scholarly journals Adherence to Oral Medications During Maintenance Therapy Among Children and Adolescents With Acute Lymphoblastic Leukemia: A Medication Refill Analysis

2017 ◽  
Vol 35 (2) ◽  
pp. 86-93 ◽  
Author(s):  
Yelena P. Wu ◽  
David D. Stenehjem ◽  
Lauri A. Linder ◽  
Bin Yu ◽  
Bridget Grahmann Parsons ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Medication Adherence ◽  
Maintenance Therapy ◽  
Pediatric Patients ◽  
Electronic Monitoring ◽  
Lymphoblastic Leukemia ◽  
Maintenance Phase ◽  
National Sample ◽  
Oral Medications ◽  
Medication Refill

Adherence to oral medications during maintenance therapy is essential for pediatric patients with acute lymphoblastic leukemia. Self-reported or electronic monitoring of adherence indicate suboptimal adherence, particularly among particular sociodemographic groups. This study used medication refill records to examine adherence among a national sample of pediatric patients with acute lymphoblastic leukemia. Patients in a national claims database, aged 0 to 21 years with a diagnosis of acute lymphoblastic leukemia and in the maintenance phase of treatment, were included. Medication possession ratios were used as measures of adherence. Overall adherence and adherence by sociodemographic groups were examined. Adherence rates were 85% for 6-mercaptopurine and 81% for methotrexate. Adherence was poorer among patients 12 years and older. Oral medication adherence rates were suboptimal and similar to or lower than previously documented rates using other methods of assessing adherence. Refill records offer a promising avenue for monitoring adherence. Additional work to identify groups most at-risk for poor adherence is needed. Nurses are well positioned to routinely monitor for medication adherence and to collaborate with the multidisciplinary team to address barriers to adherence.

scholarly journals When Multiple Objective Measures of Medication Adherence Indicate Incongruent Adherence Results: An Example with Pediatric Cancer

2020 ◽  
Vol 17 (6) ◽  
pp. 1956 ◽  
Author(s):  
Caitlin J. Cain ◽  
Andrea R. Meisman ◽  
Kirstin Drucker ◽  
Evrosina I. Isaac ◽  
Tanvi Verma ◽  
...  
Keyword(s):  
Medication Adherence ◽  
Pediatric Cancer ◽  
Electronic Monitoring ◽  
Lymphoblastic Leukemia ◽  
Healthcare Providers ◽  
Dose Intensity ◽  
Maintenance Phase ◽  
Objective Measures ◽  
Treatment Regimens ◽  
Household Environment

Previous research suggests that children and adolescents with acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) often have difficulty adhering to complex treatment regimens during the maintenance phase of therapy. Measurement of treatment adherence can be done via objective (e.g., electronic monitoring (EM), pharmacological assays) or subjective methods (patient, parent, or physician reports). This paper provides an illustration of recommended strategies for comparing discrepancies between two objective measures of medication adherence (e.g., behavioral adherence using electronic monitoring versus pharmacological adherence using 6-mercaptopurine (6MP) metabolite data) within a relatively large cohort of pediatric patients with ALL or LBL (N = 139) who had longitudinal data for both measures of medication adherence over a 15-month period. Additionally, individual- and family-level factors such as gender, socioeconomic status, household environment, and dose intensity will be examined to identify possible sources of discrepancies between adherence measures. This information will provide practical advice for physicians, healthcare providers, and psychologists in identifying nonadherence and the caveats therein so patients achieve the best possible health outcomes.

scholarly journals Optimizing Therapy in the Modern Age: Differences in Length of Maintenance Therapy in Acute Lymphoblastic Leukemia

Blood ◽  
2020 ◽  
Author(s):  
David T Teachey ◽  
Stephen P. Hunger ◽  
Mignon L. Loh
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Maintenance Therapy ◽  
Randomized Clinical Trials ◽  
Lymphoblastic Leukemia ◽  
Maintenance Phase ◽  
High Rate ◽  
Intrathecal Therapy ◽  
Cooperative Groups ◽  
Significant Burden ◽  
Multi Agent

