Sleep during the maintenance phase of treatment for acute lymphoblastic leukemia: a comparison of dexamethasone and prednisone

2021 ◽  
Author(s):  
Lauren Daniel
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Maintenance Phase

No Advantage of Dexamethasone Over Prednisolone for the Outcome of Standard- and Intermediate-Risk Childhood Acute Lymphoblastic Leukemia in the Tokyo Children's Cancer Study Group L95-14 Protocol

2005 ◽  
Vol 23 (27) ◽  
pp. 6489-6498 ◽  
Author(s):  
Shunji Igarashi ◽  
Atsushi Manabe ◽  
Akira Ohara ◽  
Masaaki Kumagai ◽  
Tomohiro Saito ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Controlled Trial ◽  
Survival Rates ◽  
Maintenance Phase ◽  
Childhood Acute Lymphoblastic Leukemia ◽  
Intermediate Risk ◽  
Free Survival ◽  
Prospective Randomized Controlled Trial ◽  
Standard Risk

Purpose To evaluate whether dexamethasone (DEXA) yields a better outcome than prednisolone (PRED) in a prospective, randomized, controlled trial for the treatment of childhood acute lymphoblastic leukemia (ALL). Patients and Methods Two hundred thirty-one standard-risk (SR) patients and 128 intermediate-risk (IR) non–B-cell ALL patients were registered from March 1995 to March 1999. After random assignment in each group, the PRED arm patients received PRED 60 mg/m2 during induction followed by PRED 40 mg/m2 over four intensifications in the SR group and three intensifications in the IR group. DEXA arm patients received DEXA 8 mg/m2 during induction and DEXA 6 mg/m2 during the intensifications. The maintenance phase was continued until week 104. Results Event-free survival rates at 8 years in the DEXA and PRED arms were 81.1% ± 3.9% (n = 117) and 84.4% ± 5.2% (n = 114), respectively, in the SR group (P = .217) and 84.9% ± 4.6% (n = 62) and 80.4% ± 5.1% (n = 66), respectively, in the IR group (P = .625). The primary reason for treatment failure was marrow relapse. Only two extramedullary relapses occurred in the DEXA arm compared with seven relapses in the PRED arm. Although complications were more prevalent in the DEXA arm than in the PRED arm, fatal toxicity was rare both groups. Conclusion DEXA administered at 8 mg/m2 during induction and 6 mg/m2 during intensification showed no advantage over PRED administered at 60 mg/m2 during induction and 40 mg/m2 during intensification in both the SR and IR groups.

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 2699. Pneumococcal Vaccination During Chemotherapy in Children Treated for Acute Lymphoblastic Leukemia

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S949-S949
Author(s):  
Sarah Dorval ◽  
Léna Coïc ◽  
Denis Blais ◽  
Jean-Marie Leclerc ◽  
Caroline Laverdière ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Pneumococcal Infection ◽  
Pneumococcal Vaccination ◽  
Booster Vaccination ◽  
Maintenance Phase ◽  
Vaccination Schedule ◽  
Serum Samples ◽  
Group 2 ◽  
Group 1

Abstract Background Children undergoing therapy for acute lymphoblastic leukemia (ALL) are at high risk of invasive pneumococcal disease (IPD). Immunization with conjugated vaccines following chemotherapy is recommended for pediatric patients. In an attempt to provide an earlier protection against invasive pneumococcal infection, we aimed to assess immunity to S. pneumoniae among children vaccinated during chemotherapy for ALL. Methods We retrospectively analyzed the rate of seroprotection among ALL children treated in our institution in accordance with the DFCI ALL Consortium protocol between 2007 and 2014. A pneumococcal conjugate vaccine (PCV) booster was given to all subjects after the end of chemotherapy (groups 1 and 2). In group 2, a PCV dose was also administered during the maintenance phase. Clinical characteristics as well as individual immunization records were collected from our local immunization database. All children were up to date with their vaccination schedule at diagnosis. Serum samples were obtained on a routine follow-up visit, after the end of chemotherapy and after the PCV vaccine booster to measure serotype-specific IgG pneumococcal antibodies. Antibody level ≥0.35µg/mL was considered protective. Patients with seroprotective antibodies level for ≥ 50% of serotypes contained in vaccines were defined as seroprotected. Results 62 children [34 girls (54.8%)] were included in the analysis. Median age at diagnosis was 45 months (range:12–160). At the end of chemotherapy, 34.2% of children in group 1 (13/38) and 79.2% in group 2 (19/24) were seroprotected (P < 0.01). Median interval of time between the end of chemotherapy and the PCV booster vaccination was 6 months (range: 2–64 months). After PCV-13 booster, the rate of seroprotection raised to 100% (38/38) in group 1 and 91.7% in group 2 (22/24). Conclusion Rates of pneumococcal seroprotected children treated for ALL are low at the end of chemotherapy. However, PCV booster during chemotherapy could be useful to increase the level of seroprotection and shorten the period of susceptibility to IPD. After chemotherapy for ALL, children benefit from a PCV booster to enhance seroprotection. Disclosures All authors: No reported disclosures.

