Hepatotoxicity in Adolescent and Young Adult Hispanic Patients Treated with Pediatric Regimens for Acute Lymphoblastic Leukemia

Abstract Introduction: Pediatric or pediatric-inspired regimens are used in the treatment of adolescent or young adult (AYA) patients with acute lymphoblastic leukemia (ALL). While overall survival is improved with these regimens, hepatotoxicity and metabolic complications are common adverse events related to the increased dosages of asparaginase and steroids used vs adult ALL regimens. Among ethnicities, prevalence of metabolic syndrome and hepatic steatosis is highest in the Hispanic population, which comprises ~20% of the US population and carries an increased risk of ALL. Surprisingly, there is limited literature describing hepatotoxicity in this at-risk population. Herein we describe our experience with this adverse effect in AYA Hispanic patients (<50 yrs) treated with pediatric ALL regimens at an urban academic medical center. Methods: Single-center retrospective chart review of patients with ALL treated from January 1, 2010 to May 30, 2021 at the University of Illinois at Chicago. Patients with an associated ALL diagnosis were identified through an internal pathology database. Demographic information, clinical characteristics, treatment history and complications [grade 3/4 transaminitis, development of non-alcoholic fatty liver (NAFLD) on imaging, non-alcoholic steato-hepatitis (NASH)/fibrosis/cirrhosis on biopsy, pancreatitis, treatment change or drug discontinuation secondary to hepatotoxicity] were abstracted from the EMR. Descriptive statistics were used to determine outcome frequencies. Results: We identified 33 Hispanic (n= 20) and Non-Hispanic White (NHW; n = 13) patients with either B-ALL or T-ALL, with each demographic stratified by pediatric or adult regimen therapy (Table 1). Pediatric regimens include Children's Oncology Group protocols and E1910; the adult regimen was HyperCVAD. Of 16 Hispanic patients who received pediatric regimens, 7 (44%) had pre-existing diabetes, 1 had fatty liver on baseline imaging and 1 biopsy-confirmed NASH. During treatment, 12/16 (75%) developed grade 3/4 hepatotoxicity, 11 (69%) developed mild-severe NAFLD on imaging, 2 additional patients developed cirrhosis, and 4 (25%) pancreatitis. Treatment-related adverse events prompted therapy change or drug discontinuation in 25%. Hispanic patients, (n = 4), on adult and NHW patients, (n = 7), on pediatric regimens had low rates of pre-existing comorbidities, but of the older NHW patients, (n = 6), on an adult regimen, 4/6 (67%) and 1/6 had underlying diabetes or NAFLD, respectively. We found similar high rates of grade 3/4 hepatotoxicity in Hispanics on an adult regimen (100%) and NHW patients on either a pediatric (71%) or adult regimen (50%). However, fewer patients developed NAFLD (4/17, 24%), only 1 (Hispanic) patient developed fibrosis, and none developed pancreatitis. There was no difference in mean BMI between Hispanic and NHW patients. Conclusions: While grade 3/4 transaminitis is described during ALL treatment, in this retrospective analysis we observed that Hispanic AYA patients treated on pediatric protocols frequently develop more serious complications including hepatic steatosis, cirrhosis or pancreatitis. Co-existing metabolic syndrome is associated with a higher incidence of simple steatosis (SS; 70% in obesity, 90% in diabetes), and Hispanic patients have a higher baseline SS incidence (45% in Hispanics vs 33% in NHW), which in the context of use of higher doses of steroids and asparaginase may explain their increased frequency of progression to NASH and fibrosis. As few underwent biopsy, the true incidence is likely underrepresented. Additionally, Hispanics treated on a pediatric regimen more frequently developed pancreatitis than NHW patients on the same regimen. SS is related to the accumulation of hepatic free fatty acids and triglycerides, thus patients with SS or at risk may have impaired free fatty acid metabolism that predisposes to pancreatitis with asparaginase use. Limitations of this study include a small sample size, partial availability of baseline imaging, and non-standardized radiographic interpretations of the degree of steatosis. However, our findings suggest further investigation is warranted and a multi-center study is in progress. Our study highlights the need for closer monitoring of Hispanic patients to mitigate the risk of serious liver disease with the use of curative pediatric regimens for ALL. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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Inosine-Triphosphate-Pyrophosphatase Genotype Is a Determinant of Severe Fever with Neutropenia Following Treatment of Acute Lymphoblastic Leukemia with Combination Chemotherapy That Includes Mercaptopurine Adjusted for Thiopurine-S-Methyltransferase Genotype.

