An exploration of mercaptopurine/methotrexate tolerance during maintenance therapy in children with acute lymphoblastic leukemia

2020 ◽  
pp. 107815522096355
Author(s):  
AC Whiley ◽  
V Price ◽  
T MacDonald
Keyword(s):  
Risk Stratification ◽  
Maintenance Therapy ◽  
Disease Risk ◽  
Lymphoblastic Leukemia ◽  
Retrospective Chart Review ◽  
Maximum Tolerated Dose ◽  
Future Research ◽  
Sex Diagnosis ◽  
Treatment Interruptions ◽  
The Mean

Purpose Mercaptopurine (6MP) and methotrexate (MTX) cause myelosuppression and interruptions in therapy in children with lymphoblastic leukemia (ALL). Length of time off of therapy is related to poorer outcomes. To date the dose at which most children tolerate these agents without drops in blood counts has not been identified. This study attempts to determine the maximum tolerated dose of both 6MP/MTX. Methods A retrospective chart review of 77 ALL children, median age 4.5 years. Time to first interruption and dose, along with total number of interruptions were collected. Absolute neutrophil and platelet counts recorded at time of interruption. Subgroup analysis of age, sex, diagnosis and risk stratification were also completed. REB approval was gained. Results Of the 77 patients that were studied, 9 of them had no treatment interruptions. Descriptive statistics are reported using Strata software. The mean number of interruptions during maintenance was 3.2, the mean time to first interruption was 149.8 days. The mean dose percent of MTX and 6MP at first interruption was 94.4% and 106% respectively. Maintenance therapy was interrupted independent of age, sex, diagnosis or disease risk stratification. Conclusion Few patients complete maintenance therapy without interruptions at the current dose escalation schedules outlined by the Children’s Oncology Group protocols. The interruptions are due in part to intolerance of dose escalations of MTX and 6 MP above 100%. Future research should investigate doses of 6MP and MTX in maintenance therapy in relation to leukemia outcomes.

Hyperglycemia and obesity in patients (pts) with acute lymphoblastic leukemia (ALL): Association with prevalence, response, and survival

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7074-7074
Author(s):  
K. D. Vu ◽  
V. R. Lavis ◽  
S. Strom ◽  
S. H. Faderl ◽  
M. Konopleva ◽  
...  
Keyword(s):  
Cox Regression ◽  
Lymphoblastic Leukemia ◽  
Univariate Analysis ◽  
Retrospective Chart Review ◽  
Hematologic Malignancies ◽  
Serum Glucose ◽  
High Dose ◽  
Baseline Serum ◽  
Significant Difference ◽  
The Mean

7074 Increasing evidence suggests associations between obesity, diabetes and/or hyperglycemia (DM/HG) and solid tumors. Less is known about the relationship of these metabolic factors to the hematologic malignancies. To determine the prevalence of DM/HG and obesity in pts with ALL and whether these are predictors of response and survival, we conducted a retrospective chart review of 299 pts with newly diagnosed ALL, who were evaluated at our institution between November 1999 and May 2005 and received hyper-CVAD therapy: fractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone alternating with methotrexate and high-dose cytarabine. Median age was 43 yrs (range 15–83). Sixty-one percent of pts were male, and 39% female. Seventy-four percent had a diagnosis (dx) of precursor B cell ALL (22% Ph+), 18% Burkitt's ALL, 6% lymphoblastic lymphoma, 2% other. Prior to therapy, the overall prevalence of DM/HG (diabetes based on reported dx prior to ALL-dx, and hyperglycemia based on baseline serum glucose ≥200 mg/dL) was 16%. Pts with DM/HG were significantly older than those without DM/HG (median age 57 yrs vs. 40 yrs, p<0.001). Complete remission (CR) rate and the CR duration (CRD) were similar in the DM/HG vs. non-DM/HG group. However, the mean CRD was 80 wks in the HG separately group and 121 wks in the non-HG group (p=0.04). The mean CRD was 102 wks in the obese pts and 124 wks in the non-obese pts (p=.04). In univariate analysis, DM/HG, obesity, and older age were associated with shorter overall survival (OS). Mean OS of pts with DM/HG was 134 vs. 194 wks for pts without DM/HG, (p=0.2). Mean OS of obese pts was 136 vs. 199 wks for non-obese pts, (p=0.01). In a multivariable Cox regression model, the only factors that remained significant for survival were age, obesity, and white blood cell count (WBC). There was no significant difference in OS by leukemia diagnosis. In conclusion, the prevalence data suggests that DM/HG may be involved in the development of ALL. However, DM/HG has no impact on survival, probably because of its strong correlation with age. The association of obesity with shorter OS warrants further investigation. No significant financial relationships to disclose.