PERSONALIZATION OF 6-MERCAPTOPURINE THERAPY FOR CHILDREN WITH ACUTE LYMPHOBLASTIC LEUKEMIA

2015 ◽  
Vol 101 (1) ◽  
pp. e1.5-e1
Author(s):  
Goran Milošević ◽  
Lidija Dokmanović ◽  
Nada Krstovski ◽  
Jelena Lazić ◽  
Predrag Rodić ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Genetic Markers ◽  
Predictive Power ◽  
Lymphoblastic Leukemia ◽  
Maintenance Phase ◽  
Fold Increase ◽  
Therapy Outcome ◽  
Therapy Failure ◽  
Resistance Protein ◽  
Variant Alleles

IntroductionTreatment of acute lymphoblastic leukemia (ALL) in children has been significantly improved over past few decades. Optimal use of known antileukemic drugs has lead to four-fold increase of overall survival. Nevertheless, therapy failure occurs in 15–20% of patients. Individualized use of cytostatic drugs can help us reducing toxicity-related deaths and improve therapy outcome.Materials and methodsWe studied multidrug resistance protein 4 gene (ABCC4) and inosin triphosphate pyrophosphatase (ITPA) gene polymorphisms to assess their influence on occurrence and intensity of 6-MP toxicity during maintenance phase of ALL treatment in children as well as on treatment outcome.ResultsThiopurine S-methyltransferase (TPMT) genotype was known for all patients before start of therapy and doses were adjusted accordingly. Five patients (7%) were carriers of ITPAc.94C>A genotype. Heterozygote and homozygote carriers of variant alleles for ABCC4 rs9516519 T>G, genotype were represented in 35% and 4% of our patients, respectively. We did not show correlation of variant alleles with increased number of off-therapy weeks neither with number of episodes of leukopenia. Cross-validated AUC for each of genetic markers individually showed low predictive power (cross-validated AUC around 0.5) for predicting toxicity. However, combination of two genetic markers and known TPMT gentotype improved the predictability (cross-validated AUC was 0.65).ConclusionsOur results did not show correlation with toxicity using individual genetic markers. However, in the settings of known TPMT genotype, we showed the potential of using all three genetic markers (including TPMT) in predicting who might be in danger of having increased toxicity.

Infection-related mortality in children with acute lymphoblastic leukemia: an analysis of infectious deaths on UKALL2003

Blood ◽  
2014 ◽  
Vol 124 (7) ◽  
pp. 1056-1061 ◽  
Author(s):  
David O’Connor ◽  
Jessica Bate ◽  
Rachel Wade ◽  
Rachel Clack ◽  
Sunita Dhir ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Maintenance Phase ◽  
Induction Phase ◽  
Pediatric Acute Lymphoblastic Leukemia ◽  
Children With Down Syndrome ◽  
Low Intensity ◽  
Key Points ◽  
Treatment Related Mortality ◽  
Related Mortality

Key Points Infection is the major cause of treatment-related mortality in pediatric acute lymphoblastic leukemia and is greatest during the induction phase. Children with Down syndrome are at high risk for infection-related mortality throughout all treatment phases, including the low-intensity maintenance phase.

scholarly journals Adrenal Suppression in Pediatric Patients during Treatment for Acute Lymphoblastic Leukemia

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4863-4863
Author(s):  
Mary-Pat Schlosser ◽  
Daniel Burd ◽  
Alexandra Ahmet ◽  
Sarah Lawrence ◽  
Mylene Bassal
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Adrenal Insufficiency ◽  
Hpa Axis ◽  
Lymphoblastic Leukemia ◽  
Maintenance Phase ◽  
Adrenal Suppression ◽  
Adrenal Crisis ◽  
Significant Morbidity ◽  
Steroid Use ◽  
Testing Protocol