Blood ◽

10.1182/blood.v110.11.2827.2827 ◽

2007 ◽

Vol 110 (11) ◽

pp. 2827-2827

Author(s):

Gabriele Stocco ◽

Meyling Cheok ◽

Wenjian Yang ◽

Thierry Dervieux ◽

Kristine Crews ◽

...

Keyword(s):

Logistic Regression ◽

Acute Lymphoblastic Leukemia ◽

Adverse Events ◽

Lymphoblastic Leukemia ◽

Variant Allele ◽

Inosine Triphosphate Pyrophosphatase ◽

Life Threatening ◽

Variant Alleles ◽

Grade 3 ◽

Tpmt Gene

Abstract Germline polymorphisms can be significant determinants of toxicity to anti-leukemic therapy. For mercaptopurine (6MP) it is established that variant alleles of the thiopurine-S-methyl-transferase (TPMT) gene, resulting in low enzymatic activity, are associated with an increase in the concentration of thioguanine-nucleotide metabolites (TGN) and in the risk of hematotoxicity. Polymorphisms of genes encoding other enzymes involved in 6MP metabolism could also influence its pharmacokinetics and consequently its efficacy and toxicity. Among possible candidate genes, inosine-triphosphate-pyrophosphatase (ITPA) has been related to adverse events to thiopurine treatment of inflammatory bowel disease, but it has not been fully investigated for leukemia therapy. The aim of this study was to assess the association between severe life-threatening toxicities (Grade 3–4) during the continuation treatment of acute lymphoblastic leukemia (ALL) and the variant alleles of TPMT and ITPA genes, and the influence of these variant alleles on the concentration of 6MP metabolites, TGN and methylated nucleotides (MMPN). Patients with ALL on the St. Jude Total 13B protocol were assessed for toxicity according to NCI criteria. Relevant variant alleles of TPMT (SNPs rs1142345, rs1800462, rs1800660) and ITPA (SNP rs41320251) were determined using PCR assays. The association between the variant alleles and the development of adverse events during the continuation phase of treatment was assessed using weighted logistic regression. Concentrations of the two main metabolites of 6MP were measured in erythrocytes by HPLC; the association between genotypes and the concentrations of 6MP metabolites was evaluated using mixed linear effects models. TPMT and ITPA genotypes were determined for 233 patients; 13 (5.2%) were heterozygous for variant alleles of the TPMT gene and 31 (13.3%) for the ITPA gene; no patient had two variant alleles of either gene and 1 patient (0.4%) had a variant allele for both TPMT and ITPA. Since 6MP dose was individualized based on the TPMT variant allele among patients treated in the protocol, genetic polymorphisms of TPMT, not surprisingly, were not associated with toxicity. On the other hand, the presence of an ITPA variant allele was significantly associated with the incidence of Grade 3–4 fever with neutropenia in the univariate and in the multiple weighted logistic regression (odds ratio 3.0, 95% C.I. 1.2–7.8, p = 0.021). 6MP metabolites were measured in 257 samples from 108 patients, and the results revealed that variant alleles of both candidate genes were associated with changes in the concentration of the MMPN metabolites: TPMT with a reduction (p = 0.048) and ITPA with an increase (p = 0.047). Genetic polymorphism of ITPA rs41230251 is a significant determinant of severe and life-threatening fever with neutropenia and of 6MP metabolism in patients with ALL who are treated with 6MP doses individualized based on TPMT genotype.