The majority of children and young adults with acute lymphoblastic leukemia (ALL) are cured with contemporary multi-agent chemotherapy regimens. The high rate of survival is largely the result of 70 years of randomized clinical trials performed by international cooperative groups. Contemporary ALL therapy usually consists of cycles of multi-agent chemotherapy given over 2-3 years that includes central nervous system (CNS) prophylaxis, primarily consisting of CNS-penetrating systemic agents and intrathecal therapy. While the treatment backbones vary between cooperative groups, the same agents are used and the outcomes are comparable. ALL therapy typically begins with 5-9 months of more intensive chemotherapy followed by a prolonged low intensity maintenance phase. Historically, a few cooperative groups treated boys with one more year of maintenance therapy than girls; whereas, the majority of groups treated boys and girls with equal therapy lengths. This practice arose because of inferior survival in boys with older less-intensive regimens. The extra year of therapy adds significant burden to patients and families and has short- and long-term risks that can be life-threatening and debilitating. The Children's Oncology Group (COG) recently changed its approach as part of their current generation of trials in B-ALL and is now treating boys and girls with the same duration of therapy. We provide the rationale behind this change, a review of the data and differences in practice across cooperative groups, and our perspective regarding the length of maintenance therapy.

scholarly journals 2448 The effect of allopurinol on pediatric patients undergoing maintenance chemotherapy for acute lymphoblastic leukemia or lymphoblastic lymphoma

2018 ◽  
Vol 2 (S1) ◽  
pp. 48-49
Author(s):  
Mariam M. Bhuiyan ◽  
Gordon Cohen ◽  
Stacy Cooper
Keyword(s):  
Data Analysis ◽  
Acute Lymphoblastic Leukemia ◽  
Pediatric Patients ◽  
Chemotherapy Regimen ◽  
Lymphoblastic Leukemia ◽  
Maintenance Phase ◽  
Lymphoblastic Lymphoma ◽  
Oral Chemotherapy ◽  
Toxic Metabolite ◽  
Maintenance Chemotherapy

OBJECTIVES/SPECIFIC AIMS: This study aims to assess the safety, feasibility, clinical benefits and pharmacodynamics of adding allopurinol to standard maintenance therapy that includes 6-mecaptopurine (6-MP) in pediatric patients with acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma. Our goal is to investigate if allopurinol improves hepatotoxicity and GI toxicity, if it safely decreases acute neutrophil count (ANC), if it reduces the 6-MP dose required during chemotherapy, and if it works through our hypothesized mechanism by lowering the levels of the toxic metabolite, 6-methylmecaptopurine (6-MMP) and by raising the levels of the active metabolite, 6-thioguanine (6-TGN). METHODS/STUDY POPULATION: This is a single arm, nonblinded pilot study of patients under age 30 years who were being treated in the maintenance phase of therapy for ALL or lymphoblastic lymphoma, and had adverse effects such as high 6-MMP:6-TGN ratio, high ANC, and high liver enzymes. Patients enrolled were started with allopurinol in addition to ongoing oral chemotherapy. Data from beginning maintenance to end of chemotherapy was collected in the electronic medical record, EPIC for the 13 patients enrolled at Johns Hopkins, and data analysis was conducted using STATA and Excel. RESULTS/ANTICIPATED RESULTS: Initial data analysis reveals that the required dose of 6-MP after addition of allopurinol to the chemotherapy regimen was significantly lower compared with that before the addition of allopurinol in 11 out of the 12 patients assessed (p<0.05). Among the 10 patients that were assessed for 6MMP:6TG ratio, all had lower average 6MMP:6TGN ratios after allopurinol compared to before allopurinol; the percentage of weeks that goal 6MMP:6TGN ratio (<40) were maintained were statistically significant in 6 patients (p<0.05) and close to significance in 2 other patients (p=0.057). The percentage of weeks that patients maintained alanine aminotransferase levels below 120 was significantly greater after addition of allopurinol compared to before the addition of allopurinol in 9 out of 13 patients assessed, suggesting that allopurinol may be associated with reduced hepatotoxicity. Further data analysis is ongoing to assess the percentage of weeks that patients maintained goal total bilirubin, direct bilirubin, and ANC, as well as average number of admissions for infections and average number of therapy holds after allopurinol addition compared to before allopurinol addition. DISCUSSION/SIGNIFICANCE OF IMPACT: Allopurinol is associated with reduction in required 6-MP dose, decrease in the percentage of weeks that patients have hepatotoxicity, and reduction in the ratio of toxic metabolite to active anti-leukemic metabolite in several patients. We hope that the results of this study can be used for further research and for guiding clinical practice since there are no established guidelines in pediatric oncology regarding addressing side effects of oral chemotherapy using 6-MP. If allopurinol indeed is safe and effective, adding it to the standard chemotherapy regimen can lead to better tolerance and compliance to oral maintenance chemotherapy, and hopefully improved outcomes for children with ALL and lymphoblastic leukemia.

