scholarly journals Dexamethasone and High-Dose Methotrexate Improve Outcome for Children and Young Adults With High-Risk B-Acute Lymphoblastic Leukemia: A Report From Children’s Oncology Group Study AALL0232

2016 ◽  
Vol 34 (20) ◽  
pp. 2380-2388 ◽  
Author(s):  
Eric C. Larsen ◽  
Meenakshi Devidas ◽  
Si Chen ◽  
Wanda L. Salzer ◽  
Elizabeth A. Raetz ◽  
...  
Keyword(s):  
Young Adults ◽  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Lymphoblastic Leukemia ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Oncology Group ◽  
Oncology Group Study ◽  
Dose Methotrexate ◽  
Children And Young Adults

Purpose Survival for children and young adults with high-risk B-acute lymphoblastic leukemia has improved significantly, but 20% to 25% of patients are not cured. Children’s Oncology Group study AALL0232 tested two interventions to improve survival. Patients and Methods Between January 2004 and January 2011, AALL0232 enrolled 3,154 participants 1 to 30 years old with newly diagnosed high-risk B-acute lymphoblastic leukemia. By using a 2 × 2 factorial design, 2,914 participants were randomly assigned to receive dexamethasone (14 days) versus prednisone (28 days) during induction and high-dose methotrexate versus Capizzi escalating-dose methotrexate plus pegaspargase during interim maintenance 1. Results Planned interim monitoring showed the superiority of the high-dose methotrexate regimens, which exceeded the predefined boundary and led to cessation of enrollment in January 2011. At that time, participants randomly assigned to high-dose methotrexate during interim maintenance 1 versus those randomly assigned to Capizzi methotrexate had a 5-year event-free survival (EFS) of 82% versus 75.4% (P = .006). Mature final data showed 5-year EFS rates of 79.6% for high-dose methotrexate and 75.2% for Capizzi methotrexate (P = .008). High-dose methotrexate decreased both marrow and CNS recurrences. Patients 1 to 9 years old who received dexamethasone and high-dose methotrexate had a superior outcome compared with those who received the other three regimens (5-year EFS, 91.2% v 83.2%, 80.8%, and 82.1%; P = .015). Older participants derived no benefit from dexamethasone during induction and experienced excess rates of osteonecrosis. Conclusion High-dose methotrexate is superior to Capizzi methotrexate for the treatment of high-risk B-acute lymphoblastic leukemia, with no increase in acute toxicity. Dexamethasone given during induction benefited younger children but provided no benefit and was associated with a higher risk of osteonecrosis among participants 10 years and older.

scholarly journals Letting Kids Be Kids: A Quality Improvement Project to Deliver Supportive Care at Home After High-Dose Methotrexate in Pediatric Patients With Acute Lymphoblastic Leukemia

2020 ◽  
Vol 37 (3) ◽  
pp. 212-220 ◽  
Author(s):  
Lori Ranney ◽  
Mary C. Hooke ◽  
Kathryn Robbins
Keyword(s):  
Quality Of Life ◽  
Quality Improvement ◽  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Supportive Care ◽  
Lymphoblastic Leukemia ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Dose Methotrexate

The Children’s Oncology Group recommends children with high-risk acute lymphoblastic leukemia (ALL) receive high-dose methotrexate (HD MTX) throughout treatment. Historically, patients have been hospitalized for at least 54 hours for HD MTX. Literature supports the safety and efficacy of the transition of supportive care interventions of intravenous (IV) fluids and leucovorin to ambulatory care. The goal of this quality improvement (QI) project was to implement a system to support the safe delivery of supportive care in the home after inpatient HD MTX in children with high-risk ALL. An interdisciplinary team implemented system changes including an ambulatory supportive care protocol, standard computerized order sets, family education, and education of staff in the inpatient, outpatient, and home care setting. Measurements included laboratory results of renal function and medication clearance, length of hospitalization, and family-reported quality of life. During project implementation, 10 patients completed a total of 38 cycles. The system safely and effectively supported transition to the outpatient setting for all patients. Average length of stay was decreased by 37.8 hours per HD MTX cycle. Families reported that quality of life improved in most domains with family time and sleep having largest improvement, while level of stress remained the same. Ambulatory monitoring post-HD MTX requires a multidisciplinary approach to meet individualized patient needs. Future QI efforts should consider outpatient administration of HD MTX in addition to supportive care as a means to improved quality of life.