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Paediatric-Inspired Acute Lymphoblastic Leukemia Protocols, Are They Too Toxic for Young Adults?

Blood ◽

10.1182/blood.v128.22.5162.5162 ◽

2016 ◽

Vol 128 (22) ◽

pp. 5162-5162

Author(s):

Melissa G. Ooi ◽

Wee J Chng ◽

Chin-Hin Ng ◽

Yi Ching Yuen ◽

Allen Eng Juh Yeoh ◽

...

Keyword(s):

Young Adults ◽

Acute Lymphoblastic Leukemia ◽

Young Adult ◽

Complete Remission ◽

Adverse Events ◽

Lymphoblastic Leukemia ◽

Main Concern ◽

Induction Phase ◽

Free Survival ◽

Paediatric Patients

Abstract BACKGROUND In children with acute lymphoblastic leukemia, (ALL), current therapies yield complete remission (CR) rates of 98% and event-free survival (EFS) rates of 70% to 80% at 5 years[1]. In adults, even if the CR rate reaches 85% to 90%, therapeutic results remain less satisfactory, with a disease-free survival (DFS) rates of only 30% to 40% at 5 years. The largest adult trial conducted by the British Medical Research Council (MRC) and Eastern Cooperative Oncology Group (ECOG) has recently reported a 90% CR rate with a 5-year overall survival (OS) rate of 43% in patients with Philadelphia chromosome (Ph)-negative ALL [2]. In a study that retrospectively compared two trials, one designed for children and the other for adults, adolescents and young adults age 15 to 20 years old markedly benefited from a pediatric approach[3]. Whether pediatric or pediatric-inspired treatments might also improve the outcome of adults older than age 20 years remained unresolved. The main concern was the perceived worse tolerance of higher cumulative doses of chemotherapy. MASPORE, a BFM based paediatric ALL protocol, has been used successfully in Singapore and Malaysia's paediatric cohort. In this single centre study, we wanted to investigate if the young adults with ALL (<30 years age) will also benefit from MASPORE and to investigate if they can tolerate a paediatric type regiment. METHODS We looked at our young adult patients (18-30 years old inclusive) over a period of 8 years. There was a total of 15 patients who was diagnosed with ALL (either T or B cell). Patients who were Philadelphia positive were excluded from this trial. The grading for the adverse events was done according to the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0. RESULTS Our patients appeared to have a number of adverse events on this paediatric protocol. The grade 3/4 adverse events were 50% of all events collected. Table 1 demonstrated the type and incidence of events. As our serious adverse events appear to be L-asparaginase related, we focused in on those events associated with L-asparaginase and compared our data with our paediatric counterpart. Our patients had a high incidence of pancreatitis (13.3%) and thrombosis (40%), compared to the paediatric patients, who reported an incidence of 2.05% pancreatitis and 2.6% thrombosis. If line related thrombosis was removed from the equation, our thrombosis risk was still 13.3% which is 6.5 times the paediatric rate. Interestingly, the pancreatitis that our patients experienced was a biochemical pancreatitis with no clinical symptoms. Although fewer paediatric patients suffer from pancreatitis, there appear to be sicker with pancreatitis needing intervention. CONCLUSION The young adult cohort appears to have a much higher incidence of adverse events when compared to the paediatric patients. The thrombosis and pancreatitis incidence rate appear to be 6.5 times more frequent compared to the paediatric patients. The limitation of this study is the small number of young adult ALL. Our department has instituted a policy change since this data was analysed. To reduce the incidence of line related thrombosis, the use of a peripherally inserted central catheter is discouraged during induction phase. We are also minimising the days off thromboprophylaxis; the low molecular weight heparin is only withheld on the day of the intrathecal chemotherapy. Since this protocol change, there has been no more line related thrombosis and other thrombosis noted. Our future work would be to reanalyse our thrombosis data after this protocol change and to investigate further as to why the young adults suffer more with pancreatitis compared to the children. References 1. Pui, C.H. and W.E. Evans, Treatment of acute lymphoblastic leukemia. N Engl J Med, 2006. 354(2): p. 166-78. 2. Goldstone, A.H., et al., In adults with standard-risk acute lymphoblastic leukemia, the greatest benefit is achieved from a matched sibling allogeneic transplantation in first complete remission, and an autologous transplantation is less effective than conventional consolidation/maintenance chemotherapy in all patients: final results of the International ALL Trial (MRC UKALL XII/ECOG E2993). Blood, 2008. 111(4): p. 1827-33. 3. Boissel, N., et al., Should adolescents with acute lymphoblastic leukemia be treated as old children or young adults? Comparison of the French FRALLE-93 and LALA-94 trials. J Clin Oncol, 2003. 21(5): p. 774-80 Disclosures Chng: Celgene: Honoraria, Research Funding.