scholarly journals Ancestry and TPMT-VNTR Polymorphism: Relationship with Hematological Toxicity in Uruguayan Patients with Acute Lymphoblastic Leukemia

2020 ◽  
Vol 11 ◽  
Author(s):  
Gabriela Burgueño-Rodríguez ◽  
Yessika Méndez ◽  
Natalia Olano ◽  
Agustín Dabezies ◽  
Bernardo Bertoni ◽  
...  
Keyword(s):  
Native American ◽  
Acute Lymphoblastic Leukemia ◽  
Pediatric Patients ◽  
Lymphoblastic Leukemia ◽  
Variable Number Tandem Repeat ◽  
Maintenance Phase ◽  
Variable Number ◽  
Hematological Toxicity ◽  
Ancestry Informative Markers ◽  
Native American Ancestry

6-Mercaptopurine (6-MP) is a thiopurine drug widely used in childhood acute lymphoblastic leukemia (ALL) therapy. Genes such as TPMT and NUDT15 have an outstanding role in 6-MP metabolism. Mutations in both genes explain a significant portion of hematological toxicities suffered by ALL Uruguayan pediatric patients. A variable number tandem repeat in the TPMT promoter (TPMT-VNTR) has been associated with TPMT expression. This VNTR has a conservative architecture (AnBmC). To explore new causes of hematological toxicities related to ALL therapy, we genotyped the TPMT-VNTR of 130 Uruguayan pediatric patients. Additionally, individual genetic ancestry was estimated by 45 ancestry-informative markers (AIMs). Hematological toxicity was measured as the number of leukopenia events and 6-MP dose along the maintenance phase. As previously reported, we found TPMT*2 and TPMT*3C alleles were associated to TPMT-VNTR A2BC and AB2C, respectively. However, contrasting with other reports, TPMT*3A allele was found in a heterogeneous genetic background in linkage equilibrium. Patients carrying more than 5 A repeats present a significant higher number of leukopenia events among patients without TPMT and/or NUDT15 variants. Native American ancestry and the number of A repeats were significantly correlated with the number of leukopenia events. However, the correlation between Native American ancestry and the number of leukopenia events was lost when the number of A repeats was considered as covariate. This suggests that TPMT-VNTR alleles are more relevant than Native American ancestry in the hematological toxicity. Our results emphasize that TPMT-VNTR may be used as a pharmacogenetic biomarker to predict 6-MP-related hematological toxicity in ALL childhood therapy.

Predictors of Osteopenia/Osteoporosis in Children with Acute Lymphoblastic Leukemia.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 905-905 ◽  
Author(s):  
Uma Athale ◽  
Colin Webber ◽  
Ronald Barr
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Maintenance Therapy ◽  
Bone Mineral ◽  
Lymphoblastic Leukemia ◽  
Maintenance Phase ◽  
Risk Category ◽  
Z Score ◽  
Z Scores ◽  
Effect Of Age