Prevalence and Predictors of Non-Adherence to 6-Mercaptopurine (6MP) in Children with Acute Lymphoblastic Leukemia (ALL) - a Children’s Oncology Group Study.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 897-897
Author(s):  
Smita Bhatia ◽  
Doojduen Villaluna ◽  
Wendy Landier ◽  
Alexandra Schaible ◽  
Lindsey Hageman ◽  
...  
Keyword(s):  
High School ◽  
Household Income ◽  
Lymphoblastic Leukemia ◽  
Systemic Exposure ◽  
Small Sample ◽  
Future Research ◽  
Annual Household Income ◽  
Increased Risk ◽  
The Mean ◽  
The Impact

Abstract Use of contemporary risk-based therapy in children with ALL has resulted in five-year survival rates exceeding 80%. Achievement of durable remissions requires a maintenance phase composed of oral administration of antimetabolites (6-mercaptopurine and methotrexate) for approximately two years. Previous studies have shown that low systemic exposure to oral 6MP adversely affects prognosis, thus emphasizing the critical need for therapeutic levels throughout maintenance. However, significant inter-patient variability in red cell thioguanine nucleotide (6TGN – a major metabolite of 6MP) concentrations exists, and could in part be related to failure to adhere to prescribed therapy. Non-adherence in pediatric ALL patients has been reported – however, small sample sizes and varying methods of assessment make it difficult to understand the magnitude of this problem. The purpose of our study was to describe adherence to oral 6MP in a large multi-ethnic cohort of children with ALL. Patients were eligible to participate if they were diagnosed with ALL at age less than 22 years, belonged to one of four ethnic/racial groups (Asian, African-American, Caucasian, or Hispanic), and had completed at least 24 weeks of maintenance therapy. We have restricted the current report to Caucasians, where we have completed our target accrual. To measure 6MP adherence, we used the Medication Event Management System (MEMS) and supplied each patient with a MEMS TrackCap. This electronic cap allowed the collection of real-time data by recording the date and time(s) when the 6MP bottle was opened over a 6-month period. The MEMS data was downloaded at the end of the 6-month study period. Patients/parents also completed a self-administered sociodemographic questionnaire. Longitudinal analysis was performed using the Generalized Estimating Equations. A total of 173 Caucasian patients provided 26,424 person-days of observation for 6MP adherence. The median age at diagnosis was 5 years (1 to 19), and at study participation was 6 years (range, 2 to 20); median time from diagnosis was 18.8 months, and from start of maintenance, 8.1 months; 67% were males. NCI criteria for high-risk disease were present in 42% of the patients. The median annual household income was between $50K and $75K; 79% of the mothers and 72% of the fathers had received education beyond high school. The median number of household members (including patient) was 4 (range, 2 to 10). Adherence was defined as the ratio of 6MP bottle openings to actual 6MP doses prescribed, calculated as a percentage (“percent adherence”). Prescribed doses for the entire 6-month period were reviewed for each patient, and instances when 6MP was withheld by the prescriber due to toxicity or illness were taken into account for purposes of calculating adherence. The mean percent adherence over the 6-month study period was 85% (range 11% to 100%). The mean monthly percent adherence declined significantly over the 6-month study period (p=0.002). Multivariate analysis identified certain subgroups that were at increased risk of lower percent adherence (Figure): age >8 years at study entry (p=0.01); households that included members other than the mother, father, and patient (<0.001); father’s education ≤ high school or ≥ college degree (p=0.05), and annual household income <$20k or ≥ $100K (p=.045). In this study, 19% of the study participants were <80% adherent at the end of the first study month; this increased to 30% by the end of the 6-month study period. Over 6% of patients were <50% adherent at the end of the first month, and this increased to 11% at month 6 – demonstrating that over 10% of the patients were taking less than 50% of their prescribed doses of 6MP. This study demonstrates that non-adherence to 6MP is prevalent in children undergoing treatment for ALL and increases with time on maintenance. It further delineates certain sociodemographic variables that define those at highest risk for non-adherence. Patients from this study will be followed long-term to understand the impact of non-adherence on outcome. Future research needs to focus on developing targeted, multidisciplinary interventions to reduce non-adherence to therapy. Figure Figure