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Comparison of CALGB 10403 (Alliance) and COG AALL0232 toxicity results in young adults with acute lymphoblastic leukemia

Blood Advances ◽

10.1182/bloodadvances.2020002439 ◽

2021 ◽

Vol 5 (2) ◽

pp. 504-512

Author(s):

Anjali S. Advani ◽

Eric Larsen ◽

Kristina Laumann ◽

Selina M. Luger ◽

Michaela Liedtke ◽

...

Keyword(s):

Young Adults ◽

Acute Lymphoblastic Leukemia ◽

Adverse Events ◽

Lymphoblastic Leukemia ◽

Survival Rates ◽

Standard Of Care ◽

Transaminase Elevation ◽

Improved Outcomes ◽

Grade 3 ◽

Historical Controls

Abstract Adolescents and young adults (AYAs) with acute lymphoblastic leukemia have improved outcomes when treated with pediatric-inspired regimens. CALGB 10403 was the largest prospective study to evaluate the feasibility of using a pediatric regimen in AYAs with acute lymphoblastic leukemia up to 40 years of age. This article presents the toxicity events observed in the CALGB 10403 study and compares these toxicities vs those observed among AYAs treated on the same arm of the companion Children’s Oncology Group (COG) AALL0232 study. Toxicities in CALGB 10403 were similar to those observed in COG AALL0232. Some grade 3 to 4 adverse events were more often reported in CALGB 10403 compared with COG AALL0232 (hyperglycemia, hyperbilirubinemia, transaminase elevation, and febrile neutropenia). Adverse events correlated with body mass index ≥30 kg/m2 and some with increasing age. The mortality rate in CALGB 10403 was low (4%) and similar to that in the COG AALL0232 trial. A caveat to this analysis is that only 39% of CALGB 10403 patients completed all planned protocol treatment. In COG AALL0232, although 74% of patients aged <18 years completed treatment, only 57% of patients aged ≥18 years completed treatment. This scenario suggests that issues associated with age and treating physician may be a factor. Due to its improved survival rates compared with historical controls, the CALGB 10403 regimen is now a standard of care. The hope is that the rate of protocol completion will increase as more familiarity is gained with this regimen. These trials were registered at www.clinicaltrials.gov as #NCT00558519 (CALGB 10403) and #NCT00075725 (COG AALL0232).

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Pharmacogenomic Association with Neurotoxicity in Hispanic Children with Acute Lymphoblastic Leukemia (ALL)

Blood ◽

10.1182/blood.v128.22.3962.3962 ◽

2016 ◽

Vol 128 (22) ◽

pp. 3962-3962 ◽

Cited By ~ 1

Author(s):

Claire A McClain ◽

M Brooke Bernhardt ◽

Amanda Berger ◽

Ryan Winslow ◽

Michael E Scheurer ◽

...

