scholarly journals High dose methotrexate in the treatment of children with acute lymphoblastic leukemia

2007 ◽  
Vol 47 (1) ◽  
pp. 1 ◽  
Author(s):  
Johannes Bondan Lukito
Keyword(s):  
High Risk ◽  
Lymphoblastic Leukemia ◽  
Plasma Concentrations ◽  
Risk Groups ◽  
Observation Time ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Dose Methotrexate ◽  
Minor Disease ◽  
State Concentration

Background It has been claimed that around 70% of childhoodacute lymphoblastic leukemia (ALL) can be cured. One of theimportant role is high dose methotrexate (HDMTX) administrationduring the consolidation therapy.Objective To determine the safety and effectiveness of HDMTXin children with ALL.Methods We reviewed patients with ALL in Pantai Indah KapukHospital, Jakarta during the period August 2000 through July 2005with observation time run through September 2006. Only patientswith normal kidney function were allowed to have HDMTX. Besidesgood hydration and alkalinization, patients were supported with goodhygiene (mouth, skin and anal area). MTX was given in loadingdose of 10% from the total dose in ½ hour and the rest 23½ hours for90%. Leucovorin rescue was started 12 hours after discontinuationof 24 hour MTX IV infusion. Leucovorin was given until the MTXconcentration reached 0.1 uM/L. Patients were stratified to low,intermediate and high risk groups; 2 gram/m 2 was given to low riskgroup and 5 gram/m2 to intermediate and high risk groups.Results There were 20 patients eligible for study. All methotrexatesteady-state plasma concentrations (MTX Cp ss ) were above 16 uM/L, and steady state concentration in CSF was always below 0.5 uM/L for 2 gram/m 2 and above 0.5 uM/L for 5 gram/m 2 doses. All 20cases went through the procedure with only mild side effects i. e,mild mucositis, anal furuncle and diarrhea, which recovered 2 weekslater. Only 1 high risk case with initial WBC 612X10 9 /L, succumbedafter he went through the HDMTX program smoothly and relapsedsubsequently during reinduction phase.Conclusion HDMTX can be given safely to ALL patients with normalkidney function with good supportive care. Five gram/m 2 HDMTXeffectively treat the minor disease and/or prevent CNS and testicularleukemia. This study has also given an impression that HDMTXmay increase event-free survival.

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 High cure rate with a moderately intensive treatment regimen in non-high-risk childhood acute lymphoblastic leukemia. Results of protocol ALL VI from the Dutch Childhood Leukemia Study Group.

1996 ◽  
Vol 14 (3) ◽  
pp. 911-918 ◽  
Author(s):  
A J Veerman ◽  
K Hählen ◽  
W A Kamps ◽  
E F Van Leeuwen ◽  
G A De Vaan ◽  
...  
Keyword(s):  
High Risk ◽  
Maintenance Treatment ◽  
Lymphoblastic Leukemia ◽  
Intrathecal Therapy ◽  
First Year ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Cure Rate ◽  
High Cure Rate ◽  
Dose Methotrexate

PURPOSE Here we report the results of a nationwide cooperative study in the Netherlands on acute lymphoblastic leukemia (ALL) in children. The aim of the study was to improve the cure rate and to minimize side effects in a group of non-high-risk ALL patients, especially with regard to the CNS. A second aim was to study potential prognostic factors. METHODS Children (age 0 to 15 years) with non-high-risk ALL (WBC count < 50 x 10(9)/L, no mediastinal mass, no B-cell phenotype, and no CNS involvement) were treated with a uniform protocol, ALL VI. The treatment protocol used 6-week induction regimen with three drugs (vincristine, dexamethasone, and asparaginase), three weekly doses of intravenous (IV) medium high-dose methotrexate (2 g/m2), and 2-year maintenance therapy that consisted of alternating 5-week periods of methotrexate and mercaptopurine and 2-week periods of vincristine and dexamethasone. In the first year of maintenance, triple intrathecal therapy was administered every 7 weeks. RESULTS From December 1, 1984 until July 1, 1988, 291 children with ALL were diagnosed; 206 were categorized as non-high-risk (71%), and 190 were treated according to protocol ALL VI. At 8 years, the event-free survival (EFS) rate was 81% (SE = 3%) and survival rate 85% (SE = 2.9%); the median follow-up time was 7.3 years (range, 36 to 117 months). The CNS relapse rate was 1.1% (two of 184 patients who achieved a complete remission [CR]). The only factor found to be of negative prognostic importance in terms of EFS (P = .05) was a positive acid phosphatase reaction. CONCLUSION For children with non-high-risk ALL, the combination of IV medium high-dose methotrexate (2 g/m2 times three), triple intrathecal therapy in the first year of maintenance treatment, and the use of dexamethasone for induction and pulses during maintenance treatment has proved to be highly effective, especially in the prevention of CNS relapse. A high cure rate was achieved without the use of anthracyclines, alkylating agents, and cranial irradiation.

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.

scholarly journals Reduced dose folinic acid rescue after rapid high-dose methotrexate clearance is not associated with increased toxicity in a pediatric cohort

2021 ◽  
Author(s):  
Riitta Niinimäki ◽  
Henri Aarnivala ◽  
Joanna Banerjee ◽  
Tytti Pokka ◽  
Kaisa Vepsäläinen ◽  
...  
Keyword(s):  
Folinic Acid ◽  
Lymphoblastic Leukemia ◽  
High Dose ◽  
Optimal Dosage ◽  
High Dose Methotrexate ◽  
Reduced Dose ◽  
Dose Methotrexate ◽  
Antileukemic Effect ◽  
Folinic Acid Rescue ◽  
High Doses

Abstract Purpose Low doses of folinic acid (FA) rescue after high-dose methotrexate (HD-MTX) have been associated with increased toxicity, whereas high doses may be related to a decreased antileukemic effect. The optimal dosage and duration of FA rescue remain controversial. This study was designed to investigate, whether a shorter duration of FA rescue in the setting of rapid HD-MTX clearance is associated with increased toxicity. Methods We reviewed the files of 44 children receiving a total of 350 HD-MTX courses during treatment for acute lymphoblastic leukemia according to the NOPHO ALL-2000 protocol. Following a 5 g/m2 HD-MTX infusion, pharmacokinetically guided FA rescue commenced at hour 42. As per local guidelines, the patients received only one or two 15 mg/m2 doses of FA in the case of rapid MTX clearance (serum MTX ≤ 0.2 μmol/L at hour 42 or hour 48, respectively). Data on MTX clearance, FA dosing, inpatient time, and toxicities were collected. Results Rapid MTX clearance was observed in 181 courses (51.7%). There was no difference in the steady-state MTX concentration, nephrotoxicity, hepatotoxicity, neutropenic fever, or neurotoxicity between courses followed by rapid MTX clearance and those without. One or two doses of FA after rapid MTX clearance resulted in a 7.8-h shorter inpatient time than if a minimum of three doses of FA would have been given. Conclusion A pharmacokinetically guided FA rescue of one or two 15 mg/m2 doses of FA following HD-MTX courses with rapid MTX clearance results in a shorter hospitalization without an increase in toxic effects.

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