Correlation of Altered Expression of RIZ1 to Diagnosis, Risk Stratification, and Disease Progression in 56 Acute Leukemia Patients.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2627-2627
Author(s):  
Qiubai Li ◽  
Xiaojian Zhu ◽  
Xiaoqing Li ◽  
Xiangjun Chen ◽  
Yong You ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Complete Remission ◽  
Risk Stratification ◽  
Acute Leukemia ◽  
Disease Progression ◽  
De Novo ◽  
Disease Risk ◽  
Lymphoblastic Leukemia ◽  
Altered Expression ◽  
Healthy Donors

Abstract Abstract 2627 Poster Board II-603 RIZ1 expression is altered in a variety of human cancers and is now considered to be a candidate tumor suppressor in many types of human tumors, including breast cancer, liver cancer, colon cancer, neuroblastoma, melanoma, lung cancer, and osteosarcoma. Previous studies indicate that suppression of RIZ1 expression may have an important role in leukemogenesis and RIZ1 is downregulated during CML progression and displays tumor suppressor properties in CML cell lines. To deeply investigate the expression of RIZ1 and its correlation to diagnosis, risk stratification, and disease progression in human acute leukemia, we analysed the differential expression of RIZ1 by quantitative real-time reverse-transcription polymerase chain reaction assay in 56 acute patients with or without complete remission and in 9 healthy donors. Our results showed that the expression of RIZ1 was significantly decreased in both de novo acute leukemia patients and patients with no remission (n = 35) (P = 0.009, compared with healthy donors) and significantly increased in acute leukemia patients with complete remission (P = 0.001, compared with de novo acute leukemia patients and patients with no remission). When compared with healthy donors, acute leukemia patients with complete remission (n = 21) owned the statistically same expression of RIZ1 (P = 0.595). The expression of RIZ1 was significantly higher in acute myeloid leukemia (AML, n = 17) than acute lymphoblastic leukemia (ALL, n =15) (P = 0.009), with a good correlation to diagnosis of AML or ALL (r = 0.514). The patients (n = 16) with high-risk leukemia had significantly higher expression of RIZ1 than the patients with standard-risk (n = 18) (P = 0.031), with the correlation (r = 0.431) of RIZ1 expression to disease risk-stratification. In addition, the weak correlations of RIZ1 expression were shown to both age and gender ( r = 0.158 and 0.003, respectively). This relatively simple analysis provides an important role of RIZ1 expression in acute leukemia. Taken together, our results suggest the potential for using RIZ1 expression in predication of disease progression or recovery in acute leukemia. We demonstrate that RIZ1 expression can contribute to the diagnosis of AML or ALL and the evaluation of risk-stratification in acute leukemia. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Higher Caloric Refeeding Is Safe in Hospitalised Adolescent Patients with Restrictive Eating Disorders