Keyword(s):

Acute Lymphoblastic Leukemia ◽

Conflicts Of Interest ◽

Lymphoblastic Leukemia ◽

Poor Metabolizers ◽

Extensive Metabolizers ◽

Hispanic Children ◽

Significant Difference ◽

Hispanic Patients ◽

Grade 3 ◽

Intermediate Metabolizers

Abstract Introduction Vincristine is vital in the treatment of acute lymphoblastic leukemia (ALL), but is dose-limited by the development of disabling neuropathies. Vincristine is metabolized extensively by polymorphically expressed CYP3A4/5, which contributes to its 10-fold inter-patient pharmacokinetic variability. Further, there is more recent evidence that an inherited polymorphism in the CEP72 rs924607 gene contributes to vincristine sensitivity. Hispanic children have among the lowest rates of ALL survival when compared to other ethnicities, and pharmacogenomic variability among races is postulated to contribute. This is the first study to examine specifically both CYP3A5 polymorphisms and CEP72 gene expression in correlation with vincristine neurotoxicity in a large cohort of Hispanic ALL patients. Methods Banked germline blood samples from 300 self-identified Hispanic patients with ALL treated at Texas Children's Hospital between 1990 and 2015 were interrogated for allelic discrimination of CEP72 and at the CYP3A5*3, *6, and *7 polymorphic loci using TaqMan assays. Patient medical records were electronically searched for evidence of neuropathic events. Neuropathies were categorized as motor or sensory and graded using the Modified ("Balis") Pediatric Scale of Peripheral Neuropathies. Missing administered vincristine data was imputed using the patient's known treatment protocol and date of event coupled with protocol specifics retrieved from the literature. Multivariate analysis was run modeling the influences of CYP3A5 and CEP72 genotypes on the development and time to development of greater than or equal to Grade 3 neuropathies. Descriptive statistics were used to identify the prevalence of CYP3A5 and CEP72 genotypes and the associated phenotypes in this patient population. Time to neuropathy analysis was performed using the Kaplan-Meier failure estimates and log-rank test in Stata V.12.1 (College Station, TX). Results Based on CYP3A5 polymorphisms, overall, we found that 5% of our patients were extensive metabolizers of vincristine, 33% were intermediate metabolizers, and 62% were poor metabolizers. Additionally, we found that the TT risk CEP72 genotype is a rare finding in our cohort (9.3%). Clinically, we found that 18.4% of our patients experienced greater than or equal to Grade 3 neurotoxicity. Assessing the influence of being both a CYP3A5 intermediate or poor metabolizer and having the TT risk CEP72 genotype was limited by the paucity of patients with both genotypes (n=25). However, CYP3A5 poor metabolizers experienced neurotoxicity more often than intermediate or extensive metabolizers, although we did not find a statistically significant correlation between phenotype and incidence of neurotoxicity. Additionally, we found that there was a statistically significant difference in time to development of neurotoxicity within the first 100 days of treatment between intermediate and poor CYP3A5 metabolizers (P=0.036), with poor metabolizers experiencing greater than or equal to Grade 3 neurotoxicity sooner (Figure 1). Conclusions For the first time, we show that CYP3A5 poor metabolizers experienced greater than or equal to Grade 3 neurotoxicity significantly sooner than intermediate metabolizers within the first 100 days of treatment. We found a low prevalence of the minor allele of CEP72 rs924607TT in our Hispanic cohort. However, classification of CYP3A5 metabolizers and genotypes within our Hispanic population as well as our incidence of neurotoxicity are consistent with current literature. Further testing in a larger cohort should be performed but this study reinforces the significance of CYP3A5 metabolism of vincristine in leading to significant neurotoxicity and suggests that, at least in Hispanic patients, vigilance to early development of neurotoxicity should be performed by practitioners. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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Pegasperagase Toxicity in Adult Patients with Acute Lymphoblastic Leukemia: A Single Center Experience Comparing Patients Older and Younger Than 35 Years of Age

Blood ◽

10.1182/blood-2019-129041 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 5067-5067

Author(s):

Jun H Choi ◽

Jacques Azzi ◽

Tsivia Hochman ◽

Mary Lynn R. Nierodzik ◽

Shella Saint Fleur-Lominy ◽

...

