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

Jastaniah, Wasil; Elimam, Naglla; Abdalla, Khalid; AlAzmi, Aeshah; Aseeri, Mohammed; Felimban, Sami

doi:10.1016/j.lrr.2018.10.001

Cited by 5 publications

(6 citation statements)

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“…This finding was mainly related to a higher cumulative incidence of remission deaths in females receiving high intensity regimens (Arm B and C regimens). The cause for gender related differences in treatment related toxicity is not clear, but may be due to gender-related pharmacokinetic differences suggested in our population [26]. Our observations are supported by those reported by the Children’s Oncology Group study that showed a higher likelihood of treatment-related death in females undergoing treatment for high-risk ALL [27].…”

Section: Discussionsupporting

confidence: 87%

Early vs. late MRD response- and risk-based treatment intensification of childhood acute lymphoblastic leukemia: a prospective pilot study from Saudi Arabia

et al. 2018

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BackgroundRefinement of risk-based treatment stratification by minimal residual disease (MRD) at different time points has improved outcomes of childhood acute lymphoblastic leukemia (ALL). In this prospective study we evaluated effects of such stratification, including intensification of therapy based on response assessment at day-15 and MRD at day-29 of induction to test if treatment intensification would improve outcomes.Methods241 patients, 1–14 years old, newly diagnosed with ALL, were recruited and stratified by risk and MRD response into three treatment Arms (A, B, or C). Arm A was modified from COG AALL0331, B from AALL0232, and C from AALL0232 and AALL0434. Assignments were according to NCI risk, phenotype, rapid vs. slow early response (SER), steroid pretreatment, MLL rearrangement (MLLR), CNS3, and testicular involvement. Patients on Arm A had treatment intensified early based on day-15 marrow results or late based on end-of-induction MRD.Results5-year OS, EFS, and CIR were 89.5% ± 4.0%, 87.6% ± 4.3%, and 7.1% ± 3.5%. No significant difference was found by B- vs. T cell phenotype. 5-year OS, EFS, and CIR for B-cell ALL were 90.5% ± 2.4%, 88.7% ± 2.6%, and 6.4% ± 2.0%. Outcomes for patients with t(1;19)/TCF3-PBX1 and MLLR were significantly (p ≤ 0.05) worse than for other patients. MRD level at end-of-induction associated with outcomes, but association with a specific MRD value at end-of-induction varied significantly by NCI-risk group. Late treatment intensification based on end-of-induction MRD significantly improved survival outcomes for NCI-SR patients, however, patients with NCI-HR and positive MRD at end-of-induction had significantly inferior outcomes despite intensification. MRD transitions between day-15 and day-29 of induction associated with differences for OS and EFS.ConclusionsArm switching to a more intensive protocol had mixed results. Assigning patients by end-of-induction MRD-risk alone did not reflect response kinetics of the different NCI-risk groups. Although late treatment intensification improved outcomes of NCI-SR patients with positive MRD at end-of-induction, further refinement is needed to improve outcomes of NCI-HR with SER. Integration of NCI-risk group with specific MRD value and time point allows more refined treatment stratification.Trial Registration Protocols were approved by King Abdullah International Medical Research Center and Ethics Review Committee RC08053J

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Section: Discussionsupporting

confidence: 87%

Early vs. late MRD response- and risk-based treatment intensification of childhood acute lymphoblastic leukemia: a prospective pilot study from Saudi Arabia

et al. 2018

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“…The poor response of patients with t (1;19) ALL in our population was different from that reported by COG and merits further study. The inferior survival observed in female ALL patients also suggests a population difference . Pharmacokinetic/pharmacogenomic differences by gender could account for this.…”

Section: Discussionmentioning

confidence: 99%

Improving survival outcomes of childhood acute lymphoblastic leukemia: A 25‐year experience from a single center in Saudi Arabia

