High body mass index is an independent predictor of differentiation syndrome in patients with acute promyelocytic leukemia

Jeddi, Ramzi; Ghédira, Hèlà; Mnif, Samia; Gouider, Emna; Fenaux, Pierre; Meddeb, Balkis

doi:10.1016/j.leukres.2009.09.017

Cited by 34 publications

(29 citation statements)

References 10 publications

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“…Our results are in keeping with the observations originally reported by Jeddi et al who analyzed a series of 36 patients, 11 of whom developed differentiation syndrome. 28 Six of the 9 patients (66.6%) with a BMI more than 30 kg/m 2 versus 5 of 27 patients (18.5%) with a BMI less than 30 kg/m 2 developed a differentiation syndrome in that study. 28 However, multivariate analysis in the study of Jeddi et al showed that both an increased BMI and a WBC more than 20 ϫ 10 9 /L were independent factors predictive of differentiation syndrome, 28 whereas our analysis identified only an increased BMI as a strong predictor of the syndrome.…”

Section: Discussionmentioning

confidence: 64%

“…28 Six of the 9 patients (66.6%) with a BMI more than 30 kg/m 2 versus 5 of 27 patients (18.5%) with a BMI less than 30 kg/m 2 developed a differentiation syndrome in that study. 28 However, multivariate analysis in the study of Jeddi et al showed that both an increased BMI and a WBC more than 20 ϫ 10 9 /L were independent factors predictive of differentiation syndrome, 28 whereas our analysis identified only an increased BMI as a strong predictor of the syndrome. Increased WBC counts as well as elevated creatinine levels were predictive factors for differentiation syndrome in a larger study of the Spanish PETHEMA group.…”

Section: Discussionmentioning

confidence: 64%

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Increased BMI correlates with higher risk of disease relapse and differentiation syndrome in patients with acute promyelocytic leukemia treated with the AIDA protocols

Breccia

Mazzarella

Bagnardi

et al. 2012

Blood

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We investigated whether body mass index (BMI) correlates with distinct outcomes in newly diagnosed acute promyelocytic leukemia (APL). The study population included 144 patients with newly diagnosed and genetically confirmed APL consecutively treated at a single institution. All patients received All-trans retinoic acid and idarubicin according to the GIMEMA protocols AIDA-0493 and AIDA-2000. Outcome estimates according to the BMI were carried out together with multivariable analysis for the risk of relapse and differentiation syndrome. Fifty-four (37.5%) were under/ normal weight (BMI < 25), whereas 90 (62.5%) patients were overweight/obese (BMI > 25). An increased BMI was associated with older age (P < .0001) and male sex (P ‫؍‬ .02). BMI was the most powerful predictor of differentiation syndrome in multivariable analysis (odds ratio ‫؍‬ 7.24; 95% CI, 1.50-34; P ‫؍‬ .014). After a median follow-up of 6 years, the estimated cumulative incidence of relapse at 5 years was 31.6% (95% CI, 22.7%-43.8%) in overweight/obese and 11.2% (95% CI, 5.3%-23.8%) in underweight/normal weight patients (P ‫؍‬ .029). Multivariable analysis showed that BMI was an independent predictor of relapse (hazard ratio ‫؍‬ 2.45, 95% CI, 1.00-5.99, in overweight/obese vs under/normal weight patients, P ‫؍‬ .049). An increased BMI at diagnosis is associated with a higher risk of developing differentiation syndrome and disease relapse in APL patients treated with AIDA protocols. (Blood. 2012;119(1):49-54) IntroductionObesity has received considerable attention in the medical community because of its negative impact on human health. More recently, excess of body weight has been associated with an increased risk of a wide range of malignancies. [1][2][3] In a meta-analysis of cohort studies, Larsson and Wolk reported epidemiologic evidence suggesting that an excess of body weight is a risk factor for several hematologic cancers, including leukemia, non-Hodgkin lymphoma, and multiple myeloma. 4 In particular, compared with nonoverweight persons, the relative risk of leukemia for overweight and obese persons was reported to be 1.14 and 1.39, respectively, whereas a 5-kg/m 2 increase in body mass index (BMI) was associated with a 13% increased risk of leukemia. 4 As to the impact of BMI on treatment response and outcome, a number of studies have shown that obesity is associated with a poorer overall survival and disease-free survival in patients with breast cancer. 5,6 By contrast, the correlation between BMI and treatment outcome has not yet been investigated in patients with leukemia.Acute promyelocytic leukemia (APL), once known as the most rapidly fatal leukemia subtype, is nowadays considered the most frequently curable acute leukemia of adults. 7 Indeed, modern combined approaches with all-trans retinoic acid and anthracycline chemotherapy yield complete remission rates greater than 90% and long-term cure rates of 70% to 75%. [8][9][10][11] Disease relapse and death during induction because of hemorrhage, infection, or differentiation syndro...