Keyword(s):

Acute Lymphoblastic Leukemia ◽

Adverse Events ◽

Conflicts Of Interest ◽

Lymphoblastic Leukemia ◽

Adult Population ◽

Prospective Trial ◽

Philadelphia Chromosome ◽

Treatment Protocol ◽

Adult Patients ◽

Grade 3

Background: The treatment paradigm of adult patients with acute lymphoblastic leukemia (ALL) is primarily derived from successful pediatric chemotherapy regimens. Pegasparagase (PEG) is a key component of pediatric therapy and is the backbone of cytotoxic ALL regimens. However, among the adult population the use of PEG has been limited by the difficulty in tolerating prolonged asparagine depletion. Hepatotoxicity is among the most common adverse events reported with the use of PEG, with grade 3/4 hepatotoxicity seen in 20% of young adults compared to 40-60% of older adults. Incorporating PEG into the treatment of ALL patients under 40 remains an accepted practice despite some studies that report up to 75% of patients have grade 3/4 adverse events as a result of asparagine depletion. In a study of 85 patients with ALL, 3-year overall survival (OS) was significantly different between patients older and younger than 35 (52% vs 83% p = 0.003). Whether this difference is due to PEG toxicity or to other factors remains to be determined. At NYU hospitals, PEG-containing protocols are frequently deployed to treat adult ALL. In our study, we sought to look at the difference in PEG toxicity and response rate (RR) in patients older and younger than 35 and whether these toxicities contributed to a delay in subsequent treatments and to a worse outcome. Methods: We conducted a retrospective chart review of patients older than 18 diagnosed with ALL or lymphoblastic lymphoma, who received at least 1 dose of PEG at our institution between 2014 and 2018. All patients received PEG as part of their first line treatment protocol. Our main objective was to compare the tolerability and toxicity profile of intravenous PEG in patients ≥35 years old versus <35. Our secondary objective was to investigate its effects on chemotherapy delay, RR, and relapse rate. Results: Out of a total of 50 patients, 23 were age ≥ 35 (46%). Mean age was 34.4 (Range: 18.9-63.1). The 2 groups shared similar distributions in gender, race, and Philadelphia chromosome (Ph) subtypes (Table 1). The older group received significantly less PEG, 5114.8 vs. 25353.7 units (p=0.0007) and 1.65 vs. 3.59 doses (p<0.0001) compared to the younger group. Grade 1-4 toxicity profiles were similar as both groups had high hepatotoxicity rates: transaminitis 100% vs. 89% (p=0.079) and hyperbilirubinemia 78% vs. 78% (p=0.104) in the older vs younger group, respectively. Grade 3-4 hepatotoxicity was significantly more pronounced in patients ≥35 years old (transaminitis 65% vs. 33% [p=0.0245], hyperbilirubinemia 48 vs. 15% [p=0.0111]). Coagulopathy rates evaluated with hypofibrinogenemia and thrombosis were similar between the older and the younger groups at 52% vs. 44% [p=0.104] and 17% vs. 7%, [p=0.855], respectively, and the frequency of pancreatitis and anaphylaxis were 4% vs. 18.5% (p=0.422) and 0% vs. 14.8% (p=0.115), respectively. In the older group, only 13% completed the planned PEG dosages compared to 59% in the younger group (p=0.0008), and delay in other chemotherapy by more than 30 days due to PEG hepatotoxicity occurred in 55% of older patients compared to 22% of younger patients (p=0.02). MRD negativity rate after induction was similar in the older and younger group (50% vs. 60% [p=0.491], respectively), but the 12-month relapse free survival was significantly lower in the older group (41%, [95% CI: 55.7%-89%] vs. 77%, [95% CI: 21%-61%], p=0.022) (Figure 1). Conclusions: Patients aged ≥ 35 received significantly less PEG during their treatments but were more likely to develop severe grade 3-4 hepatotoxicity compared to their younger counterparts. The response rates were similar with comparable MRD negativity rates after induction regardless of total amount of PEG administered. However, relapse occurred more frequently in the older group, possibly resulting from more frequent delays in administering other chemotherapy agents due to PEG toxicity. Incorporation of PEG is important in the treatment of ALL but should be used with caution in patients ≥35 years old, and will likely require dose and schedule modifications. A larger prospective trial investigating adequate dosing and scheduling of PEG in this age group is warranted, specifically comparing delays in chemotherapy, relapse, and survival rates in regimens with and without PEG. Disclosures No relevant conflicts of interest to declare.