Improved Outcome for Children and Young Adults with T-Cell Acute Lymphoblastic Leukaemia (ALL): Results of the United Kingdom Medical Research Council (MRC) Trial UKALL 2003.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 908-908 ◽  
Author(s):  
Ajay Vora ◽  
Rachel Wade ◽  
Christopher D Mitchell ◽  
Nicholas Goulden ◽  
Sue Richards
Keyword(s):  
Young Adults ◽  
T Cell ◽  
High Risk ◽  
Intrathecal Methotrexate ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Cranial Radiotherapy ◽  
E Coli ◽  
Dose Methotrexate ◽  
Children And Young Adults

Abstract UKALL 2003 is an ongoing randomised controlled trial investigating whether treatment can be adjusted according to Minimal Residual Disease (MRD) levels measured by RQPCR at the end of induction and week 11 in children and young adults (up to age 25 years) with ALL. Although the results of the randomised interventions remain blinded, we have observed a significant improvement in 4 year event-free (EFS) and overall survival (OS) in the trial overall compared with its predecessor, ALL 97/99. Here we report a comparison of the outcome for T cell patients in the two trials, in whom the majority of events occur within 3 years. Both UKALL 2003 and ALL97/99 included risk stratification by NCI risk, blast karyotype, and morphological marrow response at day 8/15 of induction to allocate patients to one of 3 treatment regimens (A, B and C – escalating intensity from A to C). NCI standard risk (SR) patients received a 3 drug induction whilst high risk (SR) patients received 4 drugs including daunorubicin. Patients with a slow early response at day 8 (NCI HR) or day 15 (NCI SR) of induction and those with poor risk cytogenetics were transferred to Regimen C. The only differences in treatment administered to all patients between the two trials was the use of Pegylated E. Coli Asparaginase (Peg-ASP) (Oncospar, Medac UK) and Dexamethasone in UKALL 2003 instead of native E. Coli Asparaginase and a Dexamethasone vs Prednisolone randomisation respectively in ALL97/99. Only patients with overt CNS disease (CNS3) at presentation received cranial radiotherapy and high dose Methotrexate was not part of the protocol in either trial. CNS directed therapy comprised 19 – 26 doses of intrathecal methotrexate given over 2 – 3 years depending on regimen and gender. Less than 2% of patients, with high risk cytogenetics or day 28 BM3 marrow, were eligible for first remission transplantation. The outcome for 190 (12%) T-cell patients recruited to UKALL 2003 at 30/10/07 was compared with 92 (10%) patients in ALL97/99. In UKALL 2003, the proportions of T-cell ALL patients treated on the 3 regimens was A= 14%, B= 54% and C= 32% (51%, 26% and 23% respectively in trial overall). For ALL97/99 this was A=14%, B=57% and C=29% (59%, 24% and 16% respectively for the trial overall). EFS and OS are significantly better for T-cell patients in UKALL 2003 (3 year: EFS 86% (se 3.3), OS 90% (se 2.8)) compared with ALL97/99 (EFS 73% (se 4.6), OS 78% (se 4.3)) (p = 0.03 for EFS, p=0.04 for OS). The actuarial incidence of CNS relapse in UKALL 2003 and ALL 97/99 respectively was 3% vs 4% isolated (p=0.7) and 4% vs 7% any CNS (p =0.3). There is a suggestion of a difference in the effect of WCC (<100, ≥ 100) by age on EFS in T-cell patients in both trials, with the effect of WCC not seen in those aged <10, p(heterogeneity)=0.01. Treatment related mortality for T-cell patients was similar in both trials. Only a third of T-cell patients have been entered into the MRD randomisations, hence the observed differences in outcome are unlikely to be due to the randomised interventions. Over 85% of children and young adults with T-cell ALL at all ages and presenting white cell count can be cured without cranial radiotherapy or high dose methotrexate. The observed improvements in outcome are likely to be due to the use of Dexamethasone and Pegylated asparaginase.

scholarly journals High-dose methotrexate vs. Capizzi methotrexate for the treatment of childhood T-cell acute lymphoblastic leukemia

2018 ◽  
Vol 10 ◽  
pp. 44-51 ◽  
Author(s):  
Wasil Jastaniah ◽  
Naglla Elimam ◽  
Khalid Abdalla ◽  
Aeshah A. AlAzmi ◽  
Mohammed Aseeri ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Lymphoblastic Leukemia ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Dose Methotrexate ◽  
Cell Acute Lymphoblastic Leukemia
Sign in / Sign up

Export Citation Format

Share Document