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Section: Discussionmentioning

confidence: 64%

Section: Discussionmentioning

confidence: 64%

Increased BMI correlates with higher risk of disease relapse and differentiation syndrome in patients with acute promyelocytic leukemia treated with the AIDA protocols

Breccia

Mazzarella

Bagnardi

et al. 2012

Blood

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“…However, there is a risk of additional toxicities with chemotherapy agents (i.e., myelosuppression and cardiac toxicity), which was not evaluated in this study. 14 In two small-scale studies conducted by Jeddi et al, 24,25 DS was more frequently reported for APL patients presenting with a high WBC at diagnosis, although the cut-off values were different in each study (>10 Â 10 9 /L (p ¼ 0.08) and !20 Â 10 9 /L (p ¼ 0.025), respectively). One of these studies also found that high body mass index (BMI, !30) was an independent prognostic factor for DS by multivariate analysis (p ¼ 0.044).…”

Section: Risk Factorsmentioning

confidence: 91%

“…22,25 There is wide variation with the exact cut-off value (!20 Â 10 9 /L vs. >5 Â 10 9 /L), and additional studies are necessary to confirm these results. Nevertheless, patients with a starting WBC greater than 5 Â 10 9 /L should be monitored closely for any signs and symptoms of DS during induction therapy.…”

Section: Rogers and Yang 111mentioning

confidence: 99%

Differentiation syndrome in patients with acute promyelocytic leukemia

Rogers

Yang

2011

J Oncol Pharm Pract

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“…Retinoic acid differentiation therapy saves the lives of the majority of APL patients, but pan-retinoids are also known for their teratogenicity. With the recognition that retinoid receptors have various ligands with distinct selectivity, significant effort has been made in several areas [Jeddi et al 2010;Tallman and Altman, 2009]. First, understanding the molecular basis of the leukemogenic events that cause APL and the mechanism(s) involved in RA action during therapy and the absence of a therapeutic potential for variant APLs and all non-APL AML patients.…”

Section: Discussionmentioning

confidence: 99%

High prevalence of obesity in acute promyelocytic leukemia (APL): implications for differentiating agents in APL and metabolic syndrome

Tedesco

Qualtieri

Head

et al. 2011

Therapeutic Advances in Hematology

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Abstract:Background: Between January 1999 and December 2008, 469 patients treated for acute myeloid leukemia (AML) were included in this single-institution study. Methods: We performed a casecontrol analysis to study the rate of obesity among patients with acute promyelocytic leukemia (APL) and non-APL AML. Results: A total of 81% of APL patients analyzed were obese compared with 41.7% in the non-APL group (p < 0.001). Body mass index (BMI) >30 was seen in 57% of APL patients compared with 31% for the non-APL group (p ¼ 0.01). Neither obesity nor the chemotherapy dosing based on ideal body weight affected survival. Conclusions: Our findings generate the hypothesis that APL and metabolic syndromes may share a common pathogenic pathway via retinoic acid receptors (RARs), the ligand-controlled transcription factors that function as heterodimers with retinoid X receptors (RXRs) to regulate cell growth and survival. If this link is confirmed in larger studies, our data will instigate further studies using RXR and RAR modulators as a preventive strategy among obese individuals.

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High body mass index is an independent predictor of differentiation syndrome in patients with acute promyelocytic leukemia

Cited by 34 publications

References 10 publications

Increased BMI correlates with higher risk of disease relapse and differentiation syndrome in patients with acute promyelocytic leukemia treated with the AIDA protocols

Increased BMI correlates with higher risk of disease relapse and differentiation syndrome in patients with acute promyelocytic leukemia treated with the AIDA protocols

Differentiation syndrome in patients with acute promyelocytic leukemia

High prevalence of obesity in acute promyelocytic leukemia (APL): implications for differentiating agents in APL and metabolic syndrome

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