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.

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 Chemotherapy-induced mucositis pursuant to different phase of chemotherapy in children with acute lymphoblastic leukemia at Hasan Sadikin Hospital Bandung

2008 ◽  
Vol 20 (1) ◽  
Author(s):  
Arlette Suzy Puspa Pertiwi
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Oral Mucosa ◽  
Cancer Chemotherapy ◽  
Oral Mucositis ◽  
Lymphoblastic Leukemia ◽  
Maintenance Phase ◽  
Induction Phase ◽  
Maintenance Chemotherapy ◽  
Consolidation Phase ◽  
Maintenance Group

Acute Lymphoblastic Leukemia is the most common Leukemia seen in children. This disease has a manifestation in the oral mucosa, which is caused by either the disease itself or its treatment by chemotherapy, such as mucositis. Oral mucositis is one of a common, debilitating complication of cancer chemotherapy. Mucosal toxicity depends on Several factors; one of them is the duration of the therapy. The aim of this study is to evaluate chemotherapy-induced mucositis pursuant to a different phase of chemotherapy in children with Acute Lymphoblastic Leukemia. Twenty children diagnosed with Acute Lymphoblastic Leukemia who received induction, consolidation, and maintenance chemotherapy of Hasan Sadikin Hospital were included in this study. The criteria used for assessing mucositis was based on general mucositis scale from WHO. Data were collected and presented in the form of tables and percentages. The results showed that every child had developed mucositis during the course of chemotherapy in the induction and consolidation phase, except one child in the maintenance group did not the. at the induction phase 14,3% had developed mucositis at scale 2 and 86,7 at scale 3, consolidation phase 50% at scale 2 and 50% at scale 1, and in maintenance phase 14,3% in scale 28,6% in scale 1, and 57,1 in scale 2. Generally, it was concluded that mucositis develops in every phase of chemotherapy but the scale is slighter as the course of chemotherapy enters the advanced phases.

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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