Jastaniah

2019

Pediatric Blood & Cancer

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Introduction:The development of cancer programs in developing countries to meet the standards observed in high-income developed countries is not well documented.Methods: An analysis of patient care of children with acute lymphoblastic leukemia (ALL) at the Princess Noorah Oncology Center over 25 years was performed. A number of improvements were introduced over time including optimizing the cancer care delivery culture, improving access to care, optimizing supportive care, and refining diagnostic and therapeutic capabilities. Outcomes were evaluated over three time periods (period 1, 1989-2000; period 2, 2001-2007; and period 3, 2008-2014). These findings were compared with results of collaborative clinical trials (CCT). Results:Of the 686 patients treated, the five-year overall survival (OS) rate improved from 74% ± 2.7% in period 1 to 89.5% ± 2.3% in period 3 (P < 0.0001). Among all patients, the five-year cumulative incidence of death decreased from 26% in period 1 to 10.5% in period 3 (P < 0.0001). This decrease was mainly due to reduction in the incidence of death from disease (P < 0.00001). In contrast, significant improvement in T-cell ALL survival outcomes (P < 0.0001) was observed overtime (from period 1 to period 3) as a result of significant reduction in both toxic deaths (P = 0.005) and disease-related deaths (P = 0.001). Conclusions:Survival outcomes in Saudi Arabia have improved with five-year OS rate now approaching 90%. However, further population-based research is needed to understand variance in outcomes from those reported by CCT groups. K E Y W O R D Sacute leukemia, ALL, developing country, outcomes research, pediatric Hematology/oncology, treatment

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“…9 The expression of multidrug resistance gene polymorphisms, like ABCC2, affects folate metabolism and causes MTX toxicity. The ALT levels have remained a surrogate marker to assess toxicity in the study by Jastaniah et al 5 The highest value of ALT documented in our study was 812 U/L, none of the children developed deranged prothrombin time (PT)/activated partial thromboplastin time (APTT) or signs of liver failure. Ursodeoxycholic acid was routinely used in children with elevated transaminases and response to therapy in the form of decreasing trend of liver enzymes was documented in 100% of the children.…”

Section: Discussionmentioning

confidence: 50%

“…The other studies which have shown comparable results of the Capizzi and HD MTX in T ALL have utilized an intensified intrathecal therapy up to 28 doses in males and 21 doses in females. 5 Thus, the Capizzi regimen is increasingly gaining importance in various aspects of ALL management. Reports of comparable toxicity and ease of administration of HD MTX regimens exist, while the literature on toxicity encountered with the Capizzi MTX has been addressed by very few studies in the past.…”

Section: Discussionmentioning

confidence: 99%

Administration and Toxicity Profile of the Capizzi Interim Maintenance—Retrospective Study from a Tertiary Care Cancer Centre

Viswanathan

Kumar

Kaushik

et al. 2021

Indian J Med Paediatr Oncol

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Introduction The Capizzi-style methotrexate (MTX) is an integral part of acute lymphoblastic leukemia (ALL) treatment. The escalating dose of MTX originally used in the United Kingdom and Children’s Oncology Group protocols along with L-asparaginase has been modified in the Indian Childhood Collaborative Leukemia (ICiCLe) group protocol where L-asparaginase has been omitted. The data regarding the incidence of toxicities and ease of administration on the Capizzi-style interim maintenance is not robust. Objectives We have compiled our experience with administration and toxicity profile in children with intermediate-risk ALL. Materials and Methods A retrospective data collection of all children diagnosed with intermediate-risk ALL as per the ICiCLe risk stratification in the year 2019 was included in the analysis. Each cycle of MTX was started after ensuring an absolute neutrophil count of >750/mm3 and transaminases <2 upper limit of normal. As a unit protocol, pre- and post-MTX hydration was administered in all our children. No urine pH or midcycle biochemical parameter monitoring was done. Statistical analysis was done using Microsoft Excel and SPSS version 24 IBM Corp. in Armonk, New York, United States. Results Forty-six children were included in the study. The median age of children in our study was 6 years (range: 1 year 2 months–12 years). Undernutrition was associated with a significant increase in toxicity (p = 0.02). Fifty-two percent of children had evidence of toxicity, elevated transaminases being the most common. There were recurring symptoms resulting in 53 episodes of toxicities overall. Incidence of toxicity was more in the early cycles (<3). Conclusion The pre- and post-MTX hydration is an effective way to reduce toxicities with the Capizzi-style MTX and this course can be administered with ease on outpatient basis with minimal need for monitoring or admission.

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

Cited by 5 publications

References 30 publications

Early vs. late MRD response- and risk-based treatment intensification of childhood acute lymphoblastic leukemia: a prospective pilot study from Saudi Arabia

Early vs. late MRD response- and risk-based treatment intensification of childhood acute lymphoblastic leukemia: a prospective pilot study from Saudi Arabia

Improving survival outcomes of childhood acute lymphoblastic leukemia: A 25‐year experience from a single center in Saudi Arabia

Administration and Toxicity Profile of the Capizzi Interim Maintenance—Retrospective Study from a Tertiary Care Cancer Centre

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