Abstract Background: Hypothalamic-pituitary-adrenal (HPA) axis suppression is a form of adrenal insufficiency that can be found following the use of corticosteroids. Individuals with adrenal insufficiency may have non-specific symptoms or even no regular symptoms, however if presented with a physiologic stress such as infection, injury, or surgery, they are at risk of adrenal crisis. Adrenal crisis typically manifests with hypoglycemia, hypotension and critical illness; this condition is associated with significant morbidity and even mortality. Children being treated for leukemia are at increased risk of infection and may require surgical procedures, thus putting them at risk of adrenal crisis in the context of adrenal suppression. It is known that adrenal suppression exists in the short term after the induction phase of treatment in patients with acute lymphoblastic leukemia (ALL), but the prevalence and duration of suppression is still not fully understood. In addition, adrenal suppression has not been specifically evaluated during the maintenance phase of therapy. During maintenance there may be ongoing adrenal suppression from steroid use in induction, or new suppression from steroid use for maintenance therapy itself. There does not yet exist an accepted protocol to monitor for adrenal insufficiency in ALL. Knowing the prevalence and duration of adrenal suppression in maintenance will enable care teams to better recognize and manage the condition, potentially preventing significant morbidity and mortality. Methods: All cases of ALL treated at the Children's Hospital of Eastern Ontario from 2000 to 2014 were retrospectively reviewed for adrenal suppression. Patient characteristics, clinical features, laboratory data, treatment protocol utilized, adverse events and outcomes were examined. Results: 176 patients were diagnosed with new ALL at The Children's Hospital of Eastern Ontario between 2000 and 2014. Prompted by clinical suspicion, 24 had testing done to investigate for adrenal suppression during this time period. 9 of those patients had cortisol levels indicative of adrenal suppression and required further management for the same. Adrenal suppression was identified in early phases of treatment for ALL. Adrenal suppression was also identified in patients during the maintenance phase of treatment. Many more patients had symptoms that could be attributed to adrenal suppression, but never had cortisol levels tested. Conclusion: Adrenal suppression is found in children being treated for ALL, including during the maintenance phase of therapy. Adrenal suppression may have been present in greater numbers of children, but no routine testing protocol exists to identify these patients. Identifying and reviewing cases of adrenal suppression in children during treatment for ALL, including the maintenance phase, gives a better understanding of the risk of HPA axis suppression in this population. This study also provides background data for the development of a prospective study to further look at adrenal suppression in the maintenance phase of ALL. These studies will guide development of a testing protocol to better identify and manage adrenal suppression, thereby reducing its morbidity and mortality, in children being treated for ALL. Disclosures No relevant conflicts of interest to declare.

scholarly journals Causes of Death in Childhood Acute Lymphoblastic Leukemia at Hue Central Hospital for 10 Years (2008-2018)

2020 ◽  
Vol 7 ◽  
pp. 2333794X2090193
Author(s):  
Tran Kiem Hao ◽  
Pham Nhu Hiep ◽  
Nguyen Thi Kim Hoa ◽  
Chau Van Ha
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Maintenance Phase ◽  
Childhood Acute Lymphoblastic Leukemia ◽  
Induction Phase ◽  
Central Hospital ◽  
Female Ratio ◽  
Cancer Group ◽  
Almost All ◽  
And Control

Aim. To analyze the common cause of death in childhood acute lymphoblastic leukemia patients. Methods and Materials. A retrospective descriptive study on children with acute lymphoblastic leukemia who died at Hue Central Hospital between 2008 and 2018. All the patients were treated with the same protocol of modified Children’s Cancer Group 1882 and 1881. Results. A total of 238 children with acute lymphoblastic leukemia who were cared for at our center were enrolled. Of these, there were 74 deaths. Among the death group, the male-to-female ratio was 2.7:1. Twenty-six (35.1%) occurred in maintenance phase, 18 (24.3%) occurred in induction phase, and 9 (12.2%) occurred in delayed intensification. Infection was responsible for deaths in 32 of 74 (43.2%) cases. Pseudomonas aeruginosa was found in 3 of 32 infected cases (9.4%) and resistance to almost all antibiotics in our hospital. Relapse, abandonment, and bleeding were documented in 20 (27.0%), 7 (9.5%), and 6 (8.1%) cases, respectively. Twenty-seven (84.3%) patients had absolute neutrophil count <500/µL. Of 32 infectious deaths, pneumonia occurred in 40.6%. Regarding 20 relapse death, bone marrow was the major site of relapse and it occurred in 13 (65%) cases. And there were 65% patients with very early relapse. Conclusions. Infection is the major cause of mortality in acute lymphoblastic leukemia patients in our study. To improve outcome, we should improve supportive care, especially prevention and control infection.

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.

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