Abstract Background: Loss of bone mineral is a major problem in children with acute lymphoblastic leukemia (ALL), resulting in acute and chronic morbidity. About 30–40% of children with ALL will develop osteopenia/osteoporosis (OP) and about 10–15% will suffer from fractures. Identifying a population at high risk for OP is important to implementing a preventive strategy (e.g. biphosphonate therapy). So far predictors of OP in association with ALL in children are uncertain. Hence we undertook the following study to evaluate predictors of OP in children with ALL treated according to Dana-Farber Cancer Institute protocols. Aim: To evaluate the relationship between lumbar spine bone mineral density (LS-BMD) Z scores in patients with ALL during maintenance therapy and the variables of age at diagnosis (< 10 vs. ≥ 10-years), risk group [Standard (SR) vs. high-risk (HR)], gender (male vs. female) and LS-BMD at diagnosis. Methods: Children (≤ 18-years) diagnosed with ALL during the period 1995–2006 who were in first clinical remission, were included in the study. LS-BMD was measured using dual-energy X-ray absorptiometry (DEXA) at the time of diagnosis (n=88) and during the maintenance phase of therapy (n=119). The actual values of LS-BMD were expressed as age and gender matched Z-scores based on local population norms. Regression analyses were used to evaluate the risk of osteopenia, defined as LS-BMD Z score < -1.00, and osteoporosis, defined as LS-BMD Z score < -2.00. We evaluated the effect of age at diagnosis, gender, ALL risk category and LS-BMD at diagnosis on the LS-BMD during maintenance phase of therapy. Results: Of the 119 patients, 19 (16%) were ≥ 10-years of age, 46 (39%) were girls and 41 (34.5%) had HR ALL. At diagnosis 29 of 88 (33%) patients had osteopenia and 6 (6.8%) had osteoporosis whereas, during maintenance therapy, 47/119 patients (39.5%) had osteopenia and 10 (8.4%) patients had osteoporosis. LS-BMD at diagnosis had a positive linear relationship with LS-BMD during maintenance therapy (Pearson correlation coefficient 0.721, p<0.001). Older children and children with HR ALL had a significantly higher risk of osteopenia compared to younger children (p=0.01) and children with SR ALL (p=0.019). Age and risk category were confounding variables since all children ≥ 10 years were classified as HR ALL. Gender by itself had no significant effect. However, the effect of age on the LS-BMD during maintenance phase was gender-dependent with older girls having lower LS-BMD compared to older boys. Conclusions: Osteopenia and osteoporosis (OP) are common in children with ALL. Age over 10-years, female gender, HR ALL and lower LS-BMD at diagnosis are predictors of lower LS-BMD during the maintenance phase of therapy. Using these variables it is feasible to develop a predictive model to define the risk of OP during the maintenance phase of therapy. Larger prospective studies will better define this risk.

scholarly journals Evaluasi Toksisitas Hepatologi Akibat Penggunaan 6-Merkaptopurin dalam Fase Pemeliharaan pada Pasien Pediatri Kanker Leukimia Limfoblastik Akut di RS Kanker Dharmais Jakarta

2017 ◽  
Vol 4 (1) ◽  
Author(s):  
Nazhipah Isnani ◽  
Dyah Aryani Perwitasari ◽  
Rizka Andalusia ◽  
Haridini Intan Mahdi
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Pediatric Patients ◽  
Lymphoblastic Leukemia ◽  
Maintenance Phase ◽  
Inclusion Criteria ◽  
Cross Sectional ◽  
Cancer Hospital ◽  
Phase Data ◽  
Observational Design ◽  
Level 2

