high risk pts (WBC >10). According to Frankel’s criteria 16 pts (32%) developed DS. Median time onset of DS was 15 days (range,2-29).Weight gain, pericardial effusion and hypotension were noted respectively in 50%,37.5% and 18.7% of pts who developed DS whereas hypertension was observed in 7 pts (43.7%) of whom only one has a documented history of hypertension. 4 pts died from DS.
By univariate analysis using Fisher exact test (2-sided), age ≥40 (p=0.034), BMI ≥30 (p=0.009), baseline WBC ≥ 10(p=0.034), serum creatinine >1.4mg (p<0.001) and absence of additional cytogenetic abnormalities (p=0.009) were associated with DS. Of note was the significant correlation between hypertension crisis and occurrence of DS (p=0.024) and this fact was particularly independent from the use of steroid prophylaxis (p=0.49), but significantly associated with high BMI (p=0.003).

Given the strong associations between leptin, sympathico-activation and hypertension, we can speculate that a pick secretion of leptin lead to hypertension crisis predicting and of interest preceding the occurrence of DS.

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Revised Text:

Cardiovascular manifestations observed during DS, a life threatening side effect of ATRA, include; hypotension, weight gain and pericardial effusion. The observation that several APL patients develop hypertension crisis before the occurrence of DS led us to investigate its predictive value for such complication.

Fifty one patients (31 female, 20 male) with genetically confirmed APL, either by t (15,17) or PML/RARA, were treated with the Spanish PETHEMA LPA99 trial between 2004 and 2010. The median age was 40 years (range, 7-71). According to the Sanz score,2 pts (4%), 33 pts (61%) and 18 pts (35%) were considered respectively as low, intermediate and high risk.

Additional cytogenetic abnormalities were observed in 39%. The median body mass index was 24 kg/m2 (range, 14-40). Forty-three patients achieved CR (86%). DS prophylaxis included prednisone 0.5mg/kg, from d1 to d15 in high risk patients (WBC >10). According to Frankel’s criteria, 16 patients (32%) developed DS. Median time onset of DS was 15 days (range,2-29). Weight gain, pericardial effusion and hypotension were noted respectively in 50%, 37.5% and 18.7% of patients who developed DS, whereas hypertension was observed in 7 patients (43.7%), of whom only one had a documented history of hypertension. Four patients died from DS.

By univariate analysis using Fisher exact test (2-sided), age ≥40 (p=0.034), BMI ≥30 (p=0.009), baseline WBC ≥ 10(p=0.034), serum creatinine >1.4mg (p<0.001) and absence of additional cytogenetic abnormalities (p=0.009) were associated with DS. Of note was the significant correlation between hypertension crisis and occurrence of DS (p=0.024). This fact was particularly independent of the use of steroid prophylaxis (p=0.49), but significantly associated with high BMI (p=0.003).

Given the strong associations between leptin, sympathico-activation and hypertension, we can speculate that a pick secretion of leptin leads to hypertension crisis predicting and is of interest preceding the occurrence of DS.

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