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Elizabeth K. Parker ◽  
Sahrish S. Faruquie ◽  
Gail Anderson ◽  
Linette Gomes ◽  
Andrew Kennedy ◽  
...  
Keyword(s):  
Eating Disorders ◽  
Weight Gain ◽  
Statistical Significance ◽  
Caloric Intake ◽  
Tube Feeding ◽  
Retrospective Chart Review ◽  
Refeeding Syndrome ◽  
Restrictive Eating ◽  
Weight Restoration ◽  
The Mean

Introduction. This study examines weight gain and assesses complications associated with refeeding hospitalised adolescents with restrictive eating disorders (EDs) prescribed initial calories above current recommendations.Methods. Patients admitted to an adolescent ED structured “rapid refeeding” program for >48 hours and receiving ≥2400 kcal/day were included in a 3-year retrospective chart review.Results. The mean (SD) age of the 162 adolescents was 16.7 years (0.9), admission % median BMI was 80.1% (10.2), and discharge % median BMI was 93.1% (7.0). The mean (SD) starting caloric intake was 2611.7 kcal/day (261.5) equating to 58.4 kcal/kg (10.2). Most patients (92.6%) were treated with nasogastric tube feeding. The mean (SD) length of stay was 3.6 weeks (1.9), and average weekly weight gain was 2.1 kg (0.8). No patients developed cardiac signs of RFS or delirium; complications included 4% peripheral oedema, 1% hypophosphatemia (<0.75 mmol/L), 7% hypomagnesaemia (<0.70 mmol/L), and 2% hypokalaemia (<3.2 mmol/L). Caloric prescription on admission was associated with developing oedema (95% CI 1.001 to 1.047;p=0.039). No statistical significance was found between electrolytes and calories provided during refeeding.Conclusion. A rapid refeeding protocol with the inclusion of phosphate supplementation can safely achieve rapid weight restoration without increased complications associated with refeeding syndrome.

scholarly journals Can an amino acid mixture alleviate gastrointestinal symptoms in neuroendocrine tumor patients?

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Aman Chauhan ◽  
Satya Das ◽  
Rachel Miller ◽  
Laura Luque ◽  
Samuel N. Cheuvront ◽  
...  
Keyword(s):  
Amino Acid ◽  
Neuroendocrine Tumor ◽  
Gastrointestinal Symptoms ◽  
Retrospective Chart Review ◽  
Final Analysis ◽  
Acid Mixture ◽  
Tumor Patients ◽  
Short Gut Syndrome ◽  
Oral Rehydration ◽  
The Mean

Abstract Background Neuroendocrine tumors, although relatively rare in incidence, are now the second most prevalent gastrointestinal neoplasm owing to indolent disease biology. A small but significant sub-group of neuroendocrine tumor patients suffer from diarrhea. This is usually secondary to carcinoid syndrome but can also be a result of short gut syndrome, bile acid excess or iatrogenic etiologies. Recently, an amino acid based oral rehydration solution (enterade® Advanced Oncology Formula) was found to have anti-diarrheal properties in preclinical models. Methods A retrospective chart review of all NET patients treated with enterade® AO was performed after IRB approval. Results Ninety-eight NET patients who had received enterade® AO at our clinic from May 2017 through June 2019 were included. Patients (N = 49 of 98) with follow up data on bowel movements (BMs) were included for final analysis. Eighty-four percent of patients (41/49) had fewer BMs after taking enterade® AO and 66% (27/41) reported more than 50% reduction in BM frequency. The mean number of daily BMs was 6.6 (range, 3–20) at baseline before initiation of therapy, while the mean number of BMs at 1 week time point post enterade® AO was 2.9 (range, 0–11). Conclusions Our retrospective observations are encouraging and support prospective validation with appropriate controls in NET patients. This is first published report of the potential anti-diarrheal activity of enterade® AO in NET patients.