ABSTRAK Merkaptopurin merupakan obat kemoterapi yang digunakan pada fase konsolidasi dan pemeliharaan pada pasien pediatri kanker leukimia limfoblastik akut (LLA). Merkaptopurin diduga memiliki hubungan erat dengan terjadinya toksisitas pada hepatologi. Penelitian ini bertujuan untuk mengetahui angka kejadian, derajat keparahan dan penatalaksanaan toksisitas serta faktor risiko yang mempengaruhi terjadinya toksisitas hepatologi penggunaan 6-MP dalam fase pemeliharaan pada pasien pediatri kanker leukimia limfoblastik akut di RS Kanker Dharmais Jakarta. Penelitian ini dilakukan dengan desain observasional cross sectional dengan mengambil data pasien secara retrokspetif dan prospektif selama periode Maret–April 2014. Subyek penelitian adalah pasien kanker LLA anak yang berobat di RS Kanker Dharmais Jakarta dari tahun 2013 sampai dengan periode Maret-April 2014 yang sedang dalam fase pemeliharaan. Subyek yang memenuhi kriteria inklusi adalah 23 pasien LLA yang mendapatkan 6-MP pada fase pemeliharaan. Pengumpulan data dilakukan dengan melihat rekam medik untuk mendapatkan data identitas pasien dan data hepatologi. Hasil penelitian menunjukkan bahwa angka kejadian toksisitas hepatologi paling banyak terjadi pada peningkatan SGPT sebesar 13,05%. Derajat keparahan pada toksisitas hepatologi paling banyak terjadi pada derajat 2 (8,70% dan 13,04%). Berdasarkan faktor-faktor yang mempengaruhi terjadinya toksisitas hepatologi, tidak terdapat perbedaan yang signifikan pada hasil penelitian. Kata kunci : 6-merkaptopurin, toksisitas, hepatologi, leukimia limfoblastik akut ABSTRACT Mercaptopurine is a chemotherapy drug that used in the consolidation and maintenance phase in pediatric patients with acute lymphoblastic leukemia (ALL). Mercaptopurine is supposed to have relationship with the occurrence of toxicity in hepatology. This study was aimed to determine the patient incidence, severity and management of toxicity and risk factors that affect the occurrence of hepatologic toxicity using of 6 - MP in the maintenance phase in pediatric patients with acute lymphoblastic leukemia in Dharmais Cancer Hospital Jakarta. This research was carried out by cross-sectional observational design with data was taken retrospectively and prospectively during the period from March to April 2014. The study subjects were patient who have been getting treatment of maintenace phase in Dharmais Cancer Hospital Jakarta from 2013 until March-April 2014. The Subjects who met the inclusion criteria were 23 patients of ALL received 6 - MP in the maintenance phase. Data was collected by looking at the medical records for getting of the patient's identity and data hepatology. The results showed that there the incidence of the increased of SGPT was the most prevalent (13, 05 %) . The severity of the most common hepatologic toxicity was at level 2 (8,70% and 13,04%). Based on the influence of the hepatology toxicity factors, there were not different significant of the result of research. Keywords : 6-mercaptopurine, toxicity, hepatology, acute lymphoblastic leukemia

scholarly journals HUBUNGAN KARAKTERISTIK PASIEN DENGAN TOKSISITAS HEPATOLOGI AKIBAT PENGGUNAAN 6-MERKAPTOPURIN DALAM FASE PEMELIHARAAN PADA PASIEN PEDIATRI KANKER LEUKIMIA LIMFOBLASTIK AKUT DI RS KANKER DHARMAIS JAKARTA

2020 ◽  
Vol 3 (2) ◽  
pp. 361-368
Author(s):  
Nazhipah Isnani ◽  
◽  
Dyah Aryani Perwitasari ◽  
Rizka Andalusia ◽  
Haridini Intan Mahdi ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Medical Records ◽  
Pediatric Patients ◽  
Lymphoblastic Leukemia ◽  
Maintenance Phase ◽  
Inclusion Criteria ◽  
Cross Sectional ◽  
Cancer Hospital ◽  
Phase Data ◽  
Observational Design

Mercaptopurine is a chemotherapy drug that used in the consolidation and maintenance phase in pediatric patients with acute lymphoblastic leukemia ( ALL). Mercaptopurine is supposed to have relationship with the occurrence of toxicity in hepatology. This study was aimed to determine the patient incidence , severity and management of toxicity and risk factors that affect the occurrence of hepatologic toxicity using of 6 - MP in the maintenance phase in pediatric patients with acute lymphoblastic leukemia in Dharmais Cancer Hospital Jakarta. This research was carried out by cross-sectional observational design with data was taken retrospectively and prospectively during the period from March to April 2014. The study subjects were patient who have been getting treatment of maintenace phase in Dharmais Cancer Hospital Jakarta from 2013 until March-April 2014. The Subjects who met the inclusion criteria were 23 patients of ALL received 6 - MP in the maintenance phase. Data was collected by looking at the medical records for getting of the patient's identity and data hepatology. The result showed that there was a correlation between patient characterision on hepatology toxicity, on SGOT age and weight with SGPT both of them has significant value, it was 0,036 (P<0,05)

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