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Increased Levels of Adipocyte and Epidermal Fatty Acid-Binding Proteins in Acute Lymphoblastic Leukemia Survivors

Journal of Clinical Medicine ◽

10.3390/jcm10081567 ◽

2021 ◽

Vol 10 (8) ◽

pp. 1567

Author(s):

Katarzyna Konończuk ◽

Eryk Latoch ◽

Beata Żelazowska-Rutkowska ◽

Maryna Krawczuk-Rybak ◽

Katarzyna Muszyńska-Rosłan

Keyword(s):

Metabolic Syndrome ◽

Fatty Acid ◽

Acute Lymphoblastic Leukemia ◽

Binding Proteins ◽

Lymphoblastic Leukemia ◽

Fatty Acid Binding Proteins ◽

Fatty Acid Binding ◽

The Metabolic Syndrome ◽

Increased Risk ◽

Significant Difference

Childhood cancer survivors are highly exposed to the development of side effects after many years of cessation of anticancer treatment, including altered lipid metabolism that may result in an increased risk of overweight and metabolic syndrome. Adipocyte (A-FABP) and epidermal (E-FABP) fatty acid-binding proteins are expressed in adipocytes and are assumed to play an important role in the development of lipid disturbances leading to the onset of metabolic syndrome. The aim of this study was to investigate the association between serum A-FABP and E-FABP levels, overweight, and components of the metabolic syndrome in acute lymphoblastic leukemia survivors. Sixty-two acute lymphoblastic leukemia (ALL) survivors (34 females) were included in the study. The mean age at the time of the study was 12.41 ± 4.98 years (range 4.71–23.43). Serum levels of A-FABP and E-FABP were analyzed using a commercially available ELISA kit. The ALL survivors presented statistically higher A-FABP levels in comparison with the healthy controls (25.57 ± 14.46 vs. 15.13 ± 7.61 ng/mL, p < 0.001). The subjects with body mass index (BMI) above the normal range (18 overweight, 10 obese) had a greater level of A-FABP compared to the ALL group with normal BMI (32.02 ± 17.10 vs. 20.33 ± 9.24 ng/mL, p = 0.006). Of all participants, 53.23% had at least one risk factor of metabolic syndrome; in this group, only the A-FABP level showed a statistically significant difference compared to the healthy control group (30.63 ± 15.91 vs. 15.13 ± 7.61 ng/mL, p < 0.001). The subjects with two or more metabolic risk factors (16.13%) presented higher levels of both A-FABP (33.62 ± 17.16 vs. 15.13 ± 7.61 ng/mL, p = 0.001) and E-FABP (13.37 ± 3.62 vs. 10.12 ± 3.21 ng/mL, p = 0.021) compared to the controls. Univariable regression models showed significant associations between BMI and systolic blood pressure with the A-FABP level (coeff. 1.02 and 13.74, respectively; p < 0.05). In contrast, the E-FABP level was only affected by BMI (coeff. 0.48; p < 0.01). The findings reported herein suggest that the increased levels of A-FABP and E-FABP may be involved in the pathogenesis of overweight and the onset of metabolic syndrome in acute lymphoblastic leukemia. However, further longitudinal, prospective studies of fatty acid-binding proteins and their potential role in the pathogenesis of obesity and metabolic syndrome in ALL survivors remain to be performed.

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