scholarly journals Quantitative disease risk scores from EHR with applications to clinical risk stratification and genetic studies

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Danqing Xu ◽  
Chen Wang ◽  
Atlas Khan ◽  
Ning Shang ◽  
Zihuai He ◽  
...  
Keyword(s):  
Risk Stratification ◽  
Disease Risk ◽  
Association Studies ◽  
Large Datasets ◽  
Risk Scores ◽  
Sequencing Data ◽  
Case Definitions ◽  
Phenotypic Data ◽  
Clinical Risk ◽  
Phenotypic Features

AbstractLabeling clinical data from electronic health records (EHR) in health systems requires extensive knowledge of human expert, and painstaking review by clinicians. Furthermore, existing phenotyping algorithms are not uniformly applied across large datasets and can suffer from inconsistencies in case definitions across different algorithms. We describe here quantitative disease risk scores based on almost unsupervised methods that require minimal input from clinicians, can be applied to large datasets, and alleviate some of the main weaknesses of existing phenotyping algorithms. We show applications to phenotypic data on approximately 100,000 individuals in eMERGE, and focus on several complex diseases, including Chronic Kidney Disease, Coronary Artery Disease, Type 2 Diabetes, Heart Failure, and a few others. We demonstrate that relative to existing approaches, the proposed methods have higher prediction accuracy, can better identify phenotypic features relevant to the disease under consideration, can perform better at clinical risk stratification, and can identify undiagnosed cases based on phenotypic features available in the EHR. Using genetic data from the eMERGE-seq panel that includes sequencing data for 109 genes on 21,363 individuals from multiple ethnicities, we also show how the new quantitative disease risk scores help improve the power of genetic association studies relative to the standard use of disease phenotypes. The results demonstrate the effectiveness of quantitative disease risk scores derived from rich phenotypic EHR databases to provide a more meaningful characterization of clinical risk for diseases of interest beyond the prevalent binary (case-control) classification.

scholarly journals Correlation between fundus autofluorescence and visual function in patients with cone-rod dystrophy

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Satoru Kanda ◽  
Takumi Hara ◽  
Ryosuke Fujino ◽  
Keiko Azuma ◽  
Hirotsugu Soga ◽  
...  
Keyword(s):  
Visual Field ◽  
Significant Relationship ◽  
Fundus Autofluorescence ◽  
Univariate Analysis ◽  
Retrospective Chart Review ◽  
Mean Deviation ◽  
Wide Field ◽  
The Mean ◽  
The Relationship ◽  
Field Imaging

AbstractThis study aimed to investigate the relationship between autofluorescence (AF) signal measured with ultra-wide field imaging and visual functions in patients with cone-rod dystrophy (CORD). A retrospective chart review was performed for CORD patients. We performed the visual field test and fundus autofluorescence (FAF) measurement and visualized retinal structures with optical coherence tomography (OCT) on the same day. Using binarised FAF images, we identified a low FAF area ratio (LFAR: low FAF/30°). Relationships between age and logMAR visual acuity (VA), central retinal thickness (CRT), central choroidal thickness (CCT), mean deviation (MD) value, and LFAR were investigated. Thirty-seven eyes of 21 CORD patients (8 men and 13 women) were enrolled. The mean patient age was 49.8 years. LogMAR VA and MD were 0.52 ± 0.47 and − 17.91 ± 10.59 dB, respectively. There was a significant relationship between logMAR VA and MD (p = 0.001). LogMAR VA significantly correlated with CRT (p = 0.006) but not with other parameters. Conversely, univariate analysis suggested a significant relationship between MD and LFAR (p = 0.001). In the multivariate analysis, LFAR was significantly associated with MD (p = 0.002). In conclusion, it is useful to measure the low FAF area in patients with CORD. The AF measurement reflects the visual field deterioration but not VA in CORD.

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